Medical education ENT, CMF & Neurosurgery - Bonalive · Medical education ENT, CMF & Neurosurgery...

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Osteostimulation* Inhibition of Bacterial Growth Bioactive Bone Bonding *non-osteoinductive Bone Regeneration Medical education ENT, CMF & Neurosurgery Natural Hydroxyapatite Formation

Transcript of Medical education ENT, CMF & Neurosurgery - Bonalive · Medical education ENT, CMF & Neurosurgery...

Page 1: Medical education ENT, CMF & Neurosurgery - Bonalive · Medical education ENT, CMF & Neurosurgery Natural Hydroxyapatite Formation 2 MECHANISM OF ACTION Inhibition of Bacterial Growth

Osteostimulation*Inhibition of Bacterial Growth

Bioactive Bone Bonding

*non-osteoinductive

Bone Regeneration

Medical education ENT, CMF & Neurosurgery

Natural Hydroxyapatite Formation

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MECHANISM OF ACTION

Inhibition of Bacterial Growth

In contact with body fl uids bioactive glass works by leaching out ions leading to an alkaline environment (high pH) and increased osmotic pressure. Th is mechanism has been shown to eff ectively inhibit bacterial growth.

BonAlive® granules (bioactive glass S53P4) is a CE-marked class III medical de-vice that is used in surgical procedures to regenerate bone. BonAlive® granules is osteostimulative* which means that it activates genes responsible for bone forma-tion in osteogenic cells. It also has the special property of eff ectively inhibiting bacterial growth, which makes it a very unique material for regenerating bone.

BonAlive® granules Composition: • 53% SiO2, 23% Na2O, 20% CaO, 4% P2O5

BonAlive® granules Indications:• Bone cavity fi lling in cranio-maxillofacial area including the jaw• Frontal sinus obliteration after severe chronic sinusitis or fractures

in the frontal bone area• Mastoid cavity obliteration and nasal cavity narrowing

Bone Bonding and Osteointegration

Th e surface reactions develop a silica gel layer on the bioactive glass, which attracts the Ca and P that has been released from the granules. Th e precipitated CaP crystallizes to natural hydroxyapatite, which is similar to the mineral component of bone. Th e newly formed natural surface will promote bone bonding and osteointegration.

Silica Gel Layer Formation

NaCa

PSi

Osmotic Pressure

NaOH

pH Increase

Na

BonAlive® granules

Inhibition of Bacterial Growth

BonAlive® granules

Silica Gel LayerSSiilli

CaP Crystallizes into Hydroxyapatite

CaP

CaP

Formation of Natural Hydroxyapatite

*non-osteoinductive

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INHIBITION OF BACTERIAL GROWTH

One of the most striking features of BonAlive® granules is its ability to inhibit bacterial growth. Th is phenomenon has been evidenced with more than 50 clini-cally relevant aerobic and anaerobic bacterial species through in vitro studies, and indirectly by empirical observation of patient data over the past 15 years.

Chronic bone infections play a large role in surgery as the infection can be dif-

fi cult to eradicate and might require several operations. Antibiotic resistance has become an increasing threat and new tools that are not based on antibiotics can bring signifi cant benefi ts in fi ghting chronic bone infections. Th e effi cacy of BonAlive® granules towards methicillin-resistant (MR) Pseudomonas aeruginosa, Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE) has been tested and proven eff ective.

References Antibiofi lm Agents Against MDR Bacterial Strains: Is Bioactive Glass BAG-S53P4 Also Eff ective? Bortolin M, De Vecchi E, Romanò CL, Toscano M, Mattina R and Drago L. J Antimicrob Chemother. 2016 Jan;71(1):123-7.Antimicrobial Activity and Resistance Selection of Diff erent Bioglass S53P4 Formulations Against Multidrug Resistant Strains. Drago L, De Vecchi E, Bortolin M, Toscano M, Mattina R and Romanò CL. Future Microbiol. 2015;10(8):1293-9.In Vitro Antibiofi lm Activity of Bioactive Glass S53P4. Drago L, Vassena C, Fenu S, De Vecchi E, Signori V, De Francesco R, Romanò CL. Future Microbiol. 2014;9(5):593-601.Antibacterial Eff ects and Dissolution Behavior of Six Bioactive Glasses. Zhang D, Leppäranta O, Munukka E, Ylänen H, Viljanen MK, Eerola E, Hupa M, Hupa L. J Biomed Mater Res. 2010;93A(2):475-483.Bactericidal Eff ects of Bioactive Glasses on Clinically Important Aerobic Bacteria. Munukka E, Leppäranta O, Korkeamäki M, Vaahtio M, Peltola T, Zhang D, Hupa L, Ylänen H, Salonen JI, Viljanen MK, Eerola E. J Mater Sci: Mater Med. 2008;19(1):27-32.Antibacterial Eff ect of Bioactive Glasses on Clinically Important Anaerobic Bacteria In Vitro. Leppäranta O, Vaahtio M, Peltola T, Zhang D, Hupa L, Ylänen H, Salonen JI, Viljanen MK, Eerola E. J Mater Sci: Mater Med. 2008;19(2):547-551.In Situ pH within Particle Beds of Bioactive Glasses. Zhang D, Hupa M, Hupa L. Acta Biomaterialia. 2008;4(5):1498-1505.Factors Controlling Antibacterial Properties of Bioactive Glasses. Zhang D, Munukka E, Hupa L, Ylänen H, Viljanen MK, Hupa M. Key Engineering Materials. 2007;330-332:173-176.Comparison of Antibacterial Eff ect on Th ree Bioactive Glasses. Zhang D, Munukka E, Leppäranta O, Hupa L, Ylänen H, Salonen J, Eerola E, Viljanen MK, Hupa M. Key Engineering Materials. 2006;309-311:345-348.Interactions Between the Bioactive Glass S53P4 and the Atrophic Rhinitis-Associated Microorganism Klebsiella Ozaenae. Stoor P, Söderling E, Grenman R. J Biomed Mater Res. 1999;48(6):869-874.Antibacterial Eff ects of a Bioactive Glass Paste on Oral Micro-Organisms. Stoor P, Söderling E, Salonen JI. Acta Odontol Scand. 1998;56(3):161-165.Interactions Between the Frontal Sinusitis-Associated Pathogen Heamophilus Infl uenzae and the Bioactive Glass S53P4. Stoor P, Söderling E, Andersson OH, Yli-Urpo A. Bioceramics. 1995;8:253-258.

