Focus Meeting Hotel Cicerone – Rome Final Programme

Final Programme

#ICRSFOCUSMEETING

One Step Cartilage Repair ICRS June 5 – 7, 2019 Focus Meeting Hotel Cicerone – Rome Final Programme

www.cartilage.org

International Cartilage Regeneration & Joint Preservation Society INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration & Joint Preservation Society 3

INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY

INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY

International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society Aesculap Biologics Facing a New Frontier in Cartilage Repair

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Vancouver 15 Th World Congress of the International Cartilage Canada Regeneration & October 5–8, 2019 Joint Preservation Society Early Bird Registration Deadline – June 11, 2019 International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration & Joint Preservation Society

INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY

Mark your agenda!

International Cartilage Regeneration & Joint Preservation Society www.cartilage.org

INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY

International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration of the International Cartilage WELCOME & Joint Preservation Society 5 Canada Regeneration & Joint Preservation Society October 5–8, 2019 Dear Colleagues & Friends INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY On behalf of the ICRS Executive Committee, we would like to welcome you Early Bird Registration Deadline – June 11, 2019 to the the Focus Meeting entitled “One Step Cartilage Repair” Rome - Caput Mundi - the Capital of the World and the Eternal City, as INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION defined by the Roman poet Tibullus in the 1st Century & BC,JOINT PRESERVATIONhas a SOCIETYvery long & JOINT PRESERVATION SOCIETY history that spans over 28 centuries. Most recently defined as the Global City, Rome will embrace you with its history, its monuments, its famous Ital- ian cuisine, its climate and world renowned romantic ambience. It will be International Cartilage Regeneration & an unforgettable experience!! I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society The congress will be held at the centrally located Cicerone Hotel in downtown. The hotel is located within easy walking distance from Piazza di Spagna, Via Veneto, Via dei Condotti and the Vatican City, St. Peters Ba- silica, the largest church in the world and home to the Pope. Rome is easily accessible from all over the world and offers the opportunity to continue your visit to the wonderful cities of Florence, Naples and Venice, complet- ing an amazing Italian historic tour.

We are excited over the innovative faculty, which combines Clinicians and Scientists, all leaders in the field of cartilage repair. They will offer partici- pants a complete overview of every possible single one-step treatment for Final Programme focal cartilage defects, from marrow stimulation to the latest advances in orthobiologics, regenerative medicine and focal resurfacing. The two-dayICRS Focus Meeting – One Step Cartilage Repair meeting will be completed by an optional half day interactive practical HOTEL CICERONE - ROME workshop on associated surgical treatments such as femoral, tibial and JUNE 5 – 7, 2019 patella-femoral osteotomies, meniscus transplant, bone marrow aspiration Final Programme and stem cell withdrawal. ICRS Focus Meeting – One Step Cartilage Repair Final Programme It is our sincere pleasure to welcome you to the ICRS Focus Meeting RomeHOTEL CICERONE - ROME 2019. JUNE 5 – 7, 2019 ICRS Focus Meeting – One Step Cartilage Repair

HOTEL CICERONE - ROME Fabio Valerio Sciarretta (IT) & Martyn Snow (UK) JUNE 5 – 7, 2019 Course Directors Endorsed By: Endorsed By:

Endorsed By:

Upcoming ICRS Events - Mark your agenda!

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Oct. 05–08, 2019 - Vancouver, Canada • Vancouver Endorsed By• : Aesculap Early Bird Registration Deadline: June 11 at noon CEST • Anika Arthrex • • Biogend Therpeutics ICRS Focus Meeting - Imaging, Diagnosis, Treatment • CPC Life • Geistlich Nov. 21–23, 2019 - Vienna, AustriaList of adverts • JRF • Lipogems Early Bird Registration Deadline: August 30 at noon• Vancouver CEST • Regenlab • Aesculap • Zimmer Mark your agenda! • Anika • Arthrex Biogend Therpeutics • International Cartilage Regeneration • CPC Life • Geistlich Welcome & Joint Preservation Society www.cartilage.org • JRF List of adverts • Lipogems Dear Colleagues & Friends, • Regenlab • Vancouver • Zimmer • Aesculap • Anika • Arthrex • Biogend Therpeutics • CPC Life Welcome • Geistlich Dear Colleagues & Friends, • JRF • Lipogems • Regenlab • Zimmer

Welcome

Dear Colleagues & Friends, INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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A regenerative medicine company Focusing on Bone & Joints repair International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration & Joint Preservation Society Major technology platforms BiCRI Biphasic cartilage repair implant One-step autologous chondrocyte repair system

OIF Osteoinductive factors Growth factor belongs to BMP-2 Cooperation model Licensing-out platform product Investment to BioGend Inc, Taiwan Planned IPO schedule: 2019 Q1-Q2 Investment to BioGend Inc., Taiwan and JV INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALcompany in CARTILAGE China JOINT PRESERVATION REGENERATION SOCIETY PotentialREGENERATION exit: acquisition of JV companySOCIETY by China & orthopedic company or IPO in& China market

CONTACT INFORMATION

BioGend Therapeutics Co., Ltd. 4F., No.3, Park ST., Nangang Dist., Taipei City 115, TAIWAN (R.O.C.)

+886-2-2655-8366 [email protected] https://www.biogend.com.tw

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International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration BioGend & Joint Preservation Society 7 BioGend Therapeutics Co., Ltd.

INTERNATIONALCell-free CARTILAGE biologicalJOINT PRESERVATIONmatrix enabling INTERNATIONALauto- CARTILAGE JOINT PRESERVATION A regenerative medicine company ACKNOWLEDGMENT TO OUR REGENERATION SUMMIT& SOCIETY SPONSORSREGENERATION & SOCIETY regeneration of articular cartilage defects

Focusing on The ICRS acknowledges the followingChondroFiller Industry is a biological Partners cartilage implant for composed their of pure native collagen for regeneration-promoting filling of generous & continuedcartilage defects support applicable to lesions in joints such as knee, ankle, hip, finger, toe and shoulder.

Bone & Joints repair INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY Diamond Partner:

International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society

Major technology platforms

Platinum Sponsors:

BiCRI

Biphasic cartilage repair implant

One-step autologous chondrocyte repair system

 auto -regenerative  auto-regenerative biological matrix biological matrix  single procedure  single procedure OIF Osteoinductive factors  acellular, no cell culture Gold Sponsors: acellular, no cell culture  individual filling of defects  individual filling of defects grade I-IV grade I-IV

Growth factor belongs to BMP-2  arthroscopically injectable  minimally invasive

implant implant   no fibrin glue, no microfracturing no microfracturing  individual size adjustment  two -chamber syringe  easy handling  easy handling  short surgery time Cooperation model  short surgery time  ready to use  ready to use

Silver Sponsor: Licensing-out platform product meidrix biomedicals GmbH Schelztorstr. 54-56 Investment to BioGend Inc, Taiwan 73728 Esslingen phone +49 (0)711 933414-10 [email protected] www.amedrix.de Planned IPO schedule: 2019 Q1-Q2

Investment to BioGend Inc., Taiwan and JV company in China Potential exit: acquisition of JV company by China Exhibitors: orthopedic company or IPO in China market

CONTACT INFORMATION

BioGend Therapeutics Co., Ltd. 4F., No.3, Park ST., Nangang Dist., Other Sponsor: Taipei City 115, TAIWAN (R.O.C.)

+886-2-2655-8366 [email protected] https://www.biogend.com.tw INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

ICRS Focus Meeting Rome

International Cartilage Regeneration & Joint Preservation Society InternationalOne Step Cartilage Regeneration &Cartilage Joint Preservation Society Repair

GEISTLICH

AMIC® Chondro-Gide® INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALLearn more CARTILAGE about JOINT PRESERVATION REGENERATION & SOCIETY the AMICREGENERATION® technique& SOCIETY from cartilage experts during the ICRS Hands-On Workshop

Friday, 7 June 2019, 15:00–18:15 / Cicerone Room Experts Prof. Roland Jakob Dr. Tomasz Piontek Prof. Phillip Niemeyer Dr. Fabio Sciarretta

INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY

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ChondroFiller liquid

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meidrix biomedicals GmbH

Schelztorstraße 54–56 Tel: +49 (0)711 93 34 14-10 DE-73728 Esslingen [email protected] www.meidrix.de

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International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration ORGANIZATION & Joint Preservation Society 11

Course Organizing Office SadlikINTERNATIONAL Bougoslaw CARTILAGE JOINT (PL) PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Salzmann Gian (DE) Cartilage Executive Office GmbH Schiavone Panni Alfredo (IT) Spitalstrasse 190- Haus 3 Sciarretta Fabio Valerio (IT) 8623 Wetzikon Switzerland Slynarski Konrad (PL) Phone +41 44 503 73 70 Snow Martyn (UK) INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION Email: [email protected] Sofat& NidshiJOINT PRESERVATION (UK) SOCIETY & JOINT PRESERVATION SOCIETY Stone Kevin (US) Tirico Luis (BR) Invited Faculty Tudisco Cosimo (IT) Vadalà Gianluca (IT) International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION Abazovic Dzihan (MNE) van Heerwaaden& JOINT PRESERVATION SRonaldOCIETY (NL) Joint Preservation Society Abelow Stephen (US) Van Osch Gerjo (NL) Allegra Francesco (IT) Verdonk René (BE) Becher Christoph (DE) Vonk Lucienne (NL) Beck Olaf Thorsten (DE) Wilson Adrian (UK) Berruto Massimo (IT) Zorzi Claudio (IT) Beyzadeoglu Tahsin (TR) Bobic Vladimir (UK) Brittberg Mats (SE) ICRS Executive Board Buschmann Michael (US) Correa Diego (US) President – Alberto Gobbi (IT) de Bari Cosimo (UK) First Vice President – Tom Minas (US) Demange Marco (BR) Second Vice President – Elizaveta Kon (IT) Dhollander Aad (BE) Secertary General – Daniel Grande (US) di Martino Alessandro (IT) Treasurer – Christian Lattermann (US) Erggelet Christoph (CH) Past President – Ken Zaslav (US) Espregueira-Mendes Jõao (PT) Fernandes Julio (CDN) Ferracini Riccardo (IT) Venue & Official Course Hotel Gobbi Alberto (IT) Grande Daniel (US) Hotel Cicerone Jakob Roland (CH) Via Cicerone, 55/C Kley Kristian (DE) Rome, Italy Kon Elizaveta (IT) Lane John (US) Madry Henning (DE) Faculty / Course Dinner McDermott Ian (UK) McNicholas Mike (UK) Les Etoiles Restaurant Niemeyer Philippe (DE) Via Giovanni Vitelleschi 34, Peretti Giuseppe (IT) 00193 Rome, Italy Roato Ilaria (IT) INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration & Joint Preservation SocietyEXPERIENCE THE DIFFERENCE

Lipogems® allows your body to heal the natural way by supporting the repair, reconstruction and

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FDA cleared for use in Orthopeadics and Arthroscopic Surgery

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International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration FINAL PROGRAMME & Joint Preservation Society 13

Wednesday, June 5, 2019 INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY 09:30–13:00 Registration

11:00–12:00 Welcome Coffee (Partially sponsored by Anika)

INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION 12:00–12:45 Industry Sponsored Satellite Symposium& JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY Hyalofast, the Hyaluronic Acid-Based Scaffold for One-Step Cartilage Repair Moderator: Alberto Gobbi (IT)

EXPERIENCE International Cartilage Regeneration 15 min. Hyalofast plus BMAC in Osteochondral Lesions of the Knee: Long Term Clinical Evidence, & I NTERNATIONAL C ARTILAGE R EGENERATION Alberto Gobbi (IT) & JOINT PRESERVATION S OCIETY Joint Preservation Society 15 min. From Bench to Bedside – 18 Years of my Experience with Hyalofast Scaffold, Konrad Slynarski (PL) THE DIFFERENCE 15 min. Hyalofast Aarthroscopic Implantation in the Hip: Surgical Technique & Clinical Evidence, Gorav Datta (UK)

13:00–13:10 Official Opening & Introduction Francesco Falez (IT), Alberto Gobbi (IT), Giuseppe Milano (IT) Fabio Sciarretta (IT), Martyn Snow (UK)

® 13:10–15:45 Session I – Bone Marrow Stimulation, Autologous & Allogenic Transplants Lipogems Moderators: Daniel Grande (US), Kevin Stone (US)

15 min. 1.1 Microfracture – The Science behind its Success & Failure allows your body to heal Michael Buschmann (US) 15 min. 1.2 Modifying Hole Size – Drilling VS Standard AWL Technique Giuseppe Peretti (IT) the natural way 15 min. 1.3 OATS / Mosaicplasty – How to Decide Actual Correct Indications & Use Joao Espregueira-Mendes (PT) 15 min. 1.4 Paste technique Kevin Stone (US) by supporting the repair, 15 min. 1.5 Can Non-Expanded Chondrocytes Induce Repair Lucienne Vonk (NL) 15 min. 1.6 Autologous Minced Cartilage reconstruction and Gian Salzmann (CH) 15 min. 1.7 Allogenic Surface and Minced Cartilage Luis Tirico (BR) replacement of damaged 15 min. 1.8 Amniotic Membrane Allograft Daniel Grande (US) 15 min. 1.9 Umbilical Cord Allograft or injured tissue Boguslaw Sadlik (PL) 20 min. Discussion

FDA cleared for use in Orthopeadics 15:45–16:30 Coffee Break & Exhibition and Arthroscopic Surgery www.lipogems.com INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

FINAL PROGRAMME

16:30–18:10 Session II – Orthobiologics Moderators Stephen Abelow (US), John Lane (US)

15 min. 2.1 The Inflammatory Environment in Cartilage Lesions & OA Gerjo Van Osch (NL) 10 min. 2.2 PRP Stephen Abelow (US) International Cartilage Regeneration & Joint Preservation Society International10 min. Cartilage2.3 Cellular Matrix (Regen Lab) Regeneration Alberto Gobbi (IT) 10 min. 2.4 Biocue (Zimmer Biomet) & Joint PreservationJohn Lane (US) Society 10 min. 2.5 Nstride (Zimmer Biomet) Elizaveta Kon (IT) 10 min. 2.6 Lipogems Claudio Zorzi (IT) 10 min. 2.7 Bone Marrow Concentrate in Knee OA Stefano Zaffagnini (IT), Alessandro Di Martino (IT) 10 min. 2.8 Regenerative Treatment of Knee Osteoarthritis with Infusion of Low Manipulated Adipose Tissue – Riccardo Ferracini (IT), Ilaria Roato (IT) 15 min. Discussion

19:00–21:30 Welcome Reception at „Stadio di Domiziano“ Piazza Navona Underground

Visit the ruins of the Stadium of Domitian (UNESCO World Heritage Site) in Piazza Na- vona, which are located about 4.50 meters below street level. The archaeological site is all that remains of the first and only example of a masonry stadium up to now known in Rome. The Stadium was built in order to import in Rome the Greek athletic games appreciated by Domitian, but scarcely loved by the Romans, because the games were not tough and violent enough, but at the same time they also considered them as immoral; as a matter of fact, it was a mix of sports and artistic competitions where the clothing was rather lascivi- ous. A visionary project with the purpose of “Romanize” the Greek Olympics.

18.45 Meet at the Cicerone Hotel Lobby (15 min Walking Distance)

INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY

INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY

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Thursday, June 6, 2019 INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY 8:30–11:00 Session III – Scaffolds Moderators: Fabio Sciarretta (IT), Julio Fernandes (CA)

15 min. 3.1 Chondro-Gide Collagen Scaffold (Geistlich) INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION Philipp Niemeyer (DE) & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY 15 min. 3.2 Hyalofast (HA Scaffold) (Anika) Boguslaw Sadlik (PL) 15 min. 3.3 Chondrotissue (PGA. + HA Scaffold) (Biotissue) Ian McDermott (UK) International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION 15 min. 3.4 Alpha Chondroshield (PGA Scaffold)& –JOINT (Swiss PRESERVATION Biomed) S OCIETY Joint Preservation Society Christoph Erggelet (CH) 15 min. 3.5 Gelrin C PEG-DA Scaffold (Regentis) Aad Dhollander (BE) 15 min. 3.6 CarGel (Smith & Nephew) Julio Fernandes (CA) 15 min. 3.7 PRF Tahsin Beyzadeoglu (TR) 15 min. 3.8 Chondrofiller (Meidrix) Olaf Thorsten Beck (DE) 15 min. 3.9 Arthroscopic Technique – Tips & Technical Pearls Tomasz Piontek (PL) 15 min. Discussion

11:00–11:30 Coffee Break & Industry Exhibition

11:30–12:30 Session IV – Case Discussions Moderators: Martyn Snow (UK), Mike McNicholas (UK)

60 min. Contained/Unconfined, Mal-Alignment, Meniscal Loss, Instability, Multiple Procedures, Patella/Condyle Panellists: Christoph Erggelet (CH), Cosimo Tudisco (IT), Julio Fernandes (CA), Ian McDermott (UK), Gianluca Vadalà (IT), Boguslaw Sadlik (PL)

12:30–13:15 Industry Sponsored Satellite Symposium – Joint Preservation with Lipogems® Moderators: Fabio Sciarretta (IT); Claudio Zorzi (IT)

12:30 Introduction & My Experience Claudio Zorzi (IT) 12:40 Adipose Tissue Mesenchymal Stem Cells: The Scientist’s Vision Diego Correa (USA) 12:50 Lipogems Technique in Orthopaedics: My Indications, Outcomes & Perspectives Thomasz Piontek (PL) 13:00 The Registry: My Experience Nima Heidari (UK) 13:10 Q&A

13:15–14:00 Lunch Break INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

FINAL PROGRAMME

14:00–16:00 Session V – Stem Cells Moderators: Alberto Gobbi (IT), Elizaveta Kon (IT)

15 min. 5.1 Bone Marrow Concentrate – What is in It & How It could Work? Cosimo De Bari (UK) 15 min. 5.2 BMAC on a Scaffold Alberto Gobbi (IT) International Cartilage Regeneration & Joint Preservation Society International15 min. Cartilage5.3 BMAC in Hydrogel Regeneration Martyn Snow (UK) 15 min. 5.4 CartiONE-Co – Culture (Chondrocytes and BMAC) & Joint PreservationKonrad Slynarski (PL) Society 15 min. 5.5 Adipose Derived Cells – What is in it & and how could It work? Diego Correa (US) 15 min. 5.6 Stromal Vascular Fraction + Microfracture vs Microfracture Alone Cosimo Tudisco (IT) 15 min. 5.7 Adipose on a Scaffold Fabio Sciarretta (IT) 15 min. Discussion

16:00–16:30 Coffee Break & Exhibition

16:30–18:15 Session VI – Unloading Procedures & Focal Resurfacing Moderators: Mats Brittberg (SE), Joao Espregueira-Mendes (PT)

12 min. 6.1 Meniscal Scaffolds and Transplant René Verdonk (BE) 12 min. 6.2 Atlas (Moximed) Konrad Slynarski (PL) 12 min. 6.3 Nusurface (Active Implants) Claudio Zorzi (IT) 12 min. 6.4 Episealer (Episurf) Mats Brittberg (SE) 12 min. 6.5 Hemicap (Arthrosurface) Christoph Becher (DE) 12 min. 6.6 Biopoly (BioPoly) Mike McNicholas (UK) INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL18 min. CARTILAGEDiscussion JOINT PRESERVATION 15 min. Best Poster Abstract Presentation REGENERATION & SOCIETY REGENERATION & SOCIETY 19:30–23:00 Faculty / Course Dinner Restaurant Les Etoiles (EURO 80.00)

19.00 Meet at the Cicerone Hotel Lobby (10 min Walking Distance)

On the top floor of the Hotel Atlante Star is our world renowned Les Étoiles panoramic roof garden restaurant with unique unobstructed view of The Vatican City and surround- ings. Les Étoiles restaurant is Rome’s most contended spot by international TV networks and film production companies for its incomparable scenic backdrop

INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY

International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration FINAL PROGRAMME & Joint Preservation Society 17

Friday, June 7, 2019 INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY 08:00–08:30 Industry Sponsored Symposium – Arthrosurface Motion Preserving Knee/PF Joint Technologies Moderator: Fabio Sciarretta (IT)

INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION 15 min. Welcome - Learning about Solutions for &the JOINT Active PRESERVATION & SOCIETY Independent patients& JOINT PRESERVATION SOCIETY Fabio Sciarretta (IT) 15 min. Background & Clinical Results using Inlay Resurfacing Technologies Christoph Becher (DE) International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION 08:30–10:00 Session VII – Subchondral Bone & JOINT PRESERVATION S OCIETY Joint Preservation Society Moderators: Henning Madry (DE), Gianluca Vadalà (IT)

15 min. 7.1 Subchondral Bone – Its Importance for Normal Function Henning Madry (DE) 15 min. 7.2 Osteochondral Allograft Luis Tirico (BR) 15 min. 7.3 Maioregen (Finceramica) Elizaveta Kon (IT) 15 min. 7.4 Bone Graft and Cartilage Repair Roland Jakob (CH) 15 min. 7.5 Agili C (CartiHeal) Elizaveta Kon (IT) 15 min. Discussion

10:00–11:00 Session VIII – Subchondral Oedema Moderators: Demange Marco (BR), Bobic Vladimir (UK)

12 min. 8.1 Subchondral Oedema-What is It? Why Does It Occur? Should We Treat It? Nidhi Sofat (UK) 12 min. 8.2 Subchondral Oedema-Conservative Treatment Massimo Berruto (IT) 12 min. 8.3 Subchondroplasty: Indications and Surgical Technique PRO’s Marco Demange (BR) 12 min. 8.4 Subchondroplasty: Indications and Surgical Technique – CON’s Vladimir Bobic (UK) 12 min. Discussion

11:00–11:45 Coffee Break & Exhibition

11:45–12:45 Session IX – Patellofemoral Chondral Defect Panel Moderators: Martyn Snow (UK), René Verdonk (BE)

45 min. Case Discussions: OCD, Previous Failed Repair, The Poor Biologic Candidate, AVN, Persistent Pain Following Successful Repair (OEDEMA) Panellist: Massimo Berruto (IT), Marco Demange (BR), Alfredo Schiavone Panni (IT), Vladimir Bobic (UK), Nidhi Sofat (UK), Francesco Allegra (IT)

12:45–13:00 Closing Remark / Adjourn INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

PRP & Cell Therapy Specialists

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International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration FINAL PROGRAMME & Joint Preservation Society 19

Optional Hands-On Workshop INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY PRP & Cell Therapy Specialists (Advanced separate registration and payment is needed for this practical Workshop. A limited number of tickets is available.)

The two-day meeting will be completed by an optional half day interactive practical workshop on associated surgical treatments. This premier hands-on workshop provides training for simple and complex INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION cartilage and meniscal procedures. It features ample hands-on& JOINT PRESERVATION lab time SOCIETY with world renowned& JOINT PRESERVATION faculty SOCIETY and industry-sponsored separate sessions, anticipated by specific didactic procedure presentations by Premium medical devices for the easy preparation faculty experts and followed by interactive discussions and debates, and expert demonstrations. We of autologous Platelet Rich Plasma (PRP) will cover the following techniques: Microfracture/Chondroplasty, OATS, Autologous Matrix Induced Chondrogenesis (AMIC), Meniscal Sutures, Collagen Meniscal Scaffolds, Tibial & FemoralInternational Osteotomies, Cartilage Regeneration & and Bone Marrow Concentrate (BMC). I NTERNATIONAL C ARTILAGE R EGENERATION Don’t miss ! Focal Resurfacing Implants & JOINT PRESERVATION S OCIETY Joint Preservation Society

Booth 14:00–14:10 Welcome and Introduction #12 Fabio Sciarretta (IT) Martyn Snow (UK) 14:10–14:50 Osteotomies Moderators: Roland Jakob (CH), Adrian Wilson (UK),

10 min. 10.1 Osteotomy Planning Ronald van Heerwaarden (NL) 10 min. 10.2 Tibial Osteotomy-Technique Adrian Wilson (UK) 10 min. 10.3 Femoral Osteotomy-Technique Kristian Kley (DE) 10 min. 10.4 Patello-Femoral Osteotomies Martyn Snow (UK) RegenExtracell® BMC | RK-EXB/T 14:50–15:30 Meniscal Transplants & Stem Cells Moderators: Fabio Sciarretta (IT) René Verdonk (BE)

10 min. 11.1 AMIC Technique Fabio Sciarretta (IT) 10 min. 11.2 Meniscal Transplant – Techniques & Pearls René Verdonk (BE) 10 min. 11.3 Liposuction for Orthopaedic Surgeons Fabio Sciarretta (IT) 10 min. 11.4 Bone Marrow Aspiration – Technique & Optimisation Dedicaded Kits for Dzihan Abazovic (ME) specific preparations + 170 published studies 15:30–15:45 Coffee Break

15:45–18:00 Practical Stations / Hands-on Skills RegenKit has an excellent safety profile with Instructors: Ronald van Heerwaarden (NL) Adrian Wilson (UK) Kristian Kley (DE) over 2 Milion patients treated. Martyn Snow (UK) Fabio Sciarretta (IT) René Verdonk (BE) Dzihan Abazovic (ME) Roland Jakob (CH)

Regen Lab SA, En Budron B2 CH1052 - Le Mont, Switzerland operates a Quality Management 18:00–18:15 Closing Remark / Adjourn System which complies with the requirements of ISO 13485:2016. www.regenlab.com/patents © Copyright 2019, Regen Lab SA, All Rights Reserved

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Abazovic Dzihan, MD, Renova Clinic Belgrade, Ulcinj, Montenegro Dzihan Abazovic is an emergency medicine specialist. He graduated from University of Bel- grade Medical Faculty in 2007 and after graduation he got a fellowship and opportunity to work with Prof Dr Rui Fernando Pilotto in Hospital das Clinicas in Brazil where they worked in the field of clinical genetics and intercellular signalling. In the next year Dr Abazovic started a fellowship in the Netherlands and in collaboration with Dr Peter Everts gained valuable knowledge in blood management. During residency Dr Abazovic did a fellowship International Cartilage Regeneration & Joint Preservation Society International Cartilageat the Clinical centre of Serbia, Regeneration Belgrade, and after he got a licence to practice emergency medicine and traumatology, he started with his own clinical practice in Ulcinj, Montenegro and in Belgrade, Serbia. He was also a chef of emergency medicine department in the & JointEmergency MedicinePreservation Centre of Montenegro in Ulcinj (2013-2018) Society and since 2010 Dr Abazovic works on a project on the Institute for Biochemistry and Molecular Biology. Along with his colleagues Dr Abazovic was the first doctor in Serbia who introduced regenerative medicine in clinical practice. Research of stem cell and blood derivatives in orthopaedics is one of his greatest interests and together with his orthopaedic team he introduced novel technique in the treatment of different pathologies. Nowadays Dr Abazovic holds lectures and training courses in the most reputable world centres in the field of orthopaedic.

Abelow Stephen, MD, PhD, Lake Tahoe Sports Medicine Center, South Lake Tahoe, United States of America Stephen Abelow is a Clinical Professor of Orthopaedic Sports Traumatology at the Clinica CEMTRO, Madrid Spain and a Professor of Orthopaedic Sports Medicine and Traumatol- ogy, Hon. at the Universidad Catholica San Antonio de Murcia, Spain. He is also Medical Director of the Lake Tahoe Sports Medicine Center, South Lake Tahoe, California, USA. Dr Abelow received his MD at Hahnemann Medical College, Philadelphia, Pennsylvania and completed a specialization in orthopaedic surgery in 1978 at Tufts New England Medical Center, Boston, Massachusetts, USA. He is a member of the numerous international organisations and was the Medical Director of the World Professional Ski Tour for 19 seasons. He has been a Master Instructor for the Arthroscopy Association of North America for knee arthroscopy and shoulder arthroscopy and an Associate Master Instructor for ankle arthroscopy. He has given numerous presentations, symposiums, and instructional course lectures on cartilage repair and regeneration. Dr Abelow was one of the first orthopaedic surgeons to help develop and publish arthroscopic techniques for matrix autologous chondrocyte implantation (MACI). Dr Ablow’s clinical interests include sports injuries, cartilage regeneration, ligament and tendon regeneration. He is currently pursuing a PhD in cartilage regeneration in Madrid, Spain.

Becher Christoph, MD, PhD, ATOS Clinic, HKF, Heidelberg, Germany Professor Christoph Becher is a board-certified orthopaedic surgeon specialized in knee, INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGEankle and achilles tendonJOINT surgery. He isPRESERVATION on the Editorial Board of Knee Surgery, Sports Traumatology, Arthroscopy (KSSTA), and Advisory Board of Archives of Orthopaedic and REGENERATION SOCIETY REGENERATIONTrauma Surgery (AOTS). HeSOCIETY is member of the patellofemoral committee of AGA – Society & for Arthroscopy &and Joint Surgery, Europe’s largest professional society for arthroscopy. He completed medical school at the Ruprechts-Karls-University of Heidelberg and started his career in orthopaedic surgery at the center of knee and foot surgery at the ATOS clinic center in Heidelberg, Germany. After two years at the Department of Orthopaedic Surgery at the University of Marburg, Germany, he became a board-certified orthopaedic surgeon at the Department of Orthopaedic Surgery of Hannover Medical School in 2011. Since 2013, he works clinically as a senior physician focussing on joint preservation, arthroplasty and reconstructive surgery. From January 2016, he practices at the ATOS clinic at the HKF – International Center for Hip, Knee and Foot Surgery.

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Beck Olaf Thorsten, MD, ArthropraxINTERNATIONAL Orthopädie CARTILAGE JOINT PRESERVATION Unfallchirurgie, INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Hilden, Germany For 7 years I have been working in my own practice and working with regenerative joint therapy methods. By using PRP, stem cells and cartilage induction, so many prosthesis implants could be avoided. For the cartilage induction I developed a special applicator, which allows arthroscopic cartilage induction at shoulder and hip joint. There is a patent for INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION this. Based on my experience, in the past& IJOINT have PRESERVATION lectured SOCIETY on this procedure& JOINT at PRESERVATION international SOCIETY congresses (ESSKA Barcelona, Sporting Surgeons Portugal, ACCART Colombia). I am currently working on a multicenter study for this procedure.

