I C R S n e w s l e t t e r

2014 | Winter Issue 18www.car t i lage.org

Coming Up:

2 nd ICRS Summit Meeting Zermatt – Switzerland

www.cartilage.org

Featured: Interview with Lisa Fortier

http://tinyurl.com/ICRS-ANGEL-2014© 2013, Arthrex Inc. All rights reserved.

AD1-0050-EN_A

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http://tinyurl.com/ICRS-ANGEL-2014© 2013, Arthrex Inc. All rights reserved.

AD1-0050-EN_A

REVOLUTIONARY FLEXIBILITYPRP formulations tailored to your patient’s needsWhat sets Angel apart from the competition is technology. The Arthrex Angel utilizes a proprietary platelet sensor and one button automation to prepare customized PRP formulations. The Angel is the only PRP device that can deliver platelet concentrations up to 18x baseline with adjustable leukocyte concentrations.

Features & Benefits:• Proprietary platelet sensor system • Adjustable platelet concentrations• Adjustable WBC concentrations• Flexible processing volume 40-180ml• Each processing kit can process three cycles up to 180ml on the same patient• Programmable - can store up to 30 custom processing protocols• Closed system, delivers PRP, PPP and RBCs into separate, sterile compartments

ARTHREX

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Editor-in-Chief: Mats Brittberg, MD, PhD Gothenburg University, Sweden

EditorMats Gothenburg University, Sweden

Top 10 Cited Articles from Cartilage

1. ICRS Recommendation Document: Patient-Reported Outcome Instruments for Use in Patients with Articular Cartilage Defects by Ewa M.Roos, Luella Engelhart, Jonas Ranstam, Allen F. Anderson, Jay J. Irrgang, Robert G. Marx, Yelverton Tegner, Aileen M. Davis

2. A Review of Arthroscopic Bone Marrow Stimulation Techniques of the Talus: The Good, the Bad, and the Causes for Concern by Christopher D. Murawski, Li Foong Foo, John G. Kennedy

3. Radiological Assessment of Accelerated versus Traditional Approaches to Postoperative Rehabilitation following Matrix-Induced Autologous Chondrocyte Implantation by Jay R. Ebert, Michael Fallon, William B. Robertson, David G. Lloyd, M.H. Zheng, David J. Wood, Timothy Ackland

4. A Prospective, Randomized Comparison of Traditional and Accelerated Approaches to Postoperative Rehabilitation following Autologous Chondrocyte Implantation: 2-Year Clinical Outcome by Jay R. Ebert, William B. Robertson, David G. Lloyd, M. H. Zheng, David J. Wood, Timothy Ackland

5. Knee Cartilage Defect Patients Enrolled in Randomized Controlled Trials Are Not Representative of Patients in Orthopedic Practices by C.N. Engen, L. Engebretsen, A. Årøen

6. Mesenchymal Stem Cells: The Past, the Present, the Future by Arnold I. Caplan7. Preclinical Studies for Cartilage Repair: Recommendations from the International Cartilage Repair

Society by Mark B. Hurtig, Michael D. Buschmann, Lisa A. Fortier, Caroline D. Hoemann, Ernst B. Hunziker, Jukka S. Jurvelin, Pierre Mainil-Varlet, C. Wayne McIlwraith, Robert L. Sah, Robert A. Whiteside

8. The Treatment of Osteochondral Lesions of the Talus with Autologous OsteochondralTransplantation and Bone Marrow Aspirate Concentrate: Surgical Technique by John G. Kennedy, Christopher D. Murawski

9. Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair: International Cartilage Repair Society Recommendations Based on Current Scientific Evidence and Standards of Clinical Care by Kai Mithoefer, Daniel B.F. Saris, Jack Farr, Elizaveta Kon, Kenneth Zaslav,Brian J. Cole, Jonas Ranstam, Jian Yao, Matthew Shive, David Levine, Wilfried Dalemans, Mats Brittberg

10. One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions: Results at 2-Year Follow-up by Alberto Gobbi, Georgios Karnatzikos, Celeste Scotti, Vivek Mahajan, Laura Mazzucco, Brunella Grigolo

2 0 1 5

Mark your agenda!

Chicago – USAMay 8 – 11, 201512th World Congress of the International Cartilage Repair Society

www.cartilage.org

Early Bird Registration Deadline: February 15, 2015

21 CMEAMA PRA

Category 1 Credit

#ICRS15

5

Presidents’ Voice 7

Executive Office News 8

Cover Story – Reaching the Summit 10

Upcoming ICRS Events – Chicago 14

Upcoming ICRS Events – Zurich 16

Report from Past ICRS Meetings 17

News from Cartilage Clubs around the World 19

Event Calendar 20

Industry News – Vericel/Genzyme/Aastrom 25

Interview with Lisa Fortier, DVM, PhD, DACVS 26

ICRS Journal Club 28

Mini Study – Clinical Case 30

Editorial 31

Index2 0 1 5

Mark your agenda!

Chicago – USAMay 8 – 11, 201512th World Congress of the International Cartilage Repair Society

www.cartilage.org

Early Bird Registration Deadline: February 15, 2015

21 CMEAMA PRA

Category 1 Credit

#ICRS15

The Episealer® femoral condyle for the treatment of localized cartilage defects in the knee condyle.

The implants are customized to fit each person’s own joint anatomy, position and size of injury, based on patient images (MRI). By recreating a smooth and continuous joint surface the goal is to help patients regain full movement and reduce pain. www.episurf.com

Episealer® Femoral Condyle

Episealer® Knee Trochlea

Episealer® Knee TrochleaBased on Episurf's patented technology

the Episealer® Knee Trochlea is an individually customized resurfacing

implant system intended for the treatment of localized cartilage

defects in the knee trochlea.

7

Presidents’ Voice

Dear Colleagues & Friends

The year 2014 is coming to an end. We have seen extraor-dinary educational events in the field of cartilage repair such as the surgical skills course in Larissa/Greece hosted by Konstantinos Malizos and Michael Hantes as well as the Laboratory Skills Course in Fort Collins USA hosted by Wayne McIl-

wraith and John Kisiday at Colorado State University. The Focus Meeting – The Knee in Zurich/Switzerland showed once again the value of small and concise meetings on a high level. All these courses were sold out quite well in advance.

Additionally ICRS was invited to numerous meetings (ES-SKA, SIGASCOT, ACRS - to name only a few) as an ambas-sador for cartilage repair. An eye-opener for me was the growing interest of orthopaedic societies and authorities from all over the world for joint projects, consulting, edu-cation and political statements. This shows the solid po-sition the ICRS has reached over the years as a compact and intense international group of scientists, clinicians and industry partners. We should value this situation and continue our efforts to provide a comfortable home for this special group of people. Even from our custom-ers/patients we are more and more recognized as prime knowledge provider in the field of cartilage problems and osteoarthritis which is reflected by the number of ques-tions and inquiries the office receives. The planned pa-tient & public information platform will support an even better service for the patients as from the year 2016.

But quite often we are still living in our small cartilage world which is quite tiny in relation to the enormous soci-oeconomic impact of musculoskeletal disorders. What do you do when you want to see what the neighbours are do-ing and how it looks beyond your little village - climb on the rooftop - et voilâ - a new perspective! Insights come

from "outsights". Instead of a rooftop ICRS will climb the mountains to Zermatt/Switzerland in January 2015 to join for the Summit Meeting "The Aging Cartilage" near the majestic Matterhorn.

Aging affects all the tissues in the human body - how do other disciplines deal with the problem of aging? Where is the line between aging cartilage and osteoarthritis. Participants will have the chance to hear about new ap-proaches, techniques or avoidable problems - and hope-fully will leave the mountains with a broader view!

In May 2015 we will get another chance to show the world what we can (!) - expect in the future of cartilage repair. Come to join us at the 12th ICRS World Congress in Chi-cago/USA! A spectacular venue is waiting for you as well as a fresh and interesting programme, put together under the lead of Tim Spalding & Daniel Grande. Susan Chubins-kaya & Brian Cole, as our local hosts will spare no efforts to make you feel welcome in their home town. Mark your agenda and stay tuned for any news.

Speaking of which - why don't you show your continuous interest in ICRS by using our social media channels (Linked-In, Facebook, GooglePlus and Twitter) to share your ideas, MRI's and cases. USE our network. Every click, like, tweet and posting will grow the impact of ICRS and the value of your membership. The links to our social media network can be found easily on our website. I wish you all the best for the upcoming holiday season. Share a few days with your loved ones, don't ruin your cartilage on slopes or boards and come back next year with even more enthusi-asm for YOUR International Cartilage Repair Society.

Christoph Erggelet, ICRS President 2014-2015

Chris Erggelet

Holiday Season

The ICRS wishes you a

very happy and peaceful

holiday season

with your families.

The Cartilage

Executive Office will

be closed from

December 20, 2014 until

January 05, 2015.

Mark your Agenda !

ICRS 2015 World Congress, Chicago, USASurgical Skills Pre-Course:

May 06 – 07, 2015

Congress Dates: May 08 – 11, 2015

Early Bird Registration Deadline: Feb 15, 2015

The Episealer® femoral condyle for the treatment of localized cartilage defects in the knee condyle.

The implants are customized to fit each person’s own joint anatomy, position and size of injury, based on patient images (MRI). By recreating a smooth and continuous joint surface the goal is to help patients regain full movement and reduce pain. www.episurf.com

Episealer® Femoral Condyle

Episealer® Knee Trochlea

Episealer® Knee TrochleaBased on Episurf's patented technology

the Episealer® Knee Trochlea is an individually customized resurfacing

implant system intended for the treatment of localized cartilage

defects in the knee trochlea.