Mechanism

Th e bacterial growth inhibiting eff ect of BonAlive® granules is based on two simultaneous processes that occur when the bioactive glass re-acts with body fl uids.

1. Sodium is released from the surface of the bioactive glass and induces an increase in pH (alkaline environment), which is not favourable for the bacteria.

2. Th e released Na, Ca, Si and P ions give rise to an increase in osmotic pressure due to an elevation in salt concentration, i.e. an environment where the bacteria cannot grow.

Th ese two mechanism will together eff ectively inhibit the adhesion and colonization of bacteria on the granule surface.

0 1 2 3 4 5 6 7 8

Blood pH 7,4

9 10 11 12 13 14

Increase in pH

Increase in

Osmotic

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Gram Positive Bacteria

Bacillus cereusBifi dobacterium adolescentisClostridium diffi cileClostridium perfringensClostridium septicumCorynebacterium ulceransEnerobacter cloacae Enterococcus faecalisEnterococcus faeciumEubacterium lentumListeria monocytogenesMicrococcus sp.Mycobacterium tuberculosisPeptostreptococcus anaerobiusPeptostreptococcus magnusPropionibacterium acnesPropionibacterium propionicusStaphylococcus aureusStaphylococcus epidermidisStaphylococcus hominisStaphylococcus lugdunensisStreptococcus agalactiaeStreptococcus mutansStreptococcus pneumoniaeStreptococcus pyogenes

Streptococcus sanguis

BonAlive® granules is eff ective in inhibiting bacterial growth of more than 50 common bacteria species (including MRSA, MRSE).

Gram Negative Bacteria

Acinetobacter baumannii

Bacteroides fragilisBacteroides thetaiotaomicronChryseobacterium (former Flavobacterium) meningosepticumEnterobacter aerogenesEnterobacter amnigenusEscherichia coliFusobacterium necrophorumFusobacterium nucleatumHaemophilus infl uenzae

Klebsiella pneumoniaeMoraxella catarrhalisNeisseria meningitidisPasteurella multocidaPorphyromonas gingivalisPrevotella intermediaPrevotella melaninogenicaProteus mirabilisPseudomonas aeruginosaSalmonella typhimurium Shigella sonnei Veillonella parvulaYersinia enterocolitica

Methicillin-resistant bacteria

Pseudomonas aeruginosa

Staphylococcus aureus (MRSA)

Staphylococcus epidermidis (MRSE)

Hydroxyapatite (HA) BonAlive® granules

Bacteria

(Adherence)

Bacteria

(Non-Adherence)

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The images illustrate the impact of S53P4 on methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae and Acinetobacter baumannii. The inhibition of bacterial growth can be seen as changes in the morphology of the bacteria; deformation of the cells and hole formation in the cell membranes.

Bacteria test with pigmented Porphyromonas gingivalis shows that bacteria cannot adhere and grow on BonAlive® granules surface.

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Broad Spectrum Effi cacy

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Hydroxyapatite starts to form on BonAlive® granules surface.

BonAlive® granules bond to bone and stimulate new bone formation (osteostimulation*).

OSTEOINTEGRATION AND OSTEOSTIMULATION*

An osteoconductive material functions as a scaff old that allows bone growth on its surface or into its three-dimensional structure. BonAlive® granules is osteocon-ductive in nature, providing a supportive material for the osteoblast cells during bone formation. As a result of the osteoconductive process, bone grows onto and

between the bioactive glass granules. Furthermore, the bioactive glass granules have been proven to activate a biological process that stimulates bone regenera-tion in a fashion far superior to mere osteoconductive materials. Th is is defi ned as osteostimulation*.

Hydroxyapatite covers BonAlive® granules surface.

*non-osteoinductive

1 Day 1 Week 6-12 Weeks

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“The bioactive glass surface is not only conductive but also osteoproductive in promoting migration, replication, and diff erentiation of osteogenic cells and their matrix production.”

Virolainen et al. 1997

Collagen Fibres

BonAlive® granules Surface

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Illustration of a BonAlive® bioactive glass granule to show the characteristics of the reaction surface.

Scanning electron microscopy (SEM) image (10 000 x magnification) presenting the hydroxyapatite surface that resembles the mineral phase found in natural bone.