International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society Berruto Massimo, MD, Gaetano Pini Orthopaedic Institute, Milano, Italy 57 years old, born in Turin (Italy) grew up in Milan (Italy) where got the degree in Medicine and the fellowship in Orthopaedics and Traumatology. Since 1987 work at Orthopaedic Institute Gaetano Pini of Milan, in the Dept of Knee Surgery and Arthroscopy, until 1997 as assistant, then as vice-chairman, and since 2010 as Chairman. In 1988 spent 1 year in Burlington, at Dept. of Orthopaedics of University of Vermont, as fellow researcher developing an experimental study on the strain of ACL. In 1989 spent six months at Birmingham, at Alabama Sports Medicine, with Professor Jimmy Andrews and Bill Clancy as fellow ob- server. He developed an over 30 years’ experience in knee surgery and arthroscopy and he is able to perform all the techniques involving the knee joint from arthroscopy to total knee replacement. He is the Vice-President of SIGASCOT (Italian Society of Knee Arthroscopy Cartilage Sport and Orthopaedic Technology)

Beyzadeoglu Tahsin, MD, PhD, Beyzadeoglu Clinic Orthopaedics and Traumatology, Istanbul, Turkey Prof. Tahsin Beyzadeoglu was born in Bursa, Turkey in 1971. After graduating Trakya University Faculty of Medicine in 1994, he has accomplished his specialty residency at Istanbul University Cerrahpasa Faculty of Medicine, Department of Orthopaedics and Trau- matology in 2000. Between January 2001 and August 2005, he has worked at Private Umut Hospital in Istanbul. Between August 2005 and September 2012, he has worked at Yeditepe University Hospital Department of Orthopaedics and Traumatology and got his Associate Professorship degree. Since September 2012, he is owner of an Orthopaedic practice group, Beyzadeoglu Clinic in Istanbul. He had Professorship degree in 2013 from Halic University, Istanbul and still continues giving lectures both for graduate and after graduate physiotherapy and medical faculty students. His main specialties are; Sports Injuries, Arthroscopic Surgery and Hand Surgery. Beyzadeoglu has served as Head Team Physician of Turkish Men’s National Basketball Team. He has also been a member of The Executive Board of Health Committee of Turkish Football Federation, Health Committee of Turkish Basketball Federation and Health Committee of Paralympic Federation. He consults most of the basketball teams in Euro league and Turkish League and mainly Fenerbahce Sports Club. He has 56 articles; 156 oral and poster presentations; 23 book chapter writings; and 211 conference, panel and seminary lectures published in national and international scientific platforms. He speaks English and German. He is fan of Fenerbahce Sports Club. He is married and father of two sons. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

INTERNATIONAL FACULTY

Bobic Vladimir, MD, PhD, Nuffield Health, The Grosvenor Hospital Chester, United Kingdom Professor Vladimir Bobic is a Consultant Orthopaedic Knee Surgeon in full-time clinical and surgical practice. He is the director and founder of Chester Knee Clinic and Cartilage Repair Centre. The clinic, founded in 1996, is based at the Grosvenor Hospital in Chester, UK, where it is recognised as an ISAKOS-approved teaching centre. Professor Bobic has over twenty-three years of extensive experience in all aspects of knee surgery, including International Cartilage Regeneration & Joint Preservation Society International Cartilagearthroscopic surgery, ligament Regeneration reconstruction, knee arthroplasty, and particularly in articular cartilage repair. He is involved in national and international collaborative clinical and basic science research related to knee articular cartilage imaging, repair, rehabilitation and & Jointfunctional outcomes. Preservation His clinical and surgical practice includesSociety all contemporary articular cartilage repair technologies, including stem cell therapies. He organised one of the first UK seminars on the use of Autologous Stem Cell Therapies in Orthopaedics which was held in Chester in June 2013. He has over twenty years of experience in clinical and arthroscopic imaging, including digital image and video editing, and over sixteen years of experience in clinical and MR digital imaging of articular cartilage and subchondral bone. Prof Bobic introduced the first web-based MRI Teleradiology units at the Grosvenor Nuffield Hospital in Chester in 2004, in collaboration with Dr David Ritchie, Consultant Musculoskeletal Radiologist, Kodak and Alliance Medical. He is one of the founding members of the ICRS and a founder and former chairman of the ICRS Articular Cartilage Imaging and Rehabilita- tion Committees. He continues to focus on articular cartilage repair and autologous biological treatment options, which are his main clinical, imaging and research interests.

Brittberg Mats, MD, PhD, Kungsbacka Hospital, Göteborg University, Sweden Mats Brittberg is a member of the Cartilage Research Unit at University of Gothenburg and an orthopaedic surgeon at Region Halland Orthopaedics at the Kungsbacka Hospital, Kungsbacka, Sweden. He received his MD at the University of Gothenburg in 1978 and completed a specialization in orthopaedics in 1985. In 1992 he passed the Swedish Or- thopedic Board Exam (S.O.B.E.), and in 1996 he earned a PhD. He is now a professor of orthopaedics connected to the Institution of clinical sciences and orthopaedic department, University of Gothenburg. Mats Brittberg’ s research has been focused on cartilage repair and with main focus on cartilage regeneration with in vitro expanded autologous chondrocytes. Today the main interest is the European Connective Tissue Engineering centre (ECTEC) which is research collaboration between the Sahlgrenska Academy at University of Gothenburg with the institution of Polymer Technology, Chalmers Technical University. Mats Brittberg has also had research collaboration with Virginia Tech in USA on biotribology in cartilage and osteoarthritis as well as research collaborations with other centres in Europe and North America and central America. In September 2010, Mats Brittberg received the ICRS Genzyme Lifetime Achievement Award in cartilage research and in 2012, the Shetty- Kim Foundation (SKF) Scientific award. In 2014, Mats Brittberg also received the SKF and UK Cartilage Club’s Lifetime achieve- INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALment Award. CARTILAGEMats Brittberg has been on the boardJOINT of TESi (TissuePRESERVATION engineering Society International) and has been chairing the Cartilage Committee of ESSKA 2006-08. Since the start 1997, he has been working with ICRS, REGENERATION SOCIETY as REGENERATIONa secretary, Vice-president and President (2006-2008)SOCIETY and finally Past-President (2008-2009). He is since Janu- & ary 2013 Editor-in-Chief for the Sage journal& ¨CARTILAGE. He has also been associate editor with ESSKA journal as well as being on the editorial board of Osteoarthritis and Cartilage.

Buschmann Michael, PhD, George Mason University, Fairfax, United States of America Michael Buschmann received a B. Engineering Physics from the University of Saskatchewan in 1984, and a Ph.D. in Medical Engineering and Medical Physics from MIT and Harvard University in 1992. From 1994 to 2017, Dr. Buschmann was Professor of Biomedical En- gineering and Chemical Engineering at Polytechnique de Montréal. He is now Chair of Bioengineering at George Mason University.

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Correa Diego, MD, PhD, UniversityINTERNATIONAL of CARTILAGEMiami,JOINT United PRESERVATION States INTERNATIONALof America CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Diego Correa currently holds a joint appointment as Assistant Professor between the De- partment of Orthopaedics and the Diabetes Research Institute at University of Miami, Miller School of Medicine. His lab focuses on the Biology of Mesenchymal Stem Cells (MSCs), and their potential application for musculoskeletal conditions and during islet cell transplantation in diabetic patients. Dr. Correa finished Medical School at Pontificia Universidad Ja- INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION veriana in Bogotá (Colombia). During his& medical JOINT PRESERVATION practice, SOCIETY he enrolled in &an JOINT MSc PRESERVATION program SOCIETY in Mechanical Engineering at the Universidad de Los Andes in Bogotá (Colombia), where he started the research area of Tissue Engineering and received the Engineering School Fellowship. He then received his PhD in Cellular and Molecular Physiology from Yale Uni- versity where he was recipient of the George Robert Pfeiffer Fellowship from the GustavusInternational and Louise Cartilage RegenerationPfeiffer & I NTERNATIONAL C ARTILAGE R EGENERATION Research Foundation. Dr. Correa then moved to Harvard University& JOINT where PRESERVATION he S OCIETYcompleted his graduateJoint Preservation dissertation. Society He then joined the laboratory of Arnold Caplan at Case Western Reserve University, as postdoctoral fellow and then as Sr. Research Associate, leading the projects related with the use of MSCs in the areas of Orthopaedic Tissue Engineering and the description of their role during the process of distant Cancer Metastasis. Throughout his career, Dr. Correa has approached Medicine and Science in a multidisciplinary manner, using the musculoskeletal system as a primary platform. He has analysed it from various perspectives, including a clinical view of skeletal diseases, an engineering analysis of tissue mechanical properties, a basic science study of the cellular and molecular underpinnings of skeletal development using genetic models, and the development of novel therapeutic approaches to treat skeletal diseases based on stem cell therapy. He is an expert in in MSC biology and their clinical applications in Regenerative Medicine. He holds various patents; is author and co-author of a significant number of scientific publications in recognized journals; serves on the editorial board and as peer reviewer of several recognized scientific journals and various national and international funding agencies (e.g.: CIRM); and is an invited speaker and lecturer in national and international scientific and medical meetings.

De Bari Cosimo, PhD, University of Aberdeen, Aberdeen, United Kingdom Professor Cosimo De Bari is a clinically active rheumatologist and a translational scientist with expertise in musculoskeletal regenerative medicine and arthritis pathophysiology. He has a long-standing interest and track record in the study of joint health and disease, with a focus on osteoarthritis and cell-based therapies for cartilage repair. Cosimo graduated in Medicine (summa cum laude) from the University of Bari (Italy), where he underwent specialist training in Rheumatology. He obtained his PhD from the University of Leuven (Bel- gium). In 2003 Cosimo moved to King’s College London, where in 2005 he was awarded an MRC Clinician Scientist Fellowship. Since 2007 Cosimo holds a clinical chair in Trans- lational Medicine at the University of Aberdeen. Cosimo is the founder and director of the Aberdeen Centre for Arthritis and Musculoskeletal Health (ACAMH – http://www.abdn.ac.uk/acamh/), leads the Arthritis and Regenerative Medicine Laboratory, and is deputy director of the Arthritis Research UK Tissue Engineering Centre and the EULAR Centre of Excellence in Rheumatology at Aberdeen.

Demange Marco, MD, PhD, University of São Paulo, Sao Paulo, Brazil Assistant Professor of Orthopedic Surgery, University of São Paulo – Brazil, Chief of Knee Surgery Division, Hospital das Clínicas – FMUSP, Private Practice at HCor – SP – Brazil, Medical Degree – Unicamp – State University of Campinas – Brazil, Orthopaedic Training – University of São Paulo – Brazil, Knee Surgery Training – University of São Paulo – Brazil Master of Science (M.Sc.) – University of São Paulo – Brazil, Ph.D. – University of São Paulo – Brazil, Post-Doctoral Fellowship – Harvard Medical School – Brigham and Women’s Hospital – Cartilage Repair Center – Boston – USA, Post-Doctoral Fellowship – Hospital for Special Surgery – NY – USA, Memberships: SBOT (Sociedade Brasileira de Ortopedia e Traumatologia), SBCJ, SLARD, ISAKOS, International Affiliate Member – AAOS. ECFMG Certified (U.S. – Educational Committee for Foreign Medical Graduates) INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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Dhollander Aad, MD, PT, PhD, Orthopedische Heelkunde BVBA, Brasschaat, Belgium Aad Dhollander studied physiotherapy (PT, 2002) and afterwards medicine (MD, 2009) at the Ghent University. In 2009, he began his residency in Orthopaedic Surgery and Trau- matology at the Ghent University Hospital (Heads of the Department: Prof. Dr. Jan Victor and Prof Dr Rene Verdonk). After his training, he did a one-year fellowship at the Fowler Kennedy Sports Medicine Clinic in London, Ontario, Canada. He has now a position as International Cartilage Regeneration & Joint Preservation Society International Cartilageknee surgeon in AZ Klina, Brasschaat, Regeneration Belgium. His clinical and research interests focus on knee surgery and sports traumatology. He finished his PhD under supervision of Professor Dr. G. Verbruggen involving basic research focusing on metabolic characteristics of differ- & Jointent connective Preservation tissue cell types and clinical research focusing Society on the outcome of several cartilage repair strategies. Aad Dhollander is a member of various scientific societies, such as the ICRS since 2010.

Di Martino Alessandro, MD, Rizzoli Orthopaedic Institute, Bologna, Italy Alessandro Di Martino, MD, is an orthopaedic surgeon, expert on knee surgery with special focus on degenerative diseases and new treatment for cartilage and meniscus regeneration and OA prevention. He received his M.D. degree by the University of Studies of Campania Luigi Vanvitelli and completed the Residency Program in Orthopaedic and Traumatology in the same University. In 2004, he started a fellowship at the Department of Orthopedic Surgery at the James Paget Hospital in Great Yarmouth, England, where he performed outpatient and inpatient activities. In 2005, Dr. Di Martino started his activity in Orthopedic Rizzoli Institute. The main research activity is focused on translational and clinical research for the application and development of novel musculoskeletal tissue treatments, regenerative medicine, and minimally invasive surgical techniques. He is Principal Investigator in several research projects centred on the use of Stem Cells and Platelet Rich Plasma (PRP). He takes and took part in 31 research project or clinical trial. Member of several scientific societies (member of Cartilage Board of SIGASCOT Italian Society of Knee Arthroscopy Cartilage Sport and Orthopaedic Technology). Author of numerous papers on international pre-reviewed Journals (H-index 28). He presented his research works in several national and international meetings of Regenerative Medicine and Orthopaedics. Winner of “Hightly Cited Research” award in 2016 by The Knee Journal. Co-author of paper award in 2016 by Arthroscopy Journal (The Journal of Arthroscopic and Related Surgery) with Certify for “Highly Cited Research”. Poster Award Cum Laude, ICRS World Congress, 2015 and 2013.

Erggelet Christoph MD, PhD, Alfaclinic, Zürich, Switzerland Christoph Erggelet is an orthopaedic surgeon in Zurich/Switzerland affiliated with the De- partment for Orthopaedic Surgery and Traumatology, University Medical Center, University INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGEof Freiburg/Germany. HeJOINT received his MDPRESERVATION in 1986 and passed the board exam for Ortho- paedic Surgery in 1993. A PhD was granted by the University of Essen/Germany in 1987. REGENERATION SOCIETY REGENERATIONSince 2002 he is faculty SOCIETYmember of the University Medical School, University of Freiburg & Germany. Research& interests focus on biologic regeneration of joint function, e.g. culture of autologous chondrocytes, meniscus regeneration and ligament repair. He served as a founding board member of the Bio Valley initiative, a tri-national tissue engineering group, which enabled the setup of a licenced GMP laboratory at the university of Freiburg. Inter- national collaborations included board membership of the EU-funded EUROCELL program and the international Cartilage Repair Registry. Recent research has been done on stress loading of cartilage defects and stability of biodegradable scaffolds in collaboration with the Swiss Federal Institute of Technology Zurich/Switzerland. Chris- toph Erggelet is member of ICRS since the foundation in 1997 and served as a board member. He was President of ICRS for the term office 2013-2015.

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Espregueira-Mendes Joao, PhD,INTERNATIONAL Clínica CARTILAGE do DragãoJOINT PRESERVATION - Espregueira-MendesINTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Sports Centre Porto, Portugal Chairman of Clínica do Dragão – Espregueira-Mendes Sports Centre, FIFA Medical Centre of Excellence, FC Porto Stadium, Chairman and Professor of the Orthopaedic Department of Minho University, Portugal, Treasurer and Chairman of the Publications Committee of the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION (ISAKOS), Board Member of the Patellofemoral& JOINT PRESERVATION Foundation, SOCIETY Professor of& JOINTPorto PRESERVATION University SOCIETY – Co-Chairman of the Post-graduate in Sports Medicine, 3B’s/ICVS Senior Researcher – Minho University, President of the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) 2012-2014 International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society Fernandes Julio, MD, M Sc, PhD, MBA, Hopital du Sacre Coeur de Montreal, Canada Dr. Julio Fernandes was born in Curitiba, Brazil, and graduated in medicine from the Federal University of Curitiba, Brazil in 1988. He obtained post-graduate qualifications in Orthopedic Surgery in Brazil and he completed his training at the University of Montreal in 1994. He was a visiting Fellow with Dr Freddie Fu at Pittsburgh University in 1990. He is a certified Ortho- pedic Surgeon by the Quebec’s Board of Orthopedic Surgery and the College des Médecins du Québec. He holds a M.Sc. degree from the University of Montreal in 1995, along with M Sc and PhD degrees from the Federal University of Curitiba, Brazil. He holds an MBA degree from the John Molson School of Business in Montreal, Canada since 2007. Professional Activities. He began practicing at the CHUM Hospital in downtown Montreal in 1996 and at Sacre Cœur Hospital since 2002 in Hip and Knee Reconstruction and Orthopedic Sports Medicine and Arthroscopy. Dr. Fernandes is the Chief-of-Staff of the Orthopedic Surgery Department of Sacre Cœur Hospital, the largest Orthopedic Surgery Program in the Province of Quebec. He is past Chairman of the University of Montreal Orthopedic Surgery Research Committee. He serves on the editorial board of several scientific publications. Dr. Fernandes is a Full Professor in orthopaedics at the University of Montreal. He has been invited as a visiting professor and lecturer at many universities and learned societies in the United States and around the world, including McGill, Duke (N Carolina), Sherbrooke (Canada), Evangelica (Brazil), Jiao Tong (Shanghai, China), Beijing (China), Clermont-Ferrand (France), Zurich, Vien- na and Mainz (Germany). Dr. Fernandes has published over 64 scientific articles and book chapters, 112 abstracts and 39 invited speaker speeches. He holds 3 patents on nanotechnology and surgical instrumentation. In addition to lecturing world-wide in his area of specialization, he often speaks on topics relating to the business of medicine and has appeared weekly in his national CBC/Radio Canada television chronicle on issues of Orthopedic Surgery and musculoskeletal health. Dr. Fernandes is the Past President and CEO of BioEmergens Biotechnologies, a private company specialized in biotechnology transfer to emerging countries.

Ferracini Riccardo, MD, Azienda Ospedaliera Universitaria San Giovanni Battista, Torino, Italy My clinical education is in orthopedics surgery, but my early background started in a laboratory where I was involved in the early steps of oncogene mediated sarcoma cancerogenesis, which is the subject of my PhD thesis. Due to this biological background my interest deeply evolved in orthopedics where the biological aspects are relevant and improvements for treatments could take advantage of biological studies. My research group is focused on two main research areas: osteoncology, i.e. the study of bone alterations in cancer patients, and regenerative medicine applied to bone and cartilagine reconstruction, i.e. the process of replacement and regeneration of bone tissue for the treatment of fractures and / or musculoskeletal disorders. In the osteocological field, our interest is focused on understanding the molecular mechanisms that regulate the development of bone metastases in frequent and aggressive solid tumors, such as non-small cell lung cancer, breast cancer, adenocarcinoma of the kidney. Specifically, the research is aimed at defining the role of cancer stem cells in the formation of metastases and their interaction between bone and the immune system. In the field of regenerative medicine, studies are aimed at the use of mesenchymal stem cells derived from adipose tissue for the treatment of knee and hip arthritis, thanks to their ability to differentiate into osteoblasts, chondrocytes, myoblasts, stromal cells and therefore potentially repairing damaged tissues, generating bone and cartilage. My publications fully addressed all these topics. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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Gobbi Alberto, MD, Orthopaedic Arthroscopic Surgery International, Milan, Italy Alberto Gobbi graduated in 1983 and completed his residency program in 1988 in Orthopaedic surgery at Milan University and Sports Medicine in Genova in 1992. Dr. Gobbi himself was an athlete at national level and served the Italian National Olympic Committee, for the World Moto- cross Championship, African Rallies, offshore boat racing, down-hill ski, volley and basketball. He was nominated “azzurro d’Italia” in 1998. His participation in high-risk sports led him to focus on trauma, surgical technique and advanced rehabilitation, he became a point of reference for many International Cartilage Regeneration & Joint Preservation Society International CartilageInternational athletes. He worked Regeneration for several years with many major International experts in orthopaedic surgery, arthroscopy and regenerative medicine who are now considered the Giants. He was one of the first Europeans to join the International Cartilage Repair Society. In 1996 he be- & Jointcame an International Preservation member of the American Academy of OrthopaedicSociety Surgeons (AAOS) and then Honorary Member of the Arthroscopy Association of North America (AANA). Since then he has collaborated with the most important scientific Societies including ISAKOS and ESSKA. Dr Gobbi pioneers research on biological therapies of orthopaedic injuries, establishing an international reputation in the field of regenerative medicine and developing advanced surgical techniques with the use of mesenchymal stem cells and growth factors. He performs highly qualified scientific, surgical and educational activities at International level. He served as a reviewer for many journals, is Associate Editor of “Cartilage” since 2010 and in 2012 he received the award for Best International Publication in an American Journal. In 2011 he was ac- knowledged as a Visiting Professor at Kobe & Osaka University, Japan, in 2014 he was nominated Visiting Professor in the Department of Orthopaedic Surgery directed by Prof. David Amiel at the University of California San Diego – UCSD. In 2018 received certificate of appreciation from Yonsei University Korea and he was nominated Honorary professor at the University of Peking and at the N.U.S. National University of Singapore where he also delivered the VK Pillay Lecturer. He founded OASI Bioresearch Foundation Gobbi Onlus (NPO) which is recognized as an International Teaching Center by ISAKOS and ICRS and has dedicated his time to teaching hundreds of fellows during the last 20 years. He has published over 200 scientific papers in international peer-reviewed journals, edited several books and contributed many chapters in scientific publications. He currently serves on the board of directors of ISAKOS and he is the ICRS President.

Grande Daniel, PhD, Feinstein Institute North Shore-Long Island Manhasset, United States of America Daniel Grande is associate investigator and director of orthopaedic research at the Feinstein Insti- tute for Medical research. He is also associate professor at the newly accredited Hofstra School of Medicine. He completed his PhD at New York University and his post-doctoral fellowship ion biomechanics at the Hospital for Special Surgery. He has worked extensively in the area of regenerative medicine and tissue engineering. His early work developed the first use of cell based therapy for cartilage repair, currently known as autologous chondrocyte transplantation. He has served on committees with the Orthopaedic Research Society as spine topic chair and the basic science committee. Dr. Grande is significantly involved in mentoring and teaching of orthopaedic residents for his department. He has been a reviewer for a number of journals including: Journal of Orthopaedic Research, INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALClinical Orthopaedics, CARTILAGE Osteoarthritis and Cartilage,JOINT American Journal PRESERVATION of Sports Medicine, Nature Reviews Rheumatology and Applied Biomaterials. He has been awarded eight patents and helped found two companies in the orthopaedic REGENERATION SOCIETY surgeryREGENERATION field of use. He has served as a member SOCIETYof several companies scientific advisory boards. He completed a five & year rotation with OREF to assist in grant reviews.& He also regularly serves on NIH study sections for RO1, R21, and SBIR/ STTR grants specific to musculoskeletal applications.

Jakob Roland, MD, Môtier, Switzerland Professor Emeritus of University of Berne, Former Chairman of Orthopaedic Surgery of Cantonsspital, Fribourg (1995-2007), Founding President of ICRS 1997-98, Past President of Swiss Orthopaedic Society (1994-96), ISAKOS (1999-2001), AO Switzerland (2002-09 Honours: • Corresponding member Austrian AO-Chapter (2000) • Godfather Herodicus Society USA, 2000 • Surgeon in Chief pro temp. The Hospital For Special Surgery New York, 2002 • Honorary Member of ANA (American Society of Arthroscopy, 2004) • Honorary Member of ISAKOS (International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine), 2007 • Honorary Fellow of ICRS (International Cartilage Repair Society), 2007 • Honorary Member of Swiss Society of Accident Surgery and Insur- ance Medicine, 2008 • Honorary Member of Swiss Orthopaedic Society, 2009

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Kley Kristian, MD, GelenkchirurgieINTERNATIONAL Orthopädie CARTILAGE JOINT PRESERVATION Hannover, GermanyINTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Kristian Kley completed his medical training at Hannover Medical School in 2006 and then started a residency in orthopaedic trauma in Hannover with Prof Philipp Lobenhoffer. He is now working as fellow in a group practice in Hannover (Gelenkchirurgie Orthopädie Han- nover) with Prof. Lobenhoffer. Kristian Kley early developed a strong interest in osteotomy around the knee. He is an active member of the Hannover team treating 300 patients per INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION year with osteotomy around the knee and& JOINT developing PRESERVATION SOCIETY new techniques and& JOINT instruments PRESERVATION SOCIETY to ease these procedures. He has been active on national and international meetings and is also guest member of the Joint Preservation Expert Group of AO Foundation. Kristian Kley has developed unique techniques of minimal-invasive osteotomy of femur and tibia which are now used clinically in Hannover on a regular basis. International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society

Kon Elizaveta, MD, Humanitas University Rozzano, Milan, Italy Associated Professor Humanitas University, Milan. Orthopedic surgeon, Center of Functional and Biological Reconstruction of the knee, Humanitas Research Hospital, Milan 2nd Vice President of International Cartilage Repair Society. Till 2017 Director of Nano-Bio- technology Laboratory and orthopaedic surgeon, Rizzoli Orthopedic Institute and Assistant Professor, University of Bologna. Coordinator of numerous research projects and clinical trials regarding biotechnology applications in orthopaedics, into the framework of Italian and European research. Author of over 180 scientific articles in peer-reviewed journals and over 30 chapters in textbooks in orthopaedic surgery (H-index 64). Faculty of more than 400 society meetings all over Europe, Asia and America. Associated Editor of BMC Musculoskeletal Disorders Journal, International Orthopedics, Journal of Experimental Orthopedics and Joints. Reviewer for more than 20 Orthopaedics Journal. Travelling Fellow ESSKA/AOSSM European/North American Sports Medicine Traveling Fellowship, 2009 and ICRS Travelling Fellowship, North America, 2004 Winner of several awards as Most cited and Most downloaded publication 2011-2016 in Arthroscopy Journal, Leading article Knee Surgery Sports Traumatology Arthroscopy Journal, 2013 and 2016, Poster Award Cum Laude, ICRS World Congress, 2015 and 2013, Most cited publication 2009-2010 in American Journal of Sports Medicine, Scientific exhibit award of excellence AAOS Annual Meeting 2011

Lane John, MD, La Jolla, United States of America John G. Lane MD is a clinician in San Diego who has a voluntary Clinical Associate Profes- sor appointment at the University of California, San Diego in the Department of Orthopedic Surgery. Dr. Lane completed his residency at the University of Michigan and performed fellowship training in sports medicine at UCSD. Dr. Lane is a member of AAOS, AANA, AOSSM, ISAKOS and ICRS. Currently he is the chair of the membership committee of the ICRS and a member of the education committee of ISAKOS. His clinical field of practice focuses on complex knee and shoulder injuries. He has published 27 peer-reviewed manu- scripts and four book chapters. He has collaborated with Professor Amiel at UCSD since 1989 working in the fields of ligament and cartilage. Cartilage research has focused on the Effects of the Holmium: YAG laser upon articular cartilage for which he was awarded an Orthopedic Research and Education Foundation grant. Other grants in the field of articular cartilage he has participated in include NIH/ SBIR grants for “Cartilage-Cartilage adhesion by Photopolymerization” and “A Novel Engineered Composite Con- struct for Articular Cartilage Repair. Ongoing cartilage research includes autologous chondrocyte implantation evaluation and BMAC implantation. Shoulder related research includes collaboration with Dr. Sam Ward and participation in an NIH grant dealing with: “The physiological basis of rotator cuff muscle rehabilitation.” Research into rotator cuff injury and the effect of diabetes is also ongoing. An NIH grant was obtained in conjunction with the Professor Christine Chung of the radiology department for “UTE MRI of Tissue Response in Meniscal Repair” evaluating healing in a meniscal repair model. He is also conducting research on the effects of valgus unloader knee bracing upon cartilage and bone healing. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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Madry Henning, MD, Saarland University, Homburg, Germany Henning Madry is a clinician-scientist, a tenured Professor and Chair of Orthopaedic Re- search and Director of the Center of Experimental Orthopaedics at Saarland University in Germany. Dr. Madry received his M.D. from Humboldt University, Berlin, under the mentorship of Detlev Ganten. His postdoctoral research fellowship was at Harvard Medi- cal School in Boston, with Steven B. Trippel at the Massachusetts General Hospital and at Massachusetts Institute of Technology in Cambridge, with Gordana Vunjak-Novakovich. Dr. International Cartilage Regeneration & Joint Preservation Society International CartilageMadry received calls to Professorships Regeneration at the Humboldt University Berlin, the University of Regensburg and the Albert-Ludwigs-University Freiburg. He is the Founding Editor-in-Chief of the Journal of Experimental Orthopaedics, the basic science journal of the European So- & Jointciety for Sports Preservation Traumatology, Knee Surgery and Arthroscopy Society (ESSKA). As a clinically active orthopedic surgeon, he has special expertise in regenerative treatments for cartilage defects and osteoarthritis. His research program translates novel molecular, cell biology and tissue engineering approaches into clinical applications in orthopedic surgery with a focus on translational aspects of osteochondral regeneration. Henning Madry was recently a visiting professor at the Sorbonne Université Paris in France.

McDermott Ian, MB BS, MS, FRCS(Orth), FFSEM(UK) London Sports Orthopaedics, Managing Partner, London, United Kingdom Mr Ian McDermott is a consultant orthopaedic surgeon specialising purely in knees. Ian was the youngest ever surgeon to be elected as a Council Member and Trustee of the Royal College of Surgeons of England, and he has also been appointed as an Honorary Professor Associate in the School of Sport & Education at Brunel University. Ian is one of the UK’s leading experts in the fields of meniscal transplantation, complex knee reconstruction and custom-made knee replacements. Ian’s practice is a Hospital Innovations designated ‘Centre of Excellence’ for meniscal transplantation. His practice is also a Vivostat designated ‘Centre of Excellence’ for the use of biological glues in knees. Ian is also part of the ConforMIS Surgical Visitation Program, teaching visiting surgeons the techniques for implantation of ConforMIS custom-made knee replacements. Ian is one of the founders and the current President of the UK Biological Knee Society. Ian left the NHS in 2007, and in 2008 he founded the London Sports Orthopaedics practice, based in the heart of the City of London, which is now one of the UK’s most successful private orthopaedic and sports medicine practices: www.sportsortho.co.uk

McNicholas Mike BSc,FRCSEd (Tr & Orth), FFS, MD, University Hospital Aintree Teaching Hospital, Consultant Trauma & Knee, Surgeon Liverpool, United Kingdom Mike McNicholas works as a Consultant Trauma and Knee Surgeon in the UK at Liverpools INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGEUniversity Hospital Aintree.JOINT He is an Honorary PRESERVATION Professor in the Directorate of Sport at the University of Salford and Honorary Senior Lecturer, Musculoskeletal Biology Department of REGENERATION SOCIETY REGENERATIONthe University of Liverpool.SOCIETY He has a longstanding interest in articular cartilage biology. He & regularly lectures& and teaches surgical skills in the UK and internationally. His MD Thesis “Meniscectomy and Osteoarthritis” included collaborative work with Stefan Lohmander on the biological markers of articular cartilage metabolism, comparing these to Nitric Oxide metabolism and received the AANA Richard OConnor Award. He participated in the ACTIVE and Summit Trials comparing marrow stimulation with cell based treatments. He was a member of the world medical advisory group for arthroscopic MACI. He has worked as a consultant for Schwartz Biomedical for four years and is one of four UK surgeons studying the clinical outcomes of the BioPoly implant, he was the first surgeon to insert the Biopoly racetrack implant. Other current research areas include the effects of delivery method on chondrocyte viability, stem cell augmentation of ACL graft incorporation and novel offloading implants versus osteotomy for the management of the varus arthritic knee.