New Junior Members Decker Rebekah Philadelphia USAKyriakidis Theofylaktos Brussels BelgiumLee Paul East Brunswick USAManferdini Cristina Bologna ItalyNeogi Devdatta Dharwad, Karnataka IndiaRubio-Avila Jorge Zapopan MexicoSouza Eduardo Sorocaba BrazilVezeridis Peter Boston USAWaller Kimberly Providence USA

New Ordinary Members Abe Satomi Asahikawa JapanAgorastakis Dimitrios Thessaloniki GreeceAlkaff Mohammed Jeddah Saudi ArabiaAlves Analiz Botucatu BrazilAngeline Michael Williams Bay USAAttar Fahad Prescot UKBaack Hans Hamburg GermanyBerta Ágnes Budapest HungaryBlum Michelle Syracuse USAChang Chih-Hung Taipei TaiwanDallo Ignacio Santa Fe ArgentinaDe Menezes Daniel Biel SwitzerlandDunn Allan North Miami USAGlass John New Lambton Australia

Automatic Renewal of your ICRS Membership for 2015 Being an active member of the ICRS Network is to be part of the Worldwide Cartilage Community and to fully benefi t from one of the most dynamic specialized or-thopaedic networks in the world.

We would like to remind all our members that the re-newal of the Membership within the ICRS is automatic as per bylaws and becomes effective always in Decem-ber for the upcoming year. If a member does not want to renew his/her membership for 2015, a short written notice of cancellation should be sent to our offi ce by email until end of December 2014. Please proceed to pay your membership online by accessing your per-sonal member account and you will not miss the fi rst issue of our journal “Cartilage” which will only be sent to members with paid fees 2015. If you need further as-sistance, please contact our executive offi ce by email: offi ce@cartilage.org.

Changed your Address?When accessing your personal ICRS member account, do not forget to check/update your personal informa-tion, mailing address and other contact details. If you have any problems in accessing your ICRS account, please contact our offi ce by phone: +41 44 503 73 70 or by email offi ce@cartilage.org

Grantner Mary Chicago USAHenrotin Yves Liège BelgiumHeuberer Philipp Vienna AustriaHiemstra Laurie Banff CanadaKoch Thomas Guelph CanadaLa Gioia Marino Coulommiers FranceLeone Armand Glen Rock USAMalanga Gerard Cedar Knolls USAMandalia Vipul Exeter UKMuthukumar Subramanian Chennai IndiaNishi Sergio Sao Jose BrazilPal Fodor Tg.Mures RomaniaPapasoulis Efthymios Thessaloniki GreecePelttari Karoliina Basel SwitzerlandPostnikov Victor Novosibirsk RussiaRassi Claudia Goiania BrazilSinghal Anil Bulandshahr IndiaSingla Amit Delhi IndiaStone James Franklin USASubramanian Anu Nebraska USATaylor Mark Stuttgart GermanyTorrent Anna Palafolls SpainTsolos Ioannis Athens GreeceTytherleigh-Strong Graham Cambridge UKWells Ryan Nashville USAYandaw Sanjay Bulandshahr India

Welcome New Members (49 New Members since July 2014)

Executive Office News

Message from the Membership & ByLaws Committtee The tasks of the ICRS Membership and Bylaws Commit-tee include the regular review of the ICRS bylaws, ex-tending the clinical and basic-science membership and the identifi cation of potential Fellow members of the society. In this ICRS newsletter, we would like to under-score that the committee invites all members to share their views on the current bylaws and membership is-sues, as well as give you a short update of its current activities.

Bylaw Change “Second Vice President”The committee has been actively approaching members for their input and visions on the current Bylaws. Based on these discussions, the creation of a new Executive Board position “Second Vice President” was submitted to a formal electronic vote to our general membership between October 17 – November 3 at noon.

Yes, I accept the proposed Bylaw changes: 93 / 86.11%

I abstain from my vote: 2 / 1.85%

No, I do not accept the proposed Bylaw changes: 13 / 12.04%

108 Members have voted and the motion was approved by 86.11% of valid votes

9

Executive Office News

Apply for Fellow Membership of the ICRSAn additional important task of the committee is to se-lect and propose members to become “Fellows” of the ICRS. This is a senior membership status and is an ap-preciation of the society for the significant the contribu-tions of the member to the ICRS or to the field of car-tilage repair. Fellow Members are members who have made a significant contribution to cartilage repair and/or related regenerative medicine or to the Society. Fel-low members are subject to pay membership fees but are considered as opinion-leaders within our society and are thus more often approached to moderate or speak during ICRS events. Eligibility includes at least 3 years ordinary membership of the ICRS. We would urge eligible ICRS members, who would like to be considered for a Fellow membership to file their application (includ-ing curriculum vitae) and send this to the Membership and Bylaws Committee Chair, Dr. Jos Malda (j.malda@umcutrecht.nl).

We are looking forward to your applications!Jos Malda, Chair of the Membership & Bylaws Committee

Committee Elections 2015/2016 – Call For Nominations It is our pleasure to invite all eligible ICRS members to consider nominating themselves to join one of our Standing Committees. According to the ICRS By Laws, the Committee Chairs are members of General Board and will therefore be eligible to stand for election to the Executive Board in the future. Election as a new commit-tee member now will therefore pave the way for a possi-ble future leading role as a committee chair or even Ex-ecutive Officer of the ICRS. We are very keen to bring in new and motivated members who have not previously participated in committees. We are particularly keen to receive more applications from laboratory-based scien-tists, as this group has been under-represented on our committees in recent years.

Eligibility Criteria: Before nominating yourself, you should make sure you are eligible. The criteria for mem-bers to be eligible are:

1. You should have been fully paid members of ICRS for at least one calendar year before the date of the elec-tion.

2. You should previously have served no more than 1 term of office on that committee.

3. You must commit to attending the World Congress and the General Assembly where results will be an-nounced (Please note that The World Congress will be in Chicago, USA from May 8-11)

4. You have read and agree with the guidelines “Ad-vise and Instructions for ICRS committee & Board Members”to be found on our website.

5. You must be able to dedicate time to engage with the respective committee members and chairs for the re-lated tasks and responsibilities.

The Election Process: All committee positions are open for elections (existing members who wish to serve a second term will have to stand for election). More de-tails on committees and vacant positions for clinicians, scientists and industry representatives will be informed in due time by email to all active members. Stay Tuned!

ICRS Basic Science Travelling Fellowship 2015The objectives of this new programme are to provide young postdoctoral scientists with an opportunity for international exchange in a stimulating environment and to gain exposure to high quality basic research in laboratories that are world famous for their work on articular cartilage injury, repair, and regeneration. Se-lected as potential leaders in the field of cartilage re-generation and repair, fellows will be accompanied on a 7–10 day tour to several laboratories, led by a dis-tinguished and experienced scientist who will act as a mentor throughout the trip. Together they will partici-pate in scientific symposia with host scientists, view research facilities and participate in social and cultural events with the hosting cartilage repair community. They will also discuss with experienced scientists the process of grant writing and building a scientific repu-tation. The Fellowship Programme includes attending the ICRS World Congress. The programme will alternate between either in Europe, North America or Asia and alternatively candidates from different regions will be considered. Fellowship recipients will be required to provide a written summary of their fellowship experi-ences to the ICRS to be published in the next Newslet-ter and agree to present their experiences at the next ICRS World Congress during a special session. Up to 4 Fellowships will be available for each programme, hold every 18 months. The Fellows will be selected in open competition by an expert panel established through the ICRS Fellowships, scholarships and research grants committee. For further information and application pro-cess, please visit our website.

Eligibility: Candidates must be ICRS Members in good standing. Scientists with completed PhD, below age of 40 with a dedicated interest in cartilage repair with strong publication record in cartilage repair. Candidates must not have benefited previously from any ICRS Fel-lowship programme and candidates must speak English fluently (entire programme held in English). Candidates must reside outside the continent being visited (for 2015 outside North America) Application Deadline: January 31, 2015

2nd ICRS Summit – Alexander Seiler Convention Center January 14–17, 2015, Zermatt – Switzerland

We trust, that the 50 selected participants are looking forward to coming together in Zermatt at 5300 ft. height, for a genuine “Summit Meeting" within the giant Swiss mountains and what we hope will be an unusual and interesting scientifi c event. The key to its success will be for all of you as delegates to fully engage in extend-ed discussion. We have instructed speakers to express strong and controversial views and to stimulate plenty of debate. But it is your participation that will make the meeting memorable so please come ready to play your part. This will be an exclusive meeting with world-class speakers and intensive discussion designed to move the fi eld forward in a new directions. It is a new concept for the Society and the plan is for each President to run one summit during his/her term of offi ce.

Cover Story – Reaching the Summit…“Climb if you will, but remember that courage and strength are nought without prudence, and that a momentary negligence may destroy the happiness of a lifetime. Do nothing in haste; look well to each step and from the beginning think what may be the end.” Edward Whymper

From 1857 – 1865, the ri-vals Englishman Edward Whymper and the Italian Jean Antoine Carrel, had an extensive neck-and-neck race, with several un-successful attempts, to climb the Matterhorn, the unconquerable King of the Alps. On July 14, 1865, Ed-ward Whymper was fi nally successful. Tragically, four of the seven men led by Edward Whymper lost their lives in the attempt.

The story of Zermatt and the tragedy on the Matterhorn was soon on everyone’s lips.

In summer 1860, Edward Whymper, an athletic, twenty-year-old English artist, visited the Alps and Zermatt for the fi rst time. According to a hotel guest book, he stayed at the Seiler’s Hotel Monte Rosa for the fi rst time from August 8-13, 1860. Edward had been hired by a London publisher to make sketches and engravings of the sce-nic mountains along the border of Switzerland and Italy. He was also interested in mountaineering, and decided to attempt the yet unconquered Matterhorn (15.000 ft.).

Upcoming ICRS Events – Summit Zermatt

Whymper soon discovered that Jean-Antoine Carrel, an Italian guide, also had strong ambitions to be the fi rst to reach the summit of the Matterhorn, and had already made several unsuccessful attempts to climb the moun-tain. During the years 1861-1865, both made several at-tempts by the south-west ridge together, but became progressively arch-rivals. Carrel patriotically believing that a native Italian like himself and not an Englishman like Whymper, should be the fi rst to set his foot on the summit. English climbers had already deprived Italians of the conquest of Monte Viso, the Piedmont’s peak par excellence; the Matterhorn remained as the last uncon-quered great alpine summit. Whymper attempted to persuade Carrel to try an ascent from the Zermatt side, but Carrel insisted that he wanted to climb from Italy. In 1865, Whymper, tired of the many defeats he had sustained on the south-west ridge, looked for a new way to the summit from Zermatt. However, when this new route was attempted, the mountain discharged an avalanche of stone upon the climbers, and the ascent failed. His guides refused to make any further attempts by this route.

