ARTIGO: INTRATIMPANIC INJECTION OF AUTOLOGUS BLOOD FOR TRAUMATIC PERILYNFATIC FISTULAS
AUTOLOGUS CHONDROCYTE IMPLANTATION PRIYANK
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Transcript of AUTOLOGUS CHONDROCYTE IMPLANTATION PRIYANK
JOURNAL CLUB (22-10-09)
topic autologus chondrocyte implantation
TOPIC AUTOLOGUS CHONDROCYTE IMPLANTATION
MODERATOR DR MBANSAL (MS DNB) DR P GUPTA (MS)
SPEAKER PRIYANK
GUPTA
THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT
J A L Hart and J Paddle
PURPOSE To define the role of ACI in treatment of cartilage defects in the knee joint
METHOD 106 articular cartilage defects in 79 knees of 77 patients were treated by ACI as described by Brittberg et al 1994
-435 of the lesions involved the patella -352 the femoral condyles
-167 the trochlea and -46 the tibial condyles -20 of knees had more than one defect
Associated biomechanical procedures were carried out in 887
RESULTS ASSESSED ARTHROSCOPICALLY 9 MONTHS AFTER IMPLANTATION70 lesions in 58 knees and 56 patients 4 eligible patients were not assessed The average ICRS repair score (maximum 12) was as follows
-Tibial condyle 115 (4 defects) -Patella 113 (32 defects) -Femoral condyle 110(23 defects) -Trochlea 107 (11 defects)
Synovitis was markedly reduced in all knees with well healed defects Contraindications to ACI in this series were
-Non-contained defects
-Bi-polar lesions
-Patients greater than 45 years
-Uncorrected biomechanics
-Regional pain syndrome type 1
-Limited joint movement
-Defective subchondral bone plate
CONCLUSION ACI EFFECTIVELY REPAIRS ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT PROVIDED THAT THE CONTRAINDICATIONS ARE RECOGNISED Unlike other series the results for the patella patellofemoral
joint have matched those for the femoral condyle This is attributed to the simultaneous biomechanical correction of the patellofemoral joint Stabilisation of the articular surface results in resolution of synovitis
AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP
Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252
Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of
Arthroscopy in 1999
Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were
osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)
All lesions involved the condyles and were deep (ICRS grds 3 and 4)
Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)
Patients were followed three years after the autologous
grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed
including eight with biopsy specimens for histology and
immunohisto-chemistry studies
RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and
one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash
84) Sixteen control MRIs were available and showed that
the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six
THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and
abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was
one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)
Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results
DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson
ARTICULAR CARTILAGE
Chondrocytes (cartilage cells) embedded in a Highly specialised ECM
Gives elasticityProvides resistance to
tensilecompressive and shear forces
Acts as a smooth efficient surface for motion
HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE
Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
TOPIC AUTOLOGUS CHONDROCYTE IMPLANTATION
MODERATOR DR MBANSAL (MS DNB) DR P GUPTA (MS)
SPEAKER PRIYANK
GUPTA
THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT
J A L Hart and J Paddle
PURPOSE To define the role of ACI in treatment of cartilage defects in the knee joint
METHOD 106 articular cartilage defects in 79 knees of 77 patients were treated by ACI as described by Brittberg et al 1994
-435 of the lesions involved the patella -352 the femoral condyles
-167 the trochlea and -46 the tibial condyles -20 of knees had more than one defect
Associated biomechanical procedures were carried out in 887
RESULTS ASSESSED ARTHROSCOPICALLY 9 MONTHS AFTER IMPLANTATION70 lesions in 58 knees and 56 patients 4 eligible patients were not assessed The average ICRS repair score (maximum 12) was as follows
-Tibial condyle 115 (4 defects) -Patella 113 (32 defects) -Femoral condyle 110(23 defects) -Trochlea 107 (11 defects)
Synovitis was markedly reduced in all knees with well healed defects Contraindications to ACI in this series were
-Non-contained defects
-Bi-polar lesions
-Patients greater than 45 years
-Uncorrected biomechanics
-Regional pain syndrome type 1
-Limited joint movement
-Defective subchondral bone plate
CONCLUSION ACI EFFECTIVELY REPAIRS ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT PROVIDED THAT THE CONTRAINDICATIONS ARE RECOGNISED Unlike other series the results for the patella patellofemoral
joint have matched those for the femoral condyle This is attributed to the simultaneous biomechanical correction of the patellofemoral joint Stabilisation of the articular surface results in resolution of synovitis
AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP
Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252
Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of
Arthroscopy in 1999
Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were
osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)
All lesions involved the condyles and were deep (ICRS grds 3 and 4)
Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)
Patients were followed three years after the autologous
grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed
including eight with biopsy specimens for histology and
immunohisto-chemistry studies
RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and
one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash
84) Sixteen control MRIs were available and showed that
the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six
THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and
abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was
one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)
Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results
DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson
ARTICULAR CARTILAGE
Chondrocytes (cartilage cells) embedded in a Highly specialised ECM
Gives elasticityProvides resistance to
tensilecompressive and shear forces
Acts as a smooth efficient surface for motion
HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE
Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT
J A L Hart and J Paddle
PURPOSE To define the role of ACI in treatment of cartilage defects in the knee joint
METHOD 106 articular cartilage defects in 79 knees of 77 patients were treated by ACI as described by Brittberg et al 1994
-435 of the lesions involved the patella -352 the femoral condyles
-167 the trochlea and -46 the tibial condyles -20 of knees had more than one defect
Associated biomechanical procedures were carried out in 887
RESULTS ASSESSED ARTHROSCOPICALLY 9 MONTHS AFTER IMPLANTATION70 lesions in 58 knees and 56 patients 4 eligible patients were not assessed The average ICRS repair score (maximum 12) was as follows
-Tibial condyle 115 (4 defects) -Patella 113 (32 defects) -Femoral condyle 110(23 defects) -Trochlea 107 (11 defects)
Synovitis was markedly reduced in all knees with well healed defects Contraindications to ACI in this series were
-Non-contained defects
-Bi-polar lesions
-Patients greater than 45 years
-Uncorrected biomechanics
-Regional pain syndrome type 1
-Limited joint movement
-Defective subchondral bone plate
CONCLUSION ACI EFFECTIVELY REPAIRS ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT PROVIDED THAT THE CONTRAINDICATIONS ARE RECOGNISED Unlike other series the results for the patella patellofemoral
joint have matched those for the femoral condyle This is attributed to the simultaneous biomechanical correction of the patellofemoral joint Stabilisation of the articular surface results in resolution of synovitis
AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP
Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252
Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of
Arthroscopy in 1999
Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were
osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)
All lesions involved the condyles and were deep (ICRS grds 3 and 4)
Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)
Patients were followed three years after the autologous
grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed
including eight with biopsy specimens for histology and
immunohisto-chemistry studies
RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and
one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash
84) Sixteen control MRIs were available and showed that
the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six
THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and
abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was
one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)
Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results
DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson
ARTICULAR CARTILAGE
Chondrocytes (cartilage cells) embedded in a Highly specialised ECM
Gives elasticityProvides resistance to
tensilecompressive and shear forces
Acts as a smooth efficient surface for motion
HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE
Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
RESULTS ASSESSED ARTHROSCOPICALLY 9 MONTHS AFTER IMPLANTATION70 lesions in 58 knees and 56 patients 4 eligible patients were not assessed The average ICRS repair score (maximum 12) was as follows
-Tibial condyle 115 (4 defects) -Patella 113 (32 defects) -Femoral condyle 110(23 defects) -Trochlea 107 (11 defects)
Synovitis was markedly reduced in all knees with well healed defects Contraindications to ACI in this series were
-Non-contained defects
-Bi-polar lesions
-Patients greater than 45 years
-Uncorrected biomechanics
-Regional pain syndrome type 1
-Limited joint movement
-Defective subchondral bone plate
CONCLUSION ACI EFFECTIVELY REPAIRS ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT PROVIDED THAT THE CONTRAINDICATIONS ARE RECOGNISED Unlike other series the results for the patella patellofemoral
joint have matched those for the femoral condyle This is attributed to the simultaneous biomechanical correction of the patellofemoral joint Stabilisation of the articular surface results in resolution of synovitis
AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP
Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252
Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of
Arthroscopy in 1999
Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were
osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)
All lesions involved the condyles and were deep (ICRS grds 3 and 4)
Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)
Patients were followed three years after the autologous
grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed
including eight with biopsy specimens for histology and
immunohisto-chemistry studies
RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and
one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash
84) Sixteen control MRIs were available and showed that
the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six
THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and
abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was
one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)
Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results
DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson
ARTICULAR CARTILAGE
Chondrocytes (cartilage cells) embedded in a Highly specialised ECM
Gives elasticityProvides resistance to
tensilecompressive and shear forces
Acts as a smooth efficient surface for motion
HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE
Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP
Journal of Bone and Joint Surgery - British Volume Vol 90-B Issue SUPP_II 252
Purpose of the study Spontaneous repair of lost deep chondral tissue is minimal in the knee joint A clinical trial of chondrocyte autografts as described by Brittberg and Peterson was undertaken by the Nantes University Hospital and the French Society of
Arthroscopy in 1999
Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were
osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)
All lesions involved the condyles and were deep (ICRS grds 3 and 4)
Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)
Patients were followed three years after the autologous
grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed
including eight with biopsy specimens for histology and
immunohisto-chemistry studies
RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and
one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash
84) Sixteen control MRIs were available and showed that
the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six
THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and
abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was
one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)
Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results
DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson
ARTICULAR CARTILAGE
Chondrocytes (cartilage cells) embedded in a Highly specialised ECM
Gives elasticityProvides resistance to
tensilecompressive and shear forces
Acts as a smooth efficient surface for motion
HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE
Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
Material and methods Twenty-eight patients mean age 28 years underwent surgery in eight centers Etiologies were
osteochondritis (n=14) isolated posttraumatic chondorpathy (n=7) chondropathy and full-thickness ACL tear (n=7)
All lesions involved the condyles and were deep (ICRS grds 3 and 4)
Mean surface area involved after debridement was 490 mm2 (range 150ndash1000 mm2)
Patients were followed three years after the autologous
grafting to assess functional outcome An MRI was obtained at 2ndash3 years Thirteen control arthroscopy procedures were performed
including eight with biopsy specimens for histology and
immunohisto-chemistry studies
RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and
one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash
84) Sixteen control MRIs were available and showed that
the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six
THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and
abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was
one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)
Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results
DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson
ARTICULAR CARTILAGE
Chondrocytes (cartilage cells) embedded in a Highly specialised ECM
Gives elasticityProvides resistance to
tensilecompressive and shear forces
Acts as a smooth efficient surface for motion
HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE
Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
RESULTS Twenty-six patients were reviewed at gt 2 yrs There were no general complications Three patients presented a partial avulsion of the graft treated by arthroscopy and
one underwent arthrolysis at six months FUNCTION improved in all patients except three and pain improved in all THE ICRS SCORE improved from 43 points (range 19ndash70) to 77 points (range 39ndash
84) Sixteen control MRIs were available and showed that
the graft was hypertrophic in eleven cases on level in four and insufficient in one Marginal integration was good in 11 cases and partial in five Subchondral integration was complete in ten cases and mediocre in six
THE ARTHROSCOPIC SCORE was nearly normal (score 8ndash11) in eight cases and
abnormal in five (score 4ndash7) THE HISTOLOGICAL CLASS according to Knutsen (hyaline richness) was