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Niemeyer Philippe, MD, PhD, OCMINTERNATIONAL | Hospital CARTILAGE JOINT forPRESERVATION Orthopedic INTERNATIONAL Surgery, CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Munich, Germany Professor Philipp Niemeyer is member of the Department of Orthopedic Surgery and Trau- matolgy of the Freiburg University Hospital (Germany, Director: Prof. Dr. N. P. Südkamp) and head of the divsion of knee surgery and cartilage repair. After graduating from the University of Freiburg in 2002, he began his clinical training at the Department of Ortho- INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION paedics at the University of Heidelberg (Germany,& JOINT PRESERVATION Prof. SOCIETY Dr. V. Ewerbeck),& whichJOINT PRESERVATION he continSOCIETY - ued in the Department of Orthopedics and Traumatology at the University of Freiburg. Since that time, he conducts research into preclinical and clinical aspects of the regeneration of cartilage tissue. In addition to publishing various scientific papers in this area he was awarded in 2005 with the Kurt Steim Award of the University of Freiburg in 2012 and the ResearchInternational Cartilage Prize Regeneration of the & I NTERNATIONAL C ARTILAGE R EGENERATION German Society for Orthopaedics and Orthopaedic Surgery (DGOOC).& JOINT PRESERVATION In 2013S OCIETY he became AssociateJoint Preservation Professor Society at the Freiburg University, he is executive board member of the German-Speaking Society for Arthroscopy and Joint Surgery (AGA) and the German Knee Society (DKG). Furthermore, he is initiator of the German Cartilage Registry which has been introduced in 2013. Since 2016, Philipp Niemeyer is Consultant Surgeon at the OCM in Munich, Germany (Orthopädische Chirurgie München).

Peretti Giuseppe, MD, PhD, Istituto Ortopedico Galeazzi Milano, Italy Giuseppe Peretti received his M.D. degree by the University of Milan and completed the Residency Program in Orthopaedic an Traumatology in the same University. He spent several years at the Massachusetts General Hospital, Harvard Medical School, Boston, USA, where he accomplished several research activities on basic science in orthopaedics. He is currently Full Professor and Chief of the Residency Program in Orthopaedics and Trauma- tology at the Univerity of Milan. Head of the Equipe of Regenerative and Reconstructive Orthopaedics (“EUORR”); Head of the Regenerative Medicine and Biomaterials Laboratory by the IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; Former President of the Cartilage Commission of the European Society of Sports Traumatology Knee Surgery and Arthros- copy (ESSKA); former President of the Research Committee of the Italian Society of the Knee, Arthroscopy, Sports, Cartilage, Orthopaedic Technologies (SIGASCOT); former President of the Endorsement Committee of Tissue Engineering and Regenerative Medicine International Society (TERMIS). In his career he obtained 17 national and international awards for his scientific activity and achieved more than 30 grants or contributions for research as PI or Co-Investigator. His principal research interest includes the study of strategies of regenerative medicine and tissue engineering for the repair of articular and meniscal cartilage, of osteochondral and bone tissue. His scientific production includes more than 500 publications, whose 55 on peer reviewed journals with impact factor. Giuseppe Peretti is ICRS member since 1997 and he participated to the first International Fribourg Symposium on Cartilage Repair in Switzerland in 1997.

Piontek Tomasz, MD, PhD, Medical University Poznan, Poland Graduate of the Poznan University of Medical Sciences. First degree of specialization in orthopedics and traumatology in 1999, four years later, second degree of specialization, and in 2003, defending his doctoral thesis. Tomasz Piontek is an international trainer of arthroscopic knee and hip surgical techniques. Since 2006, Tomasz Piontek has been a doctor at Rehasport Clinic. Previously, he had worked, among others, in the Depart- ment of Paediatric Orthopaedics in Poznan, was the first football physician of Amica Wronki, and in Lech Poznan. He had completed internships in Balgrist University Clinic in Zurich, Department of Orthopedics and Traumatology of Sports Medicine, Queens Medical Centre in the UK, and the University of Pittsburgh- Department of Orthopaedic Surgery, in the United States. In 2005 he achieved his Phd Title, and in 2015, Habilitation. He is interested in sport orthopeadic medicine, especially treatment of lower limb injuries. He and his team have developed the method and technique of AMIC ( Authologus Matrix Induce Chondrogenesi) in the knee, hip and talus, in an all Arthroscopic procedure; regeneration of meniscus treatment with collagen membrane; Achilles reconstruction with percutaneous methods in large and chronic ruptures using free tendons. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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Roato Ilaria, MD, PhD, Azienda Ospedaliera Universitaria San Giovanni Battista, Torino, Italy Torino, Italy I started my studies on musculoskeletal disease after my graduation in medical biotechnologies with honors. My mentor, Prof. Riccardo Ferracini got a grant for a research project on bone metastases from solid tumor, and I focused my studies on osteoclastogenesis in osteolytic bone lesions of patients affected by different kind of solid tumors. During my PhD in the Osteoncology Lab. at Center for Research and Medical Studies (CeRMS), I met and started a deep collaboration with Prof. Maria International Cartilage Regeneration & Joint Preservation Society International CartilageGrano from University of Bari, improvingRegeneration my skills and increasing my scientific competences in the field of bone research. I was introduced to the osteoimmunology field, by studying the interactions between osteoclasts and immune cells in bone metastatic patients. I also began a collaboration with & JointProf. Giancarlo Preservation Isaia (University of Torino), working on bone metabolicSociety disease such as osteoporosis, and with Prof. Marco Spada (University of Torino), working on phenylketonuria. During my PhD I presented my data to international meetings in the bone field and published many articles as first author in international peer-reviewed journals. As post doctoral fellow, I received a first grant as Principal Investigator from Ricerca Sanitaria Finalizzata and continued to work on bone metastasis, also collaborating with Dr. Daniele Santini (Campus Biomedico, Rome), a well-known clinician deeply involved in basic, translational and clinical studies on this field. In 2011, I received a grant as Young Investigator from the Italian Ministry of Health, which allowed me to acquire a strong expertise as an independent investigator. Indeed, I demonstrated the funda- mental role of cancer stem cells to directly initiate the bone metastastic process in breast, lung and renal cancer, adopting a “human-in-mice” model of bone metastases. Recently, I extended my interest to osteoarthritis. My laboratory obtained a large financial support for studies on regenerative medicine, focused on the use of mesenchymal stem cells derived from adipose tissue to treat osteochondral defects in knee and hip arthritis. This year, 2019, I received another large grant from the Italian Ministry of Health for a project on the role of NK cells in bone metastasis, in collaboration with IRCCS Ospedale Policlinico San Martino Genova and Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. Currently, I’m leading the osteoncology lab at CeRMS in Torino and my main objective is to create a strong research group on metastases and regenerative issues on bone and cartilage. Author of more than 40 indexed publications.

Sadlik Boguslaw, MD, PhD, Bielsko-Biala, Poland Education: 2009 Ph.D. in medicine, Graduation thesis: „ The meaning of quality and graft prepar- ing manner with hamstring tendons in anterior knee instability treatment with four tunnel technique” 2005 Specialization in Orthopaedics and Traumatology, 1989-1995 medicine, Silesian Medical University, Katowice, Poland 1988-1989 phisics, Jaggielonian Univerisity, Krakow, Poland - Profes- sional experience: 2015- Head of the Biological Joint Reconstruction Department at the St. Lukes Hospital, Bielsko- Biala, Poland, 2005- Orthopaedic surgeon at the St. Lukes Hospital, Bielsko- Bi- ala, Poland, 2000-2005 Resident in the Department of Orthropaedics and Traumatology at the St. Lukes Clinic, Bielsko-Biala, Poland, 1996-2005 Resident in the Department of Orthropaedics and Traumatology at the Silesian Hospital of Reumatology in Ustro, Poland. Surgical experience: Over 4000 orthopaedic surgeries. Especially arthroscopic knee and ankle surgeries ( ACL, PCL, MCL, LCL, PLC, ATFL, CFL, MPFL INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALand the other CARTILAGEligaments repairs and reconstructions,JOINT AMIC, BMAC, PRESERVATION HA-BMAC implantations, HTO and DFO alignment correction, hindfoot corrective osteotomies and arthrodesis, meniscal substitutes and allografts implantations and the oth- REGENERATION SOCIETY ers).REGENERATION Professional Memberships: Polish Foot and AnkleSOCIETY Society (The President 2016-2019), Polish Society of Orthopaedics & and Traumatology (Member of the Knee &Surgery Committees Board, 2014-2018) Polish Society of Arthroscopy Interna- tional Cartilage Repair Society, International Society of Arthroscopy Knee Surgery and Orthopaedic Sport Medicine, European Society of Sport Traumatology, Knee Surgery and Arthroscopy.

Salzmann Gian MD, PhD, Schulthess Klinik, Orthopaedic and Trauma Surgery, Zurich, Switzerland Gian Salzmann is currently consultant at the Lower Extremity Unit of the Schulthess Klinik, Zurich, Swit- zerland. He underwent his Orthopedics / Traumatology education at the Technical University of Mu- nich with Professor Imhoff as well as at the Freiburg University with Professor Südkamp. He specializes in reconstructive knee and ankle joint surgery and holds research connections to Freiburg University, the AO Institute Davos, to the ETH in Zurich, to Basel University Hospital and to the Technical Univer- sity Munich. His research focus is experimental Tissue Engineering using chondrocytes and stem cells and clinical outcome studies mostly following cartilage repair procedures also involving quantitative MR imaging methods. Gian has authored over 100 peer-reviewed publications. Furthermore he is co- president of the “Freiburger Knorpeltage“ an annual meeting at Freiburg University which will have 7-year anniversary in 2018.

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Sciarretta Fabio, MD, Casa di CusaINTERNATIONAL Nostra CARTILAGE SignoraJOINT PRESERVATION della Mercede,INTERNATIONAL CARTILAGERome,JOINT PRESERVATIONItaly REGENERATION & SOCIETY REGENERATION & SOCIETY Fabio Valerio Sciarretta was born in Rome on November 13, 1963. He is currently orthopaedic consultant at the Clinics “Nostra Signora della Mercede”, “Assunzione di Maria Santissima” and “Mater Dei” in Rome and at the “Valdisieve Hospital” in Florence. He earned his MD with honours from the University of Rome “La Sapienza” in 1988 and completed his Orthopaedic Surgery residency in the same University, gaining the special- INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION ization In Orthopaedics and Traumatology& JOINT cum PRESERVATION laude SOCIETY in 1993, under the& JOINT supervision PRESERVATION SOCIETY of Prof. Lamberto Perugia, master of knee surgery and his godfather for over 20 years. Since the years of the Bachelor, he concentrated his professional interest in the Knee Surgery, Arthroscopy and Sports Medicine, focusing particularly on techniques for cruciate ligament reconstruction and repair of meniscal tears and, subsequently, to the cartilage restoration surgery,International devoting Cartilage Regeneration years & I NTERNATIONAL C ARTILAGE R EGENERATION to all the different techniques of reconstruction of cartilage damage& JOINT PRESERVATIONin any joint, S OCIETY deepening theseJoint techniques Preservation Society with internships abroad. The last decade has been especially dedicated to regenerative medicine therapies for cartilage healing. He has published over 50 publications in national and international journals and has presented more than 150 papers in national and international conferences. He was also instructor in various courses of arthroscopic and arthroplasty surgery. He edited the Italian edition of over 30 treaties of Orthopedics and Trau- matology of the American and international literature and for some years participated to the Italian edition of the original English text of “Yearbook of orthopaedics”. Since January 1990 he is ordinary member of the Italian Orthopaedics and Traumatology Society (SIOT), Affiliate Member of the American Academy of Orthopaedic Sur- geons (AAOS) and of the European Society of Sports Traumatology Knee Surgery and Arthroscopy (ESSKA), Ac- tive member of the International Society of Arthroscopy, Knee Surgery & Orthopaedic Sports Medicine (ISAKOS), Active member of ICRS (International Cartilage Regeneration & Joint Preservation Society) and Active member of the Societé Internationale de Chirurgie Ortopedique et de Traumatologie (SICOT). He is currently Co-Chair of the ICRS (International Cartilage Regeneration & Joint Preservation Society) Education and Meeting Standing Committee, Member of the ISAKOS (International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine) Education Committee and Member of the Sports Medicine and Arthroscopy Committee of the Societé Internationale de Chirurgie Ortopedique et de Traumatologie (SICOT).

Slynarski Konrad, MD, PhD, Warszawa, Poland Dr. Slynarski completed his MD and Ph.D. degrees at The Medical University of War- saw, Poland, and completed research fellowships at Case Western University in Cleveland, USA, with Arnold Caplan on Mesenchymal Stem Cells - based cartilage repair (funded by the Polish-American Kosciuszko Foundation), and also with Matts Brittberg, Sweden. He subsequently completed a knee fellowship with Dr. Rene Verdonk, Belgium. He was a principal investigator in several comprehensive clinical studies. He works on development and improvement of knee joint preservation procedures, including iBalance osteotomy and cell-based therapies for cartilage repair. He organized several symposia and courses in the field of cartilage repair, including Warsaw ICRS World Congress in 2007, Polish Ar- throscopic Society Congresses and Warsaw Joint Preservation Congress in 2013, 2015 and 2016. Dr. Slynarski is currently Head of private sports medicine center, LEKMED Warsaw, Poland. He is a President od Polish Arthros- copy Society, member of Education Committee of International Cartilage Repair Society (ICRS) and Osteotomy Committee of European Society for Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA).

Snow Martyn, FRCS (Tr & Orth), The Sport Injuries Clinic, Bromsgrove, United Kingdom Mr. Martyn Snow has been a Consultant Orthopaedic Surgeon at The Royal Orthopae- dic Hospital since 2009, which is 1 of only 5 purely Orthopaedic Hospitals in the country. Mr Snow is a graduate of Edinburgh University and undertook his Registrar training in the Manchester region. He spent 18 months on fellowship in North America, 12 months in Hali- fax, Nova Scotia undertaking a Sports Medicine fellowship at the Sports Medicine Clinic of Nova Scotia. He subsequently spent 6 months at the Holand Orthopaedic and Arthritic Centre in Toronto, gaining further experience in Shoulder and Knee surgery. In 2008 Mr Snow was awarded the British Elbow and Shoulder Society North American travelling fellowship. This enabled him to spend a further 4 weeks visiting some of the worlds foremost shoulder surgeons in major centres such as New York, Los angeles, San Antonio and Houston. In 2006 he completed an MSc in INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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Orthopaedic Engineering from Cardiff University. Mr. Snow has since designed his own fixation device for use in ACL reconstruction, which is currently in use by Orthopaedic surgeons world wide. Mr Snow has a major interest in sporting injuries of the knee, including Anterior and Posterior Cruciate Ligament reconstruction. He treats all aspects of cartilage injuries in the young Adult, using the full spectrum of cartilage regeneration techniques, osteotomy, unicondylar and total knee replacement. He very active in the research community and is currently chief investigator in a number on-going trials. His current areas of interest include, The use of stem cells in cartilage International Cartilage Regeneration & Joint Preservation Society Internationalrepair, Improving tendonCartilage healing in rotator cuff repair Regeneration and functional improvements following ACL reconstruction.

Sofat Nidhi, MD, PhD, St George’s, University of London, United Kingdom & Joint PreservationProfessor Sofat is a Clinical Academic Society Rheumatologist at St George’s, University of Lon- don. She earned her medical degree from University College London and PhD in Medical Biochemistry from The Kennedy Institute of Rheumatology. Nidhi’s research focusses on the mechanisms of tissue damage and pain in arthritis. Her group was the first to publish the gen e expression profile of bone marrow lesions in osteoarthritis. Professor Sofat has a translational research group and she sees patients at St George’s University Hospitals Foundation Trust.

Stone Kevin, MD, The Stone Clinic, Research, San Francisco, United States of America Dr. Stone is an orthopaedic surgeon at The Stone Clinic in San Francisco who specializes in sports medicine with a special interest in knee and shoulder injuries. He was educated at Harvard College and earned his M.D. at the University of North Carolina. He trained in In- ternal Medicine at Harvard’s Beth Israel Hospital, General Surgery at the Stanford University Medical Center, Orthopaedic Surgery at the Harvard University Combined Orthopaedic Residency Program, a Knee Surgery and Sports Medicine Fellowship and a visiting Research Fellowship at the Hospital for Special Surgery. Dr. Stone is Chairman of The Stone Research Foundation, a public non profit entity dedicated focused on biologic joint replacement. He received the Albert Trillat Young Investigator’s Award from the International Society of the Knee, the Cabaud Award from AOSSM, the Resident’s Essay Award from AANA, and approximately 50 U.S. patents. He has been the principle investigator on three N.I.H. grants. Dr. Stone is the inventor of the CMI (Menaflex) and co-founder of ReGen Biologics, Inc., a medical device company that produced the first collagen scaffold for meniscus regeneration; founder and principle scientist of CrossCart, Inc., now Aperion Biologics Inc. a medical device company that removes the antigens from pig tissues to make pig ligaments, bone, and cartilage available for human use; and founder of Joint Juice, Inc., a producer of a glucosamine-enriched beverage and Rescue Reel Inc. the first personal escape device INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALfor high rise builidings.CARTILAGE JOINT PRESERVATION REGENERATION SOCIETY REGENERATION SOCIETY & Tirico Luis, MD,& University of São Paulo - Medical School, Orthopedic and Traumatology, Sao Paulo, Brazil Luis Tirico is an Orthopedic Surgeon in São Paulo, Brazil. Born and raised in Brazil, he received his medical degree from the University of São Paulo Medical School in 2003. He worked as an attending physician in the Brazilian Army in 2004 and completed his residency in Orthopedics in 2007 in the Orthopedic and Traumatology Department – Hospital das Clinicas – University of São Paulo Medical School. In 2008 he finished his fellowship in Knee Surgery in University of São Paulo and did a short-term fellowship with Dr. William Bugbee at Scripps Clinic, Green and Anderson Hospital in San Diego, CA in 2010. Since then, he has developed and been responsible for the Fresh Osteochondral Allograft program in Knee Surgery at the Orthopedic and Traumatology Department, University of São Paulo, Brazil. He was awarded the ICRS – Zimmer Scholarship Programme in 2012, spending time with Dr. Tom Minas and Dr. Andreas Gomoll in Boston, MA. In 2015 he completed his Doctor of Medicine thesis entitled “Protocol of procurement, processing and transplantation of fresh osteochondral allografts in the knee joint” from the University of São Paulo, Brazil. In 2017 he was awarded by ICRS with the Lars Peterson Travelling Fellowship representing the epitome of education and international partnership through thought leaders in cartilage repair. His main clinical and research interests are cartilage repair procedures in knee surgery.

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Tudisco Cosimo, MD, Sport TraumatologyINTERNATIONAL CARTILAGE UnitJOINT PRESERVATIONat the Tor VergataINTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY University Hospital, Rome, Italy 1995 Università degli Studi dell’Aquila. Residency in Sport Medicine cum laude. 1985 Uni- versità di Iowa City, Iowa. “Research Fellow” certification. 1982 Università degli Studi di Roma “La Sapienza”. Residency in Orthopaedics and Traumatology magna cum laude. 1979 Università degli Studi di Roma “La Sapienza” Medical Degree magna cum laude. 1972 Clas- INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION sic High School Degree. Medical License& (SpecifyJOINT PRESERVATION Authority SOCIETY that issued License& JOINT PRESERVATION and SOCIETYAttach Copy): Italian Medical License issued on May 1979. Member Of The Following Scientific So- cieties: Aaos, Epos, Siot, Sitop, Sigascot, Sia, Sotimi, Fmsi, Regal. Teaching Activity. 1999-present Teacher in the Residency program in Orthopaedics and Traumatology, Teacher in the Podiatrist Degree. 2003-present: Teacher in the Residency program of Sports Medicine. 2006-present:International Cartilage Teacher Regeneration in & I NTERNATIONAL C ARTILAGE R EGENERATION Medicine and Surgery School Degree. 2010-present: Teacher of &the JOINT Master PRESERVATION in S OCIETYPhysical Education andJoint Preservation Sports Society Activi- ties. 2015-present: Teacher in Diseases of Musculoskeletal System in the English Medical Degree Course. Working Experience: 2018-present Head of the Sport Traumatology Unit at the Tor Vergata University Hospital. 2018-present Coordinator and Teacher of “Musculoskeletal Diseases” in the English Degree Course in Medicine and Surgery. 2015-present University of Rome Tor Vergata Associate Professor of Orthopedics and Traumatology. 2008–present University Hospital of Rome Tor Vergata. Director of Sports Traumatology Unit. 2006–present University of Rome Tor Vergata. Delegate for patients with special needs appointed by the Dean of the University of Medicine and Surgery (Act 104/92). 2006–present University of Rome Tor Vergata. Aggregate Professor of Orthopedics and Traumatology. 2003–2008 Jewish Hospital, Rome Orthopaedic surgeon consultant. 2002 University Hospital of Rome Tor Vergata. First level orthopedic surgeon assistant. 2001 St. Eugenio Hospital, Rome First level orthopedic surgeon assistant. 2000 Department of Hand Surgery - University Hospital of Rome Tor Vergata. Research professor, scientific sector F16A. 1996 Department of Hand Surgery - University Hospital of Rome Tor Vergata. Assistant Professor. 1990-present Italian Football Federation Sport Traumatology for one of the National Football Teams. 1987 Department of Mus- culoskeletal pathology - University of Reggio Calabria. Assistant Professor. 1985–1987 S. Ten. Med. Attilio Friggeri Military Hospital, Rome. Orthopaedic Surgeon Consultant. 1983–1985 Military Hospital, Anzio (Rome). Orthopaedic Surgeon Consultant.

Vadalà Gianluca, MD, PhD, Campus Bio-Medico University of Rome, Orthopaedic and Trauma Surgery, Rome, Italy Gianluca Vadalà (date of birth: March 14th 1979) graduated at the Medical School of Cam- pus Bio-Medico of Rome University (UCBM) in 2003 with the thesis titled: Stem cell therapy for intervertebral disc regeneration: in vitro study. He concluded the Residency Program in Orthopaedic and Trauma Surgery at the UCBM (directed by Prof. Vincenzo Denaro) in 2008. He concluded the PhD program in “Tissue Regeneration for Functional Restoration” at UCBM in 2012. He is currently an Attending Orthopaedic Surgeon in the Dept of Orthopaedic and Trauma Surgery at UCBM. He carried out a two years Research Fellowship in the “Spine Tissue Engineering Laboratory” and in the “Growth and Development Laboratory” of the De- partment of Orthopaedic Surgery, University of Pittsburgh, USA. He worked for one year in the “Tissue Engineering Laboratory/bone division” of the Biomedical Science Park San Raffaele of Rome directed by Prof. Paolo Bianco. He collaborated with the “Experimental Orthopaedic Laboratory” of the University of Navarra, Pamplona, Spain. He is now collaborating with the “Musculoskeletal regeneration Program” of the AO Research Institute at Davos, Switzer- land. Dr. Vadalà was the Winner of the “North American Spine Society (NASS) 2004 Research travelling Fellowship Award”, of the “Michael J. Jerva MD Award for Best Poster Presentation” at the IITS 17th Annual Meeting (2005) in Munich, Germany. I was a co-investigator in the “NASS 2005 Research Grant” with the project: Mesenchymal Stem Cell Injections for Treatment of Intervertebral Disc Degeneration. He was the winner of the 2009 Grant for Integrated Research of UCBM as co-Investigator with the project: Towards tissue prototyping: fabrications of patient-specific scaffolds for the regeneration of osteochondral tissue. His major research interest is developing new biological therapies for intervertebral disc degeneration and osteoarthritis with a special focus on stem cell therapy, gene therapy and tissue engineering. He published 22 papers on international pre-reviewed Journals. He presented his research works in several international meetings of Regenerative Medicine, Orthopaedics and Spine Surgery. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

INTERNATIONAL FACULTY

Van Heerwaarden Ronald, MD, PhD, Sint Maartenskliniek, Orthopaedics, Woerden, Netherlands Ronald van Heerwaarden headed the Limb Reconstruction Center and the Limb Deformity Re- construction Units of the Sint MaartensClinics in the Netherlands for the past 13 years. As per May first 2016 he started a new practice in Mill where he will develop a Centre for Deformity Correction and Joint Preserving Surgery. He was appointed Chairman of the ESSKA Osteotomy Committee in February 2016. In the past decade, he was a member of the AO Knee expert International Cartilage Regeneration & Joint Preservation Society International Cartilagegroup, which is responsible forRegeneration development of new osteotomy techniques, osteotomy instruments and the TomoFix plates. He has performed research projects on conservative treatments of monocompartmental OA and surgical treatments with osteotomies. In the last years he was & Jointa co-editor on Preservationthe books “Osteotomies for Posttraumatic Deformities”, Society “Osteotomies around the knee” and “Kniegelen- knahe Osteotomien”. For these books he produced 17 chapters and 9 case presentations. He was a also a co-editor of the KSSTA January 2013 special issue on Osteotomies around the Knee. Starting from 2004 he has authored or co- authored more than 50 articles on deformity analysis, osteotomies around the knees and joint preservation surgery. He has been an invited speaker at osteotomy meetings all over the world.

Van Osch Gerjo, PhD, Erasmus MC, University Medical Center, Orthopaedics & Otorhinolaryngology, Rotterdam, Netherlands Gerjo van Osch studied Medical Biology at Utrecht University, the Netherlands and received a PhD from Nijmegen University based on her research on mouse models for osteoarthritis (1994). During her postdoc she started to focus on tissue regeneration. She moved to Erasmus University Rotterdam in 1995 were she has set up her own research group. Gerjo is currently appointed as full professor of Connective Tissue Regeneration in the De- partments of Orthopaedics and Otorhinolaryngology at Erasmus MC, University Medical Center Rotterdam. She is leading a research group of approx. 20 people. Her research aims to find methods to generate permanent cartilage with the use of stem cells, even in an inflamed environment such as osteoarthritis. She is co-author on over 200 publications. Gerjo is involved in several national and European funded projects (also coordinating two Horizon2020 MSCA-ITNs) and is currently the chair-elect of TERMIS-EU. She has served on the board of several (inter)national research societies such as the Dutch Society for Matrix Biology and the International Cartilage Repair Society and in editorial boards of scientific journals (a.o. Cartilage, Tissue Engineering, Journal of Tissue Engineering and Regenerative Medicine).

Verdonk René, MD, PhD, Gent, Belgium Rene Verdonk obtained his medical degree in July 1971 at Gent State University in Belgium. He was Board certified in orthopaedic surgery in 1976 and presented his PhD thesis on Viable meniscal allografts in 1992. Since 1992 he was Full time Professor of Orthopaedic Surgery and INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGEhead of the department of JOINTOrthopaedic SurgeryPRESERVATION and Traumatology, Ghent University Hospital, De Pintelaan 185, B-9000 Gent (Belgium). He is emeritus professor since 01 10 2011. In the REGENERATION SOCIETY REGENERATIONcourse of his career he hasSOCIETY been involved in the advancement of trauma surgery and in knee & pathology and takes& a special interest in cruciate and meniscal surgery. Currently, he is also involved in cartilage pathology and treatment. He has published in many review Journals. He was Editor in Chief of the KSSTA journal (knee surgery and sports trauma and arthroscopy) and later became senior editor since 2013. He is a member of many scientific societies, such as the Belgian Society for Orthopae- dic Surgery and Traumatology, of which he was President in 1991 – 1992. He is a founding member of BOTA (Belgian Orthopaedic Trauma Association). He is Past President of ESSKA (president 1995-1996) and past chairman of the basic science committee. He is a member of the ISAKOS strategic planning committee and of the ISAKOS Education Com- mittee. He is also a member of AAOS, and corresponding member of the American Orthopaedic Association (AOA) and of the Orthopaedic Trauma Association (OTA). He was nominated to the prestigious Hall of Fame of the AOSSM in 2011. During the recent meeting in Lyon in June 2015 he was awarded the prestigious honorary ISAKOS membership. He is now an active consultant in the ULB Erasmus univ Hospital dept of orthopaedics and trauma (dir. Prof Dr F Schuind ) involved in all aspect of knee pathology and treatment.

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Vonk Lucienne, PhD, UMC Utrecht,INTERNATIONAL Orthopaedics, CARTILAGE JOINT PRESERVATION Utrecht, NetherlandsINTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Lucienne Vonk studied life sciences at HU University of Applied Sciences Utrecht, The Neth- erlands. She worked as a research technician for two years on the production of recombi- nant human collagens by yeast and fungi for tissue engineering purposes at Leiden Univer- sity. In 2006 she started as a PhD student at the Academic Centre for Dentistry Amsterdam on the use of chondrocytes and chondrons for tissue engineering of cartilage. After complet- INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION ing her PhD in 2010, she joined the department& JOINT PRESERVATION of Orthopaedics SOCIETY at the & UMCJOINT PRESERVATION Utrecht SOCIETY as a postdoctoral researcher, where she is currently appointed as an assistant professor. Her research interests include cocultures with mesenchymal stromal cells (MSCs), trophic signaling by MSCs and signaling by microRNAs for cartilage repair. International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society Wilson Adrian, MD, BSc, The Harley Street Clinic, Marylebone, United Kingdom Professor Wilson is a specialist knee surgeon who qualified with a BSc in Biochemistry from Man- chester University in 1989 and then went on to study medicine at St Bartholomew’s medical school, graduating in 1994. He did his fellowship in Sports Medicine at the Brisbane Orthopaedic Centre with Peter Myers in 2004. Since becoming a consultant Adrian has developed a specialist interest in knee preservation surgery particularly focusing on complex ligament and osteotomy surgery. Most recently he has set up a dedicated centre for osteotomy surgery at The Wellington Hospital in Lon- don and has also set up “The Children’s Knee Centre” based at The Portland Hospital for Women and Children in London. This brings together a group of knee surgeons to focus on the management of the paediatric knee including a programme for ACL damage prevention in the UK. Adrian has helped to develop the instruments and surgical techniques for a number of surgical procedures. He is particularly well known for his work on the All Inside ACL and PCL ligament which Adrian helped to pioneer and he has presented and published extensively on these procedures. He has also pioneered and helped to develop several other surgical techniques including his ligament reinforcement concept for ligament reconstruction, the minimally invasive Posterolateral corner technique. Profes- sor Wilson has also helped to pioneer the new “Anterolateral Ligament Procedure” and is a member of the anterolateral ligament expert group. Professor Wilson has a particular interest in knee osteotomy surgery and is considered one of the leading world experts in this surgery and the management of the young arthritic knee. He is a co-founder of the UK Knee Osteotomy Registry (UKKOR) the first dedicated national database for osteotomy surgery. He has developed a number of instruments for osteotomy surgery and pioneered a minimally invasive technique for High Tibial Osteotomy Surgery. He co-founded the Basingstoke Osteotomy Masterclass in 2007. Professor Wilson handed on the role of vice chairman of the ESSKA osteotomy committee in 2017 he has a recognised centre for the ESSKA Osteotomy travelling fellowship. Professor Wilson is also a member of the ESSKA Osteotomy Committee and the ESSKA Arthroscopy Committee. Professor Wilson set up a successful fellowship training programme for ligament and osteotomy surgery in 2012 and has a chair at the University of Winchester where he is a visiting Professor to the department of Sport & Exercise. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

EXTENDED ABSTRACTS

Session 1 – Bone Marrow Stimulation, Autologous and Allogenic Transplant

1.1 Microfracture – The Science behind Its Success & Failure – Michael Buschmann (CA) Bone marrow stimulation (MS) initiates cartilage repair by fracturing or drilling at the base of debrided cartilage defect. The subchondral bone channels provide access to underlying bone marrow stroma rich in bone marrow stem cells (BMSCs). Upon recruitment to the lesion site, BMSCs can proliferate and differentiate into a chondrogenic phenotype forming a repair tissue. MS is relatively economical, single-stage procedure, and provides appreciable short- to International Cartilage Regeneration & Joint Preservation Society Internationalmid-term pain relief. Cartilage Incomplete regeneration, high inter-individualRegeneration variability and poor repair outcome, especially in older individuals and larger defects, are some of the shortcomings of MS. Several factors have been proposed to influence repair outcome including surgical factors such as debridement, hole type, size and depth or mechanical fac- & Jointtors such as stiffnessPreservation and density of subchondral bone and Societybiological factors including the number of BMSCs present in subchondral bone and their clonogenic and chondrogenic potential, which are generally age-dependent. Each of these features as well patient specific characteristics have been shown to influence the quality and quantity of cartilage repair. In the choice of one –step surgical treatments for cartilage repair it will become increasingly important to understand the way in which these parameters determine repair outcome and how to stimulate repair further by optimising surgical procedures and using biologically active implants to promote repair.

