{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:36:02Z","timestamp":1792524962655,"version":"4.5.0"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lausanne Orthopedics Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Purpose: To determine whether specific in vitro biologic characteristics and manufacturing kinetics of cultured human articular chondrocytes (HACs) can serve as predictive biomarkers for patient-reported and structural outcomes following second-generation autologous chondrocyte implantation (ACI) in the knee. Materials and Methods: This prospective cohort study evaluated 67 patients (mean age 25.1 \u00b1 8.3 years) treated with second-generation ACI for large focal cartilage defects (mean size 5.4 \u00b1 2.5 cm2) between 2017 and 2024. HACs were expanded under Good Manufacturing Practice (GMP) conditions using human platelet lysate-supplemented media. Four biological determinants were analyzed: (1) initial chondrocyte yield (ICY) isolated from the cartilage biopsy; (2) chondrogenic activity (relative ACAN and COL2A1 expression); (3) final culture confluence level; and (4) HAC population doubling time (PDT) pre- and post-cryopreservation. Clinical outcomes (KOOS and IKDC) and MRI outcomes (MOCART) were assessed at 2 years (T1) and at a mean final follow-up of 4.2 \u00b1 1.7 years (T2) via univariate and multiple regression analyses. Results: Static biosynthetic markers (ACAN\/COL2A1 expression) and final culture confluence did not significantly correlate with longitudinal clinical (KOOS\/IKDC) or structural (MOCART) outcomes. Conversely, the retained kinetic parameters served as strong prognostic indicators. Multiple regression revealed that higher ICY values significantly predicted improvements across most KOOS subscales from baseline to T2, including KOOS Symptoms (\u03b2 = 63.56; p &lt; 0.01), KOOS Pain (\u03b2 = 88.83; p &lt; 0.001), KOOS ADL (\u03b2 = 107.84; p &lt; 0.001), and KOOS Sport and Recreation Function (\u03b2 = 92.3; p &lt; 0.05). Furthermore, a prolonged PDT, indicative of diminished in vitro proliferative vigor, inversely correlated with functional recovery in IKDC (\u03b2 = \u221226.12; p &lt; 0.01), KOOS Pain (\u03b2 = \u221223.09; p &lt; 0.05), and KOOS ADL (\u03b2 = \u221221.71; p &lt; 0.05) scores. Conclusions: The intrinsic proliferative vigor of the HAC cellular payload (shorter PDT) and higher initial cell yields are robust kinetic biomarkers associated with markedly superior mid-term clinical outcomes following second-generation ACI for large focal chondral defects in the knee. In contrast, standard morphological and gene expression metrics failed to predict in vivo functional success. These findings advocate for a risk-based paradigm shift in GMP quality control methodologies, emphasizing dynamic HAC growth kinetics over static cellular features to optimize patient-specific regenerative potential.<\/jats:p>","DOI":"10.3390\/life16081297","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T11:43:02Z","timestamp":1786016582000},"page":"1297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predicting ACI Outcomes with GMP In-Process Control Kinetic Metrics: Initial Chondrocyte Yield and Population Doubling Time as Prognostic Clinical Biomarkers"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3544-0383","authenticated-orcid":false,"given":"Virginie","family":"Philippe","sequence":"first","affiliation":[{"name":"Orthopedics and Traumatology Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5738-8702","authenticated-orcid":false,"given":"Alexis E.","family":"Laurent","sequence":"additional","affiliation":[{"name":"Manufacturing Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-2254","authenticated-orcid":false,"given":"Andr\u00e9","family":"Berchtold","sequence":"additional","affiliation":[{"name":"Institute of Social Sciences, University of Lausanne, CH-1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Hirt-Burri","sequence":"additional","affiliation":[{"name":"Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Ann","family":"Applegate","sequence":"additional","affiliation":[{"name":"Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland"},{"name":"Center for Applied Biotechnology and Molecular Medicine, University of Zurich, CH-8057 Zurich, Switzerland"},{"name":"Oxford OSCAR Suzhou Center, Oxford University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Martin","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery Service, Fribourg Hospital, CH-1752 Villars-sur-Gl\u00e2ne, Switzerland"},{"name":"Department of Surgical Specialties, Fribourg University, CH-1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Current perspectives in stem cell research for knee cartilage repair","volume":"7","author":"Orth","year":"2014","journal-title":"Stem Cells Clon. Adv. Appl."