References Genetic Design of Bioactive Glass. Hench L. J Eur Cer Soc. 2009;29:1257-1265.Molecular Basis for Action of Bioactive Glasses as Bone Graft Substitute. Välimäki VV, Aro HT. Scand J Surg. 2006;95(2):95-102.Intact Surface of Bioactive Glass S53P4 is Resistant to Osteoclastic Activity. Wilson T, Parikka V, Holmbom J, Ylänen H, Penttinen R. J Biomed Mater Res. 2005;77A(1):67-74.Granule Size and Composition of Bioactive Glasses Aff ect Osteoconduction in Rabbit. Lindfors NC, Aho AJ. J Mater Sci: Mater Med. 2003;14(4):265-372.Histomorphometric and Molecular Biologic Comparison of Bioactive Glass Granules and Autogenous Bone Grafts in Augmentation of Bone Defect Healing. Virolainen P, Heikkilä J, Yli-Urpo A, Vuorio E, Aro HT. J Biomed Mater Res. 1997;35(1):9-17.Long Term Behaviour of Bioactive Glass Cone and Granules in Rabbit Bone. Heikkila JT, Salonen H, Yli-Urpo A, Aho AJ. Bioceramics. 1996;9:123-126.Bone Formation in Rabbit Cancellous Bone Defects Filled with Bioactive Glass Granules. Heikkila JT, Aho HJ, Yli-Urpo A, Happonen R, Aho AJ. Acta Orthopaedica. 1995;66(5):463-467.

Reaction Layers of BonAlive® granules Natural Hydroxyapatite Surface on BonAlive® granules

Th e bioactive surface of the BonAlive® granules is characterized by its ability to attach fi rmly to living tissue, facilitate tissue growth and bond chemically with surrounding bone. Osteogenic cells, such as osteoblasts and osteoclasts will be

stimulated by the released Si and Ca and the natural hydroxyapatite surface. Sub-sequently the bone formation pathway will be initiated.

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Formation of Natural Hydroxyapatite and Osteointegration

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Histological 20μm-thick section from the mastoid area at 3 months after BonAlive® granules implantation (human biopsy).

The natural hydroxyapatite layer that has been formed on the BonAlive® granules conducts and stimulates new tissue formation in the grafted area. Tissue formation can be clearly visualized around the BonAlive® granules in the microscopy image.

Th e mechanism of bone regeneration with bioactive glass has been demonstrated to be based on both surface-mediated (natural hydroxyapatite surface) and solu-tion-mediated (release of Si and Ca) processes. Th e eff ect is seen on a cellular level as promotion of particular cell stages of the osteogenic cell lineage through specifi c gene activation. Th is active role in osteogenesis has been defi ned as osteostimula-tion*. In vitro and preclinical studies with BonAlive® granules give evidence that it acts as an osteostimulative* material.

• recruitment and diff erentiation of osteogenic cells• promotion of osteogenic cells to increase the remodeling rate of bone• activation of specifi c genes in osteogenic cells as a response to ion dissolu-

tion and the natural HA surface

*non-osteoinductive

Histology 3 Months Post-Op Stimulation of Tissue Formation

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ReferencesMolecular Basis for Action of Bioactive Glasses as Bone Graft Substitute. Välimäki VV, Aro HT. Scand J Surg. 2006;95(2):95-102.Osteoblast Diff erentiation of Bone Marrow Stromal Cells Cultured on Silica Gel and Sol-Gel-Derived Titania. Dieudonné SC, van den Dolder J, de Ruijter JE, Paldan H, Peltola T, van ‘t Hof MA, Happonen RP, Jansen JA. Biomaterials. 2002;23(14):3041-3051.Histomorphometric and Molecular Biologic Comparison of Bioactive Glass Granules and Autogenous Bone Grafts in Augmentation of Bone Defect Healing. Virolainen P, Heikkilä J, Yli-Urpo A, Vuorio E, Aro HT. J Biomed Mater Res. 1997;35(1):9-17.

Osteostimulation*

Defi nition of Osteostimulation* ‘Activation of Genes Responsible for Bone Formation in Osteogenic Cells’

BonAlive® granules Plays an Active Role in:

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Th e radio-opaque nature of the bioactive glass brings signifi cant benefi ts. Th e BonAlive® granules can be visualized with imaging during surgery and the progression of the healing can be followed post-operatively.

Th e following imaging has been produced after mas-toid obliteration to detect residual cholesteatoma. In all CT scans and MRI sequences a cholesteatoma can easily be detected since the appearance of the BonAlive® granules is completely diff erent from the appearance of cholesteatoma. Th e white arrows point to where the BonAlive® granules are applied.

VISUAL APPEARANCE

CT-Scan T1-WI

T2-WI Post-Contrast T1-WI 1-Year Post-Op Non-EPI-DW MRI

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MASTOID SURGERY

Canal-wall-down (CWD) procedures can lead to burdensome postoperative treat-ment. Th e disadvantages of CWD cavities are associated with the need for fre-quent cleaning of the cavity due to debris accumulation or infections and diffi cul-ties in using hearing aids. Occasionally revision surgery to decrease or eliminate the mastoid cavity with the aim of eradicating the infection is an alternative.

Several long term studies have shown that mastoid cavities with continuous in-fections and cleaning problems can be obliterated with BonAlive® granules. Th e BonAlive® granules have been used for more than 15 years with success for mastoid obliteration. Th e unique bacterial growth inhibiting feature and slow resorption profi le of BonAlive® granules give distinct advantages when used to obliterate dis-charging and chronically infected mastoid cavities. In addition, the osteostimula-tive* property of BonAlive® granules supports new tissue formation in the cavities.