1.2 Modifying Hole Size – Drilling VS Standard AWL Technique – Giuseppe Peretti (IT) Bone marrow stimulation techniques have been developed to treat early cartilage damage, in particular localized and focal cartilage defects affecting the knee1. These lesions are characterized by poor intrinsic healing capacity and, if not treated properly, can lead to joint degeneration, chronic pain and progressive disability. Marrow stimulation procedures include subchondral drilling, abrasion arthroplasty and microfracture. Subchondral drilling was introduced in 1957 by Smillie2. This technique was advised as a treatment option in osteoarthritis by Pridie in 19593. Later in the 1990’s Steadman proposed the concept of microfracture4, which is still the most commonly performed surgical approach to improve cartilage repair. The rationale is to promote bleeding from subchondral bone and blood clot formation in the debrided cartilage lesion, aiming at the recruitment of mesenchymal stem cells (MSC) and at the deposition of fibrocartilaginous repair tissue5.

Microfracture involves the use of an arthroscopic awl in order to penetrate the subchondral plate and it has been considered superior compared to drilling. In fact, hand-driven or motorized drill may cause heat necrosis in the bone, thus jeopardizing the outcome. The hole size created in the subchondral bone may also affect the outcome of the procedure.

Channel depth plays a crucial role in cartilage repair process. Microfracture awl usually reaches a 2-4 mm depth, depending on the shape of the awl, frequency and force of hitting the awl6, 7. Furthermore, subchondral bone plate may be thickened and sclerotic in chronic lesions. Hence, standard microfracture often allows inadequate access to spongy bone and MSC. Failed marrow stimulation has been observed if a 2 mm–deep penetration into sclerotic INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALbone was carried CARTILAGE out8. Deeper bone marrow accessJOINT resulted in morePRESERVATION hyaline-like cartilage matrix, showing significant improvement in defect fill, increased glycosaminoglycan and type II collagen content and reduced type I collagen7, 9. TheREGENERATION subchondral needling procedure (nanofracture)SOCIETY proposed by Benthien in 2013 forms 9 mm-deep and 1 mm-thick REGENERATION SOCIETY 10 & holes . This technique seems to lead to &higher marrow access and correlates with improved cartilage and subchondral bone repair11.

Channel diameter significantly influences cartilage repair. The tools employed in standard microfracture produce a V- shaped channel with a 1-2 mm diameter on the articular surface. Microfracture induces surrounding bone compaction that fills the trabecular spaces around the hole, which is consequently largely sealed off from adjacent bone marrow, resulting in reduced MSC influx8, 10, 12. This is particularly true when thicker and larger awls are used, deeper holes are generated or when sclerotic bone is present. It has been reported that thin conical awl geometries allow easier perforation of dense bone and produce less bone compaction. Similarly, nanofracture needles or drilling k-wires create small subchondral holes that reflect the physiological trabecular distance, improving significantly osteochondral repair more effectively than larger holes10, 13, 14. Besides small hole diameter, drilling is characterized by clean removal of bone debris, thus leaving channels in communication with bone marrow.

In conclusion, bone compaction avoidance and maximization of MSC recruitment allowed respectively by thinner and deeper access that decreases the iatrogenic injury to the subchondral bone as well, seem to improve the quality of the repair tissue in this challenging pathology.

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References: INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Lewis P, McCarty L, Kang R, et al. Basic science and treatment options for articular cartilage injuries. J Orthop Sports Phys Ther. 2006;36:717–727 Smillie IS. Treatment of osteochondritis dissecans. J Bone Joint Surg Br. 1957;39-B(2):248-60 Pridie KH. A method of resurfacing osteoarthritic knee joints. J Bone Joint Surg Br. 1959;41:618-619

Steadman J, Rodkey W, Singleton S, et al. Microfracture techniqueINTERNATIONAL for full-thickness CARTILAGE REGENERATION chondral defects: INTERNATIONALtechnique CARTILAGE and REGENERATION clinical & JOINT PRESERVATION SOCIETY results. Operative Techniques in Orthopaedics. 1997;7:300–304 & JOINT PRESERVATION SOCIETY Min BH, Choi WH, Lee YS, et al. Effect of different bone marrow stimulation techniques (BSTs) on MSCs mobilization. J Orthop Res. 2013;31(11):1814-1819

Madry H, van Dijk CN, Mueller-Gerbl M. The basic science of the subchondral bone. Knee Surg SportsInternational Traumatol Cartilage Arthrosc. Regeneration & 2010;18(4):419-433 I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society Chen H, Chevrier A, Hoemann CD, et al. Characterization of subchondral bone repair for marrow-stimulated chondral defects and its relationship to articular cartilage resurfacing. Am J Sports Med. 2011;39(8):1731-40 Hoemann CD, Gosselin Y, Chen H, et al. Characterization of initial microfracture defects in human condyles. J Knee Surg. 2013; 26(5):347-355 Chen H, Hoemann CD, Sun J, et al. Depth of subchondral perforation influences the outcome of bone marrow stimulation cartilage repair. J Orthop Res. 2011;29(8):1178-84 Benthien JP, Behrens P. Reviewing subchondral cartilage surgery: considerations for standardized and outcome predictable cartilage remodeling: a technical note. Int Orthop. 2013;37(11):2139-2145 Zedde P, Cudoni S, Manunta L, et al. Second generation needling techniques for the treatment of chondral defects in animal model. Joints. 2017;5;5(1):27-33 Chen H, Sun J, Hoemann CD, et al. Drilling and microfracture lead to different bone structure and necrosis during bone-marrow stimulation for cartilage repair. J Orthop Res. 2009;27(11):1432-1438 Eldracher M, Orth P, Cucchiarini M, Pape D, Madry H. Small subchondral drill holes improve marrow stimulation of articular cartilage defects. Am J Sports Med. 2014 Nov;42(11):2741-50 Orth P, Duffner J, Zurakowski D, Cucchiarini M, Madry H. Small-diameter awls improve articular cartilage repair after microfracture treatment in a translational animal model. Am J Sports Med. 2016;44(1):209-19

1.3 OATS / MOSAICPLASTY – How Decide Actual Correct Indications and Use Joao Espregueira Mendes (PT) Autologous osteochondral transplantation is a viable for the treatment of limited-size chondral and osteochondral defects. It involves harvesting articular cartilage from relatively non-weightbearing areas of the knee in order to transfer them into areas of symptomatic full-thickness cartilage or osteochondral injury. The mosaicplasty is a similar technique that transplants autologous osteochondral plugs and implant in the defect area in a mosaic fashion. Associated injuries (meniscus, ligament) must be treated simultaneously or prior to the chondral repair. Any knee malalignment above 5 degrees requires simultaneously or prior osteotomy. This technique is usually indicated for young subjects (typically not older than 50) with deep osteochondral symptomatic defects (grade III and IV) of weightbearing areas of the knee. The talus, femoral head or capitulum of humerus are other potential places to transplant osteochondral cartilage. It is suitable for lesions between 1 and 4cm2, but defects as large as 9cm2 can be resurfaced with mosaicplasty but at the cost of increasing the risk of donor site morbidity. Patient compliance is crucial and must comply with weightbearing restrictions, as well as daily and sporting activities limitations. Osteochondritis dissecans is often a deep lesion, which may need an osteochondral or chondral graft in case of surgical indication and the impossibility of the native osteochondral fixation. The major disadvantage of autologous osteochondral transplantation and mosaicplasty is the inherent risk of donor site morbidity from harvesting osteochondral tissue which also limits the amount of tissue that can be harvested. The most common harvest sites are the periphery of the lateral trochlea above sulcus terminalis and peripheral medial trochlea. We harvest the osteochondral cartilage from the upper tibiofibular joint to reduce donor site morbidity, which has shown good clinical, functional and imaging outcomes at the long-term follow- up. The autologous osteochondral transplantation and mosaicplasty techniques provide good to excellent clinical and imaging outcomes, especially for the femoral condyles. Although the viability of osteochondral autografts has been shown to be up to 10 years, long-term data is still limited. Moreover, it is an excellent option to use in athletes as it provides a successful return to pre-injury level of competition and a faster return to sports (5 to 7 months in average) in comparison with other available techniques. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

EXTENDED ABSTRACTS

1.4 Osteochondral Autograft Plugs versus Paste Graft: Ex vivo Morselization Increases Chondral Matrix Production – Kevin Stone (US)

OBJECTIVE: Articular cartilage paste grafting provides significant improvements in pain, function and motion with a mean benefit time of 16.6 years. We hypothesized that ex vivo impacting of osteochondral autografts results in higher chondrocyte International Cartilage Regeneration & Joint Preservation Society Internationalmatrix production versusCartilage intact osteochondral autograft Regeneration plugs. DESIGN: This IRB approved study characterized the effects of impacting one osteochondral plug harvested from the intercon- & Jointdylar notch intoPreservation a paste, leaving one control graft intact. SocietyCell viability/proliferation, collagen type I/II, SOX-9, and aggrecan gene expression via qRT-PCR were analysed at 24 and 48 hours. Matrix production and cell morphology were evaluated using culture histology.

RESULTS: Paste samples from 16 patients (mean age 39.7 ± 13.5 years) with moderate (19%) to severe (81%) osteoarthritis, displayed 34% and 80% greater cell proliferation compared to plugs at 24- and 48-hours post processing respectively (p=0.015 and p=0.021). qRT-PCR analysis yielded a significant (p<0.001) increase of aggrecan, Sox9, Collagen type I and II at both 24 and 48 hours. Histological examination displayed cell division occurring throughout paste samples, with deep accumulation of aggrecan content around multiple chondrocytes localized in lacunae.

CONCLUSIONS: In culture, compared to intact cartilage cores, paste graft preparation resulted in increased mobility of chondrocytes by virtue of matrix disruption without loss of cell viability. Impaction stimulated chondrocyte proliferation, resulting in a cellular response to re-establish native extracellular matrix (ECM). Analysis of gene expression within the ECM supports a regenerative process of cartilage tissue formation, contradicting long held beliefs that impaction trauma leads to immediate cell death.

KEYWORDS: Cartilage repair, articular cartilage paste graft, osteochondral autograft, gene expression Level of Evidence: 1

1.5 Can Non-Expanded Chondrocytes Induce Repair – Lucienne Vonk (NL) The number of chondrocytes that can be isolated from cartilage is very low. As a consequence, culture expanded chondrocytes are used for both in vitro basic scientific cartilage research and cell therapy treatments as autologous chondrocyte implantations (ACI). During culture expansion the phenotype of the chondrocytes changes a lot due to dedifferentiation; their morphology becomes more fibroblast-like, aggrecan and type II collagen expression decreas- INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALes while type CARTILAGEI collagen increases and the energyJOINT metabolism changes PRESERVATION from substrate level phosphorylation towards oxidative phosphorylation. Even if the expanded chondrocytes are redifferentiated by for instance 3D-culture, they REGENERATION SOCIETY neverREGENERATION completely retain their original phenotype, SOCIETYand this does affect the properties of the cartilage tissue they pro- & duce. However, can non-expanded chondrocytes& be used for cartilage repair? It seems they do, but there are some conditions that need to be considered. The method by which they are isolated and the cell-carrier that is used have an influence on their initial potential and secretion of proteolytic enzymes. Moreover, they need cell-cell contact to initiate the production of neotissue. Since the amount of chondrocytes that can be isolated is often too low to be used directly for defect repair, a proliferative boost might be needed.

1.7 Allogenic Surface and Minced Cartilage – Luis Tirico (BR) Traumatic and degenerative cartilage defects occur frequently in the knee joint. These lesions do not heal spontaneously and may predispose the joint to the subsequent development of secondary osteoarthritis. Various techniques have been used to treat these lesions with variable success rates. Recent technological advances in the field of cartilage restoration methods has led to the utilization of fresh particulated juvenile allograft chondrocytes transplantation (PJCAT) at the lesion site to reproduce the native cartilaginous articular surface1. The development of PJCAT and methods of surgically implanting the same were undertaken via a series of in vitro and in vivo animal studies. The preliminary demonstration of human clinical efficacy is consistent with basic science research findings from these preclinical studies showing that new extracellular matrix can be formed between two adjacent juvenile cartilage fragments 2. Its

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efficacy has been demonstrated for pathology about the knee—suchINTERNATIONAL CARTILAGE as high-gradeJOINT PRESERVATION cartilage lesionsINTERNATIONAL CARTILAGE of theJOINT patella, PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY the femoral condyles or trochlear groove—with pain relief and improving outcomes at short-term follow-up, but the data have been limited to level IV evidence with only small cohorts of data. Another attractive surgical approach for cartilage repair is to utilize minced articular cartilage to restore chondral defects, as it is a one-staged procedure that delivers autologous tissue with chondrocytes and is inserted on a carrier that can potentially be placed arthroscopically. The principle of mincing the autologous donor cartilage is to create a larger surface area for cartilage expan- INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION sion. Placement on a scaffold carrier allows for a chondro-inductive& JOINT PRESERVATIONand chondro-conductive SOCIETY environment& JOINT PRESERVATION 3. SOCIETY Early animal and preclinical models have demonstrated hyaline-like tissue repair; however further clinical trials need to be conducted in this interesting surgical technique.

References International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION 1. Saltzman BM, Lin J and Lee S. Particulated Juvenile Articular Cartilage& JOINT Allograft PRESERVATION Transplantation S OCIETY for OsteochondralJoint Preservation TalarSociety Le- sions. Cartilage. 2017; 8: 61-72. 2. Farr J and Yao JQ. Chondral Defect Repair with Particulated Juvenile Cartilage Allograft. Cartilage. 2011; 2: 346-53. 3. McCormick F, Yanke A, Provencher MT and Cole BJ. Minced articular cartilage--basic science, surgical technique, and clinical application. Sports medicine and arthroscopy review. 2008; 16: 217-20.

1.8 Amnion-Based Orthobiologics: A Review of Current Literature and Prospective Applications in Orthopedic Surgery – Daniel Grande (US) Chronic defects of articular cartilage represent one of if not the most common disabling musculoskeletal conditions of humans worldwide, and it is estimated that these defects progress to osteoarthritis in more than 30.8 and 40 million individuals in the United States and Europe, respectively.[1 2] Often affecting major synovial joints, osteoarthritis frequently necessitates surgical intervention and imparts significant financial cost to the patient.[3] Traditional approaches to treating cartilaginous defects have included marrow-stimulating techniques such as microfracture, as well as the current standard of care, autologous chondrocyte implantation (ACI). However, these methods are not without significant risks and limitations. Microfracture successfully repairs cartilage, however, it replaces hyaline cartilage with fibrocartilage, which exhibits a relative reduction in both structural integrity and biomechanical strength. Therefore, it is not regenerative. ACI also bears the risk of fibrocartilage formation at the site of the defect, as well as donor site morbidity and a risk of dedifferentiation of the chondrocytes upon implantation.[4 5] These limitations have in turn become a major driving force behind the development of the field of orthobiologics in regenerative medicine.

One of the alternative avenues for the treatment of chondral defects that has attracted significant interest is the usage of stem cells. An especially promising candidate among these are amniotic-fluid stem cells (AFSC). Amniotic fluid samples can be obtained from amniocentesis, and the desired AFSC can be selected from the heterogenous cell population by exploitation of the c-Kit (CD117) surface marker.[6] These undifferentiated stem cells can then be expanded in culture and directed to undergo chondrogenic differentiation before being introduce into the area of chondral damage to repopulate healthy tissue.

Importantly, AFSC overcomes many of the limitations of similar stem cell options, particularly by virtue of their intermediate potency between embryonic and adult stem cells. Unlike embryonic stem cells (ESC), AFSC avoid the risk of teratoma formation and the ethical concerns borne by ESC.[7] Relative to adult mesenchymal stem cells, AFSC demonstrate an increased proliferative capacity. Additionally, the AFSC do not require the introduction of ectopic substances to induce pluripotency, nor do they bear the accumulated mutations that can often be found in adult mesenchymal stem cells.[8 -11] Not only are AFSC free of these limitations, but recent studies have demonstrated superiority of AFSC over similar stem cells in their capacity to restore chondral defects, specifically through enhanced conversion of synovial macrophages to the “pro-regenerative” M2 phenotype and the increased expression of protective cytokines and decreased expression of degradative proteases in the synovium.[12] Stimulation of chondrogenic differentiation has been well-studied and is shown to be influenced by not only external chemical factors, but by three-dimensional orientation and the material properties of supporting structures.[13]

While research has yet to make significant progression into human studies, there have been a number of in vitro and animal in vivo studies that demonstrate the utility of AFSC in chondral regeneration, particularly in the treatment of articular cartilage defects, osteoarthritis of the knee, tendinous and ligamentous injury, and plantar fasciitis. Early results have been promising and bode well for the movement of research into human clinical studies. In addition to isolated AFSC, intact amniotic membrane (AM) products have proven useful in the field of regenerative medicine, INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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particularly in the field of wound care due to the ability of AM grafts to promote scar-free healing.[14] Like isolated AFSC, intact AM has also been pursued as an option for chondral regeneration, specifically as a scaffold for the delivery of chondrocytes or the chondrogenic induction of pluripotent cells.[15-24]

References 1. Cisternas MG, Murphy L, Sacks JJ, Solomon DH, Pasta DJ, Helmick CG. Alternative Methods for Defining Osteoarthritis and the Impact on Es- timating Prevalence in a US Population-Based Survey. Arthritis Care Res (Hoboken) 2016;68(5):574-80 doi: 10.1002/acr.22721[published International Cartilage Regeneration & Joint Preservation Society InternationalOnline First: Epub Date]|.Cartilage Regeneration 2. Preitschopf A, Zwickl H, Li K, et al. Chondrogenic differentiation of amniotic fluid stem cells and their potential for regenerative therapy. Stem Cell Rev 2012;8(4):1267-74 doi: 10.1007/s12015-012-9405-4[published Online First: Epub Date]|. & Joint3. Yelin E, Weinstein Preservation S, King T. The burden of musculoskeletal diseases Society in the United States. Semin Arthritis Rheum 2016;46(3):259-60 doi: 10.1016/j.semarthrit.2016.07.013[published Online First: Epub Date]|. 4. Salzmann GM, Sauerschnig M, Berninger MT, et al. The dependence of autologous chondrocyte transplantation on varying cellular passage, yield and culture duration. Biomaterials 2011;32(25):5810-8 doi: 10.1016/j.biomaterials.2011.04.073[published Online First: Epub Date]|. 5. Schnabel M, Marlovits S, Eckhoff G, et al. Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthritis Cartilage 2002;10(1):62-70 doi: 10.1053/joca.2001.0482[published Online First: Epub Date]|. 6. Prusa AR, Marton E, Rosner M, Bernaschek G, Hengstschlager M. Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research? Hum Reprod 2003;18(7):1489-93 7. Pantalone A, Antonucci I, Guelfi M, et al. Amniotic fluid stem cells: an ideal resource for therapeutic application in bone tissue engineering. Eur Rev Med Pharmacol Sci 2016;20(13):2884-90 8. De Coppi P, Bartsch G, Jr., Siddiqui MM, et al. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 2007;25(1):100- 6 doi: 10.1038/nbt1274[published Online First: Epub Date]|. 9. Kim K, Doi A, Wen B, et al. Epigenetic memory in induced pluripotent stem cells. Nature 2010;467(7313):285-90 doi: 10.1038/ nature09342[published Online First: Epub Date]|. 10. Miranda-Sayago JM, Fernandez-Arcas N, Benito C, Reyes-Engel A, Carrera J, Alonso A. Lifespan of human amniotic fluid-derived multipotent mesenchymal stromal cells. Cytotherapy 2011;13(5):572-81 doi: 10.3109/14653249.2010.547466[published Online First: Epub Date]|. 11. Moschidou D, Mukherjee S, Blundell MP, et al. Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene- free approach. Mol Ther 2012;20(10):1953-67 doi: 10.1038/mt.2012.117[published Online First: Epub Date]|. 12. Topoluk N, Steckbeck K, Siatkowski S, Burnikel B, Tokish J, Mercuri J. Amniotic mesenchymal stem cells mitigate osteoarthritis progression in a synovial macrophage-mediated in vitro explant coculture model. J Tissue Eng Regen Med 2018;12(4):1097-110 doi: 10.1002/ term.2610[published Online First: Epub Date]|. 13. Mouser VHM, Levato R, Bonassar LJ, et al. Three-Dimensional Bioprinting and Its Potential in the Field of Articular Cartilage Regeneration. Cartilage 2017;8(4):327-40 doi: 10.1177/1947603516665445[published Online First: Epub Date]|. 14. Mamede AC, Carvalho MJ, Abrantes AM, Laranjo M, Maia CJ, Botelho MF. Amniotic membrane: from structure and functions to clinical applications. Cell Tissue Res 2012;349(2):447-58 doi: 10.1007/s00441-012-1424-6[published Online First: Epub Date]|. 15. Diaz-Prado S, Rendal-Vazquez ME, Muinos-Lopez E, et al. Potential use of the human amniotic membrane as a scaffold in human articular cartilage repair. Cell Tissue Bank 2010;11(2):183-95 doi: 10.1007/s10561-009-9144-1[published Online First: Epub Date]|. INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL16. Garcia D, LongoCARTILAGE UG, Vaquero J, et al. Amniotic membraneJOINT transplant for articularPRESERVATION cartilage repair: an experimental study in sheep. Curr REGENERATIONStem Cell Res Ther 2015;10(1):77-83 SOCIETY REGENERATION SOCIETY 17. Jin CZ, Park SR, Choi BH, Lee KY, Kang CK, &Min BH. Human amniotic membrane as a delivery matrix for articular cartilage repair. Tissue & Eng 2007;13(4):693-702 doi: 10.1089/ten.2006.0184[published Online First: Epub Date]|. 18. Krishnamurithy G, Shilpa PN, Ahmad RE, Sulaiman S, Ng CL, Kamarul T. Human amniotic membrane as a chondrocyte carrier vehicle/ substrate: in vitro study. J Biomed Mater Res A 2011;99(3):500-6 doi: 10.1002/jbm.a.33184[published Online First: Epub Date]|. 19. Lindenmair A, Nurnberger S, Stadler G, et al. Intact human amniotic membrane differentiated towards the chondrogenic lineage. Cell Tissue Bank 2014;15(2):213-25 doi: 10.1007/s10561-014-9454-9[published Online First: Epub Date]|. 20. Liu PF, Guo L, Zhao DW, et al. Study of human acellular amniotic membrane loading bone marrow mesenchymal stem cells in repair of articular cartilage defect in rabbits. Genet Mol Res 2014;13(3):7992-8001 doi: 10.4238/2014.September.29.12[published Online First: Epub Date]|. 21. Nogami M, Tsuno H, Koike C, et al. Isolation and characterization of human amniotic mesenchymal stem cells and their chondrogenic differentiation. Transplantation 2012;93(12):1221-8 doi: 10.1097/TP.0b013e3182529b76[published Online First: Epub Date]|. 22. Tan SL, Sulaiman S, Pingguan-Murphy B, Selvaratnam L, Tai CC, Kamarul T. Human amnion as a novel cell delivery vehicle for chondrogenic mesenchymal stem cells. Cell Tissue Bank 2011;12(1):59-70 doi: 10.1007/s10561-009-9164-x[published Online First: Epub Date]|. 23. Wei JP, Nawata M, Wakitani S, et al. Human amniotic mesenchymal cells differentiate into chondrocytes. Cloning Stem Cells 2009;11(1):19- 26 doi: 10.1089/clo.2008.0027[published Online First: Epub Date]|. 24. Zhou J, Yu G, Cao C, Pang J, Chen X. Bone morphogenetic protein-7 promotes chondrogenesis in human amniotic epithelial cells. Int Orthop 2011;35(6):941-8 doi: 10.1007/s00264-010-1116-3[published Online First: Epub Date]|.

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1.9 Umbalical Cord Allograft – Boguslaw Sadlik (PL)INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY MSCs for repair of osteochondral defects as well as early osteoarthritis treatment method seems to be very promising according to many recent publications. In our experience, Wharton’s jelly-derived MSCs (WJ-MSC) because of easiness and safety of the harvesting procedure and a rich number of cells contained in the umbilical cord are a preferable grafting source. It needs to be emphasized that WJ-MSCs are harvested from umbilical cord tissue and there are not cells taken from umbilical blood, what is often mistake in scientific discussion. Moreover, that source of INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION young MSCs cells seems to be very useful for early OA treatment &especially JOINT PRESERVATION in SOCIETYmiddle-aged patients.& JOINT The PRESERVATION purpose SOCIETY of this study is to either assess the safety of arthroscopic regeneration of knee cartilage using WJ-MSC and scaffold as well as present the first results of this procedure in 1-3-year follow- up. From 2015 to 2018 nineteen patients with early osteoarthritis of the knee were treated with a novel technique. Fifteen patients were available at 1-year follow-up. Cartilage re-repair was performed with umbilicalInternational cord Mesenchymal Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION Stem Cells (WJ-MSCs) embedded in a scaffold, implanted using& dryJOINT PRESERVATIONarthroscopy S OCIETY technique. The minimalJoint Preservation follow Society up was 12 months. Results were clinically evaluated in VAS score, Lysholm score and IKDC score. Radiological results were assessed in MOCART score. Presented results proved safety of cartilage regeneration with umbilical cord Mesenchymal Stem Cells embedded in a scaffold and applied by dry arthroscopy procedure in 1-year follow-up and remains results in further observation. This method also provides improvement in knee functional scores.

Session 2 – Orthobiologics

2.1 The Inflammatory Environment in Cartilage Lesions and OA – Gerjo Van Osch (NL) Inflammation after injury is an early response known to play a key role in wound healing. The inflammatory cytokines secreted during this response are important signals to attract cells to repair tissue damage. Eventually, when the wound is healed, inflammation should resolve. Cartilage injury, either as direct result of the joint trauma or as result of the osteoarthritis process, does not heal well. This incapacity to repair cartilage injury is due to the specific nature of the cartilage: a dense extracellular matrix, a low cell density and the absence of vascularisation. The persisting presence of a tissue defect might be the reason that the inflammation process does not resolve, resulting in the chronic inflammation process seen in osteoarthritis. This chronic inflammation can impair wound healing.

How inflammation plays a role in the cartilage repair processes - after injury, after surgical interventions or in osteoarthritis - is not known in great detail. We aim to get insight in which aspects of inflammation are beneficial for cartilage repair and which are impairing repair, to be able to improve the treatment of cartilage lesions. In the presentation I will discuss our recent data on: - the role of synovium, different types of macrophages and inflammatory cytokines on cartilage repair. The involves experiments with in vitro models with human cells and tissues to study effects on attraction and chondrogenesis of progenitor cells - the effect of triamcinolone on human synovium and macrophage types in vitro and on cartilage repair in a mouse model - the effect of orthobiologics such as platelet-rich plasma, mesenchymal stem cells or their secretome in a joint injury model in mice

2.2 PRP – Stephan Abelow (US) PRP: Platelet-rich plasma- “A sample of autologous blood with concentrations of platelets above baseline values.” (Hall, 2009 JAAOS)

- Created through a 2-phase centrifugation process called plasmaphoresis , in which liquid and solid components of anticoagulated blood are separated.

1) Initial soft spin (1200-1500 RPM)- plasma and platelets are separated from RBCs and WBCs. 2) Hard Spin (4000-7000 RPM)- further concentrates the platelet rich and platelet poor portions.

- Optimal platelet concentration of PRP for tissue healing believed to be 2.5-5 times higher than whole blood. - 100 x 103 cells/uL considered to be effective platelet concentration to induce an efficient local cellular response. - Platelet concentration 6x > whole blood reported to have INHIBITORY EFFECT on HEALING. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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Platelets release growth factors from alpha-granules: - Begin secretion of growth factors within 10 minutes. - 95% released within an hour of arrival. - Platelets are viable for 7 days (1/2 life = 7 days) - Most growth factors have ½ life of less than 10 minutes.

Properties of PRP: Coagulation and hemostasis; biologic glue; wound healing; anti-inflammatory; International Cartilage Regeneration & Joint Preservation Society Internationalantibacterial; analgesic; Cartilage provisional scaffold for stem Regeneration or primary cell migration and differentiation; increase glycosaminoglycan chondrocyte synthesis and cartilage matrix; intraarticular restoration of hyaluronic acid; Stimulates & Jointsuperficial zonePreservation protein (Lubricin) production by cartilage Societyand synovium. - PRP has potential effects in regulating the immune response, promoting and balancing joint angiogenesis; and Inducing cell differentiation.

Growth Factors in PRP: Platelet-derived growth factor; Platelet-derived endothelial growth factor; Vascular endothelial growth factor; Transforming growth factor-B1; Fibroblast growth factor; Epidermal growth factor; Hepatocyte growth factor; Insulin like growthbfactor-1; Endothelial cell growth factor; Platelet-derived angiogenesis factor; Con- nective tissue growth factor; Stromal cell-derived factor 1-alpha; Tumour necrosis factor alpha and beta; Interleukin-1B; Interleukin-10

Bioactive Molecules Found in the Dense Granules of Platelets: Serotonin; Histamine; Dopamine; ADP; ATP; Ca++; Adhesive proteins (Fibrinogen; Fibronectin; Vitronectin; Thrombospondin-1); Proteases and antiproteases (TIMP-4; Metalloprotease-4, MMP2, MMP9); Alpha-1 antitrypsin; Basic proteins (Platelet factor 4; Beta-thromboglobulin; End- ostatins); Membrane glycoproteins (CD40 ligand; P-selectin); Clotting factors; Fibrinolytic factors)

PRP contains factors necessary for joint repair (TGF-B1; IGF-1; Thrombospondin-1; etc.)