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Liu, Y., Shah, K.M., and Luo, J. (2021). Strategies for articular cartilage repair and regeneration. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.770655"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yue, L., Lim, R., and Owens, B.D. (2024). Latest advances in chondrocyte-based cartilage repair. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061367"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Philippe, V., Laurent, A., Hirt-Burri, N., Abdel-Sayed, P., Scaletta, C., Schneebeli, V., Michetti, M., Brunet, J.F., Applegate, L.A., and Martin, R. (2022). Retrospective analysis of autologous chondrocyte-based cytotherapy production for clinical use: GMP process-based manufacturing optimization in a Swiss university hospital. Cells, 11.","DOI":"10.3390\/cells11061016"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ahmadpoor, X., Sun, J., Douglas, N., Zhu, W., and Lin, H. (2024). Hydrogel-enhanced autologous chondrocyte implantation for cartilage regeneration-An update on preclinical studies. Bioengineering, 11.","DOI":"10.3390\/bioengineering11111164"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1177\/03635465241270152","article-title":"Factors influencing long-term outcomes after matrix-induced autologous chondrocyte implantation: Long-term results at 10 years","volume":"52","author":"Weishorn","year":"2024","journal-title":"Am. J. Sports Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, X., Li, S., Qian, J., Chen, Y., Zhou, Y., and Fu, P. (2021). Early efficacy of type I collagen-based matrix-assisted autologous chondrocyte transplantation for the treatment of articular cartilage lesions. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.760179"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Karami, P., Laurent, A., Philippe, V., Applegate, L.A., Pioletti, D.P., and Martin, R. (2024). Cartilage repair: Promise of adhesive orthopedic hydrogels. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25189984"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1177\/03635465231205309","article-title":"Minimum 10-Year outcomes of matrix-induced autologous chondrocyte implantation in the knee: A systematic review","volume":"52","author":"Wang","year":"2024","journal-title":"Am. J. Sports Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Focsa, M.A., Florescu, S., and Gogulescu, A. (2025). Emerging strategies in cartilage repair and joint preservation. Medicina, 61.","DOI":"10.20944\/preprints202412.0848.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41573-022-00476-6","article-title":"Engineering the next generation of cell-based therapeutics","volume":"21","author":"Bashor","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Capelli, C., Cuofano, C., Pavoni, C., Frigerio, S., Lisini, D., Nava, S., Quaroni, M., Colombo, V., Galli, F., and Bezukladova, S. (2023). Potency assays and biomarkers for cell-based advanced therapy medicinal products. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1186224"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20150017","DOI":"10.1098\/rstb.2015.0017","article-title":"Cell-based therapy technology classifications and translational challenges","volume":"370","author":"Mount","year":"2015","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1007\/s00264-013-2009-z","article-title":"Influence of cryopreservation, cultivation time and patient\u2019s age on gene expression in Hyalograft\u00ae C cartilage transplants","volume":"37","author":"Albrecht","year":"2013","journal-title":"Int. Orthop."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Huang, Y., He, Y., Makarcyzk, M.J., and Lin, H. (2021). Senolytic peptide FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.677576"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1064S","DOI":"10.1177\/19476035211057242","article-title":"Sequential enzymatic digestion of different cartilage tissues: A rapid and high-efficiency protocol for chondrocyte isolation, and its application in cartilage tissue engineering","volume":"13","author":"Yan","year":"2021","journal-title":"Cartilage"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ba\u010denkov\u00e1, D., Trebu\u0148ov\u00e1, M., Demeterov\u00e1, J., and \u017div\u010d\u00e1k, J. (2023). Human chondrocytes, metabolism of articular cartilage, and strategies for application to tissue engineering. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242317096"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2174\/1874325001206010150","article-title":"Cryopreservation effect on proliferative and chondrogenic potential of human chondrocytes isolated from superficial and deep cartilage","volume":"6","author":"Blanco","year":"2012","journal-title":"Open Orthop. J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Philippe, V., Jeannerat, A., Peneveyre, C., Jaccoud, S., Scaletta, C., Hirt-Burri, N., Abdel-Sayed, P., Raffoul, W., Darwiche, S., and Applegate, L.A. (2023). Autologous and allogeneic cytotherapies for large knee (osteo)chondral defects: Manufacturing process benchmarking and parallel functional qualification. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15092333"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1089\/biores.2013.0051","article-title":"Culture expansion in low-glucose conditions preserves chondrocyte differentiation and enhances their subsequent capacity to form cartilage tissue in three-dimensional culture","volume":"3","author":"Heywood","year":"2014","journal-title":"BioRes. Open Access"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1177\/0963689717724794","article-title":"Fully dedifferentiated chondrocytes expanded in specific mesenchymal stem cell growth medium with FGF2 obtains mesenchymal stem cell phenotype in vitro but retains chondrocyte phenotype in vivo","volume":"26","author":"Lee","year":"2017","journal-title":"Cell Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2519\/jospt.2014.5055","article-title":"Clinical rehabilitation guidelines for matrix-induced autologous chondrocyte implantation on the tibiofemoral joint","volume":"44","author":"Edwards","year":"2014","journal-title":"J. Orthop. Sports Phys. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1177\/0363546509331419","article-title":"Patellofemoral full-thickness chondral defects treated with second-generation autologous chondrocyte implantation: Results at 5 years\u2019 follow-up","volume":"37","author":"Gobbi","year":"2009","journal-title":"Am. J. Sports Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1177\/0363546514523927","article-title":"Autologous chondrocyte implantation in the patella: A multicenter experience","volume":"42","author":"Gomoll","year":"2014","journal-title":"Am. J. Sports Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1089\/scd.2024.0008","article-title":"Clinical evaluation of safety and efficacy of a central current Good Manufacturing Practices laboratory produced autologous adipose-derived stromal vascular fraction cell therapy product for the treatment of knee osteoarthritis","volume":"33","author":"Rogers","year":"2024","journal-title":"Stem Cells Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1158\/2159-8290.CD-22-1276","article-title":"A novel autologous CAR-T therapy, YTB323, with preserved T-cell stemness shows enhanced CAR T-cell efficacy in preclinical and early clinical development","volume":"13","author":"Dickinson","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3343\/alm.2023.0382","article-title":"Manufacturing cell and gene therapies: Challenges in clinical translation","volume":"44","author":"Lee","year":"2024","journal-title":"Ann. Lab. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"113561","DOI":"10.1016\/j.jconrel.2025.02.057","article-title":"Automated manufacturing of cell therapies","volume":"381","author":"Melocchi","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.actbio.2021.07.003","article-title":"The influence of chondrocyte source on the manufacturing reproducibility of human tissue engineered cartilage","volume":"131","author":"Middendorf","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Vonk, L.A., Ro\u00ebl, G., Hernigou, J., Kaps, C., and Hernigou, P. (2021). Role of matrix-associated autologous chondrocyte implantation with spheroids in the treatment of large chondral defects in the knee: A systematic review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137149"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cremona, M., Rusconi, G., Ferrario, A., Mariotta, L., Gola, M., and Soldati, G. (2023). Processing adipose tissue samples in a GMP environment standardizes the use of SVF in cell therapy treatments: Data on 302 patients. Biomedicines, 11.","DOI":"10.20944\/preprints202305.1216.v1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"557.e1","DOI":"10.1016\/j.jtct.2026.01.002","article-title":"From vision to viability: Developing infrastructure for cell and gene therapy programs","volume":"32","author":"Mahmoudjafari","year":"2026","journal-title":"Transplant. Cell. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shi, J., Chen, X., Hu, H., and Ung, C.O.L. (2025). The role of hospital pharmacists in supporting the appropriate and safe use of CGT\/ATMPs: A scoping review of current insights. BMC Health Serv. Res., 25.","DOI":"10.1186\/s12913-024-12026-4"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Szarzynski, A., Spadiut, O., Reisbeck, M., Jobst, G., Paterson, R.L., Kamenskaya, A., Gateau, E., Lesch, H.P., Henry, L., and Kozma, B. (2025). CGT 4.0: A distant dream or inevitable future? Smart process automation is critical to make efficient scalability of CGT manufacturing a reality. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1563878"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100411","DOI":"10.1016\/j.iotech.2023.100411","article-title":"Basics of advanced therapy medicinal product development in academic pharma and the role of a GMP simulation unit","volume":"20","author":"Johanna","year":"2023","journal-title":"Immuno-Oncol. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1136\/bjsports-2023-107352","article-title":"Two-year MRI-defined structural damage and patient-reported outcomes following surgery or exercise for meniscal tears in young adults","volume":"57","author":"Clausen","year":"2023","journal-title":"Br. J. Sports Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"355","DOI":"10.2106\/JBJS.25.00770","article-title":"Long-term trajectories of patient-reported outcomes following total knee arthroplasty: A longitudinal study of 1264 patients","volume":"108","author":"Choi","year":"2026","journal-title":"J. Bone Jt. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s11999-007-0098-y","article-title":"Management of confounding in controlled orthopedic trials: A cross-sectional study","volume":"466","author":"Vavken","year":"2008","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lara-Bertrand, A.L., Lizarazo-Fonseca, L., Correa-Araujo, L., Salguero, G., and Silva-Cote, I. (2026). Innovative technologies for articular cartilage repair: Research, development, and clinical translation\u2014A narrative review. J. Funct. Biomater., 17.","DOI":"10.3390\/jfb17030128"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Asnaghi, M.A., Power, L., Barbero, A., Haug, M., K\u00f6ppl, R., Wendt, D., and Martin, I. (2020). Biomarker signatures of quality for engineering nasal chondrocyte-derived cartilage. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00283"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13018-024-05392-6","article-title":"A prospective randomized controlled trial comparing biphasic cartilage repair implant with microfracture in small chondral lesions of knee: Findings at five-year-follow-up","volume":"20","author":"Kuo","year":"2025","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1177\/19476035241244491","article-title":"Magnetic resonance observation of cartilage repair tissue (MOCART) scores > 55 at 6 months postoperative predict ability to achieve patient acceptable symptomatic state at minimum 1 year postoperative following autologous chondrocyte implantation for Grade IV chondral defects about the patellofemoral joint","volume":"16","author":"Retzky","year":"2025","journal-title":"Cartilage"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Davies, R.L., and Kuiper, N.J. (2019). Regenerative medicine: A review of the evolution of autologous chondrocyte implantation (ACI) therapy. Bioengineering, 6.","DOI":"10.3390\/bioengineering6010022"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.jcyt.2024.05.022","article-title":"Considerations for the development of iPSC-derived cell therapies: A review of key challenges by the JSRM-ISCT iPSC Committee","volume":"26","author":"Madrid","year":"2024","journal-title":"Cytotherapy"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100099","DOI":"10.1016\/j.iotech.2022.100099","article-title":"ATMP development and pre-GMP environment in academia: A safety net for early cell and gene therapy development and manufacturing","volume":"16","author":"Silva","year":"2022","journal-title":"Immuno-Oncol. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"465","DOI":"10.2217\/rme-2018-0081","article-title":"The management of risk and investment in cell therapy process development: A case study for neurodegenerative disease","volume":"14","author":"Sebastian","year":"2019","journal-title":"Regen. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.ymthe.2017.04.010","article-title":"Perspectives on manufacturing of high-quality cell therapies","volume":"25","author":"Roy","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"655","DOI":"10.2217\/rme-2021-0026","article-title":"Comparability: What we can learn from the review of advanced therapy medicinal products","volume":"16","author":"Cockroft","year":"2021","journal-title":"Regen. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Salazar-Fontana, L.I. (2022). A regulatory risk-based approach to ATMP\/CGT development: Integrating scientific challenges with current regulatory expectations. Front. Med., 9.","DOI":"10.3389\/fmed.2022.855100"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Holland, S.M., Sohal, A., Nand, A.A., and Hutmacher, D.W. (2024). A quest for stakeholder synchronization in the CAR T-cell therapy supply chain. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1413688"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Sbirkov, Y., Redzheb, M., Forraz, N., McGuckin, C., and Sarafian, V. (2024). High hopes for the biofabrication of articular cartilage\u2014What lies beyond the horizon of tissue engineering and 3D bioprinting?. Biomedicines, 12.","DOI":"10.3390\/biomedicines12030665"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Urli\u0107, I., and Ivkovi\u0107, A. (2021). Cell sources for cartilage repair-Biological and clinical perspective. Cells, 10.","DOI":"10.3390\/cells10092496"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eads0848","DOI":"10.1126\/scitranslmed.ads0848","article-title":"Clinical relevance of engineered cartilage maturation in a randomized multicenter trial for articular cartilage repair","volume":"17","author":"Mumme","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2325967119854442","DOI":"10.1177\/2325967119854442","article-title":"A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of Matrix-Associated Autologous Chondrocyte Implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee","volume":"7","author":"Niemeyer","year":"2019","journal-title":"Orthop. J. Sports Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1177\/03635465241227969","article-title":"10-Year prospective clinical and radiological evaluation after Matrix-Induced Autologous Chondrocyte Implantation and comparison of tibiofemoral and patellofemoral graft outcomes","volume":"52","author":"Ebert","year":"2014","journal-title":"Am. J. Sports Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1177\/1947603510380902","article-title":"Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation","volume":"2","author":"Ebert","year":"2011","journal-title":"Cartilage"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"571S","DOI":"10.1177\/1947603519865308","article-title":"The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 Knee Score and Atlas","volume":"13","author":"Schreiner","year":"2021","journal-title":"Cartilage"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jcot.2017.08.017","article-title":"MR imaging of BioCartilage augmented microfracture surgery utilizing 2D MOCART and KOOS scores","volume":"9","author":"Carter","year":"2018","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2325967114550781","DOI":"10.1177\/2325967114550781","article-title":"Clinical outcome 3 years after autologous chondrocyte implantation does not correlate with the expression of a predefined gene marker set in chondrocytes prior to implantation but is associated with critical signaling pathways","volume":"2","author":"Stenberg","year":"2014","journal-title":"Orthop. J. Sports Med."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Jia, Y., Le, H., Wang, X., Zhang, J., Liu, Y., Ding, J., Zheng, C., and Chang, F. (2023). Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1271762"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"100033","DOI":"10.1016\/j.ocarto.2020.100033","article-title":"Clinical outcome is significantly better with spheroid-based autologous chondrocyte implantation manufactured with more stringent cell culture criteria","volume":"2","author":"Eschen","year":"2020","journal-title":"Osteoarthr. Cartil. Open"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1297\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T11:53:30Z","timestamp":1786017210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":61,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["life16081297"],"URL":"https:\/\/doi.org\/10.3390\/life16081297","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]}}}