ReferencesMastoid Cavity Obliteration with Bioactive Glass Granules. Schimanski G, Schimanski E. In: Recent Advances in Otolaryn-gology - Head and Neck Surgery. Lalwani A., Pfi ster M. 2016;5:249-281.Cutaneous and Labyrinthine Tolerance of Bioactive Glass S53P4 in Mastoid and Epitympanic Obliteration Surgery: Pro-spective Clinical Study. Bernardeschi D, Nguyen Y, Russo FY, Mosnier I, Ferrary E, Sterkers O. BioMed Research International Volume 2015 (2015), Article ID 242319. (An open access journal.)Obliteration von Mastoidhöhlen. 30 Jahre Erfahrung mit Empfehlungen zur Operationsstrategie. Schimanski G, Schiman-ski E. HNO 2015;63:538-545.Bioactive Glass S53P4 in Mastoid Obliteration Surgery for Chronic Otitis Media and Cerebrospinal Fluid Leakage. Sarin J, Grenman R, Aitasalo K, Pulkkinen J. Annals of Otology, Rhinology & Laryngology. 2012;121:563-569.Mastoidectomy Cavity Obliteration with Bioactive Glass: A Pilot Study. Silvola JT. Otolaryngology - Head and Neck Sur-gery. 2011;145(2):96-97.Bioactive Glass S53P4 in the Filling of Cavities in the Mastoid Cell Area in Surgery for Chronic Otitis Media. Stoor P, Pulkkinen J, Grenman R. Ann Otol Rhinol Laryng. 2010;119(6):377-382.

*non-osteoinductive

BonAlive® granules Indication

• Mastoid cavity obliteration

Obliterated mastoid cavity with BonAlive® granules.

Radical mastoid cavity.

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Surgical Technique of Mastoid Obliteration

Retroauricular incision 1 cm from the ear base. Skin from the mastoid cavity is elevated from the walls of the cavity to form new skin for the posterior canal wall.All ridges are removed and the cavity is cleaned with a dia-mond burr.

Pieces of cartilage are placed in the bottom of the cavity along the ear canal wall. The cartilage supports the new skin of the ear canal and will prevent BonAlive® granules from migrating into the ear canal.If needed, a layer of fascia from the temporal region can be placed between the skin and the cartilage to provide addi-tional support for the canal wall.

The cavity is partially obliterated with moistened BonAlive® granules during this stage, since the external auditory canal needs to be shaped and tamponed first.

The posterior ear canal wall is shaped from the external ear canal according to the desired anatomy. Silicon sheets are inserted along the external ear canal and the tampons are placed to give support to the ear canal wall.

The mastoid is filled up with moistened BonAlive® granules to the level of the cortical bone. If suitable cartilage pieces are available they can be placed on top of the granules.The musculoperiosteal flap will be placed to cover the granules and the incision is sutured.

According to clinical experiences, edematous swelling can be reduced and excess fluid can be evacuated by applying a vacume drain into the area that has been obliterated with BonAlive® granules. The drain can be removed within a few days postop-eratively, when the vacuum maintains for 8–12 hours.

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Obliteration of a Chronic Ear with Eff usion and Caloric Stimulus

Patient: A 46-year old male with a radical cavity in the left ear. Th e patient was operated 2 years previ-ously, which resulted in a chronic ear with recurrent eff usion, incomplete cleaning and caloric stimulus. It was diffi cult for the patient to wear a hearing aid causing eff usion.

Preoperative Finding: Th ere was no overview to the terminal cell with a 30° endoscope and the ex-ternal ear canal had a very narrow entrance.

Operation: With a retroauricular incision a tym-panoplasty/mastoidplasty was performed. A mas-sive cholesteatoma epithelium was removed from the terminal cell. Th e dura middle fossa cranii was

visible. Th e mastoid and middle ear area was thor-oughly cleaned from scar tissue. Th e incus was ab-sent and the mobile stapes (type III) was covered with thick cartilage. Th e cartilage was removed and a VARIAC-Titanium prosthesis (partial 2.5) im-planted with a thin plate of cartilage underneath the tympanic membrane. Th e visible dura was covered with perichondrium. Obliteration of the mastoid was performed with 5 cc BonAlive® granules, cov-ered by overlapping thinned pieces of cartilage from the cavum conchae after the meatoplasty and fas-cia from the m. temporalis. Th e attic was only fi lled with cartilage. No postoperative treatment with an-tibiotics was given.

Clinical Outcome: At 3 weeks postoperatively the silicon sheets and the package (tampons) were re-moved from the external ear canal. An incomplete epithelization of the posterior ear wall was observed. Th e external ear canal (meatus) was treated with ear-drops. At 5 months postoperatively the skin of the external ear canal (meatus) was slightly reddish and swollen.

At 14 months the meatus had healed well presenting a normal anatomy. At 3.5-year follow-up the patient was fully healed and presented a normal ear.

Pre-Op 5-Month Post-Op 14-Month Post-Op

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Obliteration of an Old Chronically Infected Mastoid Cavity

Patient: A 57-year old male (bank employee) who underwent a radical mastoidectomy in the left ear at the age of 14. Th e patient suff ered from continu-ous secretion/eff usion with pain requiring frequent treatment by an ENT-specialist. Th e patient was not able to use a hearing aid.

Preoperative Finding: Th e patient had a cavity with granulation in the sinus dura angle. Th ere was no control of the mastoid/terminal cell with a 30° endoscope.

Operation: With a retroauricular incision a mas-toidplasty was performed. Th e mastoid was cleaned and all granulation tissue was removed. Th e dura medial fossa cranii was visible, the epithelium was removed from the attic (malleus head and incus were absent) and the middle ear was kept untouched. Th e mastoid was obliterated with 4.5 cc BonAlive® gran-ules and covered with overlapping thinned pieces of cartilage from the cavum conchae and fascia from the m. temporalis. No postoperative treatment with antibiotic was given.

Clinical Outcome: At 2 months postoperatively the meatus was still reddish and swollen. Th e external ear canal (meatus) was treated with ear drops (con-sisting of dexamethasone, neomycin and polymyx-in) for 2 weeks. At 5 months the meatus had healed well presenting a normal anatomy and the patient could wear a hearing aid without problems.