Nevertheless, Carrel had fi nally agreed with Whymper to try another attempt together, from the Swiss side on July 11. On the morning of the July 9, Whymper was sur-prised to meet Carrel with a traveller, who was coming up with a great deal of baggage. He questioned Carrel, who told him that he would be unable to serve him anymore. Whymper found out 3 days later that Carrel was planning another serious attempt without him through the Italian

E. Whymper – 1860

July 14, 1865 – Croz, Douglas, Hadow, Hudson (behind) Taugwalder father & son, Whymper (front)

11

Upcoming ICRS Events – Summit Zermatt

side. Deceived, he hurried to Zermatt and quickly assem-bled a group for an immediate attempt via the Swiss ridge. On his way, he encountered another young Englishman with a guide. It was Lord Francis Douglas, who agreed to come along with him to Zermatt. When the three arrived in Zermatt, they engaged two local porters and returned to the Hotel Monte Rosa, where they encountered Michel Croz and Reverend Charles Hudson. They came to Zer-matt with the same intention, to attempt to ascend the Matterhorn. Hudson, Croz and his friend Hadow decided spontaneously to join Whymper and Douglas, and that same evening, everything was settled - they were to start their ascent, early the next day.

The party started from the Hotel Monte Rosa on 13 July at half-past five in the morning. The seven members in-cluded Whymper, Douglas, Croz, Hudson, Hadow and Taugwalder father and son, both locals, acting as por-ters. Before twelve o’clock, they had found a good po-sition for a tent at a height of 11,000 feet. On the next morning they started early at dawn. They knew that at the same time, on the Italian side, Antoine Carrell was making his own attempt and therefore they had to rush. At 6.30 AM, they reached a height of 12,800 feet, and at 10.00 AM, they stopped for fifty minutes rest at a height of 14,000 feet. At this point of the ascent, Whymper wrote that the less experienced Hadow "required con-tinual assistance". Having overcome some difficulties, the group finally arrived near the summit. When they saw that only two hundred feet of easy snow remained, Croz and Whymper detached themselves from the rope and reached the top first.

After having checked that no footprints were pre-sent on the summit, made by the Italian expedition, Whymper saw Carrel and party at a great distance be-low. Whymper and Croz yelled and poured stones down the cliffs to attract their attention. When seeing his rival on the summit, Carrel and party gave-up and went back to Italy – deeply disappointed.

"We remained on the sum-mit for one hour - One crowded hour of glorious life," wrote Whymper. An hour later, they began their descent with great care, only one man moving at a time. Down in Zermatt, a sharp-eyed boy ran into the Hotel Monte Rosa and said to Alexander Seiler that he had seen an ava-lanche fall from the sum-mit. They boy was scolded

for telling idle stories; however, he was right, and this was what he saw.

It started with a slip by Douglas Hadow, a "gentle, simple-minded pious youth" who had done little climbing. Hadow suddenly slipped and fell onto Croz, dislodging him and dragging Douglas and Hudson to their deaths. The rope parted, saving the other three. "For a few seconds we saw our unfortunate companions sliding on their backs, and spreading out their hands, endeavouring to save them-selves. They passed from our sight uninjured, disappeared one by one, and fell from precipice to precipice, a distance of nearly 4,000 feet in height. From the moment the rope broke it was impossible to help them," wrote Whymper.

They remaining 3 climbers were stunned by the acci-dent, and for quite a while could not move nor speak. Whymper finally asked to see the broken rope and saw, that it had been employed by mistake, as it was the weak-est and oldest of the three ropes they had brought. They frequently looked, but in vain, for traces of their fallen companions. At daybreak, the descent was resumed and the three finally reached Zermatt. Alexander Seiler met Whymper at the hotel door and followed him in silence to his room, but did not lose time in useless lamentations, and organized quickly a rescue team for the victims. The bodies of Croz, Hadow and Hudson were found on the bottom of the mountain, but the body of Lord Francis Douglas was never found. Following the tragic accident, the names Zermatt, Matterhorn and Whymper soon be-came known across the world. No accident in the his-tory of mountaineering has created such a sensation. Wymper’s opponent Jean Antoine Carrel, together with his Italian party successfully ascended Matterhorn for the first time from the Italian side just three days later.

The Disaster – by G. Doré The Conquest – by J. Keay

THE ROOTS

OF ALPINE HOSPITALITY

The Seiler Hotels are proud to host

the 2nd ICRS Summit 2015 in Zermatt

Mont Cervin Palace *****S Hotel Monte Rosa ****www.seilerhotels.ch

SH_Advertising_Seiler_A4_EN_Print.indd 1 26/11/14 10:44

13

On July 27th, 1865, a leading article in the London News-paper “The Times” questioned 'why the best blood of England waste itself scaling hitherto inaccessible peaks'. Because of the death of Lord Francis Douglas, Queen Victoria planned to issue a ban. She said that she would never again permit English royal blood to be wasted on the Matterhorn. Her suggestion triggered curiosity and a thirst for action amongst British Alpinists. They came now to Zermatt in masses to see, and to climb, the Matterhorn. The tourist development of Zermatt, as well as of the Seil-er Hotels, had its beginnings here. Alexander Seiler leased or built more and more hotels, including the Hotels Mont Cervin, National, Victoria, Beau Site, Schwarzsee, Riffel-berg & the Riffelalp Grand Hotel, which he aimed to make the best mountain hotel in the Alps. It opened in 1884. Since it was about half a mile away from the railway sta-tion, the Seiler family applied for a concession to run their own electric tram, to bring their guests in comfort to the hotel - this at a time when the normal mode of transport was still by horse and carriage. It was the highest- and probably due to its 500 meters in length, also the short-

est tramline in the world at 2220 meters (7300 ft.) height. The Seiler Hotel Group quickly reached close to 1200 beds

and employed over 600 staff members in the small village of Zermatt. It was probably the largest Swiss Hotel com-pany during the "Belle Epoch". At this time, the Seiler Ho-tels turned into a sort of alpine "playground" for the high society, such as the Kennedys, Morgans, Rockefellers, Vanderbilts, Michelins and Pirellis, as well as for many aristocrats and politicians such as Winston Churchill.

Whymper and Carrell became friends, and organized an ex-pedition together to Ecuador in 1879, designed primarily to collect data for the study of altitude sickness and the effect of reduced pressure on the human body. On 4th of January 1880, Whymper and Carrell claimed the first ascent to the Volcano Chimborazo (20,000 ft.) and a few other peaks.

Jean-Antoine Carrell died in 1890 from exhaustion on the Matterhorn after bringing his employers into safety through a snowstorm. Whymper died alone in a hotel room in Chamonix in September 1911, at age 71.

Story by Stephan Seiler (Alexander Seiler’s great-grandson), based on Edward Wymper’s book from 1871 “Scrambles amongst the Alps”

Upcoming ICRS Events – Summit Zermatt

Seiler’s Mont Cervin 2014

Hotel Mont Cervin (around 1910)

Lobby Hotel Mont Cervin 1945 – A Friendly Holiday Place for the US Army

THE ROOTS

OF ALPINE HOSPITALITY

The Seiler Hotels are proud to host

the 2nd ICRS Summit 2015 in Zermatt

Mont Cervin Palace *****S Hotel Monte Rosa ****www.seilerhotels.ch

SH_Advertising_Seiler_A4_EN_Print.indd 1 26/11/14 10:44

Upcoming ICRS Events – Chicago

6th ICRS Surgical Skills Course, Rosemont – Chicago, USA, AAOS – OLC Facilities, May 7–8, 2015

The ICRS is proud to announce the 6th ICRS Surgical Skills Course (wet lab) directly preceding the 2015 ICRS World Congress in Chicago. The course will be held on May 6 – 7 at the brand new AAOS Orthopaedic Learning Center in Rosemont conveniently located close to Chicago's In-ternational O’Hare Airport. The 6th ICRS Surgical Skills Course will encompass a review of the international perspective on cartilage repair, meniscus management and associated procedures related to the comprehensive management of the young arthritic knee. Participants will enjoy a balance of didactic lectures, case presen-tations and a hands-on cadaveric (arthroscopic & open surgery) experience.

At the end of this 1.5-day course, participants will be shuttled to the downtown Chicago Sheraton for the ICRS World Congress to continue this unique experi-ence. Participants will be required to book their ac-commodation for the pre-course at our offi cial Hotel in Rosemont from May 6 – 8, 2015. The course can only be booked in conjunction with the World Congress Chi-cago and a separate registration fee for this course is required as this workshop is not included in the regular congress registration fees. For further information on registration, accommodations, programme and faculty, please visit our website.

Brian Cole & Andreas GomollSkills Course Co-Chairs

The Sheraton ChicagoWelcomes ICRS!

Located along the Chicago Riverwalk, enjoy

the convenience of being only steps away from

Navy Pier, Michigan Avenue shopping and

Millennium Park.

Enjoy the luxury of five restaurants and bars

including Shula’s Steak House, and relax with

our complimentary Sheraton Fitness Center

featuring an indoor heated pool, dry sauna

and sun deck.

learn more at sheratonchicago.com

Sheraton Chicago Hotel & Towers. 301 E North Water St. Chicago, IL 60611. 312-464-1000

The new AAOS Learning Center Project

Chicago Air View

15

ICRS 2015 – 12th World Congress, Chicago – USAMay 8–11, 2015 at Sheraton Chicago Downtown

We would like to invite you to attend the 12th World Con-gress of the International Cartilage Repair Society. Set your sights on being in Chicago May 8-11, 2015 for this special event. The programme chairs and local organiz-ing committee have planned a meeting that will be both provocative and entertaining. The setting will be on the shores of Lake Michigan and it will be springtime in the windy city. We are excited about providing a program that will be of interest to both clinicians and basic scien-tists with several new session topics and timely debates on clinical management. Several new sessions that cov-er emerging trends in our field will be spotlighted.

Over 500 Abstracts from all over the world have been received and are currently being blind-reviewed. Noti-fication letters will be sent out to all abstract submit-ters end of January.

