Arthroscopy Association of North America (AANA) Hip Arthroscopy
Biologics in Sports Medicine · Biologic augmentation of RC repair with MSC during arthroscopy...
Transcript of Biologics in Sports Medicine · Biologic augmentation of RC repair with MSC during arthroscopy...
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CLINICAL SYMPOSIUM 2017:
WHAT’S NEW IN SPORTS & SHOULDER
California Orthopedic Association
Annual Meeting 2017
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Biologics in
Sports Medicine
Tal S. David, MD
Synergy Specialists Medical Group
San Diego, CA
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Disclosures:
• Arthrex Inc: Product Royalties / Paid Consultant
• SLACK Inc: Publication Royalty
• AAOS: Sports Medicine Program Committee
• AOSSM: Committee of Delegates
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Sometimes the Solution isn’t a
Mechanical One…
• Degeneration of tendon
or cartilage
• “Unsolvable” b/c there
is NO biologic stimulus
• It likely isn’t
Repairable…you would have
to ask it to REGENERATE
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Biologics
Offers the allure of the Holy Grail
Can we effect de-generation?
Can we stimulate re-generation?
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Our generation’s solution to find…
➢Mesenchymal Stem Cells
➢Platelet-Rich Plasma
➢Growth Factors/Cytokines
Qs: Sources, Concentrations and Applications
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Regulators are not comfortable with
the rise of Biologics
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FDA & Regulatory Environment:
• Minimal manipulation of cell tissue
• Homologous use
• Cannot be combined with drug or device
• Autologous use
• Point-of-care (no lab use)
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Mesechymal Stem Cells (MSC)
Bone Marrow:• Microfracture• Bone Marrow Aspirate
Concentration (BMAC)
WHAT?
Adipose:• Liposuction• Fat Pad
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MSC Definition:
Int’l Society for Cellular Therapy (ISCT)
EXPRESS
CD 105
CD 73
CD 90
NOT EXPRESSED
CD 45
CD 34
CD 14
CD 19
CD 79α
CD 11b
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Mesechymal Stem Cells (MSC)
Directly:• Differentiating into
damaged cell types
HOW?
Indirectly:• Stimulate angiogenesis• Limiting Inflammation• Recruiting Progenitors
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About MSCs:
What we Know:
✓ Cultured in monolayer (plastic-adherent)
✓ Can differentiate into: Osteoblasts, Adipocytes,
Chondroblasts
What we Don’t Know:
✓ Specifics of lineage induction
✓ Whether the desired lineage is induced before MSC
delivery
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Clinical Applications:
Is It Safe?
Does It Work (RCT)?
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Is It Safe?
• A Prospective, Single-Blind, Placebo-Controlled
Trial of BMAC for knee OA (Level 2)
Shapiro SA, et al. Am J Sports Med 2017
• Clinical Outcomes of autologous BMAC injection
in degenerative arthritis of the knee
Kim JD, et al. Eur J Orthop Surg Traumatol 2014
• Multi-center study: 3012 procedures
Centeno CJ, et al. Int. Orthop 2016
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Is It Safe?
• A Prospective, Single-Blind, Placebo-Controlled
Trial of BMAC for knee OA (Level 2)
Shapiro SA, et al. Am J Sports Med 2017
• Clinical Outcomes of autologous BMAC injection
in degenerative arthritis of the knee
Kim JD, et al. Eur J Orthop Surg Traumatol 2014
• Multi-center study: 3012 procedures
Centeno CJ, et al. Int. Orthop 2016
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Does It Work?Knee OA
Concentrated Bone Marrow Aspirate for the
Treatment of Chondral Injuries and OA of the knee: A
Systematic Review of Outcomes
Chahla J, et al. Orthop J Sports Med 2016
• 11 studies (3 for OA; 8 for focal chondral injury)
• All reported “good/excellent outcomes” but
marginal quality studies (Level 4)
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Does It Work?For Mild-Mod Knee OA
A Prospective, Single-Blind, Placebo-Controlled
Trial of BMAC for knee OA
Shapiro SA, et al. Am J Sports Med 2017
• N=25 with knee pain
• BMAC (52ml spun to 6cc) v. Saline (6cc)
Similar relief of pain in both BAC and saline
tx’ed knees
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Does It Work?For Tendinopathy (RC)
Biologic augmentation of RC repair with MSC
during arthroscopy improves healing and prevents
further tears: a case-controlled study
Hernigou P, et al. Int Orthop 2014
• N= 90 pts. (45 RCR + BMAC / 45 RCR - BMAC)
• Minimum 10 year F/U
• @ 6 months: 100% RCR+BMAC healed (v. 67%)
• @ 10 years: 87% v. 44%
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Platelet-Rich Plasma (PRP)
Sample of autologous blood with platelet
concentrations above baseline
• Platelets
• Plasma
• Leukocytes
WHAT?
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Platelet-Rich Plasma (PRP)
Differentiation:
HOW?
Indirectly:• Growth Factors
✓ Chemoattractants
✓ Stimulate cell proliferation✖
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Platelet-Rich Plasma (PRP)
Inflammatory Cytokines
What else does PRP contain?
Matrix MetalloProteinases
Known to increase tissue damage
✓ TNFα✓ IL-1
✓ MMP2✓ MMP9
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Clinical Applications:
Is It Safe?
Does It Work?
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Is It Safe?
PRP versus saline for knee osteoarthritis
Smith PA. Am J Sports Med 2016
• Level 1 study
• 12 month follow-up
• No adverse events
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Is It Safe?
