{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:24:26Z","timestamp":1790720666671,"version":"4.1.0"},"reference-count":194,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T00:00:00Z","timestamp":1615593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007201","name":"Utah Science Technology and Research","doi-asserted-by":"publisher","award":["University Technology Acceleration Grant"],"award-info":[{"award-number":["University Technology Acceleration Grant"]}],"id":[{"id":"10.13039\/100007201","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003882","name":"Institute of International Education","doi-asserted-by":"publisher","award":["Whitaker International Fellowship"],"award-info":[{"award-number":["Whitaker International Fellowship"]}],"id":[{"id":"10.13039\/100003882","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Articular cartilage defects represent an inciting factor for future osteoarthritis (OA) and degenerative joint disease progression. Despite multiple clinically available therapies that succeed in providing short term pain reduction and restoration of limited mobility, current treatments do not reliably regenerate native hyaline cartilage or halt cartilage degeneration at these defect sites. Novel therapeutics aimed at addressing limitations of current clinical cartilage regeneration therapies increasingly focus on allogeneic cells, specifically mesenchymal stem cells (MSCs), as potent, banked, and available cell sources that express chondrogenic lineage commitment capabilities. Innovative tissue engineering approaches employing allogeneic MSCs aim to develop three-dimensional (3D), chondrogenically differentiated constructs for direct and immediate replacement of hyaline cartilage, improve local site tissue integration, and optimize treatment outcomes. Among emerging tissue engineering technologies, advancements in cell sheet tissue engineering offer promising capabilities for achieving both in vitro hyaline-like differentiation and effective transplantation, based on controlled 3D cellular interactions and retained cellular adhesion molecules. This review focuses on 3D MSC-based tissue engineering approaches for fabricating \u201cready-to-use\u201d hyaline-like cartilage constructs for future rapid in vivo regenerative cartilage therapies. We highlight current approaches and future directions regarding development of MSC-derived cartilage therapies, emphasizing cell sheet tissue engineering, with specific focus on regulating 3D cellular interactions for controlled chondrogenic differentiation and post-differentiation transplantation capabilities.<\/jats:p>","DOI":"10.3390\/cells10030643","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T22:13:10Z","timestamp":1615759990000},"page":"643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Trends in Articular Cartilage Tissue Engineering: 3D Mesenchymal Stem Cell Sheets as Candidates for Engineered Hyaline-Like Cartilage"],"prefix":"10.3390","volume":"10","author":[{"given":"Hallie","family":"Thorp","sequence":"first","affiliation":[{"name":"Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA"},{"name":"Department of Biomedical Engineering, University of Utah, 36 S Wasatch Dr, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungsook","family":"Kim","sequence":"additional","affiliation":[{"name":"Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5978-0043","authenticated-orcid":false,"given":"Makoto","family":"Kondo","sequence":"additional","affiliation":[{"name":"Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Maak","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Utah, 590 Wakara Way, Salt Lake City, UT 84108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Grainger","sequence":"additional","affiliation":[{"name":"Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA"},{"name":"Department of Biomedical Engineering, University of Utah, 36 S Wasatch Dr, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruo","family":"Okano","sequence":"additional","affiliation":[{"name":"Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA"},{"name":"Institute of Advanced Biomedical Engineering and Science, Tokyo Women\u2019s Medical University, Wakamatsucho, 2\u22122, Shinjuku-ku, Tokyo 162-8480, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrrheum.2014.157","article-title":"Repair and Tissue Engineering Techniques for Articular Cartilage","volume":"11","author":"Makris","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Memon, A.R., and