one in group 1 (gt60) three in group 2 (gt 40) four in group 3 (lt40) and one in group 4 (bony or fibrous tissue)
Function score (r=078 and MRI score (r=076) were correlated with arthroscopic sores There was no correlation with the histological results
DISCUSSION CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80 OF CASES SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES The arthroscopic and histological results were equivalent to those reported by Knutsen but inferior to those reported by Bentley or Peterson
ARTICULAR CARTILAGE
Chondrocytes (cartilage cells) embedded in a Highly specialised ECM
Gives elasticityProvides resistance to
tensilecompressive and shear forces
Acts as a smooth efficient surface for motion
HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE
Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
ARTICULAR CARTILAGE
Chondrocytes (cartilage cells) embedded in a Highly specialised ECM
Gives elasticityProvides resistance to
tensilecompressive and shear forces
Acts as a smooth efficient surface for motion
HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE
Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
HYALINE CARTILAGE STRUCTURE1048715THE ldquoSTUFFrdquo OF CARTILAGE
Functions of the Articular Cartilage ndash Distribute loadndash Absorb shock
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
CHONDRAL INJURIES
Deficient in type II collagen
Lower load bearing capacity
INEVITABLE lsquoSHORT TERMrsquo RECOVERY
Commonly these injuries heal by scar tissue formation
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
PREVALENCE AND INCIDENCE
993 consecutive arthroscopies ndash 66 articular cartilage pathology 11 full thickness localised lesions suitable for repair procedures
Aroen A Loken S Heir S et al Am J Sports Med 2004 32 211-15
31000 arthroscopic procedures ndash 63 articular cartilage lesions
Curl WW Krome J Gordon ES et al Arthroscopy 1997 13 456-60
1000 consecutive arthroscopies ndash 19 localised chondralosteochondral lesionsHjelle K et al Arthroscopy 2002 18 730-4
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
CARTILAGE INJURY OCCURS IN MANY FORMS
Trauma sports or work related
Chronic instability long term effects ACL and othermeniscal deficiency
Mal-aligned joint - deformityvarus Valgus
Osteochondritis Dissecans [OCD]
Genetic pre-disposition earlyarthritis
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
bull Most full-thickness defects are symptomaticndash Pain swelling locking catching grinding
bull Left untreatedmay progress to significant articular defects
ARTICULAR CARTILAGE DEFECTS A TREATMENT CHALLENGE
bullMay lead to debilitatingosteoarthritis
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
Arthroscopic Debridement
Arthroscopic lavage
Subchondral drilling
Microfracture MARROW STIMULATION TECHNIQUES Abrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage and may deteriorate over time)
AND WHAT IS IN OUR BASKET
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
AUTOLOGUS CHONDROCYTE IMPLANTATION
SO IT LED US TO SEARCH OF MORE PROMISING OPTION
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
JBJS [Am] 1987 Peterson et al Gothenburgndash first application of cell engineering in orthopaedics
NEJM 1994 Brittberg et al Swedenndash successfuly regenerated hyaline-like cartilage in isolated chondral defects
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) BACKGROUND
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
IDENTIFYING A CARTICELreg PATIENT
Patient FactorsYounger patients ndash lt age 45 - 50 (avg ~ 35 yo)
Significant impairment-Compromised daily livingactivities -Refractory to treatment
Obesity
Demanding Physical activities
Willing amp capable of rehabilitation program
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
IDENTIFYING A CARTICELreg PATIENThelliphellip
Joint FactorsSymptomatic cartilage defects -Moderate to large (gt 2cm2 d= 16) -On the distal femur (mfc lfc trochlea) -Average defect size gt 4 cm2
-Either chondral or osteochondral
Relatively healthy joint ndash -No arthritis
Co-morbidities(meniscal tear
instability or malalignment) must be corrected prior or concurrent to implantation
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
Pre-requisite for surgery
Not recommended for patients who have
Appropriate biomachenical alignment
Ligamentous stabilty
Range of motion
an unstable knee
patients sensitive to materials of bovine origins
allergic to the antibiotic gentamicin
in children
yet in any joint other than the knee
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
AUTOLOGOUS CHONDROCYTEIMPLANTATION (ACI)
StrengthsCan produce hyaline-like cartilageCan fill defects regardless of size with functional repair tissueModerate to large defects that have failed previous interventionRepair tissue which matures rather than deteriorates over timeExpected outcomeReturn to previous level of functioning
ldquoBiological Joint replacementrdquo
LimitationsMore invasiveExpenseLonger recovery
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
A ACI ndash Periosteum (cells under periosteum)
B ACI ndash Chondrogide (cells under membrane)
C MACI ndash Matrix Induced ACI (cells on membrane)
Chondrogide Membrane Porcine type IIII Inert Seal Resorbs in 3-4 months
ACI MACI
TECHNIQUES