Pre-Op 2-Month Post-Op 5-Month Post-Op

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Obliteration of a Radical Mastoid Cavity with Cholesteatoma

Patient: A 76-year old female who had undergone a tympanoplasty (canal wall down) and meatoplasty (cartilage) of her left ear 40 years ago. Her condition became chronic with recurrent secretion in her left ear, which resulted in frequent intervals of treatment (every 2 weeks). Wearing a hearing aid also caused problems.

Preoperative Finding: It was diffi cult to get an overview of the mastoid endoscopically. A posterior wall that had been partially reconstructed with carti-lage and a retraction to the attic could be visualized.

Operation: With an endaural incision a tympano-plasty/mastoidplasty was performed. Excessive cho-lesteatoma was removed and thorough cleaning of the mastoid was performed. In the middle ear, scar tissue was present and the incus and malleus heads were absent. Th e stapes was mobile (Type III) and it was interpositioned with a thin plate of cartilage. Th e mastoid and attic was obliterated with 3.5 cc BonAlive® granules and covered with 3 thinned pieces of cartilage from the tragus and fascia from the m. temporalis. No postoperative treatment with antibiotic was given.

Clinical Outcome: At 3 weeks postoperatively the silicon sheets and the package (tampons) were re-moved from the external ear canal. An incomplete epithelization of the posterior ear wall was observed.Th e external ear canal was treated 2 x with merocel sticks and eardrops (ciprofl oxacin, twice a day), for 3 weeks.

At 6 months postoperatively the skin of the external ear canal (meatus) was reddish. At 14 months heal-ing had progressed well but showed a slight retrac-tion towards the attic. At 24 months the meatus was normal and the patient had no problems wearing a hearing aid.

Pre-Op 6-Month Post-Op 14-Month Post-Op

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MANDIBLE SURGERY

Several long term studies, extending over 10 years of patient follow-up, have shown that BonAlive® granules generate outstanding clinical results in bone cav-ity fi lling applications in the cranio-maxillofacial area. Th e main applications of BonAlive® granules are fi lling of benign bone tumor cavities, fi lling of the oste-otomy site in bilateral sagittal split osteotomies and fronto-orbital trauma. Th e solid nature of BonAlive® granules provides specifi c benefi ts, such as allowing the granules to be impacted into the bone defect. Th e granules maintain their volume eff ectively, hence they do not shrink or expand. BonAlive® granules produces a high and balanced local bone regeneration by stimulating new bone formation through osteostimulation*.

BonAlive® granules Indication

• Bone cavity fi lling in cranio-maxillofacial area including the jaw

ReferencesBioactive Glass Granules as a Bone Adjunctive Material in Maxillary Sinus Floor Augmentation. Turunen T, Peltola J, Yli-Urpo A, Happonen RP. Clin Oral Implants Res. 2004;15(2)135-141.Augmentation of the Maxillary Sinus Wall Using Bioactive Glass and Autologous Bone. Turunen T, Peltola J, Kangasniemi I, Jussila J, Uusipaikka E, Yli-Urpo A, Happonen R-P. Bioceramics.1995;Vol.8:259-264.Bioactive Glass in Dentistry. Salonen J, Arjasmaa M, Tuominen U, Behbehani MJ, Zaatar EI. J Minim Interv Dent. 2009;2(4).Bioactive Glass Granules and Polytetrafl uoroethylene Membrane in the Repair of Bone Defects Adjacent to Titanium and Bioactive Glass Implants. Turunen T, Peltola J, Makkonen T, Helenius H, Yli-Urpo A. J Mater Sci Mater Med. 1998Jul;9(7):403-407.Bioactive Glass and Calcium Carbonate Granules as Filler Material Around Titanium and Bioactive Glass Implants in the Medullar Space of the Rabbit Tibia. Turunen T, Peltola J, Helenius H, Yli-Urpo A, Happonen RP. Clin Oral Implants Res. 1997Apr;8(2):96-102.

*non-osteoinductive

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Follicular Cyst in the Mandible

Patient: 30-year old female with follicular cyst.

X-ray image showing the cyst with total lack of posterior bone support for the second molar.

Surgical removal of the wisdom tooth and the cyst (20x15x30 mm). Nervus al-veolaris inferior was exposed and covered with a collagen membrane.

The second molar was saved and the defect was filled with 6 cc of BonAlive® granules.

Immediate Post-Op X-ray

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18-Month Post-Op X-ray

The BonAlive® granules were covered with collagen membrane and the wound was closed.

Outcome: At 18 months postop-eratively the area had healed and the posterior bone support for the second molar had been successfully recov-ered.

Histological section from the implanted area at 2 years after BonAlive® granules implantation. The arrow indicating resid-ual granules with surrounding bone tissue.

Operation: 6 cc of BonAlive® granules was used to fi ll the defect.

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Bilateral Sagittal Split Osteotomy (BSSO) Surgery

Patient: 45-year old female with mandibular retrognatia.

Pre-op X-ray shows the abnormal poste-rior positioning of the mandibula.

Clinical image of defect after sagittal split osteotomy and fixation with mini plate and mono cortical screws.

Filling of the osteotomy site with BonAlive® granules and application of tissue glue.

Immediate post-op X-ray shows the right positioning of the mandibula.

Operation: BSSO with a 10 mm mandibular advancement, 2.5 cc of BonAlive® granules was used for grafting on each side.

Outcome: At 12 months postopera-tively the follow-up showed unevent-ful healing with a normal contour of the inferior mandible border.

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FRONTAL SINUS & NEUROSURGERY

Most conditions of the frontal sinus requiring surgery can be treated successfully by endonasal or nasofrontal duct reconstruction procedures. However, in certain diffi cult cases, optimal exposure of the entire frontal sinus area is essential. Frontal sinus obliteration can be a treatment alternative for such frontal sinuses.