The clinical topics will include a comprehensive update on most of the available clinical strategies currently being performed. Current topics that are controversial will be hotly debated in special sessions. Additional new topics include spine [disc] and foot & ankle cartilage resurfac-

ing, and many others. Basic science sessions will include a focus on topics such as bioprinting, biology of cartilage development, and biological and engineering considera-tions for optimal design of cartilage repair. In addition, sessions on controlled release and novel scaffold mate-rial for tissue engineering of cartilage are planned.

This congress will allow a continuation of our society’s goal in bringing together clinicians and scientists from around the globe to advance our knowledge of car-tilage. It will be an excellent opportunity to enjoy a comprehensive overview of the state of the art in our field whether you are a clinician or scientist. The local organizing committee is poised to give you a taste of all the second city has to offer in addition to the Chicago style deep dish pizza! So please mark your calendars for joining us the next ICRS World Congress and we look forward to seeing you there!

Daniel Grande & Tim SpaldingScientific Programme Co-Chairs

Brian Cole & Susan ChubinskayaCongress Co-Chairs

Upcoming ICRS Events – Chicago

Invitation to our Industry Partners – ICRS 2015 – ChicagoThe cartilage repair market takes centre stage in Chicago. We invite all companies, whose technolo-gies can diagnose, rehabilitate, repair, protect or regenerate cartilaginous surfaces of joints (stem cells, growth factors, PRP, bioactive composites, synthetics, scaffolds, allografts and combinations of thereof) to join us as exhibitors and/or sponsors for this most important event for professionals and key decision-makers in clinical cartilage repair and basic cartilage research. This is the op-portunity to participate in a truly global meeting in this rapidly expanding field, with an expected attendance of over 1000 participants from more than 60 different countries. Application forms and sponsoring opportunities can be found on our website and should be booked until January 31, 2015 latest. For more information please contact Mr. Stephan Seiler at sseiler@cartilage.org.

The famous “Chicago Bean”

Chicago by Night

6th ICRS Focus Meeting – Rehabilitation & Return to Sports, FIFA Auditorium Sonnenberg, Zurich/Switzer-land – September 17–19, 2015

Rehabilitation is widely considered an essential component for successful recovery after cartilage re-pair, and return to sports represents the most impor-tant outcome parameter for the injured athlete. There-fore, next ICRS Focus Meet-ing will mainly focus on Re-habilitation & Return to Sports.

Articular cartilage injuries are frequently observed in sports activity and often result in signifi cant limitation of sports participation, or can be career ending. Current cartilage repair techniques have shown promising results in returning athletes to their sport, but opinions on reha-bilitation and return to sport are still controversial.

Upcoming ICRS Events – Zurich

This meeting has been organized to provide and share com-mon clinical guidelines to all of the practitioners involved in the patient’s recovery process – from surgery to return to sport.

The scientifi c program has been designed to promote a mul-tidisciplinary approach where the audience can understand each topic from different specialists’ point of view, including basic science experts, orthopedic surgeons, rehabilitation physicians and sports medicine physicians, physical thera-pists and sports science specialists.

An international faculty, consisting of renowned specialists and expert leaders in the fi eld, will bring and share their knowledge and experience about some topics such as reha-bilitation progression, sports specifi c reconditioning, eval-uating tests and outcome measures. During the two days, you will also have the opportunity to focus and learn more about the management of cartilage injury in the three main joints of the lower limb: hip, knee and ankle. This is a unique opportunity to meet specialists from all over the world.

We hope to see you Zurich!Stefano Della Vila, Course Chair

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17

Report from the 5th ICRS Focus Meeting – The KneeJuly 3–4, 2014 – Zurich, Switzerland

It has been almost six months since the ICRS closed its doors on a packed focus meeting, covering all aspects of articular cartilage injuries of the knee joint over the course of 2 days, at the wonderful FIFA convention Centre in Zurich, Switzerland.

The meeting was already sold out in March – and rightly so! It was a gathering of 195 high quality speakers and del-egates alike, having travelled to Zurich from no fewer than 27 countries as far away as Australia and Japan. The ma-jority of attendees were orthopedic surgeons, but as is the nature of ICRS meetings, also included scientists, sports physicians and physiotherapists. The feedback question-naire unanimously praised the event, and most delegates plan to return to Zurich in 2015. The scientifi c program stimulated plenty of discussion, as the pathologies cov-ered are frequently seen in the daily clinic.

The lectures, presentations and workshops focused on lat-est science, diagnosis, operative treatments and their indi-cations, clinical outcomes as well as rehabilitation methods and anecdotes. All highlighted the importance of a multi-disciplinary team approach when dealing with cartilage injury. At present however, we still know too little about cartilage regeneration and recovery behavior under grad-ual load, and what ‘gradual loading’ actually means. Once the anatomy has been restored and a stable platform for cartilage growth provided, it is the movement and function of the injured joint/limb that can have a detrimental effect on overall cartilage recovery. With that in mind, it is the aim of the next Focus meeting in Zurich to try to establish a con-sensus document of Cartilage Rehabilitation from experts in the fi eld in order that those working at the front line not only know when to refer for surgery, or for example inject PRP, but will also be equipped with a working document for exercise prescription in cartilage lesions. The event would not have been as successful without our 18 sponsors, who yet again supported this Focus meeting in a gracious man-ner. So a big “Thank You!” to our industry partners.

Report by Alex Nieper & Christoph Erggelet Course Co-Chairs.

Report from Past ICRS Meetings

Report from the 5th ICRS Surgical Skills Course October 23–25, 2015 – Larissa, Greece

In October 2014, the 5th ICRS Surgical Skills Course in Car-tilage repair was held in Larissa, Greece. The course was successfully organized in the modern facilities of the at-tractive 250-acre Health Sciences campus at the University of Thessaly Orthopaedic Department. Forty participants in the hands-on lab, and more than 60 for the lecture only part, registered for this special event of our society. It was

a great privilege to host 120 participants from all over the world. Thirty-seven countries and four continents were represented in this course, proving that the ICRS is a trust-worthy scientifi c society for the continuing education for cartilage repair. We also should stress that it was positive-ly encouraging that there was great interest from our local and foreign colleagues to participate only in the lectures, as the hands-on lab was fully booked several months prior.

As is customary, the ICRS family once again delivered a successful surgical skills course, completely fulfi lling the course title and subsequent aim: “Cartilage Repair- Un-derstand it, See it, Do it…” Internationally renowned sur-geons and experts in the fi eld of cartilage repair provided the participants with the newest information, tips and tricks of many options in the surgical treatment of chon-dral lesions. From the more basic procedures of bone mar-row stimulation through microfracture, to the more ad-vanced techniques of autologous osteochondral transfer, and matrix induced cell therapies, the participants had the chance to spend signifi cant time practicing in “real” surgery conditions, on human cadaveric specimens. They practiced with many scaffold matrices to understand the material properties, and to feel ready to use them in their clinical practice. In addition, meniscal procedures were also a signifi cant part of the skills course. Many of the me-niscus preservation techniques (all-inside, outside-in and inside-out suturing) were performed, as well as meniscal substitution. Finally, MPFL and ACL reconstruction, and high tibial osteotomy completed a global training of the major procedures in the sports medicine fi eld.

In parallel, and at the same high level, the lectures kept the interest of the audience, through the interactive dis-cussion and special questions. The “throwing box” micro-phone was a highlight in the amphitheater! Basic science topics for cartilage, from the molecular level to cells and tissue were analyzed, and gave the background for the current treatment options. The state-of the art for repair-ing chondral lesions was at the core of the presentations. There was a special focus on stem cells and tissue engi-neering as part of the current treatment paradigm, and as future options. The current imaging trends and classifi ca-tion systems were presented, all of which combined to provide a basis for applying bio-surgical solutions. In the end, combined lesions were analyzed, along with a spe-cial session for the patellofemoral joint problems.

We had an encouragingly high positive feedback from the participants and the faculty about the meeting. All stated that they had a great experience, and felt much more informed, and learnt new things, about cartilage repair. The outstand-ing academic programme covered the challenges of the car-tilage repair fi eld. It was another successful step for the ICRS, in its continuing efforts to provide knowledge and training.

Report by Michael Iosifi dis and Michael HantesCourse Co-Chairs.

Report from Past ICRS Meetings

Report from the 5th ICRS Laboratory Skills CourseOctober 27–29, 2014 – Fort Collins, USA

The Orthopaedic Research Center at Colorado State Uni-versity in Fort Collins hosted the 5th ICRS Laboratory Skills Course. The workshop was limited to 30 participants and was fully enrolled. In addition to Wayne McIlwraith and John Kisiday, the other faculty were Dave Frisbie, Chris Kawcak, Laurie Goodrich and Myra Barrett from Colorado State University, Stephanie Bryant from the University of Colorado Department of Chemical and Biological Engi-neering and Daniel Grande from the Feinstein Institute for

Medical Research, Hofstra North Shore-LIJ School of Medi-cine. The 30 participants included clinicians, engineers, and biologists from both academia and industry and were from the United States (10), Brazil (6), Netherlands (3), In-dia (2), Greece (2), Peru (2) and one each from New Zea-land, Mexico, Canada, Belgium and Saudi Arabia refl ecting a truly international participation. The workshop focused on translation, from the laboratory development of carti-lage repair strategies through in vivo testing and analysis.

19

Report from Past ICRS Meetings

A special emphasis was placed on animal models, which is a longstanding area of expertise for faculty at the Ortho-paedic Research Center.

The workshop opened with lectures on the use of small and large animal models, practical aspects of creating chondral or osteochondral defects, and methods for characterizing the accumula-tion of repair tissue at the ter-mination of the study. These presentations were followed by a hands-on laboratory in which defects were created in cadaver rabbit and equine

joints. The second module focused on laboratory aspect of creating or testing cartilage repair strategies, including a review of fundamental aspects of isolating and expanding cells, in vitro culturing of cell-seeded constructs, and anal-ysis of extracellular matrix. Within these lectures, the use of hydrogels to deliver cells to cartilage defects was high-

lighted. From these lectures, the afternoon laboratory in-volved two activities, creating concentrated PRP from whole blood, and the preparation and casting of fi brin hy-drogel into defects that were created previously in cadaver joints. The third module focused on clinical imaging, with lectures covering state of the art technique for imaging cartilage repair tissue in situ using MRI, ultrasound, regu-lar and contrast CT, and radiography. The lectures were fol-lowed by a discussion of images obtained from completed live animal studies from the Orthopaedic Research Center.