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
Under inert collagen membrane (ACI)
On inert collagen membrane (MACI)
Harvest 200-300mg full thickness cartilage from trochlea (non load bearing)
Cells grown on monolayer with patients serum
No cells x 20-30
ACIMACI GENERIC METHOD
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
ACI METHOD
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
TREATMENT WITH CARTICEL
Uses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee When implanted into a cartilage injury your own cells can form new cartilage this new cartilage is very similar to your original cartilage The CARTICEL implantation procedure is called Autologous Chondrocyte Implantation or ACI It is a two-step process
Knee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure surgeon assesses the extent of cartilage damage amp pt as a candidate for CARTICEL implantation
ldquoBiopsyrdquo of healthy tissue about the size of a pencil eraser ie about 200 -300 mg
From outer edge of sup Med or lat Femoral condyle or inner edge of lat Femoral condyle at the intercondylar notch
This sample is sent to product labs
Step 1 Biopsy
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
Biopsy can be stored for up to two years so you can schedule your surgery at your convenience
When you are ready your cells are cultured over three to five weeks they increase to approx 12 million cells in a vial containing 03 ndash 04 cc of medium Every step of the manufacturing process is monitored to ensure high quality and safety
CARTICEL MANUFACTURING AND DELIVERY
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
STEP 2 IMPLANTATION
Cartilage Injury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette leaving only healthy tissue
Biomachenical allignment procedures if required should be done in conjunction with implantation
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
CARTICEL IMPLANTATION
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
PERIOSTEAL PATCH
surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury
CARTICEL Implantation surgeon injects CARTICEL under the patch
When CARTICEL is surgically implanted into a cartilage injury it can grow and form new hyaline-like cartilage with properties similar to those of the original cartilage
Repairing the injury helps to reduce pain and improve movement and function
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
ACI STEPS summarised
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
MACI METHOD
Cultured chondrocytes seeded in bilayered typeIIII collagen membrane
Implanted using fibrin glue
Matrix remodelled in months replaced by extracellular matrix regenerate
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
The overall failure rate is at present quoted as being 10 The two most common complications include bullloosening of the transplant tissue bullformation of fibrous tissue at the repair site and adhesions with return of pain and locking Neither of these complications usually leaves the patient in a worse condition than hisher pre-transplantation state
Other adverse events include bullpost-op haematoma (big blood clot)bullhypertrophic synovitis (angry knee) and superficial wound infection
COMPLICATIONS
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
IMPROVEMENTS IN CLINICAL OUTCOME
ASSESMENT OF TECHNIQUE
FOLLOW UP RESULTS
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
ONE YEAR ASSESSMENT
Radiographs Alignment Bone quality
MRI Healing
cartilage Graft failure
Arthroscopy + probe Graft integrity Pressure biopsy
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
FOLLOW UP BIOPSY
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
FOLLOW UP MRI
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
Final appearance of theperiosteum sutured overfemoral condyle defect Thecartilage cells have beeninjected under the flap and thefinal suture placed to close thecover and provide a watertightseal
FOLLOW UP ARTHROSCOPIC
Arthroscopic appearance of thesame area 12 months afterCarticeltrade implantation Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
REHABILITATION GUIDELINES
Immobilization first 12-24 hours
(CPM) after 12-24 hours for about 4 weeks
Complete joint loading from about 5th week trochleapatellafrom about 8th week condyle Back to sports Low impact rarr within 6 monthsRepeated impact rarr from 8th monthHigh impact rarr from 10-12th month
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
ACI REHABILITATION
Weight bearingIt is recommended to keep you in non-weight bearing until the second week after surgery (ACI) You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery
Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
ACI REHABILITATIONIndoor exerciseYou can strenghthen your muscles surrounding the knee joint with a four point exercise as well as isometric hamstring and squatting exercises from 4 weeks to 6 weeks after surgeryYou may start performing stationary bike activity without resistance and increase the resistance gradually
Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery
Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
COMPARISON WITH OTHER METHODS OF TREATMENTS
Autologous Chondrocyte Implantation Aims to increase the best condition for cartilage defectAdvantagesbullHyaline cartilage is formed bullPermanent reconstructed cartilage tissue bullMost valuable treatment
