Original Article|Articles in Press

Atelocollagen-associated autologous chondrocyte implantation for the repair of large cartilage defects of the knee: Results at three to seven years

Published:January 09, 2023DOI:



      Recently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints.


      To evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee.


      Thirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively.


      The mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36–84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8–41 months) after A-ACI.


      The present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36–84 months).


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        • Brittberg M.
        • Lindahl A.
        • Nilsson A.
        • Ohlsson C.
        • Isaksson O.
        • Peterson L.
        Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.
        N Engl J Med. 1994 Oct 6; 331: 889-895
        • Zhang C.
        • Cai Y.Z.
        • Lin X.J.
        Autologous chondrocyte implantation: is it likely to become a saviour of large-sized and full-thickness cartilage defect in young adult knee.
        Knee Surg Sports Traumatol Arthrosc. 2016 May; 24: 1643-1650
        • Ochi M.
        • Uchio Y.
        • Tobita M.
        • Kuriwaka M.
        Current concepts in tissue engineering technique for repair of cartilage defect.
        Artif Organs. 2001 Mar; 25: 172-179
        • Krill M.
        • Early N.
        • Everhart J.S.
        • Flanigan D.C.
        Autologous chondrocyte implantation (ACI) for knee cartilage defects: a review of indications, technique, and outcomes.
        JBJS Rev. 2018 Feb; 6: e5
        • Ochi M.
        • Uchio Y.
        • Kawasaki K.
        • Wakitani S.
        • Iwasa J.
        Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee.
        J Bone Joint Surg Br. 2002 May; 84: 571-578
        • Tohyama H.
        • Yasuda K.
        • Minami A.
        • Majima T.
        • Iwasaki N.
        • Muneta T.
        • et al.
        Atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knee: a prospective multicenter clinical trial in Japan.
        J Orthop Sci. 2009 Sep; 14: 579-588
        • Adachi N.
        • Ochi M.
        • Deie M.
        • Nakamae A.
        • Kamei G.
        • Uchio Y.
        • et al.
        Implantation of tissue-engineered cartilage-like tissue for the treatment for full-thickness cartilage defects of the knee.
        Knee Surg Sports Traumatol Arthrosc. 2014 Jun; 22: 1241-1248
        • Takazawa K.
        • Adachi N.
        • Deie M.
        • Kamei G.
        • Uchio Y.
        • Iwasa J.
        • et al.
        Evaluation of magnetic resonance imaging and clinical outcome after tissue-engineered cartilage implantation: prospective 6-year follow-up study.
        J Orthop Sci. 2012 Jul; 17: 413-424
        • Kaibara T.
        • Kondo E.
        • Matsuoka M.
        • Iwasaki K.
        • Onodera T.
        • Momma D.
        • et al.
        Large osteochondral defect in the lateral femoral condyle reconstructed by atelocollagen-associated autologous chondrocyte implantation combined with anterior cruciate ligament reconstruction.
        BMC Muscoskel Disord. 2020 Jul 27; 21: 494
        • Schreiner M.M.
        • Raudner M.
        • Marlovits S.
        • Bohndorf K.
        • Weber M.
        • Zalaudek M.
        • et al.
        The MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 knee score and atlas.
        Cartilage. 2019 Aug 17; 1947603519865308
        • Smith G.D.
        • Taylor J.
        • Almqvist K.F.
        • Erggelet C.
        • Knutsen G.
        • Garcia Portabella M.
        • et al.
        Arthroscopic assessment of cartilage repair: a validation study of 2 scoring systems.
        Arthroscopy. 2005 Dec; 21: 1462-1467
        • Van Den Borne Mpj
        • Raijmakers N.J.H.
        • Vanlauwe J.
        • Victor J.
        • De Jong S.N.
        • Bellemans J.
        • et al.
        International cartilage repair society (ICRS) and oswestry macroscopic cartilage evaluation scores validated for use in autologous chondrocyte implantation (ACI) and microfracture.
        Osteoarthritis Cartilage. 2007; 15: 1397-1402
        • Mainil-Varlet P.
        • Van Damme B.
        • Nesic D.
        • Knutsen G.
        • Kandel R.
        • Roberts S.
        A new histology scoring system for the assessment of the quality of human cartilage repair: ICRS II.
        Am J Sports Med. 2010 May; 38: 880-890
        • Steinhagen J.
        • Bruns J.
        • Deuretzbacher G.
        • Ruether W.
        • Fuerst M.
        • Niggemeyer O.
        Treatment of osteochondritis dissecans of the femoral condyle with autologous bone grafts and matrix-supported autologous chondrocytes.
        Int Orthop. 2010 Aug; 34: 819-825
        • Ochs B.G.
        • Müller-Horvat C.
        • Albrecht D.
        • Schewe B.
        • Weise K.
        • Aicher W.K.
        • et al.
        Remodeling of articular cartilage and subchondral bone after bone grafting and matrix-associated autologous chondrocyte implantation for osteochondritis dissecans of the knee.
        Am J Sports Med. 2011 Apr; 39: 764-773
        • Aldrian S.
        • Zak L.
        • Wondrasch B.
        • Albrecht C.
        • Stelzeneder B.
        • Binder H.
        • et al.
        Clinical and radiological long-term outcomes after matrix-induced autologous chondrocyte transplantation: a prospective follow-up at a minimum of 10 years.
        Am J Sports Med. 2014 Nov; 42: 2680-2688
        • McCarthy H.S.
        • McCall I.W.
