PRAGUE June 2007 Meniscal Allograft Transplantation CARTILAGE PROTECTION

PRAGUE June 2007 Meniscal Allograft Transplantation CARTILAGE PROTECTION ? ? René Verdonk Peter Verdonk F. Almqvist Department of Orthopaedic Surgery Director: Prof. Dr. R. Verdonk Ghent University Hospital Belgium P. VERDONK M. D.

Meniscus lesions n After resection decreased capacity to distribute load higher peak stress on cartilage degeneration • APPROX 4% CARTILAGE VOLUME LOSS PER YEAR 1 • MORE LOSS LATERAL THAN MEDIAL² 1. Cicuttini FM J Rheumatol. 2002 Sep; 29(9): 1954 -6. 2. Chatain F et al Arthroscopy. 2003 Oct; 19(8): 842 -9 6/5/2021 P. VERDONK M. D.

The ultimate goal is to prevent cartilage degeneration relieve pain improve function by a meniscus substitute P. VERDONK M. D.

Preservation techniques for meniscal allografts Cells n Lyophilisation ACELLULAR Deep-freezing n Cryopreservation n n ACELLULAR cultured ‘VIABLE’ 6/5/2021 Mechanics P. VERDONK M. D. Logistics OK! 10 -40% OK! OK!

Viable meniscal allografts n n Allograft harvested < 24 h postmortem Culture medium: DMEM + antibiotics + L-Glut + 20 % acceptor serum In vitro culture for approx. 2 weeks Screening of donor for transmissible diseases Verbruggen G, Verdonk R, et al. Human meniscal proteoglycan metabolism in long-term tissue culture. Knee Surg Sports Traumatol Arthrosc. 1996; 4: 57 -63. Verdonk R, et al. Viable meniscus transplantation. Orthopäde. 1994; 23: 153 -9. 6/5/2021 P. VERDONK M. D.

Indication n n n Younger patient Previous total meniscectomy Moderate to severe postmeniscectomy pain Cartilage status ideally limited degeneration Not old enough to be considered for TKA Good alignment corrective osteotomy Stable joint ligament repair 6/5/2021 P. VERDONK M. D.

Surgical Technique Verdonk P et al. Surgical Technique: Viable Meniscal allograft Transplantation. JBJS Am 2006 6/5/2021 P. VERDONK M. D. Illustrations courtesy of JBJS Am and Harderer & Muller

Transplantation of Viable Meniscal Allograft SURVIVORSHIP ANALYSIS AND CLINICAL OUTCOME OF ONE HUNDRED CASES Mean follow-up 7. 2 years JBJS Am. 2005 April BY PETER C. M. VERDONK, MD, ALEX DEMURIE, MD, KARL FREDRIK ALMQVIST, MD, PHD, ERIC M. VEYS, MD, PHD, GUST VERBRUGGEN, MD, PHD, AND RENÉ VERDONK, MD, PHD Investigation performed at the Departments of Orthopaedic Surgery and Rheumatology, Ghent University Hospital, Ghent, Belgium P. VERDONK M. D.

Patients Mean age at transplantation: 35 years (range 16 -47) Mean follow-up 7. 2 years (range 2 -14. 5) 61 39 MEDIAL LATERAL TOTAL NUMBER = 100 allografts 6/5/2021 P. VERDONK M. D.

Associated Procedures Medial meniscal allografts Lateral meniscal allografts TOTAL NUMBER = 39 medial allografts 6/5/2021 TOTAL NUMBER = 61 lateral allografts = analyzed seperately P. VERDONK M. D.

Clinical Outcome & Survival analysis n n Based on modified Knee Society Score (KSS) Failure was defined as Moderate to severe pain (pain score < 30/50) Poor function (functional score < 80/100) Including conversion to TKA (N=9), capsular resuture (N=2) 6/5/2021 P. VERDONK M. D.

n Only one true survival analysis available in the literature: – van Arkel ER, de Boer HH. Survival analysis of human meniscal transplantations. JBJS (B )2002 ; 84(2): 227 -31. CRYOPRESERVED (mean follow-up 5 years) Mean Survival Time / Survival Rate at 10 y Medial allografts: 5. 75 y / 50. 6% Lateral allografts: 9. 25 y / 76. 54% 6/5/2021 Failure rate: 13/63 (21%) P. VERDONK M. D. ACL deficient knees

Clinical Outcome: PAIN Significantly improved at final follow-up 6/5/2021 P. VERDONK M. D.

Clinical Outcome: FUNCTION Significantly improved at final follow-up 6/5/2021 P. VERDONK M. D.

Failure rate Overall failure rate: 21/100 CASES FAILURES N % 39 100 11/39 MMT+HTO 13/39 33 2/13 Isol. MMT 20/39 51. 3 7/20 61 100 10/61 49/61 80. 3 9/49 28. 2 15. 4 35. 0 16. 4 18. 4 MMT LMT Isol. LMT 6/5/2021 P. VERDONK M. D.