Th e unique bacterial growth inhibiting feature of BonAlive® granules gives dis-tinct advantages in areas that are postoperatively prone to infection.

BonAlive® granules Indication

• Frontal sinus obliteration after severe chronic sinusitis or fractures in the frontal bone area

ReferencesBioactive-Glass in Oral and Maxillofacial Surgery. Profeta AC, Huppa C. Craniomaxillofac Trauma Reconstr. 2016 Mar;9(1):1-14.Clinical Applications of S53P4 Bioactive Glass in Bone Healing and Osteomyelitic Treatment: A Literature Review. van Gestel N.A.P. ,Geurts J., Hulsen D.J.W. ,van Rietbergen B.,1 S. Hofmann S. and Arts J.J. 2015;Article ID 684826. (An open access journal.)Long-Term Microscopic and Tissue Analytical Findings for 2 Frontal Sinus Obliteration Materials. Peltola M, Aitasalo K, Aho AJ, Tirri T, Suonpaa J. J Oral Maxillofac Surg. 2008;66(8):1699-1707.Long-Term Tissue Reactions of Th ree Biomaterials in Craniofacial Surgery. Peltola M, Aitasalo K, Tirri T, Rekola J, Puntala A. Key Engineering Materials. 2008;361-363:1343-1346.Bioactive Glass Hydroxyapatite in Fronto-Orbital Defect Reconstruction. Aitasalo K, Peltola M. Plast Reconstr Surg. 2007;120(7):1963-1972.Bioactive Glass S53P4 in Frontal Sinus Obliteration: A Long-Term Clinical Experience. Peltola M, Aitasalo K, Suonpaa J, Varpula M, Yli-Urpo A. Head and Neck. 2006;28(9):834-841.Bioactive Glass S53P4 in Frontal Sinus Obliteration. A 9-Year Experience. Aitasalo K, Peltola M, Suonpaa J, Yli-Urpo A. Key Engineering Materials. 2001;192-195:877-880.Obliteration of the Frontal Sinus Cavity with Bioactive Glass. Peltola M, Suonpaa J, Aitasalo K, Varpula M, Yli-Urpo M, Happonen R. Head and Neck. 1998;20(4):315-319.Behaviour of Bioactive Glass (S53P4) in Human Frontal Sinus Obliteration. Aitasalo K, Suonpaa J, Peltola M, Yli-Urpo A. Bioceramics. 1997;10:429-432.Bioactive Glass Granules and Plates in the Reconstruction of Defects of the Facial Bones. Suominen E, Kinnunen J. Scand J Plast Reconstr Surg Hand Surg. 1996;30(4):281-289.

Clinical image of obliteration with 30 cc BonAlive® granules.

Post-op CT illustrating the implanted BonAlive® granules.

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Severe Mucopyocele in Frontal Sinus Area

Patient: A 59-year old male who developed an increasing soft and tender expan-sion on the left forehead. Th e patient suff ered from headache and diplopia in the left gaze. He had been hit by a small metal fragment in the left frontal area of the head from soldering. Preoperatively the patient was treated with azithromycin 500 mg/week and methylprednisolone 5 mg/day.

3D illustration showing the effects of complicated muco-pyocele in frontal sinus, orbita and frontal lobe.

Mucopyocele intraoperatively presenting a large amount of pus. The area was throughly debrided from necrotic tissues before the reconstruction.

Filling of the frontal cavity with 25 cc BonAlive® granules and closing the frontonasal duct with a BonAlive® plate.

CT illustration showing muco-pyocele in frontal sinus, orbita and frontal lobe.

BonAlive® plate BonAlive® granules

Nasal base

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19

Clinical Outcome: At 2 months the patient had made an excellent recov-ery. Th e bacterial cultures were nega-tive.At 5 months ENT-doctors performed as planned a FESS procedure to wid-en the maxillary sinus ducts. At 2 years and 8 months follow-up the patient was symptom free and had returned to work. No signs of in-fection was shown on the MRI.

2-Day Post-Op CT 2-Month Post-Op CT 1-Year Post-Op CT

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2 Years 8 Months Post-Op MRI

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Eff ects of Bioactive Glass S53P4 or Beta-Tricalcium Phosphate and Bone Morpho-genetic Protein-2 and Bone Morphogenetic Protein-7 on Osteogenic Diff erentia-tion of Human Adipose Stem Cells. Waselau M, Patrikoski M, Juntunen M, Kujala K, Kääriäinen M, Kuokkanen H, Sándor GK, Vapaavuori O, Suuronen R, Mannerström B, von Rechenberg B, Miettinen S. J Tissue Eng. 2012;3(1).

Osteoblast Response to Continuous Phase Macroporous Scaff olds Under Static and Dynamic Culture Conditions. Meretoja VV, Malin M, Seppälä JV, Närhi TO. J Biomed Mater Res. 2008;89A(2):317-325.

Molecular Basis for Action of Bioactive Glasses as Bone Graft Substitute. Välimäki VV, Aro HT. Scand J Surg. 2006;95(2):95-102.

Intact Surface of Bioactive Glass S53P4 is Resistant to Osteoclastic Activity. Wilson T, Parikka V, Holmbom J, Ylänen H, Penttinen R. J Biomed Mater Res. 2005;77A(1):67-74.

Granule Size and Composition of Bioactive Glasses Aff ect Osteoconduction in Rab-bit. Lindfors NC, Aho AJ. J Mater Sci: Mater Med. 2003;14(4):265-372.

Osteoblast Diff erentiation of Bone Marrow Stromal Cells Cultured on Silica Gel and Sol-Gel-Derived Titania. Dieudonné SC, van den Dolder J, de Ruijter JE, Paldan H, Pel-tola T, van ‘t Hof MA, Happonen RP, Jansen JA. Biomaterials. 2002;23(14):3041-3051.