        • Williams J.M.
        • Mennan C.
        • Dugard M.N.
        • Richardson J.B.
        • et al.
        Magnetic resonance imaging parameters at 1 year correlate with clinical outcomes up to 17 years after autologous chondrocyte implantation.
        Orthop J Sports Med. 2018 Aug; 62325967118788280
        • de Windt T.S.
        • Welsch G.H.
        • Brittberg M.
        • Vonk L.A.
        • Marlovits S.
        • Trattnig S.
        • et al.
        Is magnetic resonance imaging reliable in predicting clinical outcome after articular cartilage repair of the knee? A systematic review and meta-analysis.
        Am J Sports Med. 2013 Jul; 41: 1695-1702
        • Toh W.S.
        • Brittberg M.
        • Farr J.
        • Foldager C.B.
        • Gomoll A.H.
        • Hui J.H.
        • et al.
        Cellular senescence in aging and osteoarthritis.
        Acta Orthop. 2016 Dec; 87: 6-14
        • Jeuken R.M.
        • van Hugten P.P.W.
        • Roth A.K.
        • Timur U.T.
        • Boymans T.
        • van Rhijn L.W.
        • et al.
        A systematic review of focal cartilage defect treatments in middle-aged versus younger patients.
        Orthop J Sports Med. 2021 Oct; 923259671211031244
        • Bode G.
        • Schmal H.
        • Pestka J.M.
        • Ogon P.
        • Südkamp N.P.
        • Niemeyer P.
        A non-randomized controlled clinical trial on autologous chondrocyte implantation (ACI) in cartilage defects of the medial femoral condyle with or without high tibial osteotomy in patients with varus deformity of less than 5.
        Arch Orthop Trauma Surg. 2013 Jan; 133: 43-49
        • Mehl J.
        • Feucht M.
        • Achtnich A.
        • Imhoff A.B.
        • Niemeyer P.
        • Schmitt A.
        • et al.
        Autologous chondrocyte implantation combined with anterior cruciate ligament reconstruction: similar short-term results in comparison with isolated cartilage repair in ligament intact joints.
        Knee Surg Sports Traumatol Arthrosc. 2022 Oct; 30: 3249-3257
        • Amin A.A.
        • Bartlett W.
        • Gooding C.R.
        • Sood M.
        • Skinner J.A.
        • Carrington R.W.
        • et al.
        The use of autologous chondrocyte implantation following and combined with anterior cruciate ligament reconstruction.
        Int Orthop. 2006 Feb; 30: 48-53
        • Pike A.N.
        • Bryant T.
        • Ogura T.
        • Minas T.
        Intermediate- to long-term results of combined anterior cruciate ligament reconstruction and autologous chondrocyte implantation.
        Orthop J Sports Med. 2017 Feb; 52325967117693591
        • Harris J.D.
        • Siston R.A.
        • Brophy R.H.
        • Lattermann C.
        • Carey J.L.
        • Flanigan D.C.
        Failures, re-operations, and complications after autologous chondrocyte implantation: a systematic review.
        Osteoarthritis Cartilage. 2011 Jul; 19: 779-791
        • Pareek A.
        • Carey J.L.
        • Reardon P.J.
        • Peterson L.
        • Stuart M.J.
        • Krych A.J.
        Long-term outcomes after autologous chondrocyte implantation: a systematic review at mean follow-up of 11.4 years.
        Cartilage. 2016 Oct; 7: 298-308
        • Niethammer T.R.
        • Loitzsch A.
        • Horng A.
        • Baur-Melnyk A.
        • Bendiks M.
        • Gülecyüz M.F.
        • et al.
        Graft hypertrophy after third-generation autologous chondrocyte implantation has no correlation with reduced cartilage quality: matched-pair analysis using T2-weighted mapping.
        Am J Sports Med. 2018 Aug; 46: 2414-2421
        • Niemeyer P.
        • Pestka J.M.
        • Kreuz P.C.
        • Erggelet C.
        • Schmal H.
        • Suedkamp N.P.
        • et al.
        Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint.
        Am J Sports Med. 2008 Nov; 36: 2091-2099
        • Zeifang F.
        • Oberle D.
        • Nierhoff C.
        • Richter W.
        • Moradi B.
        • Schmitt H.
        Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: a randomized clinical trial.
        Am J Sports Med. 2010 May; 38: 924-933
        • Kreuz P.C.
        • Steinwachs M.
        • Erggelet C.
        • Krause S.J.
        • Ossendorf C.
        • Maier D.
        • et al.
        Classification of graft hypertrophy after autologous chondrocyte implantation of full-thickness chondral defects in the knee.
        Osteoarthritis Cartilage. 2007 Dec; 15: 1339-1347
        • Carey J.L.
        • Shea K.G.
        • Lindahl A.
        • Vasiliadis H.S.
        • Lindahl C.
        • Peterson L.
        Autologous chondrocyte implantation as treatment for unsalvageable osteochondritis dissecans: 10- to 25-year follow-up.
        Am J Sports Med. 2020 Apr; 48: 1134-1140
        • Minas T.
        • Gomoll A.H.
        • Rosenberger R.
        • Royce R.O.
        • Bryant T.
        Increased failure rate of autologous chondrocyte implantation after previous treatment with marrow stimulation techniques.
        Am J Sports Med. 2009 May; 37: 902-908
        • Pestka J.M.
        • Bode G.
        • Salzmann G.
        • Südkamp N.P.
        • Niemeyer P.
        Clinical outcome of autologous chondrocyte implantation for failed microfracture treatment of full-thickness cartilage defects of the knee joint.
        Am J Sports Med. 2012 Feb; 40: 325-331
        • Bentley G.
        • Biant L.C.
        • Vijayan S.
        • Macmull S.
        • Skinner J.A.
        • Carrington R.W.
        Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee.
        J Bone Joint Surg Br. 2012 Apr; 94: 504-509