PRP versus saline for knee osteoarthritis
Smith PA. Am J Sports Med 2016
• Level 1 study
• 12 month follow-up
• No adverse events
YES
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Does It Work?Knee OA
Efficacy of Intra-articular Platelet-Rich Plasma
Injections in Knee Osteoarthritis: A Systematic
Review
Meheux CJ, et al. Arthroscopy 2016
• 6 articles reviewed (Level 1) / 739 patients
• Mean age 59.9 y / 38 week avg. follow-up
PRP injection results in significant clinical
improvements up to 12 months post-injection
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Does It Work?Knee OA (Advanced)
Platelet-Rich Plasma Injections for Advanced Knee
Osteoarthritis: A Prospective, Randomized,
Double-Blinded Clinical Trial
Joshi Jubert N, et al. Orthop J Sports Med 2017
• 75 patients with symptomatic K-L grade 3-4
randomized to a single LP-PRP or corticosteroid IA
injection
• VAS, KOOS, SF-36 @ 1,3 and 6 months
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Does It Work?Knee OA (Advanced)
• All variables improved in both groups
• Magnitude of improvements tended to be
greater in PRP group
For late stage OA, a single PRP IA injection has
similar results to a single shot of corticosteroid
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Does It Work?PRP v HA
A Prospective, Double-Blind, Randomized
Controlled Trial Comparing Clinical Outcomes and
Effects of IA Biology for the Treatment of Knee
Osteoarthritis
Cole BJ, et al. Am J Sports Med 2016
• Level 1
• N=99 pts randomized to 3 consecutive IA injections
• VAS, WOMAC, IKDC
• Pre- and Post- treatment synovial fluid collected
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Does It Work?PRP v HA
• Higher IKDC and lower VAS @ 24 weeks and 52
weeks in PRP cohort.
• Mild OA and lower BMI had better outcomes
• Trend toward a decrease in 2 pro-inflammatory
cytokines (IL-1β and TNFα) in the PRP cohort
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Does It Work?Hip OA
Ultrasound-Guided Injection of PRP and HA
Separately and in Combination for Hip OA:
A Randomized Controlled Trial
Dallari D, et al. Am J Sports Med 2016
• N=111
• Randomized into 3 groups: 3 weekly injections
• VAS, WOMAC, Harris Hip Score @ 2, 6 &12 months
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3 Randomized Groups:
PRP
44
VAS 21* (p<0.05)
WOMAC better at 2 and 6
months (p<0.05)
PRP + HA
31
VAS 35*
HA
36
VAS 44*
* At all follow-up timelines
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Results:
• IA PRP injections offered significant
clinical improvement in patients with hip
OA without relevant side effects
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What about PRP for
Tendinopathy?
“The Sweet Spot”
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The Effectiveness of PRP in the Treatment
of Tendinopathy: A Meta-analysis of RCT
Fitzpatrick J, et al. Am J Sports Med 2017
• 18 Studies (1066 participants)
Most significant outcomes in the PRP groups were seen in
those treated with LR-PRP preparations
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Recomendations:
• Peppering technique
• Intra-tendinous injection
• Ultrasound guidance
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Patellar Tendinopathy
PRP as a Treatment for Patellar
Tendinopathy: a double-blind, randomized
controlled trial
Dragoo JL, et al. Am J Sports Med 2014
• 23 patients randomized to LR-PRP or Dry Needling
• @ 12 weeks the PRP group had no failures (p<0.05)
• Results dissipate over time (>26 weeks)
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Lateral Epicondylitis
Efficacy of PRP for Chronic Tennis Elbow: a
double-blind, prospective, multi-center,
randomized controlled trial of 230 patients
Mishra AK, et al. Am J Sports Med 2014
• No significant differences @ 12 weeks
• LR-PRP group had better improvement @ 24 weeks
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Human Amniotic-Derived Products
• Amnion is separated from maternal Chorion
• 3 layers:
✓Epithelial cells – actively produce growth factors
✓Basement membrane
✓Avascular mesenchymal tissue
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Human Amniotic-Derived Products
• Dehydrated or Cryopreserved
• Decellularized
• Tissue falls under FDA Section 361 product
– Low safety risk “Allograft”
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Clinical Applications:
Is It Safe?
Does It Work?
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The Placenta: Applications in Orthopaedic
Sports Medicine
McIntyre JA, et al. Am J Sports Med 2017
Human Amniotic Membrane-Derived
Products in Sports Medicine
Riboh JC, et al. Am J Sports Med 2016
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PROBABLY
The Placenta: Applications in Orthopaedic
Sports Medicine
McIntyre JA, et al. Am J Sports Med 2017
Human Amniotic Membrane-Derived
Products in Sports Medicine
Riboh JC, et al. Am J Sports Med 2016
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Does It Work?
• Provide a matrix for cellular migration
• Enhance wound healing
• Reduce inflammation
• Antibacterial
• Reduce pain at application site
361 product only as a wound covering
o/w considered “off label” use
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Does It Work?
?• There are currently 6 human studies reported
• 5 of 6 applicable to Foot/Ankle pathology
• No RCT available
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Conclusions:
• Research in Biologics for Sports Medicine is
starting to bear fruit
• The role of PRP in OA and tendinopathies is
becoming more clear
• Knowledge gaps still exist with respect to
MSC
• Amniotic cells and tissue need RCT study
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THANK YOU