Course Chairman: Wayne McIlwraith and John KisidayCourse Convener: Lynsey Bosch

ICRS Expanding to China Prof. MD. Yingfang Ao is a fellow mem-ber of the ICRS, endowed to establish a new ICRS-China section, as an offi cial branch of the ICRS in China. The ICRS-China Section aims to provide an active forum, bringing together basic scien-tists and clinical researchers, engaged

or interested in cartilage biology and cartilage tissue engi-neering in this country. More importantly, ICRS-China will be a bridge for better connecting Chinese doctors and re-searchers with the ICRS. Sharing the same mission and ob-jectives, ICRS-China will dedicate itself to the development of the mission and values of the ICRS in China. Within the proposal, ICRS-China is going to set-up a local committee to better execute and facilitate local society activities . It is also planning to organize scientifi c meetings, lab courses and workshop annually in China, for doctors and research-ers sharing and exchanging their experience and expertise, and stimulating them to attend ICRS events abroad. An Chi-nese version of the ICRS website will open in the future to facilitate ICRS membership development in China, promote ICRS activities and involvement of Chinese physicians, sci-entists and clinical researchers. Join us! Let us work, grow and share together, to make our society better and better!

Yingfang Ao is the Director of Peking University Insti-tute of Sports Medicine and the President of Chinese

Society of Arthroscopy. He specializes in knee injury, ligament & cartilage repair as well as arthroscopic mini-mally invasive surgery, focusing his basic research on cartilage repair. As the fi rst institute of sports medicine in China, Peking University Institute of Sports Medicine was founded in 1959, and after 55 years of development, has become the National Key Discipline, the National Key Clinical Specialty and the only offi cially designated Ath-letic Injury Prevention and Treatment Center by Chinese Olympic Committee. Yingfang Ao is the leading specialist in sports medicine and arthroscopy in China, with out-standing achievement in both clinical practice and basic research, and numerous publications papers in indexed international journals. He has been the Principal Inves-tigator of many national competitive grants and won a number of national awards for his outstanding scientifi c & technological achievement. For his great contribution to sports medicine and arthroscopy in China, the State Council of China has honored him with the special gov-ernment allowance.

Yingfang Ao has devoted himself to cartilage repair for decades, including tissue engineering cartilage repair, the mechanism of cartilage injury and repair, the niche change during cartilage injury and repair process, genet-ics and epigenetics in cartilage repair and early diagnosis of cartilage injury etc.

News from Cartilage Clubs around the World

Event Calendar

201514.01 – 17.01, 2015

2nd ICRS Summit 2015 – "The Aging Cartilage"International Cartilage Repair SocietyZermatt, CHwww.cartilage.org

12.02 – 14.02, 2015International Shoulder CourseParis, FRwww.paris-shoulder-course.com/en/

24.03 – 28.03, 2015AAOS Annual Meeting 2015American Association of Orthopaedic SurgeonsLas Vegas, Nevada, USwww.aaos.org

26.03 – 29.03, 2015World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal DiseasesMilan, ITwww.wco-iof-esceo.org

08.04 – 11.04, 20155th International Congress Biotechnologies for Spinal Surgery 2015Regenerate Europe e. V.Berlin, DEwww.biospine.org

11.04 – 13.04, 2015XXIV International Conference on Sports Rehabilitation and Traumatology - Football Medicine Strategies for Player CareLondon, GBwww.FootballMedicineStrategies.com

06.05 – 07.05, 2015

6th ICRS Surgical Skills Course (Pre Congress Workshop)International Cartilage Repair SocietyRosemont, USwww.cartilage.org/index.php?pid=327

08.05 – 11.05, 2015

ICRS 2015 – 12th World CongressInternational Cartilage Repair SocietyChicago, USwww.cartilage.org

27.05 – 30.05, 2015EFORT - CongressPrague, CZwww.efort.org

03.09 – 04.09, 2015 (TBC)ICRS Focus Meeting – AllograftsInternational Cartilage Repair SocietyBrussels, BEwww.cartilage.org

17.09 – 19.09, 2015AGA-Congress 2015AGA Society for Arthroscopy and Joint SurgeryDresden, DEwww.aga-kongress.infoe

ven

ts17.09 – 19.09, 2015

ICRS Focus Meeting - Rehabilitation & Return to SportsInternational Cartilage Repair SocietyZurich, CHwww.cartilage.org

201614.04 – 17.04, 2016World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal DiseasesMalaga, ESwww.wco-iof-esceo.org

04.05 – 07.05, 2016ESSKA Congress 2016European Society for Sports Traumatology, Knee Surgery and Arthroscopy.Barcelona, ESwww.esska-congress.org

09.06 – 11.06, 2016

ICRS World Series & Surgical Skills CourseInternational Cartilage Repair SocietySao Paulo, BRwww.cartilage.org

15.09 – 17.09, 2016AGA-Congress 2016AGA Society for Arthroscopy and Joint SurgeryBasel, CHwww.aga-kongress.info

24.09 – 27.09, 2016

ICRS 2016 – 13th World CongressInternational Cartilage Repair SocietySorrento – Naples, ITwww.cartilage.org

08.06 – 10.06, 2017

ICRS Heritage Summit 2017International Cartilage Repair SocietyGothenburg, SEwww.cartilage.org

07.09 – 09.09, 2017AGA-Congress 2017AGA Society for Arthroscopy and Joint SurgeryMunich, DEwww.aga-kongress.info

This listing is not complete and doesnot constitute a recommendation orendorsement by ICRS. Further investigation by interested parties is always necessary.For further information, visit the ICRSonline event calendar at our website.

21

News from Cartilage Clubs around the World

luronic acid and platelet rich plasma therapies, as well as re-generative and reparative techniques for articular cartilage. Delegates were able to gain practical experience, in most cases for the fi rst time, on real cartilage tissue. Under the guidance of some of the leading cartilage repair experts in Italy, the students were guided in the use of micro-fracture, nano-fracture, OATS technique, and a variety of scaffold implantations. Autologous matrix assisted chondrgenesis (AMIC), as well as meniscal and osteochondral scaffolds, were tested on fresh frozen knee specimens, providing an im-portant opportunity for young surgeons to gain hands on ex-perience. The great demand for enrollment and enthusiasm of the participants demonstrated how this simple approach successfully engaged future generations of surgeons with a topic that is so important, and often overlooked in training.

Report by Mattia Uboldi, MD, Italy

Report from the 9th Oswestry Cartilage Repair MeetingThe 9th Oswestry Cartilage Repair Meeting, held at The Robert Jones & Agnes Hunt (RJAH) Orthopaedic Hospital NHS Foundation Trust (UK) in May this year, was a small but focused symposium in its second year as an ICRS ap-proved meeting. Delegates and faculty included research students, scientists, industry experts and orthopaedic surgeons from the UK, Canada, the United States, Argen-tina and Singapore.

This year's meeting kicked off with a ‘fi ery’ start the night before. Delegates and staff from RJAH took part in a fi re walk to raise awareness of the pain and suffering caused by osteoarthritis. Thirty brave scientists, surgeons and friends of the Hospital trust strode bare-foot across seven meters of burning embers and raised over £3,500 for Ar-thritis Research UK. This was a pertinent focus to bring together those committed to fi nding treatments for pain-ful musculoskeletal disorders such as osteoarthritis and rheumatoid arthritis.

The meeting itself began on a general theme, with talks on the musculoskeletal repair system as a whole. Profes-sor Gustavo Moviglia presented results from his clinical trials in spinal cord injury repair in Argentina and the les-sons to be learned from repair mechanisms in nerves, which could be applied to cartilage.

The second session focused on the science of cartilage, with talks on repair mechanisms in the joint as a whole (Professor Gerjo van Osch, Utrecht) and at the cellular level (Professor Cosimo De Bari, Aberdeen). Later sessions dis-cussed how chondrocytes affect bone (Dr Frances Henson, Cambridge, UK), the importance of cell potency (Dr Paul Genever, York) and more clinically focused presentations from orthopedic surgeons (Mr Andreas Gomoll (New York),

Mr Martyn Snow (Birmingham, UK), Mr Gunnar Knutsen (Tromso, Norway) and Professor Marcel Nimni (California, USA). Representatives from industry, Mr Sven Kili (Sanofi ) and Dr Mirella van den Doel (CellCoTec) gave reports on clinical trials using their products.

There were also thought provoking talks given on the topic of alternative cell sources for cartilage repair, including embryonic stem cells (Professor Sue Kimber, Manchester) and umbilical cord stem cells (Professor T T Phan, Singa-pore). The meeting was very useful and interesting for both basic researchers and clinicians working in the fi eld, with the presentations giving a thorough coverage of the mech-anisms and management of cartilage diseases.

Report by Dr Claire Mennan (post-doctoral researcher in RJAH, Oswestry and Keele University).

Report from SIGASCOT 2014

On June 28, 2014, Italian ICRS Members M. Berruto, E. Kon, M. Delcogliano and M. Ronga, part of the SIGASCOT Carti-lage Committee, offered an opportunity for 32 resident/trainee surgeons to learn about the management of cartilage lesions. This free course, held at the ICLO Teaching and Re-search Center (St. Francis de Sales, Arezzo), focused on hya-

Conference delegates take part in the Arthritis Research UK charity fi re walk on the eve of the 9th Oswestry Cartilage repair meeting. Mr Gunnar Knutsen (Norway) (top left) and Dr Alastair Channon (UK) (top right) trot over the burn-ing embers after the group of 30 fi rewalkers watch the lighting of the fi re lane before the walk (bottom centre).