Quinlan, J.F. (2012). Surgical Treatment of Articular Cartilage Defects in the Knee: Are We Winning?. Adv. Orthop., 2012.","DOI":"10.1155\/2012\/528423"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Falah, M., Nierenberg, G., Soudry, M., Hayden, M., and Volpin, G. (2010). Treatment of Articular Cartilage Lesions of the Knee. Int. Orthop., 621\u2013630.","DOI":"10.1007\/s00264-010-0959-y"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rodeo, S.A. (2019). Cell Therapy in Orthopaedics: Where Are We in 2019?. Bone Jt. J., 361\u2013364.","DOI":"10.1302\/0301-620X.101B4.BJJ-2019-0013.R1"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Abou-El-Enein, M., Elsanhoury, A., and Reinke, P. (2016). Overcoming Challenges Facing Advanced Therapies in the EU Market. Cell Stem Cell, 293\u2013297.","DOI":"10.1016\/j.stem.2016.08.012"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Haddock, R., Lin-Gibson, S., Lumelsky, N., McFarland, R., Roy, K., Saha, K., Zhang, J., and Zylberberg, C. (2017). Manufacturing Cell Therapies: The Paradigm Shift in Health Care of This Century. NAM Perspect., 7.","DOI":"10.31478\/201706c"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1089\/ten.teb.2013.0771","article-title":"Chondrogenic Differentiation of Mesenchymal Stem Cells: Challenges and Unfulfilled Expectations","volume":"20","author":"Somoza","year":"2014","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Barry, F. (2019). MSC Therapy for Osteoarthritis: An Unfinished Story. J. Orthop. Res., 1229\u20131235.","DOI":"10.1002\/jor.24343"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1177\/1759720X12448454","article-title":"Chondrogenesis, Chondrocyte Differentiation, and Articular Cartilage Metabolism in Health and Osteoarthritis","volume":"4","author":"Goldring","year":"2012","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pittenger, M.F., Discher, D.E., P\u00e9ault, B.M., Phinney, D.G., Hare, J.M., and Caplan, A.I. (2019). Mesenchymal Stem Cell Perspective: Cell Biology to Clinical Progress. NPJ Regen. Med., 1\u201315.","DOI":"10.1038\/s41536-019-0083-6"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.jconrel.2020.12.028","article-title":"Allogeneic Mesenchymal Stem Cell Sheet Therapy: A New Frontier in Drug Delivery Systems","volume":"330","author":"Kim","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Thorp, H., Kim, K., Kondo, M., Grainger, D.W., and Okano, T. (2020). Fabrication of Hyaline-like Cartilage Constructs Using Mesenchymal Stem Cell Sheets. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-77842-0"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Blain, E.J. (2009). Involvement of the Cytoskeletal Elements in Articular Cartilage Homeostasis and Pathology. Int. J. Exp. Pathol., 1\u201315.","DOI":"10.1111\/j.1365-2613.2008.00625.x"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/excr.1997.3858","article-title":"In Vitro Chondrogenesis of Bone Marrow-Derived Mesenchymal Progenitor Cells","volume":"238","author":"Johnstone","year":"1998","journal-title":"Exp. Cell Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage Potential of Adult Human Mesenchymal Stem Cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1089\/ten.1998.4.415","article-title":"Chondrogenic Differentiation of Cultured Human Mesenchymal Stem Cells from Marrow","volume":"4","author":"Mackay","year":"1998","journal-title":"Tissue Eng."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.3727\/096368910X557191","article-title":"The Effect of Two- and Three-Dimensional Cell Culture on the Chondrogenic Potential of Human Adipose-Derived Mesenchymal Stem Cells after Subcutaneous Transplantation with an Injectable Hydrogel","volume":"20","author":"Merceron","year":"2011","journal-title":"Cell Transplant."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.biomaterials.2014.10.010","article-title":"Cross-Talk between TGF-Beta\/SMAD and Integrin Signaling Pathways in Regulating Hypertrophy of Mesenchymal Stem Cell Chondrogenesis under Deferral Dynamic Compression","volume":"38","author":"Zhang","year":"2015","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13018-017-0534-y","article-title":"The Use of Mesenchymal Stem Cells for Cartilage Repair and Regeneration: A Systematic Review","volume":"12","author":"Goldberg","year":"2017","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gomez-Salazar, M., Gonzalez-Galofre, Z.N., Casamitjana, J., Crisan, M., James, A.W., and P\u00e9ault, B. (2020). Five Decades Later, Are Mesenchymal Stem Cells Still Relevant?. Front. Bioeng. Biotechnol., 148.","DOI":"10.3389\/fbioe.2020.00148"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41536-018-0055-2","article-title":"Trends in Clinical Trials for Articular Cartilage Repair by Cell Therapy","volume":"3","author":"Negoro","year":"2018","journal-title":"NPJ Regen. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kon, E., Filardo, G., Di Martino, A., and Marcacci, M. (2012). ACI and MACI. J. Knee Surg., 17\u201322.","DOI":"10.1053\/j.oto.2011.11.002"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1615\/CritRevBiomedEng.v37.i1-2.10","article-title":"The Role of Tissue Engineering in Articular Cartilage Repair and Regeneration","volume":"37","author":"Zhang","year":"2009","journal-title":"Crit. Rev. Biomed. Eng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/ar.22829","article-title":"Articular Cartilage Regeneration Using Cell Sheet Technology","volume":"297","author":"Sato","year":"2014","journal-title":"Anat. Rec."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kondo, M., Kameishi, S., Grainger, D.W., and Okano, T. (2020). Novel Therapies Using Cell Sheets Engineered from Allogeneic Mesenchymal Stem\/Stromal Cells. Emerg. Top. Life Sci.","DOI":"10.1042\/ETLS20200151"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0074-7696(04)33001-9","article-title":"Biology of Fibrocartilage Cells","volume":"233","author":"Benjamin","year":"2004","journal-title":"Int. Rev. Cytol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.addr.2018.12.015","article-title":"Articular Fibrocartilage\u2013Why Does Hyaline Cartilage Fail to Repair?","volume":"146","author":"Armiento","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_28","first-page":"1482","article-title":"A Primer in Cartilage Repair","volume":"94","author":"Minas","year":"2012","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/1941738109350438","article-title":"The Basic Science of Articular Cartilage: Structure, Composition, and Function","volume":"1","author":"Bedi","year":"2009","journal-title":"Sports Health"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kamisan, N., Naveen, S.V., Ahmad, R.E., and Tunku, K. (2013). Chondrocyte Density, Proteoglycan Content and Gene Expressions from Native Cartilage Are Species Specific and Not Dependent on Cartilage Thickness: A Comparative Analysis between Rat, Rabbit and Goat. BMC Vet. Res., 9.","DOI":"10.1186\/1746-6148-9-62"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2017.11.021","article-title":"Biomaterials for Articular Cartilage Tissue Engineering: Learning from Biology","volume":"65","author":"Armiento","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-1-4939-3305-1_5","article-title":"Fibrocartilage","volume":"Volume 171","author":"Gharpuray","year":"2016","journal-title":"Handbook of Biomaterial Properties"},{"key":"ref_33","first-page":"1","article-title":"Impact of Total Knee Replacement Practice: Cost Effectiveness Analysis of Data from the Osteoarthritis Initiative","volume":"356","author":"Ferket","year":"2017","journal-title":"BMJ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/jor.21521","article-title":"Critical-Size Defect Induces Unicompartmental Osteoarthritis in a Stable Ovine Knee","volume":"30","author":"Schinhan","year":"2012","journal-title":"J. Orthop. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Houck, D.A., Kraeutler, M.J., Belk, J.W., Frank, R.M., McCarty, E.C., and Bravman, J.T. (2018). Do Focal Chondral Defects of the Knee Increase the Risk for Progression to Osteoarthritis? A Review of the Literature. Orthop. J. Sports Med.","DOI":"10.1177\/2325967118801931"},{"key":"ref_36","first-page":"2470","article-title":"Surgical Management of Articular Cartilage Defects of the Knee","volume":"92","author":"Gomoll","year":"2010","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Akkiraju, H., and Nohe, A. (2016). Role of Chondrocytes in Cartilage Formation, Progression of Osteoarthritis and Cartilage Regeneration. J. Dev. Biol., 3.","DOI":"10.3390\/jdb3040177"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1016\/S0020-1383(13)70004-4","article-title":"Treatment of Cartilage Lesions: What Works and Why?","volume":"44","author":"Marcacci","year":"2013","journal-title":"Injury"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/S1048-6666(97)80033-X","article-title":"Microfracture Technique for Full-Thickness Chondral Defects: Technique and Clinical Results","volume":"7","author":"Steadman","year":"1997","journal-title":"Oper. Tech. Orthop."