Concept: PRP can be helpful in treating symptomatic cartilage defects; OA; or osteochondral lesions. In vitro and animal studies encouraging

No conclusive human studies to support cartilage and structure regeneration PRP Therapy may be “symptom modifying” but likely not “structure modifying”

Osteoarthritis - Filardo, Kon: AJSM, July 2015; N=433; Randomized controlled trial; Level I (3 injections) - “PRP Intra-articular Knee Injections Show No Superiority Versus Viscosupplementation” - Riboh, Saltzman, Yanke, Fortier, Cole: AJSM, March, 2016; Meta-analysis N=(6 Level 1 and 3 level 2 studies) INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL- Leukocyte Poor CARTILAGE PRP results in improved functionalJOINT outcome scores PRESERVATION compared with hyaluronic acid and placebo for treatment of knee OA. REGENERATION SOCIETY - Lin,REGENERATION Yang, Hsu, Yeh, Renn: Arthroscopy, January,SOCIETY 2019; N=87; RCT single center; Level 1 (3 inj) & - “Intra-articular Injection of PRP is Superior& to Hyaluronic Acid or Saline in the Treatment of Mild to Moderate OA: A Randomized Double-Blind, Triple-Parallel, Placebo-Controlled Clinical Trial” - Intra-articular injections of leukocyte-poor PRP can provide statistically and clinically significant functional improvement for at least 1 year in patients with mild to moderate arthritis of the knee (better outcomes with younger pts; OA grade and BMI not correlated with outcome improvement - Current data suggests that leukocyte poor formulations are optimal for improvement of symptoms of pain of knee OA. - But ratio of platelets to leukocytes and type of leukocyte (lymphocyte vs neutrophils) may be important….future study required.

“The Role of PRP in Cartilage Pathology: An Updated Systematic Review of the Basic Science Evidence,” Fice, Smyth, Cole, et al; Arthroscopy, March, 2019 - 27 studies (11 in vitro,13 in vivo,3 in vitro and in vivo) - PRP was shown to increase cell viability, cell proliferation, cell migration and differentiation - Several studies demonstrated increased proteoglycan and type II collagen content. - PRP decreased inflammation in 75% cases of in vitro studies reporting data and - PRP resulted in improved histologic quality of the cartilage tissue in 75% of the in vivo studies reporting data.

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CONCLUSIONS: INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Although the number of investigations on PRP for cartilage pathology has more than doubled since 2012, the quality of the literature remains limited by poor methodology and outcome reporting. - A majority of basic science studies suggest that PRP has beneficial effects on cartilage pathology; however, the inability to compare across studies owing to the lack of standardization of study methodology, including character- izing the contents of PRP, remains a significant limitation. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION - FUTURE BASIC SCIENCE AND CLINICAL STUDIES MUST AT A &MINIMUM JOINT PRESERVATION REPORT SOCIETY THE CONTENTS& JOINT PRESERVATION OF PRP SOCIETY TO BETTER UNDERSTAND THE CLINICAL ROLE OF PRP FOR CARTILAGE PATHOLOGY James Lubowitz, MD, Editor-in-Chief ARTHROSCOPY, April, 2015; Editorial Commentary - PRP injection shows PROMISE for Mild to MODERATE OA PAIN - However, IT REMAINS TO BE SHOWN THAT PRP EFFECTS CARTILAGE REPAIR International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION Nikkolaos K. Paschos, MD, Associate Editor ARTHROSCOPY, March,& JOINT PRESERVATION 2019, Editorial S OCIETY CommentaryJoint Preservation Society - Significant evidence suggests that application of PRP provides clinical benefit for various conditions. - “Although high quality studies exist to show clinical improvement for cartilage pathologic conditions, there is not sufficient support from basic science research to explain PRP’s mechanism of action or adequately characterization of its properties and behavior.”

TAKE AWAY: PRP Therapy may be “symptom modifying” but likely not “structure modifying”

2.3 Prospective Comparative Study between Infiltrative Treatments Using Adipose Derived Mesenchymal Stem Cells and Platelet Rich Plasma Combined with Hyaluronic Acid in Patients with Early Osteoarthritis – Alberto Gobbi

INTRODUCTION: Osteoarthritis (OA) is a chronic condition characterised by constant change in the molecular and mechanical properties of the articular cartilage. It leads to significant disability among the patients and viewed as a major health concern worldwide. Although several conservative managements have been proposed (NSAID’s, intra-articular steroids, physical therapy), none of them has shown promising result due to the poor understanding of the cell biology and molecular signalling in OA. In recent years, while more research is focused towards platelet-rich plasma (PRP), hyaluronic acid (HA), and Mesenchymal stem cells (MSC’s) in treating this common indication, which has shown promising results independently, we would like to assess the difference in the outcome obtained in patients treated with adipose derived MSC injection and patients treated using PRP combined with Hyaluronic Acid (HA) injection.

MATERIALS AND METHODS: A group of 50 patients affected by Kellgren-Lawrence grade 2 or grade 3 knee osteoarthritis were randomly allocated into two equal groups of 25 patients each. Group 1 were treated with 3 intra-articular injections (1 month apart) using autologous P.R.P combined with HA (Cellular Matrix, RegenLab, Switzerland) and group 2 patients were injected with adipose derived MSC (Lipogems, Italy) by supra-patellar approach. Outcomes were measured by collecting Tegner, Marx, VAS, IKDC and KOOS scores at before treatment, 6 months and 12 months after treatment. PRP is a rich source of growth factors like platelet derived growth factors (PDGF), insulin-like growth factors (IGF-I, IGF-II), vascular endothelial growth factor (VEGF) as well as many other cytokines which helps in downregulating the catabolic process in OA1. Hyaluronic acid (HA), is one of the major components of the synovial fluid surrounding the cartilage, providing an important role in lubrication and in promoting chondrocyte differentiation and proliferation. The rationale of using PRP in combination with HA in joint repair without altering the properties of both the products had been recently stud- ied2,3 and based on these data, it seems reasonable to use a combination of both PRP and hyaluronic acid to provide greater benefits compared to the administration of each product alone, as their effects on osteoarthritis is based on their synergistic mechanisms of action. On the other hand, Stem cells are considered to be undifferentiated precursor cells that have potential for self-renewal and are capable of differentiating into a wide variety of cell types. There has been increasing interest in adipose-derived stem cells (ASCs) for treatment of chondropathy and related disorders. This may be used as a single-stage treatment in the form of micro fragmented autologous adipose tissue. This tissue has the advantage of maintaining an intact stromal vascular niche that contains cellular elements with mesenchymal stem cell characteristics. Activated MSCs release a cascade of bioactive molecules to counteract overaggressive immune responses and to establish a regenerative microenvironment4. The aim of this study is to assess any difference in outcome obtained in patients treated with adipose derived MSC injection and patients treated using PRP combined with Hyaluronic Acid (HA) injection. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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RESULTS: Patients were prospectively evaluated in the 12-month study period between November2016-December2017. The mean age was 62.7 ± 10.7 in group 1 patients and 59.9 ± 8.7 in group 2 patients. At 12 months follow-up, patient in both groups showed improvements in all scores. Median pre-treatment values of group 1 patients were, IKDC=56.98, KOOS Scores:S=75/P=78/ADL=87/SP=40/QOL=38; VAS scale 3.7. Median pre-treatment values of group 2 patients were, IKDC=40.23, KOOS Scores:S=69.5/P=67/ADL=69/SP=35/QOL=41; VAS scale 5.1. At final follow-up median scores in group 1 are: IKDC=62, KOOS Scores:S=80/P=72/ADL=83.5/SP=40/QOL=60; VAS scale 2.1 International Cartilage Regeneration & Joint Preservation Society Internationaland at final follow Cartilage up median scores in group 2 are: Regeneration IKDC=61.49, KOOS Scores:S=75/P=86.5/ADL=89/SP=52.5/ QOL=56; VAS scale 3.6.

& JointCONCLUSION: Preservation Society This report shows, both groups lead to clinical and functional improvement at 6 and 12 months. But there is no statistical significance between the groups. However, there are subtle advantages over one another. This finding will aid clinicians in formulating an algorithm when treating patients with early osteoarthritis.

2.4 BioCUE Autologous Bone Marrow or Peripheral Blood Concentration Using Point of Care Devices – John Lane (US)

Introduction: Lateral epicondylitis is a manifestation due to tendinopathy. It can often progress to a chronic form, and it might present a challenging clinical case scenario. Recent advances in autologous treatment options by using Platelet Rich Plasma (PRP) can potentially serve as a promising treatment option for these patients. Mishra et al. performed a level-one randomized, control study examining the use of BioCUE® PRP output in patients with lateral epicondylitis [1].

BioCUE® System is a PRP concentration point of care device. Also called cBBMA (concentrated Blood and Bone Marrow Aspirate) is a key tissue healing enhancing component that can be used to deliver autologous growth factors: MSCs (mesenchymal stem cells), OPCs (osteogenic precursor cells), HSCs (hematopoietic stem cells), platelets, leucocyte rich WBCs (white blood cells), [2]. BioCUE® System could be used to process aspirated whole blood and or bone marrow. The PRP output of the device could be directly delivered to the site of the injury in case of lateral epicondylitis. It is also rarely used for certain cartilage repair procedures to aid the tissue particulates delivery at the site of the defect. In those rare cases the concentrate of the marrow aspirate is mixed with the thrombin in calcium chloride and applied for cartilage lesions in talus. The most common use of BioCUE® is for bone regeneration type procedures. When added to a chosen auto/allograft carrier it could be used to aid bone tissue regeneration. Since the procedure emerged, many anatomical sites have been used for marrow harvesting: anterior and posterior iliac crest, vertebral bodies, calcaneus, tibia, femur, and proximal Humerus [3]. The advantages of the system include an efficient aspiration due to the presence of six holes at the distal tip of the trocar. Smooth penetration through the bone is due to a trocar point stylet; facilitated motion is due to a blunt stylet. In a 15 minutes timeframe, a 3-6cc of PRP INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALfrom both blood CARTILAGE and BMA is created to be used rightJOINT away for thePRESERVATION desired location and modality. Autograft is the gold standard for bone tissue regeneration in the orthopaedic surgical settings due to the presence of theREGENERATION osteoprogenitor cells, osteoinductive factors. However,SOCIETY there are limited sources of autologous bone and various REGENERATION SOCIETY [4] & studies described donor site morbidity &. The procedure was used in the clinical practice for many years however there are certain limitations: increased operative time, second surgical site, increased blood loss, and temporary change to the primary donor site bone structure [5].

Bone marrow concentrate is frequently used in the following clinical applications: delayed union or non-union, malunion, arthrodesis, avascular necrosis of the femoral head and reconstruction of bone voids and defects. Adams et al. described the use in fracture non-union, by delivering the output into the fracture gap [6]. Guyton et al. described the use of Beta-Tricalcium Phosphate synthetic material to enhance bone healing [7]. Conclusion: PRP produced by using point of care devices offer versatile options soft tissue repair as well as a convenient option of bone marrow aspirate concentration for bone tissue regeneration.

References: [1] Mishra AK1, Skrepnik NV, Edwards SG, Jones GL, Sampson S, Vermillion DA, Ramsey ML, Karli DC, Rettig AC, “Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients,” Am J Sports Med. 2014 Feb;42(2):463-71.

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[2] Pignolo RJ, Shore EM, “Circulating osteogenic Precursor cells,” Crit Rev Eukaryot Gene Expr. 2010;20(2):171-80. INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY [3] McLain RF, Fleming JE, Boehm CA, Muschler GF, “Aspiration of osteoprogenitor cells for augmenting spinal fusion: comparison of progenitor cell concentrations from the vertebral body and iliac crest,” J Bone Joint Surg Am. 2005 Dec;87(12):2655-61. [4] Giannoudis, Peter V., Haralambos Dinopoulos, Eleftherios Tsiridis, “Bone Substitutes: An Update,” Injury 36.3 (2005): S20-S27. [5] Bezer, Murat et al., “Comparison of Traditional and Intrafascial Iliac Crest Bone-Graft Harvesting In Lumbar,” International Ortho- paedics (SICOT) 28.6 (2004): 325-328. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY [6] Adams, S. B. et al., “Cannulated Screw Delivery of Bone Marrow Aspirate& JOINT Concentrate PRESERVATION SOCIETY to a Stress Fracture Non-union: Technique Tip,” Foot & Ankle International 34.5 (2013): 740-744. [7] Guyton, Gregory P., and Stuart D. Miller, “Stem Cells in Bone Grafting: Trinity Allograft with Stem Cells and Collagen/Beta- Tricalcium Phosphate with Concentrated Bone Marrow Aspirate,” Foot and Ankle Clinics 15.4 (2010): 611-619. International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society

2.5 Duration Effects of a Single Intra-Articular Injection of Autologous Protein Solution (APS) in Patients with Knee Osteoarthritis (OA). – Elizaveta Kon (IT)

PURPOSE: Autologous anti-inflammatories (AAI) are a class of blood-derived products with high concentrations of anti-inflammatory cytokines that are currently being investigated for the treatment of mild to moderate knee osteoarthritis (OA) to determine if they can ameliorate symptoms longer or better than traditional intra-articular injections such as hyaluronic acid (HA) and steroids. The purpose of this evaluation is to determine the duration of effect from a single injection of APS before patients elect a new treatment course.

METHODS AND MATERIALS: Forty-six patients underwent a 2:1 randomization process to either one single injection of APS (n=31) or saline (n=15) (NCT02138890). APS was prepared with the nSTRIDE APS Kit (Zimmer Biomet). The 12 month double-blind outcomes of the double-blind portion of the trial were previously published(1). The APS cohort was asked to participate in unblinded long-term follow-up. Efficacy endpoints of pain and function over time (WOMAC LK 3.1, KOOS, and VAS) were measured as a change from baseline to each time point. Quality of life (SF-36), OMERACT-OARSI responder criteria, rescue medication usage, as well as yearly x-rays and 24-month MRI imaging were completed.

RESULTS: Survivorship of the APS cohort that agreed to long-term follow-up was 71% at 3 years (Figure 1). At 36 months, the mean WOMAC Pain improvement was 70%(Figure 2)(7.8 ± 4.0) in the APS cohort, which was a significant improvement compared to the baseline score(p<0.0001). APS cohort patients also showed a statistically significant improvement in their KOOS pain score (114%,33.3 ± 22.0; p<0.0001) and VAS pain score (42.7%, 2.0 ± 3.3; p=0.0012).

CONCLUSION: Intra-articular injections of APS for mild to moderate knee OA was safe and a portion of patients continue to have pain relief 3 years after a single injection. Clinical investigation (NCT03182374) to determine the long-term efficacy compared to a single injection hyaluronic acid is currently ongoing. Figure 1. Kaplan-Meier plot of failure (conversion to another knee procedure including corticosteroid injection, hyaluronic acid injection, and total knee arthroplasty).

Figure 2. Percent Change in WOMAC pain score. Data presented as mean ± SE: APS n=29 at 12 months, n=22 at 24 months, and n=19 at 36 months).

References (1) Kon E, Engebretsen L, Verdonk P, Nehrer S, Filardo G. Clinical outcomes of an Autologous Protein Solution Injection for Knee Os- teoarthritis: A 1-year Pilot Double-Blinded Randomized Controlled Trial. American Journal of Sports Medicine 2018;46(1):171-80. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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2.7 Bone Marrow Concentrate in Knee OA – Stefano Zaffagnini (IT), Alessandro di Martino (IT) Osteoarthritis (OA) is a common orthopaedic condition characterized by joint pain and decreased function, generally affecting patients over 50 years old: about 25% of ageing people experience pain and other OA-related symptoms, which may be severe and negatively affect their quality of life and productivity, with a high social and economic impact. Moreover, an increasing incidence of cartilage degeneration and OA has also been observed in younger patients, often related to sport-activity, and a significant number of patients complain of bilateral symptomatic osteo- International Cartilage Regeneration & Joint Preservation Society Internationalarthritis. Cartilage Regeneration Mesenchymal stem cells (MSCs) are emerging as a promising treatment for knee OA, but knowledge on this topic is still preliminary, as shown by the presence of low-quality clinical studies. Mesenchymal stem cells have been har- & Jointvested mostly fromPreservation the bone marrow and can be processed Society both by culture (BMSCs) or centrifugation (BMC). Cultured BMSCs and BMC differ for composition, since adult bone marrow contains heterogeneous blood cells at various differentiation stages. Thus, the harvest includes plasma, red blood cells, platelets, and nucleated cells, a small fraction of which contains adult MSCs that can be isolated through culture expansion. However, even if not expanded, the heterogeneity of cell progenitor types in BMC might positively influence tissue regeneration. Moreover, cell culture not only offers a higher number of cells but also presents high costs and some regulatory problems, since these products might be considered as pharmacological treatments by regulatory agencies. Thus, one-step techniques using BMC for the delivery of autologous cells in a single time are gaining increasing interest in the clinical setting. BMC coordinate the repair/ regeneration process and can modulate the immunological and inflammatory response. As opposed to former hypothesis, MSC do not differentiate to the target cell but work like medicinal drug cell and coordinating the healing response. The cellular activity is performed through pericytes as the acting cells. Reviews show increasing evidence of those treatment options in OA indications and can show efficacy concerning clinical outcome. Unfortunately, the studies show various applications and technology with quite substantial differences in cell content with regards to mesenchymal stem cells and composition of the product.

Nevertheless, the preliminary results and the absence of significant adverse events related to the use of BMC encour- age its use in the clinical practice and in high level clinical trials, in order to understand the indication and to profile the patients which can mostly benefit from regenerative treatments in OA.

2.8 Regenerative Treatment of Knee Osteoarthritis with Infusion of Low Manipulated Adipose Tissue – Ferracini Riccardo (IT), Roato Ilaria (IT)

Osteoarthritis (OA) is characterized by articular cartilage degeneration and subchondral bone sclerosis. Different non-surgical treatments are currently available for OA, such as infusions with collagenase-isolated Stromal Vascular Fraction (SVF) or cultured-expanded mesenchymal stem cells (ASCs). Nonetheless, these treatments require a high manipulation of the lipoaspirate, which must be performed in cell factory. To avoid this time-consuming and expensive procedure, we investigated whether articular infusions of low manipulated autologous adipose tissue is an effective treatment for knee OA patients. INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION In our pilot study, the treatment of OA patients with concentrated adipose tissue resulted safe, and all patients reported REGENERATION SOCIETY an REGENERATIONimprovement in terms of pain reduction and increaseSOCIETY of function. The analysis of osteogenic and chondrogenic & potential of ASCs, isolated from patients’& lipoaspirates, showed their regenerative capabilities. The biopsy of previously adipose tissue treated-knee joints showed new tissue formation, starting from the bone side of the osteochondral lesion.

In order to simplify and speed up the low manipulation of lipoaspirate for intra-operative settings, we focused on a novel medical device, Lipocell, which consists in a dialysis procedure through washing and brushing of the lipoaspirates, extremely fast and reproducible. The analysis of the final product showed an effective removal of blood and oil fractions and a maintained architecture of the extracellular matrix. Moreover, the procedure associated with Ringer’s lactate washing improved ASC proliferation ex vivo. Overall our data indicate that adipose tissue infusion stimulates tissue regeneration, likely due not only to ASC content, but also to the presence of other elements, such as immune cells, adipocytes, stromal cells and lipid content, which can exert anti-inflammatory and anti-oxidant activity.

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Session 3 – Scaffolds INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY

3.1 One-Step Cartilage Repair – Use of the ChondroGide TM Collagen Membrane (Geistlich) – Philippe Niemeyer (DE) Many years before matrix-augmented bone marrow stimulation (mBMS) came into focus as an one-step cartilage repair procedure yielding on an improvement of traditional bone marrow stimulation techniques such as arthroscopic INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION micro fracturing, the Chondro-Gide TM membrane originally has &been JOINT PRESERVATION developed SOCIETY as a scaffold for &substitution JOINT PRESERVATION SOCIETY of the periosteum patch used in context of autologous chondrocyte implantation (ACI). Chondro-Gide TM associated ACI has therefore been introduced as the 2nd generation of ACI in the late 1990s.

During this period of time, the scaffold, which is based upon porcine collagen type I and III, hasInternational proved Cartilage to beRegeneration both & I NTERNATIONAL C ARTILAGE R EGENERATION – safe and effective – for cartilage repair applications. Based upon& JOINT thisPRESERVATION experience, S OCIETY while matrix-augmentedJoint Preservation Society bone marrow stimulation emerged and became more popular, the AMIC TM concept has been introduced as a combination of this scaffold and underlying bone marrow stimulation. Although in some countries, the term AMIC was used to generally described the approach of combining a scaffold with subchondral bone marrow stimulation, the term has been introduced as a trademark specifically describing the use of the Chondro-Gide TM collagen membrane. While initially, some case reports have been published describing this technique as a proof of principle, scientific evidence has increased and by now even a prospective randomized controlled clinical trial is available comparing the AMIC technique with conventional arthroscopic micro fracturing demonstrating a superiority in clinical outcome at 5 years. Based upon the scientific literature the German Society of Orthopedics and Traumatology (DGOU) has published a position paper in which in matrix-augmented bone marrow stimulation in general, but also specifically the AMIC technique is an accepted one-step cartilage repair procedure for cartilage defects of the knee.

3.2 Hyalofast (Ha Scaffold) (Anika) – Boguslaw Sadlik (PL) Bone Marrow Stimulation Technique augmented with scaffold, known also as BMST plus, maintains MSCs retain- ing in larger volume and density. That technique promotes cartilage-like regeneration and offers better quality and thickness in comparison to BMST alone. The most popular AMIC technique consists of BMST covered with collagen scaffold showing a very good mid-term results in many publications. Lastly hyaluronic acid-based scaffold (Hyalofast), becomes more popular due its unique features. Hyalofast during its fitting to the shape of the defect is much more malleable and adhesive in comparison to the animal collagen scaffolds. That feature is very helpful for arthroscopic implantation. Moreover, covering defect with a double layer technique is also quite easy. BMST plus with Hyalofast covering defect gives very good results if rehabilitation protocol is strictly followed. Neglecting this protocol may result in formation of a defective cartilage regenerate or in its damage. Whereas late onset of physiotherapy may lead to graft hypertrophy or arthrofibrosis. This presentation will show arthroscopic technique of Hyalofast implantation and outline the results of treatment both in the knee and ankle joint.

3.3 Chondrotissue Grafting for Full-Thickness Cartilage Defects in the Knee – Ian McDermott (UK) Chondrotissue is scaffold made from polyglycolic acid and hyaluronic acid, and it comes as a 2cm x 3cm oblong, 1.1mm thick, like a piece of felt. I first used Chondrotissue back in 2010, and this has remained my procedure of choice for large (>2cm2) chondral defects ever since.

My version of Chondrotissue grafting involves several important steps: 1) the use of a radiofrequency probe for arthroscopic cases, to ensure a stable chondral rim, 2) debridement of the calcified cartilage layer down to true bare bone, 3) nanofracture with a Stryker Phoenix drill (not microfracture with an awl), 4) the use of ActivaNail bioabsorb- able pins to secure the graft in place, and 5) the use of Vivostat PRF (autologous platelet-rich fibrin) to ‘glue’ the graft in place, to seal over the surface of the graft (to stop the cells being washed away) and for the growth factors that are released from the platelets.

To-date, I’ve performed approximately 60 cases of Chondrotissue grafting. Increasingly, I’m now beginning to move away from arthroscopic Chondrotissue grafting and more towards mini-open or even wide-open surgery, as I think this probably gives better results. The best studies so far in the published reporting the results of Chondrotissue grafting are those by Enea et al (2013)1, Siclari et al (2014)2 and Becher et al (2015)3. However, to-date, there have been no prospective randomised trials that I am aware of comparing Chondrotissue to other alternative cartilage treatment options. We’re currently in the process of undertaking a retrospective multicentre review of about 300 Chondrotissue cases as part of the UK Chondrotissue User Group, which is affiliated to the UK Biological Knee Society, with a view INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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to us then setting up a prospective study. The next step for me will be to start adding Bone Marrow Aspirate Concen- trate (BMAC) to my Chondrotissue grafts, to improve the cell count in the scaffold in order to try and further improve healing rates and the quality of the new regenerate tissue. As with all these newer kinds of articular cartilage replacement procedures, our main problem remains a lack of high- quality robust prospective comparative trials. InternationalReferences Cartilage Regeneration International Cartilage Regeneration & Joint Preservation Society 1. Enea D, Cecconi S, Calcagno S, Busilacchi A, Manzotti S, Kaps C, Gigante A. Single-stage cartilage repair in the knee with microfracture covered with a resorbable polymer-based matrix and autologous bone marrow concentrate. The Knee 2013; & Joint20: 562–569 Preservation Society 2. Siclari A, Mascaro G, Kaps C, Boux E. A 5-Year Follow-Up After Cartilage Repair in the Knee Using a Platelet- Rich Plasma- Immersed Polymer-Based Implant. The Open Orthopaedics Journal 2014; 8: 346-354 3. Becher C, Ettinger M, Ezechieli M, Kaps C, Ewig M, Smith T. Repair of retropatellar cartilage defects in the knee with microfracture and a cell-free polymer-based implant. Arch Orthop Trauma Surg 2015; 135(7): 1003-10

3.5 GelrinC: A Unique One – Stage Cartilage Repair Technique with Sustainable Long-Term Outcomes – Aad Dhollander (BE) GOALS: To investigate the long-term effectiveness of a novel one-stage cartilage repair technique using GelrinC, a cell- free injectable biodegradable implant.

MATERIALS & METHODS: A total of 52 patients, 18-65 years old, with 1-6 cm2 ICRS grade III to IVA lesions to the femoral condyle, were successfully treated with GelrinC and followed up at specific timepoints, up to 5 years. A subgroup analysis was performed to assess the effect of GelrinC treatment for Chondral and Osteochondral lesions as well as for patients who were treated secondary to a failed cartilage repair procedure. Patient reported outcome questionnaires were used to assess clinical effectiveness whereas MOCART and T2 mapping were used to evaluate the quality of the regenerated cartilage up to 24 months following treatment.

RESULTS: The clinical results gathered up to date reveal a substantial and significant (p<0.001) improvement in all KOOS sub- scales with maximum improvement of 44.7±5.6 points in KOOS Sports/Rec at 4 years (N=22) and similar improvement of 42.2±7.0 points at 5 years (N=18) compared to baseline. Moreover, patients reported the maximum improvement in KOOS Pain (33.74±3.9 points) and KOOS ADL (33.5±4.0 points) at 4 years (N=22) with similar change of 32.69±5.0 points and 32.2±3.9 points in KOOS Pain and ADL respectively 5 years following treatment (N=18). The subgroup analysis confirms that the outcomes of patients treated with GelrinC following a failed cartilage repair procedure are as good as those treated with GelrinC as a primary treatment. Also, the MOCART scores at 24 months INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL(88.8±1.5) showed CARTILAGE similar results for the treatmentJOINT of Chondral andPRESERVATION Osteochondral lesions. REGENERATION SOCIETY CONCLUSIONS:REGENERATION SOCIETY & GelrinC is an effective cartilage repair technique& for the treatment of Chondral and Osteochondral lesions demonstrating sustainable long-term outcomes. Furthermore, GelrinC is an excellent treatment option for patients undergoing primary treatment and for patients who failed previous cartilage repair procedures.

3.6 Chitosan-Derived Therapy to Repair Articular Cartilage Lesions– Julio Fernandes (CA) • Treatment of focal cartilage lesions larger than 2cm2 is a major technical challenge. In order to reach complete hyaline- like cartilage regeneration, a cell source, either through micro fracturing or autologous chondrocyte transplantation, must be coupled with a scaffold for best results. We’ve been working with a thermo sensitive chitosan-derived gel (Cargel, Smith &Nephew, Mississauga, ON, Canada) since its first clinical studies in Canada. Cargel is an n-acetylglucosamine, 2% cationic Polymer in aqueous solution, mucoadhesive, biocompatible and biodegradable (Fig 1). • Surgical technique implies an arthroscopy for diagnosis and debridement, followed by a limited arthrotomy, micro fracturing and filling of the defect with Cargel mixed with autologous blood for 5 min. The mixture jellifies at body temperature and adheres to the subchondral bone. Full ROM and toe-touch weight bearing are allowed for 6 weeks post-surgery. • In our series of patients, defect filling and clinical results are encouraging and seem to withstand the 2-year post-op threshold (Fig 2)

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• 5-year results have been published in a pivot trial, showing betterINTERNATIONAL defect CARTILAGE fillingJOINT and PRESERVATION better cartilageINTERNATIONAL quality CARTILAGE comparedJOINT PRESERVATION to REGENERATION & SOCIETY REGENERATION & SOCIETY micro fracture-only controls (Ref 1). • In summary, Cargel is one of several scaffolds available in the market today that provide for sustained and significantly superior repair tissue quantity and quality over micro fracture alone.

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Fig 1. Defect filled with Cargel/autologous blood after microfracture

Fig 2. 4.5 cm2 OCD treated with microfracture and Cargel augmentation. Left: Pre-op arthroscan; Right: 2-year follow-up arthro-scan and second-look arthroscopy.

