{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:50:10Z","timestamp":1787313010264,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autologous chondrocyte implantation (ACI) is a cell therapy for the treatment of focal cartilage defects. The ACI product that is currently approved for use in the European Union (EU) consists of spheroids of autologous matrix-associated chondrocytes. These spheroids are spherical aggregates of ex vivo expanded human autologous chondrocytes and their self-synthesized extracellular matrix. The aim is to provide an overview of the preclinical and nonclinical studies that have been performed to ensure reproducible quality, safety, and efficacy of the cell therapy, and to evaluate the clinical data on ACI with spheroids. A systematic review was performed to include all English publications on self-aggregated spheroids of chondrocytes cultured in autologous serum without other supplements. A total of 20 publications were included, 7 pre- and nonclinical and 13 clinical research publications. The pre- and nonclinical research publications describe the development from concept to in vivo efficacy and quality- and safety-related aspects such as biodistribution, tumorigenicity, genetic stability, and potency. The evaluation of clinical research shows short- to mid-term safety and efficacy for the ACI with spheroid-based treatment of cartilage defects in both randomized clinical trials with selected patients, as well as in routine treatment providing real-world data in more complex patients.<\/jats:p>","DOI":"10.3390\/ijms22137149","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T12:03:27Z","timestamp":1625141007000},"page":"7149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Role of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids in the Treatment of Large Chondral Defects in the Knee: A Systematic Review"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5152-9532","authenticated-orcid":false,"given":"Lucienne Angela","family":"Vonk","sequence":"first","affiliation":[{"name":"CO.DON AG, 14513 Teltow, Germany"},{"name":"Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulietta","family":"Ro\u00ebl","sequence":"additional","affiliation":[{"name":"CO.DON AG, 14513 Teltow, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Hernigou","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, EpiCURA Hospital, 7331 Baudour, Belgium"},{"name":"Laboratory of Bone and Metabolic Biochemistry, Faculty of Medecine, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kaps","sequence":"additional","affiliation":[{"name":"CO.DON AG, 14513 Teltow, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Hernigou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, UPEC (University Paris-Est, Cr\u00e9teil), 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.csm.2004.08.007","article-title":"Basic Science of Articular Cartilage and Osteoarthritis","volume":"24","author":"Pearle","year":"2005","journal-title":"Clin. 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