Report from the Indian Cartilage Society

The Indian Cartilage Society under the leadership of Presi-dent Deepak Goyal, and Past-President Nishith Shah, con-tinues to makie great strides in articular cartilage educa-tion and research. An ‘International Combined Congress of Indian Cartilage Society and Asian Cartilage Repair So-ciety’ was held in Chennai, India, along with the ‘First Asian Cadaveric Workshop on Cartilage Repair’ from 8-10th No-vember 2013. Congress Chair, Deepak Goyal, and Congress Secretary P Rajasekar, had invited renowned international and national faculty for the congress. The congress was attended by over 150 national and international delegates and was a resounding success. Besides the free paper ses-sions, supported by research and clinical studies, value was added by the challenging discussions and deliberation of national and international faculties like Anjali Goyal, Ankur Shah, Anupama Patil, B H Min, David Rajan, Deepak Goyal, Henning Madry, James Hui, Kiran Acharya, Mats Brittberg, Mitsuo Ochi, N Antao, Nagraj Shetty, Norimasa Nakamura, Nishith Shah, Raju Vaishya, S Arumugam, Sachin Tapasvi and Vijay Shetty. Delegates performed hands-on surgery including various procedures like cartilage lesion stabiliza-tion, microfracture, scaffold implantation, osteochondral cylinder transplantation and meniscus repair, during the

‘First Asian Cadaveric Workshop on Cartilage Repair’. An In-dian study- ‘Comparative Tissue Specifi c Marker Analysis of Human Articular Cartilage: Cells Grown in 2 & 3 Dimensional Cultures’ won the best paper award for its indigenous and original research work. It was felt by the Indian Cartilage Society that there are many misconceptions related to car-tilage science in the Indian subcontinent, mainly because

cartilage is a new science and very little academic activities are being held in this part of the world. On the recommenda-tion of the executive committee of the ICS, it was decided to produce a white paper detailing the various effective proce-dures for a variety of lesions of the cartilage. The purpose of the project was to present to Indian surgeons, a scientifi c guideline based on a 10-year research analysis, of the effec-tiveness of the various types of cartilage repair procedure, specifi c to the types of lesions.

A Consensus Committee of the Indian Cartilage Society was formed under the leadership of Dr Deepak Goyal. He graciously accepted the challenge to achieve this goal, and within three months, this herculean task became a reality. The project started in June 2014, followed by a full day meet-ing held in Ahmedabad on 21st September’ 2014, where the methodology was scrutinised and peer reviewed, resulting in the production of a protocol to put the white paper into a proper perspective. Three groups were formed with team leaders Nicholas Antao, Nishith Shah and Deepak Goyal, and were assisted by Ujjwal Deliwala, Parvez Afzal, Vaibhav Bagaria. These groups carried out an extensive literature survey for three main cartilage procedures - Microfracture, Osteochondral Cylinder Transfer Technique and Autologu-ous Chondrocyte Implantation. Anjali Goyal did the entire groundwork on histopathology of each procedure. Each team came out with various strong consensuses and con-cerns related to each procedure based on level I/II and III studies published in last three years. The proceedings of ICS Consensus Meeting was presented at the 13th National Con-ference of the Indian Arthroscopy Society held at Hyderabad on 12th October 2014.The presentations and recommenda-tions made by the team leaders were heartily accepted by a gathering of the delegates and national and international faculty. The Project Director, Deepak Goyal and the team, prepared a small booklet of consensuses and concerns, and this booklet was distributed to the delegates.

Deepak Goyal deserves our sincere appreciation for his de-termined dedication, and hard work put in to ensure that this ambitious project saw the light of day. Now the Indian Carti-lage Society is bracing itself for the upcoming 3rd Congress, that is to be held at Ahmedabad in November 2014.

ICS & Asian Cartilage Repair Society ICS Consensus Meeting guide-lines book

News from Cartilage Clubs around the World

World Heritage Site, Mahabalipuram 1st Asian Surgical Skills Course in Chennai

Report by Nicholas Antao, Mumbai Past President, Indian Arthroscopy Society

23

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A New Era in Regenerative Medicine and Cartilage Repair.

64 Sidney StreetCambridge, MA 02139734-418-4400

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25

A New Era in Regenerative Medicine and Cartilage Repair.

64 Sidney StreetCambridge, MA 02139734-418-4400

Vericel_ICRS_A4_hires.indd 1 11/13/2014 11:52:01 AM

Vericel Corporation: A New Era in Regenerative Medicine and Cartilage Repair

Cell Therapy & Regenerative Medicine business unit within Genzyme Biosurgery, developer of landmark therapies Carticel®, MACI® and Epicel, acquired by emerging leader in cell therapy and re-generative medicine.

In May 2014, Aastrom Biosciences, Inc. announced the acquisition of the Cell Therapy and Regenerative Medicine business unit within Genzyme Biosurgery from Sanofi. With this acquisition, Aastrom became the marketer for two of the world’s first cell therapy products: Carticel® (autologous cultured chondro-cytes), a first-generation autologous chondrocyte implant (ACI) product for the treatment and repair of cartilage defects in the knee, and Epicel® (cultured epidermal autografts), an autologous skin replace-ment for severe full thickness burns. The company also acquired the rights to continue to develop and market MACI™ (matrix-applied characterized au-tologous cultured chondrocytes), a third-generation ACI product which was recently approved in the Eu-ropean Union and is a Phase 3 product candidate in the United States. Additionally, Aastrom is develop-ing its Phase 2b product candidate, ixmyelocel-T, a patient specific multicellular therapy for the treat-ment of advanced heart failure due to ischemic di-lated cardiomyopathy (DCM).

With the acquisition of Carticel, Epicel and MACI, Aastrom was instantly transformed from a leader in regenerative medicine research targeting serious health problems including dilated cardiomyopathy, to a fully integrated commercial entity handling global production and sales for proven-effective cell therapies in cartilage repair and severe burn care. It is a new and exciting era for the company, and so time for a new identity that would better reflect the business’ expanded focus and opportunities. Therefore, in October 2014, Aastrom announced that the company would change its name to Vericel Corporation and would relocate its headquarters from Ann Arbor, Michigan to Cambridge, Massachu-

Industry News – Vericel/Genzyme/A astrom

setts, the center of research and production for all three acquired products.

This new corporate identity and expanded presence in Cambridge reflect Vericel’s dynamic opportunity to build upon its leadership in regenerative medi-cine. Carticel is the first and only FDA-approved biologic for cartilage repair in the knee, and it rep-resents an important landmark in the history of cartilage repair. MACI is the first combined tissue-engineered medicine approved under the new Ad-vanced Therapy Medicinal Product regulations by the European Commission. The supply of MACI in the EU was suspended after the acquisition as the company completed a range of business-critical global integration and consolidation activities. The company is optimistic about resuming the supply of MACI in the EU in the near future. Epicel is the only FDA-approved permanent autologous skin re-placement and is indicated for full thickness burns greater than or equal to 30% of total body surface area. Finally, the company continues to develop ixmyelocel-T, a multicellular therapy manufactured from the patient’s own bone marrow using a propri-etary, highly automated, fully closed cell-processing system. This process selectively expands the popu-lation of mesenchymal stem cells and alternatively activated macrophages, which are responsible for production of anti-inflammatory and pro-angiogen-ic factors known to be important for repair of dam-aged tissue.

“Looking to the future, Vericel’s combination of ex-perience in research, product development, manu-facturing, and global marketing has positioned the company to provide important new resources and educational initiatives in a relentless effort to ad-vance the care of patients with cartilage injuries and other conditions,” says Nick Colangelo, Veri-cel’s president and CEO. “We look forward to work-ing with more members of the research and medical communities as we enhance our current products and work to develop new and improved products and procedures that represent durable, effective options for patients.”

Interview with Lisa Fortier, DVM, PhD, DACVS

It was my pleasure to inter-view Dr. Lisa Fortier for this newsletter. As a previous ICRS President 2009-10 and long serving board member, Lisa has been extremely in-fl uential in the success of the ICRS, and in generating high quality scientifi c research in the cartilage repair fi eld. I hope you enjoy reading her answers. Al Getgood, Lon-don, Ontario, Canada

Lisa Fortier is a Professor of Surgery at Cornell University in Ithaca, NY. She received her DVM from Colorado State University and completed her PhD and surgical residency training at Cornell University. She is boarded with the American College of Veterinary Surgeons and is an active equine orthopaedic surgeon at Cornell in Ithaca and at Cornell Ruffi an in Long Island, NY. Her laboratory studies the intracellular pathways involved in the pathogenesis of osteoarthritis, with particular emphasis on post-traumatic osteoarthritis. In addition, Lisa’s research program inves-tigates the clinical application of stem cells and biolog-ics such as platelet rich plasma (PRP) for cartilage repair and tendon injuries. She has received the Jaques Lemans Award from the International Cartilage Repair Society, the New Investigator Research Award from the Orthopaedic Re-search Society, and the Pfi zer Research Award for Research Excellence from Cornell University. Lisa is the Vice Presi-dent of the International Veterinary Regenerative Medicine Society and a Past President of the International Cartilage Repair Society. She has published over 100 manuscripts in subjects related to sports medicine and is a recognized world leader of regenerative medicine for both the human and equine athletes.

AG: Please outline your training? LF: I went to a small college, Moorhead State University, in Moorhead Minnesota for a couple of years of undergradu-ate studies, and was admitted early into Veterinary School at Colorado State University in Fort Collins, Colorado. After fi nishing Veterinary School, I completed a fantastic one-year internship at Illinois Equine Hospital that transformed my life, because it allowed me to gain the experience nec-essary to apply for an equine surgical residency at Cornell University. During my residency training, I embarked on a Ph.D. program and fi nished it a couple of years after com-pleting my residency training. I then did a post-doctoral fel-lowship with a basic scientist, who studied growth factor signaling, before I was hired as faculty at Cornell Univer-sity, College of Veterinary Medicine where I am now a Pro-fessor of Surgery.

AG: How did you get into cartilage research? LF: Surgery residents at Cornell are required to do a research project, and mine was in looking into IGF-I and juvenile al-

logeneic chondrocytes for cartilage repair. As a graduate student, I presented my work on cartilage repair using the horse as a model, at the ICRS, and I very clearly remember the warm reception of my work from ICRS members.

AG: Who were your mentors? LF: Were? I still rely on great mentors! I would say those that infl uenced me the greatest and inspired me to be excited about learning, and to never set limits would be my high school teachers. The teachers in my small high school (I graduated with a class of 13) taught to each student’s level and personality. In the small farming community where I was raised, everybody knew and looked after each other in and outside the classroom.