bullWith Fourth Generation ACI Use of cell ndash gel mixture (collagen hyaluronic acid and fibrin) has fast gelling properties (1 ndash 5 min) upon transplantation bullNo membrane or periosteal patch bullMinimal surgical exposure and reduced surgery time bullCorrects evenly irregular defect shapes bullApplicable to larger defects
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Abrasion arthroplastyAims to decrease the inflammation of the jointDisadvantagesbullRemoves many cartilage fragments from the jointbullSymptoms reoccur within one year
Drilling and MicrofractureAims to generate a healing responseDisadvantagesbullThe healing response in inadequate bullNo hyaline cartilage is formed but rather fibrocartilage bullHas a limited lifespan of approximately one year bullRapid deterioration after such procedures can be expected
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
Perichondral ResurfacingDisadvantagesbullIsolated cartilage defects are often too large to be covered byh perichondrum bullLong term follow-up of such procedures indicate that the implants undergo endochondral ossification
Synthetic Materials (ie Carbon Fiber Mesh)Disadvantagesbull It often results in fibrous tissue formation bullNot adequate biomechanically bullOften the cause for synovitis in the joints
Osteocartiloginous GraftsAims to reconstruct jointsDisadvantagesbullUnless fresh cartilage is transplanted the cartilage is dead bullFresh grafts are not commonly used as they inevitably carry a risk of disease transmission bullCyropreserved grafts can survive for many years but ultimately deteriorate
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
Results of the Carticeltrade procedure have been encouraging although it is not always successful An analysis was done of the US and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months The following results were obtainedbull Patients with clinical improvement 85bull Good or Excellent results 42 bull Good or Excellent results at 2 yearspersisting at 5 years post-op 97
Thus a total of 85 of patients showed some or complete improvement with theimplantation technique The Carticel procedure demonstrated good durability at 5-10 years out
CONCLUSIONS
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
CONCLUSIONS ACI Vs MACI No current evidence to justify aggressive treatment of
asymptomatic lesions with ACIMACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years(even among those with previous failed marrow stimulation techniques)
MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
RECENT ADVANCESHYAFF 3D MATRIX
HYAFF biomaterialscontain high quantities ofderivatized HA
HA-richchondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
bull Non woven felt 2 mm thick fiber diameter 10 micronsbull Chondrocytes are isolated and passaged in culture on plasticdishes up to 3 weeksbull Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 cm2 resulting in a total of 4 x 106 cm2 seeded cells pergraft
HYAFF-BASED SCAFFOLD
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
CHONDRONtrade
Uses a cell ndash gel mixture (includes collagen hyaluronic acid and fibrin) that has fast gelling properties (1 ndash 5 min) upon transplantation
This cell and gel mixture enable even cell distribution three-dimensionally moldable to fit irregular defect shape and applicable to a larger defectThus there is minimal surgical exposure and reduced surgery time
(three-dimensional reconstruction of a chondron from the growth plate of the murine long bone the model was generated from multiple sections imaged in an electron microscope plasma membranes are coloured green and internal organelles are visible within the top cell)
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
RECOVERY TO
HEALTHY ACTIVE LIFE
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-
THANK YOU
- journal club (22-10-09)
- topic autologus chondrocyte implantation
- THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TR
- Slide 4
- AUTOLOGOUS CHONDROCYTE GRAFTS MULTICENTRIC TRIAL WITH 28 KNEE
- Slide 6
- Slide 7
- Articular Cartilage
- Hyaline Cartilage Structure 1048715The ldquostuffrdquo of cartilage
- Slide 11
- Cartilage Injury Occurs in Many Forms
- Articular Cartilage Defects a treatment challenge
- AND WHAT IS IN OUR BASKET
- SO IT LED US TO SEARCH OF MORE PROMISING OPTION
- Autologous Chondrocyte Implantation (ACI) BACKGROUND
- Identifying a Carticelreg Patient
- Identifying a Carticelreg Patienthelliphellip
- Pre-requisite for surgery
- Autologous Chondrocyte Implantation (ACI)
- Techniques
- ACIMACI Generic Method
- Slide 23
- Treatment with CARTICEL
- CARTICEL Manufacturing and Delivery
- Step 2 Implantation
- CARTICEL Implantation
- Periosteal Patch
- Slide 29
- Slide 30
- Aci steps summarised
- Slide 32
- Complications
- Slide 34
- Slide 35
- FOLLOW UP Biopsy
- FOLLOW UP MRI
- FOLLOW UP ARTHROSCOPIC
- Rehabilitation guidelines
- ACI Rehabilitation
- ACI Rehabilitation (2)
- COMPARISON WITH OTHER METHODS OF TREATMENTS
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip
- COMPARISON WITH OTHER METHODS OF TREATMENTShelliphelliphellip (2)
- CONCLUSIONS
- Slide 46
- Recent advancesHYAFF 3D matrix
- HYAFF-based Scaffold
- CHONDRONtrade
- RECOVERY TO
- Slide 51
-