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gao, L., Orth, P., Cucchiarini, M., and Madry, H. (2019). Autologous Matrix-Induced Chondrogenesis: A Systematic Review of the Clinical Evidence. Am. J. Sports Med., 222\u2013231.","DOI":"10.1177\/0363546517740575"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mithoefer, K., McAdams, T., Williams, R.J., Kreuz, P.C., and Mandelbaum, B.R. (2009). Clinical Efficacy of the Microfracture Technique for Articular Cartilage Repair in the Knee: An Evidence-Based Systematic Analysis. Database Abstr. Rev. Eff. Qual. Rev., 38.","DOI":"10.1177\/0363546508328414"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1007\/s00167-014-3443-1","article-title":"Results at 10\u201314 Years after Microfracture Treatment of Articular Cartilage Defects in the Knee","volume":"24","author":"Solheim","year":"2016","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1007\/s00167-013-2676-8","article-title":"Long-Term Results after Microfracture Treatment for Full-Thickness Knee Chondral Lesions in Athletes","volume":"22","author":"Gobbi","year":"2014","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/272481","article-title":"Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques","volume":"2014","author":"Dewan","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1177\/1947603512460756","article-title":"Regulatory Challenges for Cartilage Repair Technologies","volume":"4","author":"McGowan","year":"2013","journal-title":"Cartilage"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1089\/ten.teb.2009.0590","article-title":"Strategies for Articular Cartilage Lesion Repair and Functional Restoration","volume":"16","author":"Ahmed","year":"2010","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hunziker, E.B., Lippuner, K., Keel, M.J.B., and Shintani, N. (2015). An Educational Review of Cartilage Repair: Precepts & Practice-Myths & Misconceptions-Progress & Prospects. Osteoarthr. Cartil., 334\u2013350.","DOI":"10.1016\/j.joca.2014.12.011"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1177\/0363546517701912","article-title":"Microfracture versus Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Knee: A Systematic Review of 5-Year Outcomes","volume":"46","author":"Kraeutler","year":"2017","journal-title":"Am. J. Sports Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1016\/j.arthro.2016.03.007","article-title":"Clinical Outcomes after Autologous Chondrocyte Implantation in Adolescents\u2019 Knees: A Systematic Review","volume":"32","author":"DiBartola","year":"2016","journal-title":"Arthrosc. J. Arthrosc. Relat. Surg."},{"key":"ref_50","unstructured":"(2021, March 01). FDA Approves First Autologous Cellularized Scaffold for the Repair of Cartilage Defects of the Knee. Available online: https:\/\/cartilage.org\/news\/fda-approves-first-autologous-cellularized-scaffold-for-the-repair-of-cartilage-defects-of-the-knee\/."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/jor.20502","article-title":"Matrix-Induced Autologous Chondrocyte Implantation in Sheep: Objective Assessments Including Confocal Arthroscopy","volume":"26","author":"Jones","year":"2008","journal-title":"J. Orthop. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1177\/0363546510390476","article-title":"Clinical and Magnetic Resonance Imaging-Based Outcomes to 5 Years after Matrix-Induced Autologous Chondrocyte Implantation to Address Articular Cartilage Defects in the Knee","volume":"39","author":"Ebert","year":"2011","journal-title":"Am. J. Sports Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1089\/ten.2006.0246","article-title":"Matrix-Induced Autologous Chondrocyte Implantation (MACI\u00ae): Biological and Histological Assessment","volume":"13","author":"Zheng","year":"2007","journal-title":"Tissue Eng."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.joca.2008.05.002","article-title":"Modification and Validation of the Lysholm Knee Scale to Assess Articular Cartilage Damage","volume":"17","author":"Smith","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Barber-Westin, S.D., and Noyes, F.R. (2010). The International Knee Documentations Committee Rating System. Noyes\u2019 Knee Disorders: Surgery, Rehabilitation, Clinical Outcomes, Elsevier.","DOI":"10.1016\/B978-1-4160-5474-0.00045-X"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1007\/s00167-010-1301-3","article-title":"The Use of the Tegner Activity Scale for Articular Cartilage Repair of the Knee: A Systematic