Reference Shive MS1, Stanish WD2, McCormack R3, Forriol F4, Mohtadi N5, Pelet S6, Desnoyers J7, Méthot S1, Vehik K8, Restrepo A1. BST-CarGel® Treatment Maintains Cartilage Repair Superiority over Microfracture at 5 Years in a Multicenter Randomized Controlled Trial. Cartilage. 2015, 6(2):62-72

3.7 PRF – Tahsin Beyzadeoglu (TR) Bone marrow stimulation has been a conventional treatment method of chondral injuries. Microfracture is one of the bone marrow stimulation techniques with the advantages of being cost-effective and easily accessible. However, the cartilage acquired via microfracture is fibrocartilage which is not robust enough against shearing forces due to its main type 1 collagen(1). Although satisfactory outcome can be achieved in short term, less favourable long term results have been reported after microfracture treatment of chondral lesions larger than 2 cm2(2). To eliminate the disadvantages of microfracture method, scaffolds have been applied over the micro fractured area(3). A scaffold is a transient material that helps the mesenchyme stem cells originating from the subchondral bone to accumulate, adhere, proliferate and differentiate into the injured area. The ideal scaffold is also expected to dissolve in a reasonable time. Several surgical procedures, such as AMIC® (Autologous Matrix-Induced Chondrogenesis) (Geistlich Pharma AG, Wolhusen, Switzerland) using porcine collagen membrane as the scaffold and fibrin for its fixation, have been defined for scaffold augmented micro fracturing(4,5). It has been shown that regulating the environment like joint fluid is another issue for satisfactory cartilage repair. Platelet-rich plasma (PRP), stem cells and other regenerative injections have been added to microfracture to regulate the joint fluid and enhance cartilage repair after microfracture. Vivostat® Platelet-rich fibrin (PRF) (Vivostat A/S, Allerod, Denmak) which is prepared from autologous human blood and rich in growth factors of the platelets, has been shown to survive in the joint after its application and also to enhance the migration, proliferation, viability, and differentiation of chondrocytes, thus showing a promising capacity for cartilage repair( 6 , 7, 8 ) . PRF may serve as a scaffold after intraoperative application over the micro fractured area (Fig. 1) and may be advantageous for cartilage regeneration after microfracture(9) (Fig. 2 and Fig. 3). Vivostat® is the only injectable system for on-site preparation of autologous fibrin sealant with platelet. Although promising, more controlled studies are needed to determine the results of Vivostat® - PRF application during microfracture procedure. Figure 1: Intraoperative application of Vivostat® Platelet-rich fibrin on the femoral trochlea after microfracture INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration & Joint Preservation Society Figure 2: Preoperative MRI T1 sagittal scan of the chondral lesion Figure 3: Postoperative MRI T1 sagittal scan of the chondral lesion 1 year after microfracture and intraoperative application of Vivostat® Platelet-rich fibrin

References 1. Steinwachs MR, Guggi T, Kreuz PC. Marrow stimulation techniques. Injury. 2008 Apr;39 Suppl 1:S26-31. 2. Solheim E, Hegna J, Inderhaug E. Long-term clinical follow-up of microfracture versus mosaicplasty in articular cartilage defects of medial femoral condyle. Knee. 2017 Dec;24(6):1402-1407. 3. Junji Iwasa et al. Clinical application of scaffolds for cartilage tissue engineering. Knee Surg Sports Traumatol Arthrosc. 2009 Jun; 17 ( 6 ) : 5 61 – 5 7 7. 4. Gao L et al. Autologous Matrix-Induced Chondrogenesis: A Systematic Review of the Clinical Evidence. Am J Sports Med. 2019 Jan;47(1):222-231 5. Becher C et al. Arthroscopic microfracture vs. arthroscopic autologous matrix-induced chondrogenesis for the treatment of articular cartilage defects of the talus. Knee Surg Sports Traumatol Arthrosc. 2018 Nov 3. 6. Velada JL, Hollingsbee DA. Physical characteristics of Vivostat patient-derived sealant. Implications for clinical use. Eur Surg Res. 2001 Sep-Dec;33(5-6):399-404. 7. Fattahi T, Mohan M, Caldwell GT. Clinical applications of fibrin sealants. J Oral Maxillofac Surg 2004; 62: 218-224. 8. Wong CC et al. Single-Stage Cartilage Repair Using Platelet-Rich Fibrin Scaffolds With Autologous Cartilaginous Grafts. Am J Sports Med. 2017 Nov;45(13):3128 -3142. 9. Papalia R et al. Intraoperative application Platelet rich fibrin, postoperative injections of PRP or microfracture only for osteochondral lesions of the knee: a five-year retrospective evaluation. J Biol Regul Homeost Agents. 2016 Oct-Dec; 30(4 Suppl 1):41-49.

3.8 One Step Reconstruction of Cartilage Defects with an Orthobiologic Collagen I hydrogel, by Arthroscopically and Liquid Application with a 2-Chamber Syringe – Olaf Thorsten Beck (DE) INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION INTRODUCTION: REGENERATION SOCIETY CartilageREGENERATION damage is one of the most common problemsSOCIETY in orthopaedics and trauma surgery. The various causes range & from posttraumatic damage to axial deviation& to diseases of the osteochondral complex e.g. osteonecrosis, osteochondrosis. Younger patients with isolated cartilage damage should be treated early to avoid extensive damage and the later onset of osteoarthritis and beyond that the subsequent use of artificial joints. The isolated, often small cartilage damage is a difficult to treat pre-arthritis (Furukawa 1980, Mitchell 2004). Clinical studies have shown that early operative therapy is superior to conservative measures (Bruns 1992, Saris 2003). Different studies and retrospective investigations had been carried out by this novel single-stage approach using the cell-free collagen matrix ChondroFiller liquid (Schneider 2016, Breil-Wirth 2016, Beck 2018). Until now more than 7000 ChondroFiller liquid implants have been used worldwide in more than 20 countries. A multicenter post marketing study (PMS) is running now to review the functionality, compatibility and safety of this collagen-based implants for the supply of cartilage defects in all joints, for patients with focal cartilage damage. The main advantages of this acellular implant are that collagen matrices have excellent biocom- patibility and only one step treatment is needed. The matrices serve as 3-dimentional cell carriers into which the patients‘ cells can intrude, proliferate and regenerate defective tissue to cartilage repair and focal resurfacing.

METHODS: The supply of small or medium focal articular cartilage defects with the cell-free Collagen matrix is mostly arthroscopic or minimal invasive. The biological scaffold is applied liquid by means of a two-chamber syringe and develops its

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specific final form in situ direct inside the defect. This 3-dimensionalINTERNATIONAL collagen CARTILAGE scaffoldJOINT PRESERVATION serves as a INTERNATIONALmatrix for CARTILAGE stemJOINT cells PRESERVATION and REGENERATION & SOCIETY REGENERATION & SOCIETY chondroblasts, that get the ability to migrate from the surrounding tissue and differentiate into chondrocytes inside the Or- thobiologic scaffold. Patients with small (up to 3 cm²) focal cartilage defects had been treated arthroscopically or by means of a miniarthrotomy on the knee or ankle. The defect zone was filled completely with ChondroFiller liquid. Postoperatively, the joints were temporarily sedated and partially loaded for 6 weeks. Patients in the PMS were followed up clinically to review the functionality, compatibility and safety of this one step cartilage regeneration with ChondroFiller implants. Defect INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION filling was proven by MRI examination at 12 month and by joint function.& JOINT PRESERVATIONIn addition, SOCIETY patients were interviewed& JOINT PRESERVATION for SOCIETYparam- eters as satisfaction, pain, quality of life and scored using Score Systems (IKDC) assessed at 6, 12 and 36 months. A clinical data management platform is used for reconciliation in a trial master file and for statistical analysis.

RESULTS: International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION The latest interims analysis of an open label post marketing study with& JOINT a PRESERVATION follow-up S OCIETY of 3 years will be Jointintroduced, Preservation Society also if the study is still not completed. Until now more than 100 Patients were included in the study and cartilage defects in knee (87,6%) and ankle (12,4%) were supplied. Initial diagnosis was arthrosis (48,9 %), sports injury (27,2 %), Osteochondrosis dissecans (10,9 %) or others (13,0 %). The male (61,9 %) and female (38,1 %) patients had an average age of 43,4 years. The former duration of the complaints was years (39,5 %), month (43,0 %) or weeks (17,4 %). In addition to demographic data, data are collected like the anamnesis, joint findings, therapies, previous surgeries, IKDC scores. Until now there were no complications. No patient reported a worsening of the preoperative condition, most of the operated patients would have the surgery performed again. No indication could be found in which the surgery could not lead patients to satisfactory improvement. Neither regarding age, weight or defect size, there were tendencies here.

3.9 ARTHROSCOPIC TECHNIQUE – Tips and Technical pearls – Tomasz Piontek (PL) The goal of this presentation is to present an arthroscopic technique for reconstructing damaged knee cartilage fragments using the AMIC technique in conjunction with a collagen matrix (porcine collagen type I and III (Geistlich Pharma AG, Wolhusen, Switzerland)) and fibrin glue (Tissucol, Baxter, Warsaw, Poland). Our procedure is to avoid microfracture and drilling of the defect. Instead we take marrow from the femoral condyle and we saturate the membrane. The prepared membrane should be applied in dry arthroscopy to the previously cleaned cartilage defect. We cover the defect with a fibrin glue membrane and finish the procedure. We present our results obtained throughout 2 years of patients with patella joint treatment, using the AMIC procedure without microfracture and drilling.

Session 5 – Stem Cells

5.1 BONE MARROW CONCENTRATE- What is in It and How could It Work? – Cosimo de Bari (UK) Osteoarthritis (OA) is a common degenerative joint disease, characterised by progressive cartilage breakdown, subchondral bone sclerosis and remodelling leading to synovial hyperplasia and chondro-osteophyte formation. Focal defects of the joint surface increase the risk of OA and require treatment. In the knee, focal cartilage defects are often treated with marrow stimulation techniques, such as microfracture. This technique allows communication with subchondral bone marrow to release mesenchymal stromal/stem cells (MSCs) from the marrow that form a repair tissue. How- ever, especially in large defects, the repair tissue with microfracture is predominantly fibrocartilage, which has poor mechanical properties compared with hyaline cartilage and undergoes degeneration over time with the formation of scar-like fibrous tissue or even replacement with bone. While cell therapy employing firstly culture-expanded chondrocytes and more recently MSCs (from bone marrow or other tissue sources such as adipose tissue) are also largely used clinically in ACI-like protocols, an attractive emerging approach is the use of bone marrow aspirate concentrate (BMAC). The BMAC is being investigated as a direct injectable therapeutic or an adjuvant to existing cartilage repair interventions employing biomaterials and osteochondral grafts. The BMAC has the advantage of meeting the regulatory criteria for “minimal manipulation”, which simplifies the regulatory pathway compared with the products consisting of culture-expanded cell preparations, which are subject to more stringent regulation for clinical use.

The BMAC has shown promising results in preclinical and clinical studies for the repair of joint surface defects. How- ever, the mechanism of action remains to be clarified. The BMAC contains a lot of different cells types, including platelets, white blood cells, red blood cells, and various progenitor cells. Among the progenitors, the presence of MSCs has been confirmed by phenotyping and in vitro differentiation studies after culture expansion. MSCs have ability to differentiate into chondrocytes and osteoblasts and therefore are postulated to contribute to the formation of repair cartilage and bone tissues. However, the MSCs only constitute up to 0.01% of mononuclear cells in the bone marrow INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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and whether this quantity of MSCs is enough to significantly contribute to tissue formation via chondro-osteogenic differentiation remains an important area of investigation. MSCs also elicit paracrine effects to modulate the microenvironment and support repair and anabolism, and this could be their prevailing mechanism.

The BMAC also contains platelets, which are known to release many growth factors, chemokines, and cytokines. The BMAC is thus a rich source of growth factors including TGFβ superfamily members, known to modulate MSC differentiation and induce chondrogenesis, and platelet-derived growth factor (PDGF), known to have several effects promoting International Cartilage Regeneration & Joint Preservation Society Internationalhealing. Other growth Cartilage factors such as IGF-1 and FGFs Regeneration would stimulate extracellular matrix synthesis and promote an anabolic environment, thereby favouring tissue recovery and healing. The growing evidence that the joint environment is rich in progenitor cells resident in the synovium, bone marrow and the articular cartilage itself suggests the prospect that & Jointa prevalent mode Preservation of action of BMAC would be to promote andSociety enhance residual intrinsic repair mechanisms of the damaged joint surface. The efficacy of BMAC is thus influenced by the components present in the different preparations, which are likely to depend on processing methods and patient-related factors such as age and morbidities.

In summary, the BMAC is promising for cartilage repair, as supported by preclinical and preliminary clinical studies, and has the advantages of single-stage management and limited regulatory hurdles. An understanding of the cell and molecular biology of BMAC is necessary to improve processing methods and optimise delivery in clinical settings. In addition, defining the potency of each individual BMAC in relation to patient age and morbidities will be critical to ensure consis- tency of patient benefit in both clinical and structural outcomes. Large, multicentre, prospective clinical trials will be needed to gain insight in the clinical efficacy and to identify the ideal candidates for BMAC intervention in routine clinical practice.

Acknowledgments The author is grateful to support to his research from Medical Research Council and Versus Arthritis.

5.2 BMAC Combined with Scaffold for Full Thickness Cartilage Defect – Alberto Gobbi (IT)

INTRODUCTION: Injury to the articular cartilage is prevalent and leads to early osteoarthritis. The poor healing capacity of the cartilage due to its low mitotic potential has always been a scope of research in treating these injuries. Over the years, a number of techniques has been developed in order to prolong the durability of cartilage repair. Autologous chondrocyte implantation (ACI) has shown to stimulate hyaline like tissue providing longer clinical improvement for the patient1. Evolution of this technique lead to the development and use of scaffolds that allowed cell ingrowth, however that did not eliminate the need for chondrocyte harvest and cultivation. That is why, the idea of performing a single-step procedure to avoid the two-stage surgical procedures lead to the use of bone marrow aspirate concentrate (BMAC) that contains multi-potent stem cells (MSCs) and growth factors. There have been advancements in the use of bone marrow aspirate concentrate in association with biologic scaffolding to treat knee chondropathy. Scaffolds that have been examined for clinical use in this capacity include matrices composed of type I/III collagen or hyaluronic acid-based structures.3,5 Such cartilage repair procedures have demonstrated INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALpromising medium-term CARTILAGE and long-term clinical outcomesJOINT in the treatment PRESERVATION of cartilage damage. In order to perform one-stage treatment of cartilage injury using a method that is cost-effective and capable of providing durable cartilage repair, our REGENERATION SOCIETY centerREGENERATION has examined the use of a hyaluronic acid-basedSOCIETY scaffold in conjunction with bone marrow aspirate concentrate (HA- & BMAC), which has demonstrated comparable& clinical outcomes to other methods of cell-based therapy such as autologous chondrocyte implantation.2. Unlike previous technique using chondrocyte implantation, MSC isolation does not require healthy cartilage tissue harvesting, so there is no need for cartilage biopsy surgery and subsequent chondrocyte cultivation. In our study, we compared patients treated with matrix induced autologous chondrocyte implantation with patients who have undergone treatment with MSCs combined with the same scaffold. At 3 years follow up we did not notice any statistically significant difference between the two groups and concluded that both these techniques were viable and effective 2. From our previous studies, we believe that cell-based cartilage repair performed as a single-stage procedure using a Hyaluronan based scaffold absorbed with BMAC represents an important advancement in the treatment of full-thickness cartilage injury and has potential for widespread clinical use3-4. Our long-term results: We have investigated the long-term clinical outcomes of cartilage repair in 23 patients (mean age 48.5 years) for a mean duration of 10 years, with full thickness cartilage defect in the knee using a hyaluronic acid-based scaffold embedded with bone marrow aspirate concentrate (HA-BMAC) and our results shows good to excellent clinical outcomes at long-term follow-up in lesions also in large lesions.

CONCLUSION: HA based scaffold along with BMAC has previously shown to provide comparable short- and medium-term outcomes to autologous chondrocyte implantation, while avoiding the morbidity and significantly reducing the cost of a two-stage

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procedure. Furthermore, this versatile technique can be used arthroscopically,INTERNATIONAL CARTILAGE alsoJOINT it PRESERVATIONcan be used in conjunctionINTERNATIONAL CARTILAGE withJOINT PRESERVATION bone REGENERATION & SOCIETY REGENERATION & SOCIETY grafting to restore the entire osteochondral unit in cases of associated subchondral injury. Moreover, there is greatly increasing interest in arthroscopic cell-based cartilage lesion repair. This technique can be performed arthroscopically in certain instances in the knee to decrease perioperative morbidity and can be used also in other joints such as the hip and ankle.

References: INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION 1. Gobbi A, Kon E, Berruto M, et al. Patellofemoral full-thickness chondral& JOINT defectsPRESERVATION treated SOCIETY with second-generation& JOINT PRESERVATION autologous SOCIETY chondrocyte implantation: Results at 5 years’ follow-up. Am J Sports Med 2009;37: 1083-1092 2. Gobbi A, Chaurasia S, Karnatzikos G, Nakamura N. Matrix-Induced Autologous Chondrocyte Implantation versus Multipo- tent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions: A Nonrandomized Prospective Trial. Cartilage. 2015 Apr;6(2):82-97. International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION 3. Gobbi A, Karnatzikos G, Sankineani SR. One-step surgery with multipotent& JOINT PRESERVATION stem cells S OCIETY for the treatment ofJoint large Preservation full-thickness Society chondral defects of the knee. Am J Sports Med. 2014;42(3):648-657. doi:10.1177/0363546513518007. 4. Gobbi A, Scotti C, Karnatzikos G, Mudhigere A, Castro M, Peretti GM. One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years. Knee Surg Sports Traumatol Arthrosc. January 2016. doi:10.1007/s00167-016-3984-6. 5. Sadlik B, Gobbi A, Puszkarz M, Klon W, Whyte GP. Biologic inlay osteochondral reconstruction: Arthroscopic one-step osteochondral lesion repair in the knee using morselized bone grafting and hyaluronic acid-based scaffold embedded with bone marrow aspirate concentrate. Arthrosc Tech. 2017;6(2):e383-e389.

5.3 BMAC in Hydrogel – Martyn Snow (UK) Following microfracture one of the proposed mechanisms of failure is secondary to the changes in the mechanical properties of the subchondral bone. An increase in stiffness combined with intra-lesional osteophyte leads to increased stress on the fibrocartilage regenerate. BSt-Cargel(Smith & Nephew, Andover, MA) is a chitosan hydrogel/scaffold which following the addition of peripheral blood is intended to stabilize the blood clot in a cartilage lesion following MF. In a 80 patient RCT it resulted in histologically superior repair compared to microfracture alone with reduced bone changes suggesting a positive biological effect of the scaffold. With the aim of providing a cartilage treatment that provides a source of mononucleated cells avoiding the need for subchondral perforations we investigated the combination of BMAC and BSt-Cargel to create a cell seeded implant with comparative properties to standard BSt-Cargel mixed with blood.

Design. Whole blood and bone marrow were harvested from 12 patients who underwent cartilage repair surgery using BMAC after informed consent. a validated in vitro testing model was used to assess the following 6 conditions: (1) BSt- Cargel mixed with whole blood (Cg-WB), (2) BSt-Cargel mixed with bone marrow (Cg-BM), (3) BSt-Cargel mixed with bone marrow concentrate (Cg-BMaC), (4) whole blood (WB), (5) bone marrow (BM), and (6) bone marrow concentrate and batroxobin (BMaC-BtX). Cell retention and viability within the BSt-Cargel/ BMaC clots were investigated. Results. in our study, BM and BMaC (processed using the Harvest, SmartPrep2 system and reactivated with batroxibin) when combined with BSt-Cargel produced a product that had similar clot contraction, macroscopic properties, and histological appearance to standard BStCargel mixed with blood. Mononucleated cells from the BMaC were retained within the scaffold and remained viable until clot dissolution in vitro.

Conclusions. By combining BSt-Cargel with BMaC in the manner described, bone marrow–derived mononucleated cells can be retained within the chondral defect potentially negating the need for microfracture. The early results of a subsequent clinical series will be presented.

5.5 Adipose Tissue: What is in It and How It Could Work? Infrapatellar Fat Pad-Derived MSC Response to Inflammation and Fibrosis Induces an Immunomodulatory Phenotype In- volving CD10-Mediated Substance P Degradation – Diego Correa (US)

Mesenchymal Stem Cells (MSC) exhibit immunomodulatory properties, making them an alternative to treat inflammation-related musculoskeletal conditions. The adipose tissue (AT) has been proposed as an alternative source to bone marrow MSC (BM-MSC), given its readily access and superior number per tissue volumetric unit. The infrapatellar fat pad (IFP), a special depot of AT in the knee, serves as a reservoir of MSC and with adjacent synovium plays key roles in joint disease including the production of Substance P (SP) affecting local inflammatory responses and transmitting nociceptive signals. Here, we interrogate human IFP-derived MSC (IFP-MSC) reaction to inflammatory and pro-fibrotic environments (cell priming), compared with bone marrow-derived MSC (BM-MSC). Naïve IFP-MSC exhibit increased INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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clonogenicity and chondrogenic potential compared with BM-MSC. Primed cells experienced dramatic phenotypic changes, including a sharp increase in CD10, upregulation of key immunomodulatory transcripts, and secreted growth factors/cytokines affecting key pathways (IL-10, TNF-α, MAPK, Ras and PI3K-Akt). Naïve, and more so primed MSC induced SP degradation in vitro, reproduced with their supernatants and abrogated with thiorphan, a CD10 inhibitor. These findings were reproduced in vivo in a rat model of acute synovitis, where transiently engrafted human IFP-MSC induced local SP reduction. Functionally, primed IFP-MSC demonstrated sustained antagonism of activated human peripheral blood mononuclear cells (PBMC) proliferation, significantly outperforming a declining dose-depen- International Cartilage Regeneration & Joint Preservation Society Internationaldent effect with naïve Cartilage cohorts. Collectively, our in vitro Regeneration and in vivo data supports cell priming as a way to enhance the immunoregulatory properties of IFP-MSC, which selectively engraft into areas of active synovitis/IFP fibrosis inducing SP degradation, resulting in a cell-based product alternative to BM-MSC to potentially treat degenerative/inflamma- & Jointtory joint diseases. Preservation Finally, these data provide mechanistic Societydescriptions of the actions of IFP-MSC during cell therapy, that help explain how cells mitigate some effects of OA including joint inflammation and pain.

5.6 Micro-Fragmented Stromal-Vascular Fraction Plus Microfractures Provides Better Clinical Results than Microfractures Alone in Symptomatic Focal Chondral Lesions of the Knee. A Prospective Randomized Single Blind Controlled Study – Cosimo Tudisco (IT)

PURPOSE: To evaluate clinical outcomes up to one year in patients affected by symptomatic focal chondral lesions of the knee treated with micro-fragmented stromal-vascular fraction plus microfractures compared to microfractures alone. Methods: Two groups of 20 patients were arthroscopically treated with microfractures for a symptomatic focal chondral defect of the knee. At the end of surgery, in the experimental group micro-fragmented stromal-vascular fraction was injected into the joint. Primary end point was WOMAC score at 12 months. Secondary end points were any adverse events, Oxford Knee Score, EQ-5D score, VAS for pain, analgesics and anti-inflammatory consumption.

RESULTS: All the patients were evaluated at 12 months follow-up. No adverse reactions were noted. Analgesics and anti- inflammatory consumption were similar in both groups. At 1-month follow-up, no differences were noted between groups or compared to pre-operative scores. At 3 months follow-up, patients in both groups improved from baseline in all variables. Significant lower VAS scores were found in the experimental group (4.2±3.2 vs. 5.9±1.7, p=0.04). At 6- and 12-months follow-up, patients in the experimental group scored better in all outcomes with a moderate effect size; in particular, better WOMAC scores were obtained, achieving primary endpoint of the study (17.7±11.1 vs. 25.5±12.7; p=0.03) Conclusions: Injection of micro-fragmented stromal-vascular fraction is safe and when associated with microfractures it is more effective in clinical terms than microfractures alone in patients affected by symptomatic focal chondral lesions of the knee. INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION 5.7 Adipose on a Scaffold – Fabio Valerio Sciarretta (IT) REGENERATION SOCIETY REGENERATION SOCIETY & INTRODUCTION: & Cartilage defects represent a continuous therapeutic challenge. No surgical technique has shown conclusive superiority among others. Therefore, since joint preservation and regeneration are a worldwide major goal for orthopaedic surgeons, new techniques are being proposed, based upon autologous tissues and mesenchymal stem cells with- drawn from bone marrow or adipose tissue.

Goal of our study was to assess the clinical, imaging and histologic outcome of the LIPO-AMIC technique (autologous matrix-induced chondrogenesis + ADSCs and adipose tissue transfer) consisting of osteochondral lesion accurate debridement, micro fracturing and filling of the defect with bilayer cell-free collagen scaffold soaked in adipose regenerative product.

MATERIAL & METHODS: Eighteen patients (age range: 28-58) with osteochondral lesions of the knee repaired using the LIPO-AMIC technique. After diagnostic knee arthroscopy, the first step is, under local anaesthesia, the extraction, using the simple liposuction method, of 50-80 ml of lipoaspirate from the adipose tissue of the abdomen, using a dedicated single-use kit available on the market for suction and subsequent processing (filtration and micro-fragmentation) and adipose tissue grafting (Process

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Kit Lipogems, Lipogems International SpA, Milan, Italy), for whichINTERNATIONAL use we CARTILAGE have JOINTfollowed PRESERVATION the instructionsINTERNATIONAL provided CARTILAGE JOINT by PRESERVATION the REGENERATION & SOCIETY REGENERATION & SOCIETY manufacturer. This device progressively reduces the size of the adipose tissue clusters, while at the same time eliminating the blood residues and the oily substances, with pro-inflammatory capacity, minimizing, at the same time, thanks to the completion of the whole process just within saline solution, the risks of damaging the mesenchymal cells. The fragmentation of adipose tissue consists in different steps that make it possible to obtain purified adipose clusters product ready for the desired clinical purpose. The second step in the surgical procedure is the repair of the focal chondral or osteochondral INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION defect. Once identified, the chondral or osteochondral defect is carefully& JOINT PRESERVATION cleaned SOCIETY up to obtain stable, & cleanJOINT PRESERVATION and SOCIETYperpen- dicular margins of healthy cartilage and then accurately measured. Then, a perfect copy of the defect is obtained using an aluminium model, from which the exact imprint of the defect is cut out. After carefully performing the microfractures of the subchondral bed of the defect, and having exactly cut the membrane (Chondro-Gide®, Geistlich Pharma AG, Wolhusen, Switzerland) on the basis of the model, the collagen matrix, which was immersed for a few minutesInternational in the Cartilage microfram Regeneration- & I NTERNATIONAL C ARTILAGE R EGENERATION mented adipose tissue and in the stromal vascular fraction extracted& JOINTfrom PRESERVATION the adipose S OCIETY tissue of the abdomen,Joint Preservation is insertedSociety in articulation to directly cover the defect. The remaining part of the cells obtained from the adipose tissue is injected onto the lesion site and then sealed with fibrin glue (Tissucol, Baxter, Rome, Italy).

All patients were clinically evaluated through IKDC, KOOS and VAS scores, with follow-up between 12 and 60 months. MRI examinations were performed at 6, 12 months and yearly thereafter. ADSCs have been isolated and characterized in terms of viability and cell composition using multicolour FACS analysis.

RESULTS: No complications during or after surgery were encountered. Patients showed relevant, immediate and durative improvement of the various scores already from the very initial follow-up. At intermediate and final follow-up all scores were significantly increased (p<0.001). MRI examination, completed by T2 mapping imaging, showed early subchondral lamina regrowth and progressive maturation of the repair tissue. Histological studies shown that stem cell population resided in a perivascular location (niche) with preserved architecture and where ADSCs coexisted with pericytes and endothelial cells. FACS analysis confirmed high viability and an increased percentage of endothelial cells.

DISCUSSION: Kramer et al., in 2006, demonstrated in an in vitro study that a collagen membrane is able to treat mesenchymal cells deriving from bone marrow after microfractures and that these cells have the ability to differentiate towards chondrogenic, adipogenic and osteogenic line. Dickhut et al. have performed in vitro studies demonstrating that a biphasic carrier of type I and III collagen, such as the Chondro-Gide® membrane, is able to promote the chondrogenesis of mesenchymal cells. Compared to a collagen-free membrane, it provides greater stability of the repairing tissue.

Mesenchymal stem cells (MSCs) have shown much promise with respect to their use in cartilage tissue engineering. MSCs can be obtained from many different tissue sources. Among these, adipose tissue-derived stem cells (ADSCs) have recently been under investigation as a source for cell therapies. Adipose tissue is very rich in capillary beds, thereby harbouring one of the largest depots of MSCs. Adipose tissue can, in fact, provide an abundant source of ADSC’s and stromal vascular fraction and adipose tissue cells. ADSC’s have the advantage of being abundant, easy of harvest, with rapid expansion, high proliferation potential and their ability to better maintain their phenotype with respect to BMSCs. Preparation of ADSCs is also easier and less expensive than BMSCs, and the cultured lineage has shown a similar function to BMSCs in multi-lineage differentiation. For our purposes, the main interest in ADSC’s comes from the fact that these cells are multipotent, therefore able to differentiate into different types of cells including chondrocytes. The chondrogenic potential of human ADSCs has been clearly demonstrated over several years by different works. In 2002, following an in vitro differentiation process, Erickson et al. have shown that human ADSCs maintain the phenotype of chondrocytes and form cartilaginous tissue when implanted subcutaneously in vivo in immuno-deficient mice for up to 12 weeks. In numerous other studies it has been shown that, under certain conditions, ADSCs can express the genes and proteins of different molecules that are specific to cartilage, including type II collagen and aggrecan, without expression of hypertrophic chondrocytes markers, such as type X collagen. However, under various defined conditions, ADSC’s may be induced to synthesize type I and type II collagen, suggesting that a cartilaginous phenotype is also possible. When kept in pellet culture or encapsulated in alginate beads and cultured with 10 ng / ml of TGF-β1 growth factor, ascorbate and dexamethasone, and have been shown to express a chondrocyte-like phenotype and synthesize type II collagen, aggrecan, link proteins and chondroitin sulfate in a time-dependent manner based on the analysis, immunohistochemistry, and the incorporation of mRNA radiotracers, with a significant increase in the synthesis of proteoglycans and proteins under condogenic conditions. Winter et al. concluded that the gene expression profile of ADSCs in chondrogenic conditions is similar to that of mesenchymal cells. Mesenchymal cells from adipose tissue at this time can therefore be considered to be able to form cartilaginous tissue. The Chondro-Gide® is a resorbable collagen membrane, consisting of collagen types I and III. It is INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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particularity due to its bilayer structure, with one compact and one porous side. The compact layer, which is cell occlusive, prevents cells from diffusion and also protects them from mechanical impact. The porous layer is made of collagen fibres in a loose, porous arrangement that favours cell invasion and attachment. This 3D collagen matrix stimulates the autologous cultured cells to differentiate into the chondrocyte phenotype and to produce collagen II and GAG.

The advantage of adding adipose tissue transfer containing ADSC’s is the capability to activate the chondrocytes with regard to outgrowth and proliferation. Vice versa, the cartilage cells might favour the stem cells to differentiate along the International Cartilage Regeneration & Joint Preservation Society Internationalchondrogenic lineage. Cartilage Regeneration

CONCLUSION: & JointRepair of full-thickness Preservation cartilage injuries by LIPO-AMIC techniqueSociety provides good to excellent clinical improvement, MRI defect filling and, at advanced and detailed histologic evaluation, high percentage of ADSCs and endothelial cell populations with high viability and niche preservation. Results resulted improved in respect to standard AMIC technique and comparable to MACI, but at significantly reduced costs.