Overall Survivorship Cumulative Survival (%) A Survival MMT vs. LMT 100 74. 2% MMT 90 80 CUMULATIVE SURVIVAL RATE 70 5 years 60 69. 8% LMT 50 40 10 years % S. D. MMT 86. 2 ± 5. 7 74. 2 ± 7. 4 MMT+HTO 100. 0 ± 0. 0 83. 3 Isol. MMT 84. 1 ± 8. 4 72. 4 LMT 90. 2 ± 4. 2 69. 8 Isol. LMT 90. 9 ± 4. 4 66. 8 – LMT 30 LMT-censored 20 – MMT 10 MMT-censored p=0. 733 (log rank test) 0 0 2 4 6 8 10 12 14 16 Follow-up (years) 6/5/2021 P. VERDONK M. D. ± 10. 14 years % 52. 8 ± 14. 4 7 83. 3 ± 10. 7 6 27. 2 ± 21. 1 69. 8 ± 9. 7 66. 8 ± 11. 3 ± 9. 7 ± 11. S. D. 3

Survivorship after isolated allografts transplantation B Survival of isol. MMT vs. isol. LMT Cumulative Survival (%) 100 72. 4% isol. MMT 90 80 70 CUMULATIVE SURVIVAL RATE 5 years 60 % 66. 8% isol. LMT 50 MMT 40 – Isol. LMT 30 20 0 2 4 6 8 10 12 14 52. 8 ± 14. 4 MMT+HTO 100. 0 ± 0. 0 83. 3 ± 10. 7 Isol. MMT 84. 1 ± 8. 4 72. 4 90. 2 ± 4. 2 69. 8 90. 9 ± 4. 4 66. 8 16 Follow-up (years) 6/5/2021 S. D. ± 7. 4 p=0. 680 (log rank test) 0 % 74. 2 Isol. MMT-censored 10 S. D. ± 5. 7 Isol. LMT – Isol. MMT % 14 years 86. 2 LMT Isol. LMT-censored S. D. 10 years P. VERDONK M. D. ± 10. 6 ± 9. 7 ± 11. 3 27. 2 69. 8 66. 8 ± 21. 1 ± 9. 7 ± 11. 3

Survivorship after isolated medial allografts vs. medial allografts combined with HTO C Survival of MMT+HTO vs. Isol. MMT Cumulative Survival (%) 100 83. 3% MMT+HTO 90 80 CUMULATIVE SURVIVAL RATE 70 5 years 72. 4% MMT 60 % MMT 50 30 MMT+HTO-censored 20 – Isol. MMT 10 2 4 6 8 10 12 14 S. D. 52. 8 ± 14. 4 100. 0 ± 0. 0 83. 3 ± 10. 7 84. 1 ± 8. 4 72. 4 ± 10. 6 27. 2 ± 21. 1 LMT 90. 2 ± 4. 2 69. 8 ± 9. 7 Isol. LMT 90. 9 ± 4. 4 66. 8 ± 11. 3 16 Follow-up (years) 6/5/2021 % ± 7. 4 p=0. 156 (log rank test) 0 S. D. 74. 2 Isol. MMT-censored 0 % ± 5. 7 Isol. MMT – MMT+HTO S. D. 14 years 86. 2 MMT+HTO 40 10 years P. VERDONK M. D.

Meniscal Allograft Transplantation LONG TERM CLINICAL FOLLOW-UP WITH RADIOLOGICAL AND MRI CORRELATIONS Mean follow-up 12. 1 years accepted KSSTA 2006 BY PETER C. M. VERDONK, MD, KOEN L VERSTRAETE, MD, Ph. D, KARL FREDRIK ALMQVIST, MD, PHD, KRISTOF DE CUYPER, MD, ERIC M. VEYS, MD, PHD, GUST VERBRUGGEN, MD, PHD, AND RENÉ VERDONK, MD, PHD Investigation performed at the Departments of Orthopaedic Surgery, Radiology and Rheumatology, Ghent University Hospital, Ghent, Belgium P. VERDONK M. D.

Patients Mean age at transplantation: 35. 2 years (range 16 -47) Mean follow-up 12. 1 years (range 10 -14. 8) 15 24 11/24 HTO 3/24 ACL TOTAL NUMBER = 39 allografts 6/5/2021 = analyzed seperately P. VERDONK M. D.

Clinical & Imagery outcome n Knee Society Score (KSS) – preop and postop n (N=100%) Knee Osteoarthritis Outcome Score (KOOS) – Postop n (N=81%) Standing X-rays – Baseline and postop n (N=81%) MRI – Baseline and postop 6/5/2021 (N=68%) Baseline= within 6 mo (XR) to 1 Y (MRI) after transplant P. VERDONK M. D.

Clinical outcome: KSS Mean values Significantly improved at final follow-up 6/5/2021 P. VERDONK M. D.

Clinical outcome: KOOS Mean values However, substantial disability and reduced Qo. L 6/5/2021 P. VERDONK M. D.