Histomorphometric and Molecular Biologic Comparison of Bioactive Glass Granules and Autogenous Bone Grafts in Augmentation of Bone Defect Healing. Virolainen P, Heikkilä J, Yli-Urpo A, Vuorio E, Aro HT. J Biomed Mater Res. 1997;35(1):9-17.

Bone Formation in Rabbit Cancellous Bone Defects Filled with Bioactive Glass Granules. Heikkila JT, Aho HJ, Yli-Urpo A, Happonen R, Aho AJ. Acta Orthopaedica. 1995;66(5):463-467.

Antibiofi lm Agents Against MDR Bacterial Strains: Is Bioactive Glass BAG-S53P4 Also Eff ective? Bortolin M, De Vecchi E, Romanò CL, Toscano M, Mattina R and Drago L. J Antimicrob Chemother. 2016 Jan;71(1):123-7.

Antimicrobial Activity and Resistance Selection of Diff erent Bioglass S53P4 Formu-lations Against Multidrug Resistant Strains. Drago L, De Vecchi E, Bortolin M, To-scano M, Mattina R and Romanò CL. Future Microbiol. 2015;10(8):1293-9.

In Vitro Antibiofi lm Activity of Bioactive Glass S53P4. Drago L, Vassena C, Fenu S, De Vecchi E, Signori V, De Francesco R, Romanò CL. Future Microbiol. 2014;9(5):593-601.

Antibacterial Eff ects and Dissolution Behavior of Six Bioactive Glasses. Zhang D, Leppäranta O, Munukka E, Ylänen H, Viljanen MK, Eerola E, Hupa M, Hupa L. J Biomed Mater Res. 2010;93A(2):475-483.

Bactericidal Eff ects of Bioactive Glasses on Clinically Important Aerobic Bacteria. Munukka E, Leppäranta O, Korkeamäki M, Vaahtio M, Peltola T, Zhang D, Hupa L, Ylänen H, Salonen JI, Viljanen MK, Eerola E. J Mater Sci: Mater Med. 2008;19(1):27-32.

Antibacterial Eff ect of Bioactive Glasses on Clinically Important Anaerobic Bacteria In Vitro. Leppäranta O, Vaahtio M, Peltola T, Zhang D, Hupa L, Ylänen H, Salonen JI, Viljanen MK, Eerola E. J Mater Sci: Mater Med. 2008;19(2):547-551.

In Situ pH within Particle Beds of Bioactive Glasses. Zhang D, Hupa M, Hupa L. Acta Biomaterialia. 2008;4(5):1498-1505.

Factors Controlling Antibacterial Properties of Bioactive Glasses. Zhang D, Munukka E, Hupa L, Ylänen H, Viljanen MK, Hupa M. Key Engineering Materials. 2007;330-332:173-176.

Comparison of Antibacterial Eff ect on Th ree Bioactive Glasses. Zhang D, Munukka E, Leppäranta O, Hupa L, Ylänen H, Salonen J, Eerola E, Viljanen MK, Hupa M. Key Engineering Materials. 2006;309-311:345-348.

Interactions Between the Bioactive Glass S53P4 and the Atrophic Rhinitis-Associated Microorganism Klebsiella Ozaenae. Stoor P, Söderling E, Grenman R. J Biomed Mater Res. 1999;48(6):869-874.

Antibacterial Eff ects of a Bioactive Glass Paste on Oral Micro-Organisms. Stoor P, Söderling E, Salonen JI. Acta Odontol Scand. 1998;56(3):161-165.

Interactions Between the Frontal Sinusitis-Associated Pathogen Heamophilus Infl u-enzae and the Bioactive Glass S53P4. Stoor P, Söderling E, Andersson OH, Yli-Urpo A. Bioceramics. 1995;8:253-258.

REFERENCES

*non-osteoinductive

Mechanism of Action (Osteostimulation*)

Inhibition of Bacterial Growth

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21

Frontal Sinus Surgery

Bioactive-Glass in Oral and Maxillofacial Surgery. Profeta AC, Huppa C. Craniomaxil-lofac Trauma Reconstr. 2016 Mar;9(1):1-14.

Clinical Applications of S53P4 Bioactive Glass in Bone Healing and Osteomyelitic Treatment: A Literature Review. van Gestel N.A.P. ,Geurts J., Hulsen D.J.W. ,van Riet-bergen B.,1 S. Hofmann S. and Arts J.J. 2015;Article ID 684826. (An open access journal.)

Long-Term Microscopic and Tissue Analytical Findings for 2 Frontal Sinus Oblitera-tion Materials. Peltola M, Aitasalo K, Aho AJ, Tirri T, Suonpaa J. J Oral Maxillofac Surg. 2008;66(8):1699-1707.

Long-Term Tissue Reactions of Th ree Biomaterials in Craniofacial Surgery. Peltola M, Aitasalo K, Tirri T, Rekola J, Puntala A. Key Engineering Materials. 2008;361-363:1343-1346.

Bioactive Glass Hydroxyapatite in Fronto-Orbital Defect Reconstruction. Aitasalo K, Peltola M. Plast Reconstr Surg. 2007;120(7):1963-1972.

Bioactive Glass S53P4 in Frontal Sinus Obliteration: A Long-Term Clinical Ex-perience. Peltola M, Aitasalo K, Suonpaa J, Varpula M, Yli-Urpo A. Head and Neck. 2006;28(9):834-841.

Bioactive Glass S53P4 in Frontal Sinus Obliteration. A 9-Year Experience. Aitasalo K, Peltola M, Suonpaa J, Yli-Urpo A. Key Engineering Materials. 2001;192-195:877-880.