References: 1. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell, vol. 9, no. 1, pp. 11–15, 2011. 2. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13:4279-429595 3. Gimble J, Guilak F. Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytothera- py.;5:362-369 2003. 4. Sciarretta FV, Ascani C. Adipose tissue and progenitor cells for cartilage formation. In: Doral MN, Karlsson J, eds. Sports injuries: prevention, diagnosis, treatment and rehabilitation. 2nd ed. Springer 2015, pp. 1845-1855. 5. Kramer J, Böhrnsen F, Lindner U, et al. In vivo matrix-guid- ed human mesenchymal stem cells. Cell Mol Life Sci 2006;63:616-26. 6. Dickhut A, Gottwald E, Steck E, et al. Chondrogenesis of mesenchymal stem cells in gel-like biomaterials in vitro and in vivo. Front Biosci 2008;13:4517-28. 7. Erickson GR, Gimble JM, Franklin DM, et al. Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. Biochem Biophys Res Commun 2002;290:763- 8. De Ugarte, D.A. et al. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 174, 101–109, 2003 9. Bianchi F, Maioli M, Leonardi E, Olivi E, Pasquinelli G, Valente S, Mendez AJ, Ricordi C, Raffaini M, Tremolada C, Ventura C. A new nonenzymatic method and device to obtain a fat tissue derivative highly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates. Cell Transplant. 2013;22(11):2063-77. 10. Bosetti M, Borrone A, Follenzi A, et al Human Lipoaspirate as Autologous Injectable Active Scaffold for One- Step Repair of Cartilage Defects. Cell Transplantation, Volume 25, Issue 6, pages 1043-1056

INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALSession 6CARTILAGE – Unloading ProceduresJOINT And Focal PRESERVATION Resurfacing Implants REGENERATION SOCIETY REGENERATION SOCIETY & 6.1 Meniscal Replacement using &Scaffolds & Allografts – René Verdonk (BE) Treatment of meniscal lesions is the most common surgical intervention performed by orthopaedic surgeons today. Favour- able results have been reported in the short term after partial meniscectomy. However, the risk of osteoarthritis and irrevers- ible damage occurring in the long term remains. Therefore, a novel, biodegradable, polyurethane scaffold was developed to fulfil an unmet clinical need in the treatment of patients with presenting with painful irreparable partial meniscal defects. The present study investigated 43 patients were consecutively treated for their partial meniscus defects with the scaffold technique (Actifit). These patients were prospectively clinically evaluated with a follow-up of 60 months. Magnetic resonance imaging (MRI) was used for morphologic analysis of the meniscal regeneration at 12, 24 and 60 months of follow-up.

The patients included in this study showed a significant gradual clinical improvement after implantation of the scaffold. No effect of the scaffold on the opposing cartilage was observed on MRI. In thirteen patients the treatment had failed (30.2%). Six patients were lost to follow-up (13.9%).

At five years post implantation, clinical outcome data from this study support the use of the polyurethane scaffold for the treatment of irreparable, painful, partial meniscus defects. However, well-designed, large-scale, randomized controlled trials are mandatory to confirm the initial results and the reliability of this procedure. Results of the European ACTIFIT

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study will be presented and compared to CMI ( collagen meniscalINTERNATIONAL implant CARTILAGE ) implantJOINT PRESERVATION results. In caseINTERNATIONAL of total CARTILAGE or JOINTsubtotal PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY meniscectomy the results of the meta-analysis will bring the mid- to long-term survival outcome of MAT (meniscal allograft transplantation). Potential prognosticators, with particular focus on chondral status and age of the patient at the time of transplantation, were also analysed.

An online database search was performed using following search string: “meniscal allograft transplantation” and “outcome”. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION A total of 65 articles were analysed for a total of 3157 performed MAT& JOINT with PRESERVATION a mean SOCIETY follow-up of 5.4 years.& JOINT SubjectivePRESERVATION SOCIETY and clinical data was analysed. The subjective and objective results of 2977 patients (3157 allografts) were analysed; 70% were male, 30% were female. Thirty-eight percent received an isolated MAT. All other patients underwent at least one concomitant procedure. Lysholm, Knee injury and Osteoarthritis Outcome (KOOS), International Knee Documentation Committee (IKDC) and Visual Analogue Scale (VAS) scores were analysed. All scores showed a good patient satisfactionInternational at long-term Cartilage Regeneration follow- & I NTERNATIONAL C ARTILAGE R EGENERATION up. The mean overall survival rate was 80.9%. Complication rates were& JOINT comparablePRESERVATION S OCIETY to standard meniscalJoint Preservationrepair surgery.Society There was a degenerative evolution in osteoarthritis with at least one grade in 1760 radiographically analysed patients. Concomitant procedures seem to have no effect on the outcome. Age at transplantation is a negative prognosticator. The body mass index (BMI) of the patient shows a slightly negative correlation with the outcome of MAT.MAT is a viable solution for the younger patient with chronic pain in the meniscectomised knee joint. The complications are not severe and comparable to meniscal repair. The overall failure rate at final follow-up is acceptable and the allograft heals well in most cases, but MAT cannot be seen as a definitive solution for post-meniscectomy pain. The correct approach to the chronic painful total meniscectomised knee joint thus requires consideration of all pathologies including alignment, stability, meniscal abnormality and cartilage degeneration. It requires possibly combined but appropriate action in that order.

6.4 The Episealer Mini Metal Implant (Episurf) – Matts Brittberg (SE) Today’s cartilage repair methods were developed for local traumatic defects and used either to repair only the cartilage matrix area or to repair both the cartilage and the subchondral areas.

Available are different repair approaches such as: 1. Bone marrow stimulation (BMS) techniques with or without supporting scaffolds. 2. Cartilage tissue-based repairs (Periosteum, Perichondrium, autologous or allogenic osteochondral grafts). 3. Chondrogenic cell based repairs (Autologous chondrocyte implantation (ACI)and different stem cells) 4. Synthetic or metal based mini repairs 5. Pharmacological stimulated repair (such as PRP, ACS).

To repair a cartilage defect, the techniques to use are depending on the degree of good quality shouldering cartilage. Purely cartilage tissue located repairs are subsequently much depending on good quality surrounding cartilage. Os- teochondral repair methods are less dependent on the surrounding tissues. Small to medium sized defects are mostly primarily treated by bone marrow stimulation techniques with or without scaffolds. There are many variants of such repair methods with more or less documented long-term results. For larger defects and as second line treatments, there is documented success with the use of chondrogenic cell therapies such as different generations of ACI. Similar is the situation for large defects where there is a place for allografts. All those methods are biological alternatives used for young and middle-aged patients while for large degenerative lesions in elderly patients the artificial arthroplasties are preferable. However, recently, techniques to use mini metal arthroplasty (MMA) also for local cartilage defects have been presented. One type of such mini metal implants, the Episealer implants is custom made out of special MRI sequences via DMI (digital marker imaging). The DMI gives a comprehensive view of the total joint osteochondral situation.

Animal studies: The implant has been studied in animal experiments where in adult sheep one could show that the groups with the hydroxyapatite coated cap edges showed a better quality of tissue connection to the implant. In another animal study, it was shown that such mini metal implants should be placed recessed (approx. 0.5 mm) below the surrounding cartilage in order not to negatively affect the opposing cartilage. Furthermore, in a sheep model also a firm and consistent bond to bone under weight-bearing conditions was shown up to 1 year.

Clinical use: Even the different available biological alternatives are not successful every time when used. Some patients are poor responders to local biological repairs with the techniques above 1-3 and 5. Some of them if located in a medial or lateral femoral compartment could be improved by unloading osteotomies but still some remain disabled not being candidates for larger joint arthroplasties. The first published Episealer paper is by Stålman et al. who looked upon ten patients with age 36-56 years with focal chondral defects, ICRS 3-4 of the femoral cartilage and failed earlier conservative or surgical interventions with VAS pain > 40. The patients were followed for 2 years with subjective outcome measures (VAS, INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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EQ5D, KOOS) and RSA. The customized implant and guide instruments were manufactured by computer-aided design/ computer-aided manufacturing (CAD/CAM) techniques using MRI data. Improvements that reached significance were for VAS (p ≤ 0.001), Tegner (p = 0.034) and the KOOS subscores ADL (p = 0.0048), sport and recreation (p = 0.034) and quality of life (p = 0.037). VAS and KOOS scores improved gradually at 3, 6 and 12 months. The improvements in EQ5D, KOOS pain and KOOS symptoms did not reach statistical significance. No complications occurred in the postoperative period. No radiographic signs of damage to the opposing tibial cartilage was noted. The surgical usability of implants International Cartilage Regeneration & Joint Preservation Society Internationaland instruments were Cartilage good, and RSA did not show any Regeneration implant migration. My indications for mini-metal implants like Episealer are: 1. 3rd line of treatment when other biological implants such as BMS or 3rd cell generation implants have failed in & Jointchondral defects.Preservation Society 2. 2nd line of treatment alternative after failed osteochondral repairs. 3. 1st line of treatment of localized osteonecrosis with localized bone marrow oedema (Widespread bone marrow oedema could indicate fast progress of necrosis into full OA and local repair is then not indicated). 4. 1st line of treatment in patients 45-60 years of age with lesions and degenerative changes before joint space narrowing.

All those local repairs could be combined with an unloading osteotomy if there is major malalignment documented. Summary: Focal mini metal arthroplasties (MMA) like the Episealer may be a viable option for a carefully selected group of patients. In a recent review with another type of MMA, the non-customized Hemicap, the overall conversion rate to arthroplasty was 9%. Long-term published follow ups are needed to see the joint preservation effect of a different mini metal approach, a customized implant like the Episealer.

References: Basic science publications: 1. Martinez-Carranza N, Berg HE, Lagerstedt AS, Nurmi-Sandh H, Schupbach P, Ryd L. Fixation of a double-coated titanium-hydroxyapatite focal knee resurfacing implant: A 12-month study in sheep. Osteoarthritis and Cartilage, 2014. 22(6): p. 836-844 2. Martinez-Carranza N, Ryd L, Hultenby K, Hedlund H, Nurmi-Sandh H, Lagerstedt AS, Schupbach P, Berg HE. Treatment of full thickness focal cartilage lesions with a metallic resurfacing implant in a sheep animal model, 1 year evaluation. Osteoarthritis and Cartilage, 2016. 24: p. 484-493. 3. Ryd, L. The mini-metal concept for treating focal chondral lesions and its possible application in athletes. Aspetar Sports Medicine Journal, 2016. July 2016(5): p. 292-295. 4. Martinez-Carranza N, Hultenby K, Lagerstedt A, Schupbach P, Berg HE. Cartilage Health in Knees Treated with Metal Resurfacing Implants or Untreated Focal Cartilage Lesions: A Preclinical Study in Sheep. Cartilage. 2019 Jan;10(1):120-128. 5. Schell H, Zimpfer E, Schmidt-Bleek K, Jung T, Duda GN, Ryd L. Treatment of osteochondral defects: chondrointegration of metal implants improves after hydroxyapatite coating. Knee Surg Sports Traumatol Arthrosc. 2019 Mar 16.

Clinical publications INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL6. Stålman A, Sköldenberg CARTILAGE O, Martinez-Carranza N, Roberts JOINTD, Högström M, Ryd PRESERVATION L. No implant migration and good subjective outcome of a novel customized femoral resurfacing metal implant for focal chondral lesions. Knee Surg Sports Traumatol Arthrosc. 2018 Jul;26(7):2196-2204 REGENERATION SOCIETY 7. Laursen,REGENERATION J.O., 3-Year Clinical Result of a Customized& MetalSOCIETY Mini-Prosthesis for Focal Chondral Lesion in The Knee Of A Formerly Active & 31-Year-Old Man. Journal of Exercise, Sports & Orthopedics, 2017. 4(2): p. 1-3. 8. Fuchs A, Eberbach H, Izadpanah K, Bode G, Südkamp NP, Feucht MJ.Focal metallic inlay resurfacing prosthesis for the treatment of localized cartilage defects of the femoral condyles: a systematic review of clinical studies. Knee Surg Sports Traumatol Arthrosc. 2018 Sep;26(9):2722-2732.

6.5 Resurfacing Implants (Arthosurface) – Christoph Becher (DE) The rationale of focal articular prosthetic resurfacing used as a primary arthroplasty procedure in the treatment of articular cartilage defects is still under debate. Conflicting reports raise concern about high rates of re-operations and continued development of osteoarthritis, while others have reported good outcomes. The HemiCAP contoured articular prosthetic resurfacing prosthesis (Arthrosurface Inc., Franklin, MA, USA) was introduced in 2003 to offer a focal treatment option among the currently used modalities and close the treatment gap for the middle-aged patients. It is recommended to be used when only one compartment is affected by posttraumatic, degenerative disease or necrosis associated with large unstable articular defects with significant subchondral bone exposure. The device has also been used for revision in failed biological repair attempts. Postulated advantages over biological repair options or conventional unicondylar or bicondylar arthroplasty are a generally shorter rehabilitation and preservation of physiological joint kinematics.

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A recent case report of two patients (male, 70 years; female 63 years)INTERNATIONAL with CARTILAGEa follow-upJOINT PRESERVATION of 12 years andINTERNATIONAL literature CARTILAGE reviewJOINT PRESERVATION com- REGENERATION & SOCIETY REGENERATION & SOCIETY prising 6 studies with 169 focal articular prosthetic resurfacing procedures in 169 patients (84 male, 85 female) with a mean age at implantation ranging from 44.7 to 53.7 years and a follow-up range of 20 months to 7 years suggested that focal articular prosthetic resurfacing is an effective and safe treatment option in selected cases [1]. Re-operation rates ranged from 0 to 23% depending on the length of follow-up. Meaningful clinical improvements and radiological safety were confirmed. Both surgeons and patients should recognize the importance of adhering to proper indications and place appropriate INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION expectations on focal treatment with an acknowledgement of less predictable& JOINT PRESERVATION outcomes SOCIETY with increasing& JOINTdisease PRESERVATION complex SOCIETY - ity such as revision cases, presence of osteoarthritic changes, and decreased meniscus function as already known for any kind of cartilage repair procedures.

References International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION 1. Becher C, Cantiller EB (2017) Focal articular prosthetic resurfacing for the& JOINTtreatment PRESERVATION of full-thickness S OCIETY articular cartilageJoint Preservation defects Society in the knee: 12-year follow-up of two cases and review of the literature. Arch Orthop Trauma Surg 137(9):1307-1317. Epub 2017 May 19

6.6 The BioPoly Focal Arthroplasty: One-Stage Treatment of Symptomatic Articular Cartilage lesions – Mike McNicholas (UK) Focal articular cartilage lesions can be as disabling as an osteoarthritic knee. For those lesions that remain symptomatic after rehabilitation following debridement focal arthroplasty using a metal-backed implant with a patented surface combining hydrophobic ultra - high molecular weight polyethylene (GUR 1020) with hydrophilic hyaluronic acid (Bio- Poly® RS), non-biological implant offers a single stage management option for appropriately sized and located lesions. It has better wear characteristics than UHMWPE and a wettable surface which interfaces well with articular cartilage.

Plain radiographs are needed to exclude significant osteoarthritic change. Long leg alignment views are required to assess coronal alignment. MRI is useful to demonstrate the presence of a lesion the size of the defect is best determined after debridement. Defects up to 15 x 24mm or 3.1cm2 can be treated using the implant. Satisfactory success rates are reported in a short-term (2 year) study (NCT 01473199). More of our study patients have walked through their two year review and the results continue to show significant (p<0.05) improvement from baseline at all time points. With up to 7 years follow-up, some medium term results will be presented. Longer-term outcomes are awaited.

For follow-up of any articular cartilage intervention the ICRS International Database is recommended, now available in 7 languages English, Japanese, Italian, Polish, Greek, Spanish, and Portuguese, later in 2019 Dutch, Swedish, Chinese, German language versions will go live. BioPoly also has a database available in Amplitude specific for its implants.

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A significant advantage over biological treatments is that rehabilitation after BioPoly implantation is less arduous and of shorter duration than with biological treatments.

Reference: 1. Partial Resurfacing of the Knee with BioPoly® Implant – Interim Report to 2 Years D Nathwani MJ McNicholas A Hart J Miles V Bobi JB JS Open Access. 2017 Jun 26; 2(2). International Cartilage Regeneration & Joint Preservation Society International2. https://cartilage.org/society/icrs-patient-registry/ Cartilage Regeneration

& JointSession 7 Preservation– Subchondral Bone Society

7.1 Subchondral Bone-Its Importance for Normal Function – Henning Madry (DE) The subchondral is playing an important role in osteochondral repair. The subchondral bone is the bony lamella that lies below the calcified zone of the articular cartilage, separated by the cement line. Trabeculae arising from the subchondral bone plate form a spongious network, the subarticular spongiosa. The close interaction between these two tissues of dissimilar intrinsic repair capacities is reflected in the term „osteochondral unit“. Results from translational models demonstrate the critical importance of the structural integrity of subchondral bone because its protection improves reconstructive therapies for focal cartilage defects. Given the still incomplete understanding about the mechanisms of OA and cartilage repair, enhanced knowledge of the basic science and clinical events in this frontier region will likely translate into improved therapeutic strategies for osteochondral regeneration. This talk will highlight the normal structure and pathologic features of subchondral bone during spontaneous and therapeutic repair of chondral and osteochondral defects from animal models and clinical investigations. It will also present novel translational data on the role of the subchondral bone in the field of reconstructive therapies for focal articular cartilage defects and in the development of osteoarthritis (OA). A focus will be on subchondral bone alterations in the context of marrow stimulation cartilage repair procedure, current data from translational models will be presented.

7.2 Osteochondral Allograft – Luis Tirico (PT) Fresh osteochondral allograft transplantation (OCA) has over a hundred year clinical history. Many clinical and basic scientific studies have been performed with the result that allografting is now part of the cartilage repair paradigm for the treatment of chondral or osteochondral lesions. In the knee joint, allografting has also been successfully used in complex joint reconstruction for the treatment of osteonecrosis, fracture malunion and selected cases of osteoarthritis. Unlike many other cartilage repair techniques, osteochondral allografts have the ability to restore mature, hyaline articular cartilage to the affected area. By virtue of their composite structure (cartilage and bone) allografts also can restore diseased or damaged bone often present in large or complex lesions. Surgical techniques of allografting are relatively straightforward and many clinical studies have shown excellent results. Osteochondral allografts do present the surgeon with unique and important differences from other cartilage repair techniques, such as limited allograft tissue availability and the potential INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALfor transmission CARTILAGE of infectious disease from the graftJOINT or immunologic PRESERVATION response by the recipient. Ongoing investigations continue to clarify the indications, surgical techniques, and clinical outcomes of fresh osteochondral allografts. REGENERATION & SOCIETY REGENERATION & SOCIETY 7.3 A One-Step treatment for Chondral and Osteochondral Knee Defects: Clinical Results of a Biomimetic Scaffold Implantation at 10 Years of Follow-Up – Elizaveta Kon (IT) There is an increasing interest in the role of subchondral bone. In fact, we know that structural changes to the subchondral bone are strictly involved in the pathogenic process of the chondral surface. At the same time, cartilage defects, even when focal, can lead to changes of the underlying bone structure. Therefore, an important effort has been made in order to create a biomaterial, which could help to address this issue. The ideal biomaterial in orthopaedics is an implant which should mimic biology, architecture, and functional properties of native tissue, thereby favouring cell infiltration, attachment, proliferation, and differentiation into the new healing tissue. This is in fact an arduous challenge, as bone and cartilage present intrinsic different nature and regenerative potential. Consequently, a new bioengineered strategy has been developed, which consid- ers these structures as constituents of one unit, called “osteochondral unit”, where distinct layers address both cartilage and bone tissue. In our study, we focused on the clinical and MRI evaluation of one of these scaffolds. The patients included in the study were complaining of clinical symptoms, such as knee pain, swelling, in association with grade III-IV chondral and osteochondral lesion or osteochondritis dissecans. 82 patients were enrolled, 79 of them were evaluated at 12 and 24 months, and 24 were re-evaluated at 10 years follow-up. In total, 82 defects sites were treated, using an osteochondral biomimetic scaffold, called Maioregen. Such device has a porous 3D composite structure, mimicking the anatomy of the

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three different layers that form the previously cited osteochondralINTERNATIONAL unit. The CARTILAGE deeperJOINT PRESERVATIONmineral layer is INTERNATIONALmade CARTILAGEof magnesium-JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY hydroxyapatite, nucleated onto collagen fibres and with magnesium ions add-on. Intermediate layer is a combination of Type I collagen and Mg-HA, whereas the superficial layer is made solely of Type I collagen, with a smooth surface. At the time of surgery, this scaffold was positioned in a lodge 8 mm deep made through sclerotic subchondral bone, in the site of the defect. At 24 months, IKDC subjective score increased (76.2 +\- 19.6) when compared to baseline evaluation (47.4 +\- 17.1), and similarly did the IKDC objective score, changing from 72.1% at baseline to 88.6% at 12 months follow-up. In total, INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION 65 patients (82.2%) reported improvement at 24 months follow-up. Among& JOINT PRESERVATION these, 24 SOCIETY patients were re-evaluated& JOINT PRESERVATION at 10 SOCIETY years follow-up. The improvement reached at 24 months remained stable over time up to 10 years (P < 0.0005). This improvement has slowly been seen also with MRI, even though the presence of persistent abnormalities did not correlate with the clinical picture. In conclusion, the implantation of this biomimetic scaffold to treat chondral and osteochondral knee defects proved to be effective, in terms of clinical outcomes, despite the correlation with MRI findings. International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society References 1 Pape D, Filardo G, Kon E, van Dijk CN, Madry H. Disease specific clinical problems associated with the subchondral bone. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):448–62. 1 Filardo G, Kon E, Roffi A, Di Martino A, Marcacci M. Scaffold based repair for cartilage healing: a systematic review and techni- calnote. Arthroscopy. 2013;29(1):174–86. 1 Sherwood JK, Riley SL, Palazzolo R, Brown SC, Monkhouse DC, Coates M, Griffith LG, et al. A three-dimensional osteochondral- composite scaffold for articular cartilage repair. Biomaterials. 2002;23(24):4739–51.

7.4 Bone Graft and Cartilage Repair – Jakob Roland In this abstract we deal with two different applications of Bone Grafts in osteochondral (A) and chondral lesions of the knee (B).

A. The logic of Revising a traumatic osteochondral lesion or an atraumatic Osteochondritis dissecans, usually located in the femoro-tibial and only rarely in the femoro-patellar joint is to debride the defect by removing the thickened sclerotic zone within the lesion, drilling deeply to gain a sufficient connection to the underlying cancellous bone and to fill up the defect by finger pressing fresh cancellous bone graft to the level of the neighbouring cartilage by recreating convexity of the condyle and then to suture a Collagen I/III membrane (Chondro-Gide, Geistlich, Biomaterials, Switzerland) on top and around the defect. This procedure corresponds to the House and Hold Principle, a term originally established by L. Johnson, which protects the clot against its loss through shear forces (“Hold”) and contains the MSC’s located on the trabecula of the cancellous bone and offers an environment for adhesion, proliferation and differentiation of MSC’s (“House”). Because in bigger lesions, we observe with a cancellous bone graft alone some tendency of shrinking and loss of volume within the grafted area we have since 2005 filled the defect with a 1:1 mixture of cancellous bone and granules of 2-3 mm in diameter of HA (ORTHOSS, Geistlich Biomaterials, Switzerland) that get integrated without any problem in the osseous reconstruction and diminish the shrinking tendency. This technique has proven of an advantage mainly also in osteochondral lesions of the talar dome. Regarding the articular surface reconstruction, question arises how good this is possible when doing nothing but covering the defect with a Collagen I/III membrane (Chondro-Gide, Geistlich, Biomaterials, Switzerland). We usually observe formation of a thick fibrocartilage with hyaline-like areas.B. Fol- lowing the good experience with this policy (Kusano) we have since a few years extended this principle to chronic pure cartilage lesions with sclerotic underlying bone that acts as a barrier for drilling or microfracturing. We are convinced that the Sub-Chondral Plate should be crossed-the way we have named it Osteochondroisation.

A number of more recent innovative, acellular, third generation articular cartilage repair techniques make use of the principle by which what appears to be a purely articular cartilage lesion is transformed into an osteochondral lesion to enable solid implant fixation. Although the subchondral plate was long considered a structure that should remain untouched in treating these lesions, this no longer appears to be supported among proponents of implant use. In fact, classical mosaicplasty for femoral condyle lesions which uses a similar principle in which the articular cartilage defect is further deepened creating an osteochondral “hole” which is then filled by an articular cartilage capped osteochondral graft. One disadvantage among several others of this technique however is the cyst formation at the base of the plugs that may be heat induced during osteochondral graft retrieval with consequent thermal damage. For several years now we have carefully applied a new but hopefully logic reasoning to the treatment of pure chronic articular cartilage lesions. We contend that any method to apply mesenchymal stem cells is fruitless if the recipient area displays chronic or osteoarthritic changes such as a thickened subchondral plate. For lesions like this attempting to recruit mesenchymal stem cells by picking or drilling methods alone would be less than effective. For this reason, we decided to remove the thickened subchondral plate and the underlying cancellous bone to a depth of 3-4 mm beneath it and to drill 1-2 cm deep, 1.1-1.5 INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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mm diameter tunnels. Then the lesion is covered by suture fixation of a collagen I/III matrix (Chondro-Gide, Geistlich Biomaterials, Switzerland) along the border of the intact articular cartilage. This suturing method enabled creation of a “kangaroo pocket” opening anteriorly or at some corner of the lesion for graft insertion. After retrieving fresh cancellous bone right before insertion, a surgical mortar and pestle is used to ground it into a paste prior to immediate insertion in the defect. We hypothesize that the transplanted fresh cancellous bone and the mesenchymal stem cells it carries within follows the same inherent mechanism as above to differentiate into osteoblastic and chondroblastic activation to generate separate rows of subchondral bone or articular cartilage tissue. According to Giannoudis et al. 1 gr of cancellous International Cartilage Regeneration & Joint Preservation Society Internationalbone corresponds toCartilage 45 ml of iliac crest aspirate. According Regeneration to Sakaguchi et al., trabecular bone samples contain similar numbers of nucleated cells relative to bone marrow aspirates of the same size, but the trabecular bone samples are able & Jointto form significantly Preservation more colonies, suggesting the presence Societyof more MSCs. Following the spontaneous mechanism of differentiation within the cancellous bone graft, cells at the osseous level take the osteoblast pathway, while cells on the surface migrate in the Chondro-Gide matrix to take the chondroblast pathway. Hypothetically, we believe that rather than having to acquire cumbersome and expensive marrow cell aspirates it may be more feasible and economic to use fresh cancellous bone trabecula as the MSC’s source in the way described. Clinical experience has shown how the “resected subchondral plate” reforms at a deeper located level in an undulated pattern and how the surface is filled with fibrocartilage. It is too early to conclude on this specific new technique proposed for discussion here! But it could be a logic consequence of our excellent AMIC results where fresh cancellous bone has been utilised and experience of L. Johnson’s Material.

Fig.1 Principle of Osteochondroisation

INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION Fig.REGENERATION 2 Centrally located patellar defect treated by osteochondroisationSOCIETY showing the filling over 3 years follow up (Case of Dr. R. Martin REGENERATION & SOCIETY at CHUV, Lausanne, CH) & References: 1. Baboolal TG, Boxall SA, El-Sherbiny YM, Moseley TA, Cuthbert RJ, Giannoudis PV, et al. Multipotential stromal cell abundance in cellular bone allograft: comparison with fresh age-matched iliac crest bone and bone marrow aspirate. Regen Med. 2014;9(5):593-607. PMID: 24617969 2. Johnson LL, DeLano MC, Spector M, Jeng L, Pittsley A, Gottschalk A. The Biological Response following Autogenous Bone Graft- ing for Large-Volume Defects of the Knee: Index Surgery through 12 to 21 Years’ Follow-up. Cartilage. 2012 Jan;3(1):86-99. PMID: 26069622 3. Kusano T, Jakob RP, Gautier E, Magnussen RA, Hoogewoud H, Jacobi M. Treatment of isolated chondral and osteochondral defects in the knee by autologous matrix-induced chondrogenesis (AMIC). Knee Surg Sports Traumatol Arthrosc. 2012 Oct;20(10):2109-15. PMID: 22198419 4. Martin R., Jakob.R.P. Osteo-Chondroisation a clinical working hypothesis for chronic, purely cartilaginous defects in the knee. Abstract ISAKOS Congress Shanghai, 2017 5. Sakaguchi Y. Sekiya I. Yagishita K. Ichinose S. Shinomiya K. Muneta T. Suspended cells from trabecular bone by collagenase digestion become virtually identical to mesenchymal stem cells obtained from marrow aspirates. Blood.2004; 104:2728

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7.5 A Novel Aragonite-Based Scaffold For The TreatmentINTERNATIONAL CARTILAGE Of OsteochondralJOINT PRESERVATION LesionsINTERNATIONAL CARTILAGE Of TheJOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Knee: Prospective Study At 2 Years Of Follow Up – Elizaveta Kon (IT)

BACKGROUND: The peculiar characteristics of cartilage, which is an avascular tissue, prevent its spontaneous healing once the defect is established. Many different techniques have been proposed in the last years with the aim to restore the continuity of chon- INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION dral tissue; however, with their advantages and disadvantages, none& JOINTof them PRESERVATION can SOCIETYbe identified as the ideal& JOINT PRESERVATION treatment. SOCIETY

PURPOSE: Aim of this study is to evaluate the clinical and MRI outcomes after the implantation of a nanostructured cell free aragonite-based scaffold up to 2 years of follow-up. International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society METHODS: 186 consecutive patients who had up to 3 chondral/osteochondral lesions (average defect size 2 ± 1.3 cm(2)), graded II or III on the International Cartilage Repair Society (ICRS) scale, were enrolled and treated with the implantation of a three-dimensional aragonite based scaffold. Patients were prospectively evaluated by subjective Interna- tional Knee Documentation Committee (IKDC), Tegner, Lysholm and KOOS Scores preoperatively and at 6, 12, 18 and 24-months follow-up. An MRI was also performed at the 4 follow-up times to assess the amount of defect filled by regenerated cartilage.

RESULTS: A statistically significant improvement in each of the clinical scores used was recorded from basal level to the 24 months’ follow-up. At the 2-year follow-up, the IKDC subjective score and the Tegner score significantly statistically improved (p < 0.0005)

Despite the significant improvements after surgery the Tegner score at 24 months follow up remained significantly inferior to the pre-injury level (p < 0.0005). For what concerns Lysholm score, the patients reported a significative improvement from the pre-operative baseline evaluation to the 24 months and the same result was obtained for every subscale of the KOOS scale.

CONCLUSION: This biomimetic osteochondral scaffold seems to be a valid treatment option for knee chondral and osteochondral lesions, showing good clinical and radiological outcome at 2-year follow-up. The clinical improvement was not influenced by the presence of concurrent knee osteoarthritis. E. Kon, G. Filardo, D. Robinson, J. A. Eisman, A. Levy, K. Zaslav, J. Shani and N. Altschuler, “Osteochondral regeneration using a novel aragonite-hyaluronate bi-phasic scaffold in a goat model,” Knee Surg Sports Traumatol Arthrosc, no. 22, p. 1452–1464, 2014. G. Filardo, E. Kon, A. Roffi, D. M. A and M. Marcacci, “Scaffold-Based Repair for Cartilage Healing: A Systematic Review and Technical Note,” Arthroscopy, vol. 29, no. 1, pp. 174-186, 2013.