Radiological Outcome MMT JSN Fairbanks 6/5/2021 MMT+HTO JSN Fairbanks P. VERDONK M. D. LMT JSN Fairbanks

Radiological outcome preop FU > 10 y LMT, no progression Patient D. L. 6/5/2021 P. VERDONK M. D.

Radiological outcome preop FU > 10 y MMT+HTO, progression by 1 grade Patient V. W. 6/5/2021 P. VERDONK M. D.

Radiological outcome preop FU > 10 y MMT+HTO, progression by 2 grades Patient B. J. 6/5/2021 P. VERDONK M. D.

Radiological outcome preop FU > 10 y Patient V. C. 6/5/2021 LMT, progression by 3 grades P. VERDONK M. D.

Radiological outcome n OVERALL JSN, n OVERALL Fairbanks, n 52% NO PROGRESSION 32% by 1 grade 12% by 2 grades 4% by 3 grades n 36% NO PROGRESSION 32% by 1 grade 32% by 2 grades 0% by 3 grades n n n 6/5/2021 n n n P. VERDONK M. D.

MRI outcome preop FU > 10 y Signal intensity of graft: Grade III stable articular cartilage: no progression 6/5/2021 P. VERDONK M. D. MMTX

MRI outcome MMTX Signal intensity of graft: Grade 0 stable articular cartilage (F+T): progression by 1 grade 6/5/2021 P. VERDONK M. D.

MRI outcome LMTX Signal intensity of graft: Grade 0 III articular cartilage: progression by 1 (F) and 1. 5 (T) grade 6/5/2021 P. VERDONK M. D.

MRI outcome MMTX 6/5/2021 Signal intensity of graft: Grade 0 stable articular cartilage: no progression P. VERDONK M. D.

MRI outcome: Cartilage n. OVERALL Femoral n. OVERALL n 47% Tibial NO n 41% NO PROGRESSION n 6% by. 5 grade 18% by OVERALL: n 35% no. 5 grade n 29% by progression 1 grades n 23% by 1 grades on BOTH n 12%femoral by 1. 5 grades n 12% by 1. 5 grades and tibial cartilage n 6% by 2 grades 6/5/2021 P. VERDONK M. D.

Viable Meniscal Allograft Transplantation SOME BIOLOGICAL CONSIDERATIONS preliminary data BY PETER C. M. VERDONK, MD, KARL FREDRIK ALMQVIST, MD, PHD, GUST VERBRUGGEN, MD, PHD, AND RENÉ VERDONK, MD, PHD Investigation performed at the Departments of Orthopaedic Surgery and Rheumatology, Ghent University Hospital, Ghent, Belgium P. VERDONK M. D.

Histological analysis Viable allograft, 1 Y postop, Recipient DNA 6/5/2021 P. VERDONK M. D.

Histological analysis Viable allograft, 1 Y postop, recipient DNA 6/5/2021 P. VERDONK M. D.

Histological analysis Core= No cells Deepfrozen allograft, 1 Y postop, recipient DNA 6/5/2021 P. VERDONK M. D.

Histological analysis n VIABLE GRAFT: Suggesting complete repopulation of the graft with fibrochondrocyte-like cells n DEEPFROZEN GRAFT: suggesting only superficial and low repopulation. – Phenotype of repopulating cell? ? ? (Rodeo SA et al. Histological analysis of human meniscal allografts. A preliminary report. J Bone Joint Surg Am. 2000; 82: 1071 -82. ) 6/5/2021 P. VERDONK M. D.

Discussion Preservation technique n Lyophilisation abandoned (Wirth et al. ) n No clear clinical benefit deepfrozen/cryopreservation/viable – Biological difference? ? ? – start of a propspective study deepfrozen vs. viable Surgical fixation n No clear clinical difference soft tissue vs. Bone bloc – We still prefer open sugery 6/5/2021 P. VERDONK M. D.

Discussion Associated procedures n n n ACL needs to be reconstructed! (Van Arkel and de Boer) Influence of HTO on survival of MMTx in varus knee MTx in combination with cartilage surgery? Scoring system n Clinical – Objective AND subjective n n 6/5/2021 Radiology MRI P. VERDONK M. D. NEED FOR CONSENSUS

Discussion Does it prevent further cartilage degeneration? ? n inconclusive evidence n Wirth et al. : progression observed (lyophil+deepfrozen) n Verdonk et al. : some do not progress… – CHONDROPROTECTIVE POTENTIAL… n NEED FOR CORRECT CONTROL GROUPS!!! UTOPIA? 6/5/2021 P. VERDONK M. D.

Conclusion Reduces PAIN Improves FUNCTION In approx. 70% at 10 years …Chondroprotective potential? 6/5/2021 P. VERDONK M. D.

Thank you for your attention 6/5/2021 Department of Orthopaedic Surgery and Physical Medicine, Ghent University Hospital, Ghent, Belgium P. VERDONK M. D.