AG: Did being an equine vet infl uence your interest in car-tilage, or did cartilage research infl uence your choice to become an equine vet surgeon? LF: Being an equine surgeon, observing cartilage damage arthroscopically, and learning the effects it had on athletic careers, combined with my research, inspired my interest in cartilage repair. In my lab, we always aspire to do work that simultaneously advances equine and human cartilage repair.

AG: You have a busy laboratory and a busy clinical prac-tice. How do you manage to do both? Any tips for younger members of the society on how to achieve optimal results in both? LF: It is all about loving your work and enjoying the people who you work with. I have an amazing administrative as-sistant who keeps me on task. Setting deadlines for your team, as well as yourself, is key to getting things fi nished, weather it’s a grant proposal or a manuscript, or putting to-gether a presentation. Not just setting deadlines, but also holding yourself, and others to them, will keep ideas and projects fl owing to completion.

AG: Which aspect of your job do you prefer? Surgeon or scientist? Why? LF: They are inseparable parts of my professional life at this point. Having an appreciation for both science and surgery brings reciprocal insight into both fi elds, allowing for clini-cal advancements.

AG: Please give 5 top tips on how to run a successful lab1. Frequently discuss recent data with your group, and pro-vide a frame of reference as to why this is important work scientifi cally, and how it will advance clinical treatment. Show your group why you and their peers fi nd the work ex-citing. 2. Reward everyone with continuing education – and food! 3. Encourage freethinking, innovation, and discus-sion. 4. Never ask or expect someone to lead or complete a project that they do not have a passion for. Everyone will be disappointed with the outcome. 5. Leave your door open. Turn away from the computer and do not answer the phone when team members want to talk.

27

Interview with Lisa Fortier, DVM, PhD, DACVS

AG: You have mentored many students (including me) – what do you feel is the important aspects of being a good mentor? LF: There are many important roles for a mentor, and they morph as the mentor-student relationship matures. For the most part, you mentor by example in how you conduct your research and clinics. One proactive aspect of mentor-ing is seeking or creating opportunities for students in the form of awards, speaking engagements, introducing them to leaders in the field, and putting their names forward for committees in scientific societies. Importantly, do not for-get they are people with life issues too, so listen.

AG: How did you become involved in ICRS? LF: As a PhD student, I presented my work at the ICRS meet-ing in Boston and then again in Sweden. I was elected to the general board in absentia and served as Treasurer before being elected as President.

AG: You are a role model to many people – particularly dur-ing your time as ICRS President. What were the most im-portant tasks that you were involved in/led, and what is your legacy to ICRS? LF: I learned a lot during my Presidency and enjoyed work-ing with the many cultures represented in the Society. I am very proud to have been the first Veterinarian and woman President of the ICRS, which I hope has inspired others to seek leadership roles in the ICRS and other societies. At the time of my Presidency, the ICRS was working with a man-agement company, and that alliance made it challenging to make strategic decisions important for growth and finan-cial security. We realized we needed to take the society in a new direction, therefore we become an independent soci-ety, developed a new financial model and a legal model for the society. We also set a priori goals for taking the ICRS to nations that were under represented in the general mem-bership and leadership positions. Oh, we also launched Cartilage!

AG: What leadership roles are you currently involved in? LF: My laboratory and clinical caseload have continued to grow and I sit on several grant review councils, so I have not had much spare time to engage in other leadership posi-tions. I have my eye on a few positions…

AG: You have published extensively on PRP. What is its current role in the clinic? LF: Indications for use of PRP and other biologics are be-coming clearer for joint pain, ligaments, tendons, and mus-cle. I think too much is expected from these biologics; noth-

ing is going to repair a chronic or completely degenerated tissue, yet many still use biologics only when all else has failed. Therefore, I think the role for PRP in the clinic is in early, moderate disease, when the body still has a chance at repair. There is some evidence that PRP can decrease pain as well as enhance tissue repair, which will allow early application of rehabilitation and return to function.

AG: What do you see for the future of cartilage repair? LF: In addition to filling the cartilage void so the mechanical integrity of cartilage is restored, we need treatments aimed at the source of pain - the subchondral bone and synovial membrane. Presently, and in the future, work will continue to elucidate the pathophysiology of cartilage degeneration starting at time zero, meaning at the time of trauma, when we can still intervene.

AG: You have been involved with discussions with the FDA. Do you feel regulations will change in the future to allow easier access to emerging technologies? LF: Sadly, no. Current Federal regulations are hurting inno-vation in cartilage repair. Anything new on the market is es-sentially an allograft. You know, ACI was the first and only product approved by the FDA for cartilage repair, and that was in 1997!

AG: What keeps you sane outside work? How do you strike the balance (the Holy Grail….)? LF: Run - Forest run.

AG: Name an athlete you would most like to meet? LF: Dr. J – Julius Erving. He played basketball for the New York Nicks and then the Philadelphia 76ers in the mid 70’s – mid 80’s. He changed the game of basketball with his quick, agile style.

AG: Whom do you most admire? LF: My stepfather. He has always been a source of uncondi-tional support and love. I am not so sure I would have ever made it out of my small farm town in North Dakota if it were not for him. I adore him.

AG: You are stranded on a desert island. What book, piece of music and luxury item to accompany you? LF: The book would be anything written by Laura Hillen-brand, probably Seabisquit, it is an amazing story of hope and resilience. A piece from Art Tatum, arguably the best jazz pianist of all time would be my choice of music. I am not sure how luxury they are, but I would pick a toothbrush or sunglasses to accompany me.

ICRS Journal Club

Review on “Engineered autologous cartilage tis-sue for nasal reconstruction after tumor resection: an observational fi rst-in-human trial” Ilario Fulco, Sylvie Miot, Martin D Haug, Andrea Bar-bero, Anke Wixmerten, Sandra Feliciano, Francine Wolf, Gernot Jundt, Anna Marsano, Jian Farhadi, Michael He-berer, Marcel Jakob, Dirk J Schaefer, Ivan Martin in Lan-cet, Vol. 384, p: 337-346; 2014.

The amazing versatility of human nasal chondrocytes: In their safety and feasibility fi rst-in-human study, the authors developed a new approach of engineering au-tologous cartilage for the reconstruction of the nasal alar lobule defect in fi ve patients with excised non-mel-anoma skin cancers.

Autologous cartilage grafts – harvested from rib, au-ricular concha or nasal septum - currently represent the best replacement for the stiff fi bromuscular fatty tissue of the alar lobule. Donor-site morbidity and additional surgery are however the major draw-backs.

To engineer cartilage suitable for transplantation, au-tologous nasal chondrocytes were isolated from a sep-tal cartilage biopsy, taken at the time of biopsying the affected skin. The previously established protocol for cell expansion yielded enough cells (84 million) to seed on two Chondro-Gide membranes (a total of 12.5cm2). Two weeks later, the cartilage-like tissue underwent examination for cell viability based on which, one mem-brane was used for implantation and the other for tis-sue evaluation. Inhomogeneous deposition of proteo-glycans, collagen type II and lack of collagen type I and X were observed in all non-implanted membranes with considerable, albeit expected, patient intervariability. Upon cancer excision, cartilaginous grafts were placed in a procedure identical to the implantation of autolo-gous cartilage. Analysis of biopsies taken at 6 months indicated a formation of fi brous connective tissue, mus-cle fi bres and fat cells, and the absence of a cartilagi-nous matrix, indicating full tissue remodeling. After 12 months, there were no local or systemic adverse events.

This study nicely shows that engineered cartilage can safely replace autologous cartilage for reconstruction of a two-layer defect of the alar lobule, resulting in res-toration of function, aesthetic patient satisfaction and no donor-site morbidity. Although very promising, this approach raises the issue of economic sustainability, an old foe of costly cell-based therapies.

Review on “Adult human neural crest-derived cells for articular cartilage repair” Karoliina Pelttari, Benjamin Pippenger, Marcus Mumme, Sandra Feliciano, Celeste Scotti, Pierre Mainil-Varlet, Alfredo Procino, Brigitte von Rechenberg Thomas Schwamborn, Marcel Jakob, Clemente Cillo, Andrea Bar-bero, Ivan Martin, Science Translation Medicine, Vol. 6 251ra119; 2014.

Nasal chondrocytes for articular cartilage repair: the long sought-after solution?: Taking human nasal chon-drocyte versatility a step further, in this study, the same group demonstrates the ability of these neural crest-derived cells to re-program according to the im-plantation site, and to repair articular cartilage defects better than articular chondrocytes in a goat model.

Similar, yet different to articular chondrocytes (AC), na-sal chondrocytes (NC) have a higher capacity to gener-ate cartilaginous tissue, with lower individual variability yet have a similar response to mechanical forces, as well as recovery from treatment with infl ammatory factors. In contrast to AC, which derive from the mesoderm, NC derive from the ectodermal neural crest. The origin of both cell types was determined via the expression of HOX transcription factors network. Using a duplex and subse-quently qRT-PCR, the authors show expression of HOXC4, HOXC5, HOXC8, HOXD3 and HOXD8 in AC, but not NC from 3 donors after monolayer culture. NC also demonstrated higher number of clonogenic cells, and the clones had faster proliferation rates compared to AC. In two rounds of clonal analysis, with AC and NC expansion (dedifferentia-tion) followed by redifferentiation in micro mass cultures (in vitro assay for cartilage formation) or subcutaneous implantation (ectopic in vivo assay), NC again performed better than AC. Next, NC’s environmental plasticity was shown by the acquisition of mesoderm-specifi c HOX gene expression upon subcutaneous implantation of NC-en-gineered human cartilage (produced as in the previous study) in nude mice. Importantly, the switch in HOX gene expression could not be achieved in vitro with any factor (hyaluronic acid, infl ammatory cytokines, retinoic acid, cultivation on scaffold or mechanical stimulation); solely the co-culture (direct contact) with mesodermal cells in-duced NC re-programming. NC plasticity was also con-fi rmed in a goat, where the GFP-transduced NC expressed mesodermal HOX genes 4 weeks after transplantation in a cartilage defect, and contributed to neocartilage repair tissue. A 6-month preclinical study evaluating in parallel NC and AC demonstrated superior cartilage repair by NC via O’Driscoll score and histology. Finally, the fi rst results of the ongoing clinical trial indicate no systemic or ad-verse events after 18 months, while the MRI imaging after 4 months shows fi lling of the defect.