Session 8 – Subchondral Oedema

8.2 Subchondral Oedema-Conservative Treatment – Massimo Berruto (IT)

INTRODUCTION: Many conservative solutions have been proposed for the treatment of BMES (Bone Marrow Edema Syndrome) such as: • Physiotherapy • Hyperbaric Therapy • Shockwave Therapy • Pulsed Electromagnetic fields • Ozone Therapy • Pharmacological treatment

Efficacy of Hyperbaric and Shockwave therapy need to be demonstrated (1-5). Only some studies have been published with a limited cohort of patients and in different anatomical areas .Only one study was published about the treatment with pulsed magnetic fields of femoral head osteonecrosis with good results and hip preservation in 94% when stage of osteonecrosis was between 1 and 2 (6). INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

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Pharmacological treatment is considered now the most effective for BMES. Three different types of pharmacological approach have been described in literature: • Prostacyclin derivates • Bisphosphonates • TNF Inhibitors

Prostacycline derivates International Cartilage Regeneration & Joint Preservation Society InternationalProstaglandins and Cartilage analogues have an important role Regenerationin inflammatory responses and cell differentiation. The effect of these molecules in the treatment of BMES is not cleared yet. Some studies reported their positive effects improving bone regeneration on a cellular or systemic level and microcircula- & Jointtion in the affected Preservation area, normalizing the intraosseous pressure Society and decreasing leukotrienes and cytokines release (7, 8). Mayerhoefer (9) comparing Iloprost and tramadol reported faster BME resolution and less subchondral stress fractures after iloprost treatment. In another study (10) the same author reported a reduction in SSF was observed in 100% of patients treated with iloprost in comparison to the ones treated with tramadol. Better results were reported by Claßen (11) and Jager (8) in treating early stages of BML without ON, while worst results were observed in patients graded ARCO-stadium 3 or 4. The possible side effects reported using these molecules are: headaches, nausea, temporary pain increase, flush or local erythema (12).

Bisphosphonates Bisphosphonates act as inhibitors in the BMES pathogenic pathway. These molecules lead to a reduction of the pro-inflammatory cytokines, decrease the leukocytes infiltration therefore reducing pain and normalize the altered vascular microcirculation permeability. Different Bisphosphonates were proposed during the last decades with variable results: alendronate (13, 14), clodronate (15), pamidronate (16), ibandronate(17-19), neridronate (20, 21) and zoledronate (22). Despite this evidence, at the current time the only molecule that does not present an off-label indication to the treatment of the BME is rep- resented by the neridronate. Varenna et al (20), in a multi-centre randomized double-blind place controlled study, evaluated the results of the neridronate treatment in 82 patients with CPRS who underwent 4 infusions over 10 days. A significant improvement in life quality and pain was observed during the first 40 days after the treatment in the neridronate group. A comparable trend was observed in the control group after the blind was removed and patients received thebisphosphonate therapy. In a further study randomized double-blind placebo-controlled study (21), the same author reported the results of the neridronate therapy in 96 patients with acute painful knee osteoarthritis. A significant improvement in VAS score was observed both at last infusion and last-FU evaluation, while placebo group wasn’t improved. In this group 72% of patients required long-term NSAID therapy versus 12.9% in neridronate group. Magnetic resonance WORMS score improved at 2 months in the neridronate group only. In consideration of both clinical and imaging scores improvement, the good tolerability profile and the in-lab indication, neridronate could represent the best bisphosphonates molecule in the treatment of BMEs.

TNF inhibitors INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALTNF inhibitors CARTILAGE are currently used in the treatmentJOINT of many autoimmune PRESERVATION inflammatory diseases. Despite this fact, the current literature lacks data related to their use in the of BMEs. Anandarajah (23) reported a significant reduction REGENERATION SOCIETY of REGENERATIONthe BME in patients with psoriatic arthritis andSOCIETY similar results were reported by Hirose (24) analysing a group of & patients with rheumatoid arthritis. Considering& spondylitis, a case report was published by Marzo-Hortega (25) evi- dencing promising results in BME resolution. Notwithstanding this evidence there is still a lack of studies considering patients not affected by inflammatory diseases, therefore the indication for these molecules seem right now limited in the daily practice, even in consideration of the costs of these drugs.

CONCLUSION: Different molecules have been proposed in the treatment of BME during the last decades. Prostacycline derivates could provide good clinical and radiological results, nevertheless the considerable side effects and the cost of these molecules could limit their use in daily practice. TNF inhibitors studies are limited to the autoimmune inflammatory diseases, therefore further study is required considering healthy patients. The high cost of these molecules furthermore limits their use in the clinical routine. Bisphosphonates were extensively studied in literature and different study group proposed their pharmacological protocol. At the current time the only bisphosphonates which present an in-label indication to the treatment of BME are the neridronate. This molecule presents a good tolerability profile a limited cost. Improvements in clinical scores and pain can be observed as soon as the end of the last infusion at 10 days from the beginning of the therapy. BME treatmentcould reduce patients reported symptoms, prevent the SSF? Progression and the possible evolution towards osteonecrosis and joint replacement.

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1. Bosco G, Vezzani G, Mrakic Sposta S, Rizzato A, Enten G, Abou-Samra A, et al. Hyperbaric oxygen therapy ameliorates osteonecrosis INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION in patients by modulating inflammation and oxidative stress. J Enzyme Inhib REGENERATIONMed Chem.& SOCIETY2018;33(1):1501- 5. REGENERATION & SOCIETY 2. Capone A, Podda D, Ennas F, Iesu C, Casciu L, Civinini R. Hyperbaric oxygen therapy for transient bone marrow oedema syndrome of the hip. Hip Int. 2011;21(2):211-6. 3. Algarni AD, Al Moallem HM. Clinical and Radiological Outcomes of Extracorporeal Shock Wave Therapy in Early-Stage Femoral Head Osteonecrosis. Adv Orthop. 2018;2018:7410246. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION 4. Kang S, Gao F, Han J, Mao T, Sun W, Wang B, et al. Extracorporeal shock& JOINTwave PRESERVATION treatment SOCIETY can normalize painful bone& JOINT PRESERVATION marrow SOCIETY edema in knee osteoarthritis: A comparative historical cohort study. Medicine (Baltimore). 2018;97(5):e9796. 5. Zhang Q, Liu L, Sun W, Gao F, Cheng L, Li Z. Extracorporeal shockwave therapy in osteonecrosis of femoral head: A systematic review of now available clinical evidences. Medicine (Baltimore). 2017;96(4):e5897. International Cartilage Regeneration 6. Massari L, Fini M, Cadossi R, Setti S, Traina GC. Biophysical stimulation with pulsed electromagnetic fields in osteonecrosis &of the femoral I NTERNATIONAL C ARTILAGE R EGENERATION head. J Bone Joint Surg Am. 2006;88 Suppl 3:56-60. & JOINT PRESERVATION S OCIETY Joint Preservation Society 7. Eriksen EF. Treatment of bone marrow lesions (bone marrow edema). Bonekey Rep. 2015;4:755. 8. Jager M, Tillmann FP, Thornhill TS, Mahmoudi M, Blondin D, Hetzel GR, et al. Rationale for prostaglandin I2 in bone marrow oedema--from theory to application. Arthritis Res Ther. 2008;10(5):R120. 9. Mayerhoefer ME, Kramer J, Breitenseher MJ, Norden C, Vakil-Adli A, Hofmann S, et al. Short-term outcome of painful bone marrow oedema of the knee following oral treatment with iloprost or tramadol: results of an exploratory phase II study of 41 patients. Rheumatology (Oxford). 2007;46(9):1460-5. 10. Mayerhoefer ME, Kramer J, Breitenseher MJ, Norden C, Vakil-Adli A, Hofmann S, et al. MRI-demonstrated outcome of subchondral stress fractures of the knee after treatment with iloprost or tramadol: observations in 14 patients. Clin J Sport Med. 2008;18(4):358-62. 11. Classen T, Becker A, Landgraeber S, Haversath M, Li X, Zilkens C, et al. Long-term Clinical Results after Iloprost Treatment for Bone Marrow Edema and Avascular Necrosis. Orthop Rev (Pavia). 2016;8(1):6150. 12. Baier C, Schaumburger J, Gotz J, Heers G, Schmidt T, Grifka J, et al. Bisphosphonates or prostacyclin in the treatment of bone-marrow oedema syndrome of the knee and foot. Rheumatol Int. 2013;33(6):1397-402. 13. Agarwala S, Jain D, Joshi VR, Sule A. Efficacy of alendronate, a bisphosphonate, in the treatment of AVN of the hip. A prospective open- label study. Rheumatology (Oxford). 2005;44(3):352-9. 14. Agarwala S, Shah SB. Ten-year follow-up of avascular necrosis of femoral head treated with alendronate for 3 years. J Arthroplasty. 2011;26 ( 7 ):1128 - 3 4 . 15. Varenna M, Zucchi F, Ghiringhelli D, Binelli L, Bevilacqua M, Bettica P, et al. Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. J Rheumatol. 2000;27(6):1477-83. 16. Varenna M, Zucchi F, Binelli L, Failoni S, Gallazzi M, Sinigaglia L. Intravenous pamidronate in the treatment of transient osteoporosis of the hip. Bone. 2002;31(1):96-101. 17. Bartl C, Imhoff A, Bartl R. Treatment of bone marrow edema syndrome with intravenous ibandronate. Arch Orthop Trauma Surg. 2012;132(12):1781-8. 18. Meier C, Kraenzlin C, Friederich NF, Wischer T, Grize L, Meier CR, et al. Effect of ibandronate on spontaneous osteonecrosis of the knee: a randomized, double-blind, placebo-controlled trial. Osteoporos Int. 2014;25(1):359-66. 19. Ringe JD, Dorst A, Faber H. Effective and rapid treatment of painful localized transient osteoporosis (bone marrow edema) with intravenous ibandronate. Osteoporos Int. 2005;16(12):2063-8. 20. Varenna M, Adami S, Rossini M, Gatti D, Idolazzi L, Zucchi F, et al. Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study. Rheumatology (Oxford). 2013;52(3):534-42. 21. Varenna M, Zucchi F, Failoni S, Becciolini A, Berruto M. Intravenous neridronate in the treatment of acute painful knee osteoarthritis: a randomized controlled study. Rheumatology (Oxford). 2015;54(10):1826-32. 22. Laslett LL, Dore DA, Quinn SJ, Boon P, Ryan E, Winzenberg TM, et al. Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial. Ann Rheum Dis. 2012;71(8):1322-8. 23. Anandarajah AP, Schwarz EM, Totterman S, Monu J, Feng CY, Shao T, et al. The effect of etanercept on osteoclast precursor frequency and enhancing bone marrow oedema in patients with psoriatic arthritis. Ann Rheum Dis. 2008;67(3):296-301. 24. Hirose W, Nishikawa K, Hirose M, Nanki T, Sugimoto H. Response of early active rheumatoid arthritis to tumor necrosis factor inhibitors: evaluation by magnetic resonance imaging. Mod Rheumatol. 2009;19(1):20-6. 25. Marzo-Ortega H, McGonagle D, O’Connor P, Emery P. Efficacy of etanercept in the treatment of the entheseal pathology in resistant spondylarthropathy: a clinical and agnetic resonance imaging study. Arthritis Rheum. 2001; 44(9):2112-7. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

EXTENDED ABSTRACTS

8.3 Subchondroplasty: Indications and Surgical Technique – PRO – Marco Demange (BR) Subchondral bone fracture associated with bone marrow edema syndrome are related to knee pain and progression of osteoarthritis. Bone marrow edema is a generic term classically used to describe the high-signal intensity alterations detected on magnetic resonance fluid-sensitive sequence. Subchondral bone fracture is an insufficiency fracture due to overload above the “envelope of function” causing structural trabecular bone failure. Spontaneous osteonecrosis of the knee described by Ahlback et al. in 1968 is currently believed to represent a subchondral bone fracture. Recently, several studies are focusing on the correlation of subchondral bone problems and articular cartilage degeneration. International Cartilage Regeneration & Joint Preservation Society InternationalIt may occur spontaneously, Cartilage after meniscal tears, afterRegeneration meniscal root-tear or surgical meniscectomy. Percutaneous calcium phosphate injection procedure is technically feasible to approach these orthopaedic problems. The calcium phosphate bone substitute has to have adequate properties including being injectable, flowable and producing en- & Jointdothermic reaction Preservation in the hardening process. The procedure Society isafe and technically easy to perform. The procedure is effective in pain reduction in the short and mid-term. There still no data regarding long term results.

MRI demonstranting subchondral bone fracture Percutaneous calcium phosphate injection procedure

1 Xu L, Hayashi D, Roemer FW, et al. Magnetic resonance imaging of subchondral bone marrow lesions in association with osteoarthritis. Semin Arthritis Rheum 2012;42(2):105-18 2 Bonadio MB, Filho AGO, Helito CP, et al. Bone Marrow Lesion: Image, Clinical Presentation, and Treatment. Magn Reson Insights 2017;10:1178623X17703382. 3 Cohen SB, Sharkey PF. Subchondroplasty for Treating Bone Marrow Lesions. J Knee Surg 2016;29(7):555-63. 4 Cohen SB, Sharkey PF. Surgical Treatment of Osteoarthritis Pain Related to Subchondral Bone Defects or Bone Marrow Le- sions: Subchondroplasty. Techniques in Knee Surgery 2012;11(4):170-75.

8.4 Subchondroplasty: Indications and Surgical Technique – CON – Vladimir Bobic (UK) We may have embraced the entirely new treatment concept which is possibly based on some assumptions. Subchon- droplasty is probably indicated mainly for the treatment of subchondral cysts and cavities, rather than various bone marrow oedema conditions, most of which do not seem to need surgical treatment, as they get better given time. INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALThe aetiology CARTILAGE of various conditions, known genericallyJOINT as “bone PRESERVATIONmarrow oedema” (or perhaps more correctly “bone marrow lesions”), is very different and it is still poorly understood and therefore it is difficult to decide when the surgi- REGENERATION & SOCIETY calREGENERATION treatment is necessary and what is the& most appropriateSOCIETY treatment. Bone marrow oedema, as a metabolic (possibly vascular remodelling rather than degenerative) process does not seem to lack bone, and therefore injecting bone substitute is probably not the best ingredient. To the contrary, injecting bone paste may clog subchondral microtrabecular bone spaces and may slow down or prevent subchondral repair and remodelling by blocking neurovascular pathways. It is difficult to accept that patients “should expect 3 days of severe pain” postoperatively, but even if we do this is probably not acceptable, because injected and cured bone substitute may increase intra-osseous pressure (which is already higher than normal, especially in SONK-like conditions, which are very painful to start with) and block metabolic (vascular) pathways. Unsurprisingly, in some cases, biopsy of the subchondroplasty area treated with on calcium phosphate paste has shown necrotic or nonviable bone a few years postoperatively.

However, long-lasting symptomatic bone marrow oedema and SONK-like lesions, may benefit biologically and struc- turally from the surgical treatment with more biologically desirable ingredient, such as autologous bone marrow aspirate, delivered directly to the intra-osseous area affected with bone marrow oedema. This is where subchondroplasty, using autologous bone marrow aspirate, autologous stem cells or even autologous PRP gets entirely new biological meaning and possibly becomes more useful therapeutically.

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International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration OPTIONAL HANDS-ON WORKSHOP & Joint Preservation Society 67

Workshop – Osteotomies INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY Osteotomy Planning – Ronald van Heerwaarden (NL) In this presentation the principles of osteotomy planning are presented. The importance of deformity analysis before planning and the definition of the aims of correction – which are different in patients depending on the cartilage status, additional lesions and history of previous treatments are discussed. The correlation of clinical investigation and INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION results of deformity analysis and the final steps of planning for correction& JOINT PRESERVATION and preparationSOCIETY for surgery& JOINT are PRESERVATION highlighted. SOCIETY

International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society

References 1 Miniaci A, Ballmer FT, Ballmer PT, et al (1989). Proximal tibial osteotomy. A new fixation device. Clin Orthop Relat Res: 246; 250-9. 2 Paley D, Tetsworth K (1992). Mechanical axis deviation of the lower limbs. Preoperative planning of uniapical angular deformities of the tibia or femur. Clin Orthop Relat Res; 280: 48–64. 3 Lobenhoffer P, Van Heerwaarden RJ, Staubli AE, Jakob RP, eds, Osteotomies around the knee: indications-planning-surgical techniques using plate fixators. Davos, AO Publishing, 2008. 4 R.J. van Heerwaarden, J.W. Mast, C.A.J. Paccola (2008) Diagnostics and planning of deformity correction: formation of a surgical plan. In: R.K. Marti and R.J. van Heerwaarden (eds.) Osteotomies for posttraumatic deformities. Georg Thieme Verlag, Stuttgart, New York, pp: 33-55.

Patello-Femoral Osteotomies – Martyn Snow (UK) When treating patients with patellofemoral chondral lesions it is important to identify prior to any potential surgical intervention the presence of any concomitant anatomical mal-alignment. Standard pre-operative clinical assessment should be supported with the use of appropriate imaging. This will usually include a MRI, a rotational CT scan of the lower limbs with TTTG assessment and plain x-rays (+/- long leg alignment films). Common anatomical variations that may need correcting include excessive knee valgus, increased femoral anteversion, tibial torsion, patella alta and lateralisation of the tibial tubercle. Antero-medialisation of the tibial tubercle can also be considered in patients with mainly lateral patellofemoral osteoarthritis in order to try and delay the need for joint replacement. The aim of this talk is to review the assessment of patients with patellofemoral chondral pathology and discuss the indications for potential corrective osteotomy. Surgical techniques will be discussed, and tips and tricks shared. The evidence for undertaking corrective osteotomy in association with all patellofemoral cartilage repair will be debated. INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

OPTIONAL HANDS-ON WORKSHOP

Workshop – Meniscal Transplant and Stem Cells

Bone Marrow Aspiration-Technique and Optimisation – Dzihan Abazovic (MNE) Emergency Medicine Centre of Montenegro, Podgorica, Montenegro Military Medical Academy, Belgrade, Serbia Medical faculty, University of Defence, Belgrade, Serbia Orthopedic and Traumatology Clinic, Clinical Center of Serbia, Belgrade, Serbia International Cartilage Regeneration & Joint Preservation Society InternationalClinic for Paediatric Cartilage Surgery, Institute for child and adolescentRegeneration health care Vojvodina, Novi Sad, Serbia Keywords: Bone marrow, stem cells, phenotype, quality control

& JointINTRODUCTION: Preservation Society Stem cell therapies are often used in different orthopaedic indications. Bone marrow and fat tissue are most commonly used as autologous therapy in clinical practice. Collecting the stem cells from different sources can result in different number and phenotype of targeted cells.

OBJECTIVES: To show the quantity and phenotype of bone marrow aspirate concentrate harvested from different donor site.

METHODS: Iliac creast is most common used for Bone Marrow harvesting. Common sources are also vertebral body, talus, humeral head etc. Each source show high variability in cell count and phenotype. Latest data showed that different phenotypes show various potential in regeneration and reparation of targeted tissue. Our current research is aligned with this hypothesis.

RESULTS: We collected bone marrow from 95 patients, man and women (tibia 45, iliac creast 50). The mean volume was 126mL (88-198). Viability of the obtained cells was 98.3%, with average TNC 116.7x109/L. Average absolute number of the CD271+CD90+CD45-CD34- cells was enriched six times in BMAC samples in comparison with the initial bone marrow harvest sample.

CONCLUSIONS: The bone marrow collected from proximal tibia and iliac creast show high variability in numbers and phenotype.

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INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY

International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration & Joint Preservation Society 69

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INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY

AN FDA-APPROVED OPTION FOR PATIENTS WITH ARTICULAR CARTILAGE DEFECTS OF THE KNEE AVAILABLE ONLY IN THE U.S.

THOUGHT AUTOLOGOUS International Cartilage Regeneration & Joint Preservation Society InternationalLEADER Cartilage AND Regeneration CHONDROCYTE &INNOVATOR Joint Preservation Society DELIVERY, SIMPLIFIED

autologous cultured chondrocytes on porcine collagen membrane

MACI builds on over 20 years success with Articular Cartilage Implantation (ACI)1 Utilizing a unique biocompatible membrane, MACI offers potential benefits over traditional ACI through minimal incision, simplified delivery, and suture-free fixation for the treatment of articular cartilage defects of the knee. FRESH OCA PRESUTURED DISTAL CORES TENDONS TIBIA INDICATION IMPORTANT SAFETY INFORMATION ⊲ Provide intact hyaline cartilage, ⊲ Excellent option for any ⊲ Restores glenoid with live MACI® (autologous cultured chondrocytes on porcine collagen MACI is contraindicated in patients with a known history of hypersensitivity to gentamicin, other aminoglycosides, or products viable chondrocytes, and ligament repair procedure cartilage and strong bone membrane) is an autologous cellularized scaffold product that of porcine or bovine origin. MACI is also contraindicated for patients with severe osteoarthritis of the knee, inflammatory subchondrawl bone is indicated for the repair of single or multiple symptomatic, arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders. MACI is also not indicated for ⊲ ⊲ Eliminates time to assemble No size match required full-thickness cartilage defects of the adult knee, with or use in patients who have undergone prior knee surgery in the past 6 months, excluding surgery to procure a biopsy or a ⊲ Single step treatment with no the construct without bone involvement. concomitant procedure to prepare the knee for a MACI implant. ⊲ Eliminates morbidity of patient size matching required MACI is intended for autologous use and must only be MACI is contraindicated in patients who are unable to follow a physician-prescribed post-surgical rehabilitation program. ⊲ Consistent graft quality autograft latarjet administered to the patient for whom it was manufactured. The The safety of MACI in patients with malignancy in the area of cartilage biopsy or implant is unknown. Expansion of present implantation of MACI is to be performed via an arthrotomy to INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL⊲ A great alternative CARTILAGE for focal JOINT PRESERVATION malignant or dysplastic cells during the culturing process or implantation is possible. the knee joint under sterile conditions. Patients undergoing procedures associated with MACI are not routinely tested for transmissible infectious diseases. A cartilage lesions of 20 mm or less The amount of MACI administered is dependent upon the biopsy and MACI implant may carry the risk of transmitting infectious diseases to healthcare providers handling the tissue. REGENERATION SOCIETY 2 REGENERATION SOCIETY & size (surface in cm ) of the cartilage defect. The implantation Universal precautions should be employed when handling the biopsy samples and the MACI product. & membrane is trimmed by the treating surgeon to the size and Final sterility test results are not available at the time of shipping. In the case of positive sterility results, health care provider(s) shape of the defect, to ensure the damaged area is completely will be contacted. covered, and implanted cell-side down. To create a favorable environment for healing, concomitant pathologies that include meniscal pathology, cruciate ligament Our mission is to improve quality of life through Limitations of Use instability and joint misalignment, must be addressed prior to or concurrent with the implantation of MACI. Effectiveness of MACI in joints other than the knee has not Local treatment guidelines regarding the use of thromboprophylaxis and antibiotic prophylaxis around orthopaedic surgery innovative solutions for allograft joint repair. been established. should be followed. Use in patients with local inflammations or active infections in the bone, joint, and surrounding soft tissue Safety and effectiveness of MACI in patients over the age of 55 should be temporarily deferred until documented recovery. years have not been established. The MACI implant is not recommended during pregnancy. For implantations post-pregnancy, the safety of breast feeding to infant has not been determined. Use of MACI in pediatric patients (younger than 18 years of age) or patients over 65 years of age has not been established. DISCOVER HOW JRF ORTHO The most frequently occurring adverse reactions reported for MACI (≥5%) were arthralgia, tendonitis, back pain, joint swelling, CAN MOVE YOU. and joint effusion. beyond movement Serious adverse reactions reported for MACI were arthralgia, cartilage injury, meniscus injury, treatment failure, and osteoarthritis. 877-255-6727 JRFORTHO.org For more information, please see Highlights of Prescribing Information about MACI, or visit MACI.com 1. Saris D, Price A, Widuchowski W, et al. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Two-year follow-up of a prospective randomized trial. Am J Sports Med. 2014;42(6):1384-94. MACI® is a registered trademark of Vericel Corporation. ©2018 Vericel Corporation. All rights reserved. PP.US.MAC.0261

INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY

AN FDA-APPROVED OPTION FOR PATIENTS WITH ARTICULAR CARTILAGE DEFECTS OF THE KNEE AVAILABLE ONLY IN THE U.S.

International Cartilage Regeneration & Joint Preservation Society International Cartilage Regeneration & Joint Preservation Society 71

INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONAL CARTILAGE JOINT PRESERVATION REGENERATION & SOCIETY REGENERATION & SOCIETY

AUTOLOGOUS INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE REGENERATION CHONDROCYTE & JOINT PRESERVATION SOCIETY & JOINT PRESERVATION SOCIETY DELIVERY, SIMPLIFIED International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society

autologous cultured chondrocytes on porcine collagen membrane

INDICATION IMPORTANT SAFETY INFORMATION MACI® (autologous cultured chondrocytes on porcine collagen MACI is contraindicated in patients with a known history of hypersensitivity to gentamicin, other aminoglycosides, or products membrane) is an autologous cellularized scaffold product that of porcine or bovine origin. MACI is also contraindicated for patients with severe osteoarthritis of the knee, inflammatory is indicated for the repair of single or multiple symptomatic, arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders. MACI is also not indicated for full-thickness cartilage defects of the adult knee, with or use in patients who have undergone prior knee surgery in the past 6 months, excluding surgery to procure a biopsy or a without bone involvement. concomitant procedure to prepare the knee for a MACI implant. MACI is intended for autologous use and must only be MACI is contraindicated in patients who are unable to follow a physician-prescribed post-surgical rehabilitation program. administered to the patient for whom it was manufactured. The The safety of MACI in patients with malignancy in the area of cartilage biopsy or implant is unknown. Expansion of present implantation of MACI is to be performed via an arthrotomy to malignant or dysplastic cells during the culturing process or implantation is possible. the knee joint under sterile conditions. Patients undergoing procedures associated with MACI are not routinely tested for transmissible infectious diseases. A cartilage The amount of MACI administered is dependent upon the biopsy and MACI implant may carry the risk of transmitting infectious diseases to healthcare providers handling the tissue. size (surface in cm2) of the cartilage defect. The implantation Universal precautions should be employed when handling the biopsy samples and the MACI product. membrane is trimmed by the treating surgeon to the size and Final sterility test results are not available at the time of shipping. In the case of positive sterility results, health care provider(s) shape of the defect, to ensure the damaged area is completely will be contacted. covered, and implanted cell-side down. To create a favorable environment for healing, concomitant pathologies that include meniscal pathology, cruciate ligament Limitations of Use instability and joint misalignment, must be addressed prior to or concurrent with the implantation of MACI. Effectiveness of MACI in joints other than the knee has not Local treatment guidelines regarding the use of thromboprophylaxis and antibiotic prophylaxis around orthopaedic surgery been established. should be followed. Use in patients with local inflammations or active infections in the bone, joint, and surrounding soft tissue Safety and effectiveness of MACI in patients over the age of 55 should be temporarily deferred until documented recovery. years have not been established. The MACI implant is not recommended during pregnancy. For implantations post-pregnancy, the safety of breast feeding to infant has not been determined. Use of MACI in pediatric patients (younger than 18 years of age) or patients over 65 years of age has not been established. The most frequently occurring adverse reactions reported for MACI (≥5%) were arthralgia, tendonitis, back pain, joint swelling, and joint effusion. Serious adverse reactions reported for MACI were arthralgia, cartilage injury, meniscus injury, treatment failure, and osteoarthritis.

For more information, please see Highlights of Prescribing Information about MACI, or visit MACI.com

1. Saris D, Price A, Widuchowski W, et al. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Two-year follow-up of a prospective randomized trial. Am J Sports Med. 2014;42(6):1384-94. MACI® is a registered trademark of Vericel Corporation. ©2018 Vericel Corporation. All rights reserved. PP.US.MAC.0261 INTERNATIONAL CARTILAGE REGENERATION INTERNATIONAL CARTILAGE JOINT PRESERVATION & JOINT PRESERVATION SOCIETY REGENERATION & SOCIETY

70% Improvement in Osteoarthritic Knee Pain at International Cartilage Regeneration & Joint Preservation Society International2 years following Cartilage Regeneration 3,# &a SingleJoint PreservationInjection Society

nSTRIDE® Autologous Protein Solution Kit

Treating Osteoarthritic Knee Pain

Autologous Anti-Inflammatory Therapy for Knee Osteoarthritis nSTRIDE Autologous Protein Solution (APS) was developed after an extensive INTERNATIONAL CARTILAGE JOINT PRESERVATION INTERNATIONALThe nSTRIDE APS Kit is designed CARTILAGE to produce a novel autologous anti- JOINTresearch PRESERVATIONprogram which focused on understanding the osteoarthritic disease inflammatory REGENERATIONtherapy to treat osteoarthritis pain in the knee via a single SOCIETYprocess in the knee and understanding the mode of action that an autologous REGENERATION & SOCIETY intra-articular injection. & blood-based product could have. The nSTRIDE APS Kit is a point of care cell-concentration system designed • Significantly Reduces Pain Associated with Knee OA up to 2 years1-3 to concentrate anti-inflammatory cytokines and anabolic growth factors to • Significantly Improves function in the Knee Joint associated with OA1-3 significantly decrease pain and promote cartilage health. nSTRIDE APS is • Effective for patients with Kellgren and Lawrence stage 2 and 3 following suitable for treating patients who have Kellgren & Lawrence Stage 2 or 3 and a single injection 1-3, who have failed conservative care. • 70% Improvement in Knee Pain at 2 years following a Single Injection3,#

1. Kon E, Engebretsen L , Peter Verdonk P, Nehrer S and Filardo G. “Clinical Outcomes of Knee Osteoarthritis Treated with an Autologous Protein Solution. A 1-year Pilot Double-Blinded Randomized Control Trial. American Journal of Sports Medicine, Oct. 2017. 2. Van Drumpt RA, van der Weegen W, King WJ, Toler K, Macenski M. Safety and treatment effectiveness of a single autologous protein solution injection in patients with knee osteoarthritis. BioResearch Access, Vol 5.1, 2016. 3. Kon E, Engebretsen L , Peter Verdonk P, Nehrer S and Filardo G. “Two-year Clinical Outcomes of An Autologous Protein Solution Injection For Knee Osteoarthritis.” ICRS 14th World Congress, presented, 2018. # As measured by WOMAC pain scores reported by patients continuing follow-up through 2 years (n = 22).

This material is intended for health care professionals. Check for country product clearances and reference product specific instructions for use. For product information, including indications, contraindications, warnings, precautions, and potential adverse effects, see the package insert and www.zimmerbiomet.com. Not for distribution in France. ©2018 Zimmer Biomet

nSTRIDE_Adv 18_601.indd 1 03-07-18 07:33

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International Cartilage Regeneration & I NTERNATIONAL C ARTILAGE R EGENERATION & JOINT PRESERVATION S OCIETY Joint Preservation Society