Mid-Term Clinical Outcomes of Atelocollagenassociated Autologous Chondrocyte Implantation for the Repair of Chondral Defects of the Knee

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International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine Cancun, Mexico MAY 12 16, 2019 Mid-Term Clinical Outcomes of Atelocollagenassociated Autologous Chondrocyte Implantation for the Repair of Chondral Defects of the Knee Takuma Kaibara 1, Eiji Kondo 2, Tomohiro Onodera 1, Norimasa Iwasaki 1 Harukazu Tohyama 3, Kazunori Yasuda 4 1 Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Japan 2 Department of Advanced Therapeutic Research for Sports Medicine, Hokkaido University School of Medicine, Japan 3 Faculty of Health Science, Hokkaido University, Japan 4 Sports Medicine and Arthroscopy Centeer, Yagi Orthopaedic Hospital, Sapporo, Japan

2 TAKUMA KAIBARA, MD, PhD I have no financial conflicts to disclose.

Autologous chondrocyte implantation: ACI Atelocollagen-associated ACI is applied new tissue-engineering technology to create a cartilage-like tissue in a 3D culture using atelocollagen gel 1)2) atelocollagen chondrocyte extracellular matrix Short-term good clinical results of atelocollagen-associated ACI was reported in prospective multicenter clinical trial in our previous study 3) Original knee function score Lysholm score a

Purpose To evaluate mid-term clinical outcomes and complications in patients undergoing atelocollagen-associated ACI for the repair of chondral defects of the knee

Methods 2004-2016 ü 12 cases (12 knees) underwent Atelocollagen-associated ACI (Table 1) ü Clinical (Lysholm, KOOS score) and MRI evaluations (MOCART score) at latest follow up ü Statistical analysis: The Student s t-test Table 1 Values Demographic characteristics Age at surgery, mean (range), y 35.7 (15-68) Sex, male/female, n 7/5 Follow-up periods, mean (range), y 8 (2-13) Cause of the osteochondral defect, n Trauma 6 Osteochondritis dissecans 5 Spontaneous osteonecrosis 1 Defect size, mean, cm 2 4.5 (4-6) Defect location, n Medial femoral condyle 7 Lateral femoral condyle 5 Combined surgery, n ACL reconstruction 2 Iliac bone graft 1 OATS 1 Lateral meniscus reconstruction 1

Methods: Atelocollagen-associated ACI procedure 2-stage procedure 1)2)3) 1 Cartilage harvest from unloaded area of femoral condyle 2 Implantation of autologous chondrocytes embedded in atelocollagen gel covered by a sutured periosteal flap

Results Clinical outcomes ü Lysholm score improved from 65 to 90 points (p<0.001) ü Regarding KOOS, all five subscale scores improved (p<0.05) Lysholm score (points) 100 90 80 70 60 50 40 30 20 10 P<0.001 KOOS score (points) 100 90 80 70 60 50 40 30 20 10 * * * * * * P<0.05 Preoperation Latest F/U 0 Preoperation Latest f/u 0 Pain Symptons ADL Sport/Recr QoL

Results MRI evaluation (MOCART score 4) ) Graft integration to border zone and subchondral bone Thickening of the graft in 2 cases MOCART score improved from 10 to 83 points (p<0.001) Preoperation P.O. 24M 100 90 P<0.001 Preoperation P.O. 26M MOCART score (points) 80 70 60 50 40 30 20 10 0 Preoperation Latest F/U

Results Arthroscopic & histological evaluation Needle biopsy at the implantation site was performed in four cases Well bonded to subchondral bone Cartilage-like tissue with proteoglycan-rich matrix Just monolayer different from four layers in normal hyaline cartilage Pre Post Safranin-O stain

Results Complications Partial detachment of the graft; 1 case @ 8 Mths after implantation ü Previously treated with OATS for OCD ü Osteosclerosis of the subchondral bone for implantation Total knee arthroplasty was performed 8 years after surgery in case with spontaneous necrosis of the knee 1M 6M H&E stain Toluidine Blue stain

Discussion Evaluation of outcomes of atelocollagen-associated ACI in 12 cases ü Good to excellent mid-term clinical results ü MOCART score improved significantly ü Grafted tissue: well bonded to the subchondral bone Cartilage-like tissue with a PG-rich matrix was observed in biopsy specimens 100 80 * * * * * * * p<0.05 * p<0.05 100 Preoperation 80 Latest F/U 60 40 20 KOOS score 60 40 20 0 Preoperation Latest f/u Lysholm score 0 Pain Symptons ADL Sport/Recr QoL KOOS biopsy specimen

Discussion Detachment of the graft ü Increased failure rate of ACI after microfracture due to altered subchondral plate 5)6) Partial detachment of the graft after OATS in this study ü Detached graft was histologically cartilage-like tissue ü Osteosclerosis of the subchondral bone for implantation was thought to be the reason of detachment

Conclusion & References Conclusion We evaluated the mid-term outcomes after atelocollagen-associated ACI Lysholm score and KOOS improved significantly @ 8 yrs after surgery Detachment of the graft was observed in 1 case References 1) M Ochi, Y Uchio, K Kawasaki et al Atif Organs 2001 2) M Ochi, Y Uchio, J Iwasa et al. JBJS 2002 3) H Tohyama, K Yasuda, M Ochi et al. JOS 2009 4) G Welsch, T Mamisch, S Trattnig et al. Eur Radiol. 2009 5) T Minas, A Gonmoll, T Bryant et al. AJSM 2009 6) J Pestka, G Bode, P Niemeyer et al. AJSM 2012