Obliteration of the Frontal Sinus Cavity with Bioactive Glass. Peltola M, Suonpaa J, Aitasalo K, Varpula M, Yli-Urpo M, Happonen R. Head and Neck. 1998;20(4):315-319.

Behaviour of Bioactive Glass (S53P4) in Human Frontal Sinus Obliteration. Aitasalo K, Suonpaa J, Peltola M, Yli-Urpo A. Bioceramics. 1997;10:429-432.

Bioactive Glass Granules and Plates in the Reconstruction of Defects of the Facial Bones. Suominen E, Kinnunen J. Scand J Plast Reconstr Surg Hand Surg. 1996;30(4):281-289.

Mastoid Surgery

Mastoid Cavity Obliteration with Bioactive Glass Granules. Schimanski G, Schiman-ski E. In: Recent Advances in Otolaryngology - Head and Neck Surgery. Lalwani A., Pfi ster M. 2016;5:249-281.Cutaneous and Labyrinthine Tolerance of Bioactive Glass S53P4 in Mastoid and Epi-tympanic Obliteration Surgery: Prospective Clinical Study. Bernardeschi D, Nguyen Y, Russo FY, Mosnier I, Ferrary E, Sterkers O. BioMed Research International. 2015;Ar-ticle ID 242319. (An open access journal.)Obliteration von Mastoidhöhlen. 30 Jahre Erfahrung mit Empfehlungen zur Opera-tionsstrategie. Schimanski G, Schimanski E. HNO 2015;63:538-545.Bioactive Glass S53P4 in Mastoid Obliteration Surgery for Chronic Otitis Media and Cerebrospinal Fluid Leakage. Sarin J, Grenman R, Aitasalo K, Pulkkinen J. Annals of Otology, Rhinology & Laryngology. 2012;121:563-569.Mastoidectomy Cavity Obliteration with Bioactive Glass: A Pilot Study. Silvola JT. Otolaryngology - Head and Neck Surgery. 2011;145(2):96-97.Bioactive Glass S53P4 in the Filling of Cavities in the Mastoid Cell Area in Surgery for Chronic Otitis Media. Stoor P, Pulkkinen J, Grenman R. Ann Otol Rhinol Laryng. 2010;119(6):377-382.

Dental Surgery

Bioactive Glass Granules as a Bone Adjunctive Material in Maxillary Sinus Floor Augmentation. Turunen T, Peltola J, Yli-Urpo A, Happonen RP. Clin Oral Implants Res. 2004;15(2)135-141.Augmentation of the Maxillary Sinus Wall Using Bioactive Glass and Autologous Bone. Turunen T, Peltola J, Kangasniemi I, Jussila J, Uusipaikka E, Yli-Urpo A, Happo-nen R-P. Bioceramics.1995;Vol.8:259-264.

Bioactive Glass in Dentistry. Salonen J, Arjasmaa M, Tuominen U, Behbehani MJ, Zaatar EI. J Minim Interv Dent. 2009;2(4).

Bioactive Glass Granules and Polytetrafl uoroethylene Membrane in the Repair of Bone Defects Adjacent to Titanium and Bioactive Glass Implants. Turunen T, Peltola J, Makkonen T, Helenius H, Yli-Urpo A. J Mater Sci Mater Med. 1998Jul;9(7):403-407.

Bioactive Glass and Calcium Carbonate Granules as Filler Material Around Tita-nium and Bioactive Glass Implants in the Medullar Space of the Rabbit Tibia. Tu-runen T, Peltola J, Helenius H, Yli-Urpo A, Happonen RP. Clin Oral Implants Res. 1997Apr;8(2):96-102.

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Ref. No Granule Size Unit Size

13110 0.5-0.8 mm (Small) 1 cc13120 0.5-0.8 mm (Small) 2.5 cc

Ref. No Granule Size Unit Size

13130 0.5-0.8 mm (Small) 5 cc13140 0.5-0.8 mm (Small) 10 cc

1 cc 2.5 cc 5 cc 10 cc

Small Applicator Large Applicator

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INSTRUCTIONS FOR USE

For complete instructions for use, see package insert.

Step 1.

• Peel open the pouch (start from the corners) and aseptically remove the sterile tray (see Figure 1).

• Detach the applicator from the tray

• Note that the pouch provides a sterile barrier to the device.

Step 2.

• Moisten the granules by injecting ster-ile physiological saline slowly through the cap membrane (see Figure 2).

• Make sure the granules are evenly moistened. Th e applicator can be turned upside down or tapped to allow the saline to moisten all granules.

• Note: saline injection can cause in-crease in pressure inside the applicator unless the excess pressure is released e.g. with the injection needle.

Step 3.

• In order to prevent spilling of the moistened granules from the applica-tor keep the cap facing upwards.

• Unscrew the cap (remove the stopper) and screw the shovel tightly onto the applicator body (see Figure 3).

Step 4.

• Turn the applicator to a horizontal position, and push the plunger rod to slide the moistened granules onto the shovel. Move the applicator to the defect site and implant the moistened granules from the shovel into the de-fect with the aid of a sterile instru-ment (see Figure 4).

• (Alternatively, if the shovel is not used, turn the applicator over a sterile cup, push the plunger rod to slide the moistened granules into the cup and subsequently perform the implanta-tion with a sterile instrument.)

• Avoid dropping the granules outside the bone defect. Misplaced granules must be removed.

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91316g/2

www.bonalive.com

Corporate Headquarters

BonAlive Biomaterials LtdTel. +358 401 77 44 00Biolinja 1220750 [email protected]

Regional Headquarters

BonAlive Deutschland GmbHGraf-Recke-Straße 540239 Dü[email protected]