29

ICRS Journal Club

This study demonstrates the ability of self-renewal and environmental plasticity of human neural crest-derived fully differentiated nasal chondrocytes and their tis-sue regenerative capacity in a goat model of cartilage defect. The approach differs from ACI, not only in the cell source, but also in grafting cartilage tissue, there-by shifting cell therapy towards tissue therapy. Tissue

Viability of Chondrocytes Seeded onto a Colla-gen I/III Membrane for Matrix-Induced Autologous Chondrocyte Implantation By Paul Hindle, Andrew C. Hall, Leela C Biant in J Orth Res. 2014 Nov;32(11):1495-502.

When applying the technique of matrix-assisted ACI or matrix-assisted bone-marrow aspirate concentrate procedures, to cover joint surface defects, at one point in time you have to physically touch the biomaterial and transport it into the joint. The aim of the above study was to analyse the biomechanical effect of handling the material on number of live and dead cells on the collagen membranes used for MACI (Genzyme; Geel, Belgium term their collagen membrane ACI-MaixTM), and to determine the effects of implantation on chon-drocyte viability and density. The cell-seeded mem-branes used for this study were obtained from fi ve pa-tients undergoing a MACI repair to the knee or ankle. All patients were under the age of 40 years old. Sam-ples were collected during or immediately after surgery and kept in their transport media until stained. Images were acquired under fi ve conditions: (i) pre-operative; (ii) handled during surgery; (iii) cut edge; (iv) thumb pressure applied; (v) heavily grasped with forceps. Live/dead cell stains were used to determine viability. Images were obtained for cell counting and morphol-ogy. The mean cell density was 6.60x105 cells/cm2 in specimens that did not have signifi cant trauma. The cell viability on delivery grade membrane was 75.1%, which is higher than the minimum 70% that is guaran-teed by the manufacturer. This dropped to 67.4% af-ter handling, 56.3% after being thumbed and 28.8% after crushing with forceps. When cut with scissors, there was a band of cell death approximately 275µm in width, where cell viability decreased to 13.7%. When only thumbing your membrane during surgery there is a high chance to drop viability to a mean of just over 50%. This would equate to an average of 3.61 x 105/cm2 live cells being implanted.

therapy could offer easier surgical handling and short-en postoperative rehabilitation. Providing that, this very promising clinical data demonstrates successful results, standardization, scalability and – again – cost-effectiveness will have to be addressed.

by Dobrila Nesic, University Bern, Switzerland

The relevance of this fi gure remains uncertain, as the optimal density of cells for cartilage repair has not yet been determined, even though studies on that topic have been reported. Furthermore, this study demon-strated that the cells are not in a monolayer on the MACI membrane and that the dead cells were found closer to the membrane. One possible explanation could be that the deeper cells are less able to obtain nutrition from the culture and transport media during the process of cell seeding and delivery. This effect has been previously described during bioreactor cul-ture as the ‘edging effect’. As these cells will be the furthest away from the defect when the membrane is fi xed in situ, the importance of this remains uncertain. The high magnifi cation images demonstrated that the chondrocytes on the matrix appear more fl attened and spindle-like than typical rounded chondrocytes found in mature articular cartilage. Possible reasons for the cells not appearing as typical chondrocytes include time in culture, culture conditions and a lack of normal mechanical loading. Cellular dedifferentiation, despite 3-D environment culture, being static of nature in this product, is now well accepted and underlined by ex-perimental data. This small sample experimental study nicely demonstrates how differences in handling of the membrane during surgery translates to very different cell viabilities, which may in turn affect the clinical out-come of the surgery. One has to consider that cell vi-ability, as well as quantity, can have relevant infl uence on clinical outcome and has to be considered during surgery. It therefore may be relevant to consider other ACI techniques, with which you never have to touch the biomaterial, since it can applied directly into the de-fect, using a no-touch applicator device.

By Gian Salzmann, Schulthess Klinik Zurich – Switzerland

Mini Study – Clinic al C a se

Treatment of the Pre-Osteoarthritic Joint Disease: Is there a role for DMOADs (disease-modifying osteo-arthritis drugs)? Cecilia Pascual-Garrido1, Scott Rodeo2, Susan Chubins-kaya3, 1University of Colorado, USA, 2Hospital for Special Surgery, USA, 3Rush University. Chicago, USA

Treatment of the pre-osteoarthritic joint disease is a new concept, which emphasizes the need for preventive strate-gies that will modify the course of a disease. Hip dysplasia, FAI (femoroacetabular impingement), joint trauma, menis-cus and ACL injuries are considered conditions that will ac-celerate the development of OA (osteoarthritis).

The current approach to the clinical treatment of OA is the palliation of symptoms arising from late-stage dis-ease. Early-stage disease or pre-osteoarthritis disease is clinically silent in that structural changes typically precede clinical signs and symptoms of pain, deformity, functional limitations, and disability. Metabolic changes in articular cartilage, synovium, and subchondral bone may represent the earliest measurable changes in pre-OA conditions. As such, identifi cation and validation of biomarkers for pre-OA states and at-risk joints may have wide application in clinical trials of new intervention strategies, in routine screening, as well as in activity-modifi cation programs and return to-play evaluations. The ability to observe early and reversible cartilage damage supports development of disease-modifying therapies.

In vitro studies suggest that there is a role for use of dis-ease-modifying therapies after articular cartilage injury, when progressive chondrocyte death and apoptosis have been observed within minutes to days. In vitro, preven-tion of cell death following a cartilage injury can be ob-tained using anti-apoptotic drug therapies, such as P-188 or anti-caspases (Figure 1a-b). Matrix metalloproteinases (MMPs), a diverse family of proteolytic enzymes involved in the maintenance of the extracellular matrix, were ini-tially seen as attractive drug targets for the treatment of OA. However, the development of MMP inhibitors has been limited by their tendency to elicit various undesirable mus-culoskeletal pathologies in both preclinical models and in the clinic, at effi cacious blood concentration. A human clinical trial involving knee OA patients receiving the MMP inhibitor PG-116800 (PG-530742) (NCT00041756) was un-fortunately terminated due to musculoskeletal toxicity. Although these highly specifi c MMP inhibitors may offer signifi cant therapeutic potential, no such molecules have yet been approved for use in the clinic and concerns remain that the muscle toxicity may be due to the molecule class. Yet, there are new research efforts to use siRNA (small in-terfering RNA) to inhibit MMP-13, one of the key MMPs re-sponsible for collagen degradation, as anti-MMP therapy.

Currently, the relative contribution of ADAMTS-4 and AD-AMTS- 5 proteinases to aggrecan loss and early cartilage erosion in OA has been established. Developing pharmaco-logical aggrecanase inhibitors into the clinic has proven dif-fi cult due to poor pharmacokinetic (PK) properties with this class of inhibitor resulting in poor systemic exposure un-less potency is compromised. Exploring the potential syn-ergistic effi cacy of combining an aggrecanase inhibitor with a selective MMP inhibitor or siRNA against MMP-13 and ADAMTS-4, or indeed a pro-anabolic drug may be one way forward in achieving an effi cacious therapeutic drug with suitable PK properties. Targeting anabolic pathways to pro-mote cartilage repair is an alternative strategy for prevent-ing cartilage degeneration. Many laboratories also focus on the potential of naturally present products (resveratrol, green tea, and other) as future DMOADs for joint injuries.

It will be necessary to stratify patients concerning clini-cal, biomechanical, genetic and epigenetic profi les. For example, patients with symptomatic FAI (femoroacetabu-lar impingement) could be stratifi ed using biomarkers of cartilage disease and high-resolution MRI sequences com-bined with quantitative MR techniques that will provide accurate assessment of the cartilage tissue biochemistry. These patients, if shown that they have already developed a “pre-osteoarthritic condition”, could then be offered sur-gical treatment together with DMOADs (disease-modifying osteoarthritis drugs) that could reverse their cartilage to a healthy state. The chances that these patients will have im-provement in symptoms and prevent future OA will be higher than untreated patients with a pre-osteoarthritic condition.

Figures:Anti-apoptotic drugs applied immediately following acute injury reduce the development of post-traumatic cartilage degeneration and promote cell survival after a single im-pact to human ankle cartilage

Fig1a: Cartilage explant 7 days post injury. Note the great amount of dead cells (red cells), evident in all superfi cial, medial and deep layer.

Fig. 1b. When cartilage was pre-treated with P-188 before trauma, the dead cells are only evident in the superfi cial layer, suggesting the potential for pre-vention of cartilage degenera-tion after cartilage trauma. e

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Editorial

ICRS Newsletter

The ICRS Newsletter is published bi-anually. In case of enquires, comments or if you would like to send us your contribution or adverts, please contact office@cartilage.org

Editorial Office

Cartilage Executive Office (CEO) GmbHSpitalstrasse 1908623 WetzikonSwitzerlandPhone +41 44 503 73 70Fax +41 44 503 73 72Email: office@cartilage.orgWeb: www.cartilage.org

Editor in Chief

Alan GetgoodFowler Kennedy Sport Medicine Clinic3M Centre, University of Western OntarioLondon N6A 3K7Ontario, CanadaEmail: alan.getgood@uwo.ca

Members

Nobuo Adachi, Hiroshima, JapanAad Dhollander, Gent, BelgiumDenis Evseenko, Los Angeles, USAMichael Iosifidis, Thessaloniki, GreeceMislav Jelic, Zagreb, CroatiaHenning Madry, Homburg, GermanyDobrila Nesic, Bern, Switzerland Briliantono Munardi, Jakarta, IndonesiaAlberto Siclari, Biella, ItalyGian Salzman, Freiburg, Germany

Edition

2500 print copies & 7000 electronic distributionNewsletter release in July and DecemberAll ICRS Members receive a complimentary copy of theICRS Newsletter

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Opinions expressed in the ICRS Newsletter are not necessarily those of the ICRS Society. ICRS shall not be liable for any loss or damage arising out of, or in connection with any comments, views, representations, statements, opinions, stated in this Newsletter.ed

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