Review","volume":"19","author":"Hambly","year":"2011","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1177\/1947603516638901","article-title":"Matrix-Associated Autologous Chondrocyte Implantation: A Clinical Follow-Up at 15 Years","volume":"7","author":"Gille","year":"2016","journal-title":"Cartilage"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.joca.2007.05.005","article-title":"International Cartilage Repair Society (ICRS) and Oswestry Macroscopic Cartilage Evaluation Scores Validated for Use in Autologous Chondrocyte Implantation (ACI) and Microfracture","volume":"15","author":"Raijmakers","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1302\/0301-620X.87B5.15905","article-title":"Autologous Chondrocyte Implantation versus Matrix-Induced Autologous Chondrocyte Implantation for Osteochondral Defects of the Knee. A Prospective, Randomised Study","volume":"87","author":"Bartlett","year":"2005","journal-title":"J. Bone Jt. Surg. Ser. B"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1177\/0363546509351499","article-title":"Autologous Chondrocyte Implantation Using the Original Periosteum-Cover Technique versus Matrix-Associated Autologous Chondrocyte Implantation: A Randomized Clinical Trial","volume":"38","author":"Zeifang","year":"2010","journal-title":"Am. J. Sports Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/ten.tea.2018.0138","article-title":"An Overview of the Tissue Engineering Market in the United States from 2011 to 2018","volume":"25","author":"Kim","year":"2019","journal-title":"Tissue Eng. Part A"},{"key":"ref_62","unstructured":"BlueCross BlueShield (2018). ACI (Carticel) Phased Out, BlueCross BlueShield. Available online: https:\/\/www.bluecrossnc.com\/sites\/default\/files\/document\/attachment\/services\/public\/pdfs\/medicalpolicy\/autologous_chondrocyte_implantation.pdf."},{"key":"ref_63","first-page":"2865","article-title":"Significant FDA Approvals in 1997","volume":"57","author":"Rheinstein","year":"1998","journal-title":"Am. Fam. Physician"},{"key":"ref_64","unstructured":"Ministry of Food and Drug Safety (2021, March 01). Chondron|Ministry of Food and Drug Safety, Available online: https:\/\/www.mfds.go.kr\/eng\/brd\/m_30\/view.do?seq=70954."},{"key":"ref_65","unstructured":"European Medicines Agency (2016). ChondroCelect|European Medicines Agency (Withdrawal), European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/public-statement\/public-statement-chondrocelect-withdrawal-marketing-authorisation-european-unionen.pdf."},{"key":"ref_66","unstructured":"European Medicines Agency (2021, March 01). ChondroCelect|European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/chondrocelect."},{"key":"ref_67","unstructured":"Medipost (2021, March 01). MEDIPOST Clears Product Approval Renewal of CARTISTEM by the Ministry of Food and Drug Safety (MFDS). Available online: http:\/\/www.medi-post.com\/stem-cell-therapeutic\/2019\/03\/36443\/."},{"key":"ref_68","unstructured":"Sakakibara, N. (2021, March 01). J-TEC Received Government Approval to Manufacture and Sell Autologous Cultured Cartilage JACC\u00ae in Japan. Available online: http:\/\/www.jpte.co.jp\/english\/ir\/library\/JACC_20120730E.pdf."},{"key":"ref_69","unstructured":"NIHR (2021, March 01). NOVOCART 3D for Articular Cartilage Defects of the Knee, Available online: http:\/\/www.io.nihr.ac.uk\/wp-content\/uploads\/2019\/09\/13181-Autologous-Chondrocyte-Implant-for-Articular-Cartilage-Defects-V1.0-SEP2019-NON-CONF.pdf."},{"key":"ref_70","unstructured":"European Medicines Agency (2021, March 01). Maci|European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/maci."},{"key":"ref_71","unstructured":"U.S. Food and Drug Administration (2021, March 01). MACI (Autologous Cultured Chondrocytes on a Porcine Collagen Membrane)|FDA, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/maci-autologous-cultured-chondrocytes-porcine-collagen-membrane."},{"key":"ref_72","unstructured":"Australian Department of Health-Therapeutic Goods Administration (2021, March 01). Ortho-ACI|Australian Department of Health, Available online: https:\/\/www.ebs.tga.gov.au\/servlet\/xmlmillr6?dbid=ebs\/PublicHTML\/pdfStore.nsf&docid=289402&agid=(PrintDetailsPublic)&actionid=1."},{"key":"ref_73","unstructured":"European Medicines Agency (2021, March 01). Spherox|European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/spherox."},{"key":"ref_74","unstructured":"prnewswire.com (2021, March 01). Korea Approves the World\u2019s First Cell and Gene Therapy for Knee Osteoarthritis. Available online: https:\/\/www.prnewswire.com\/news-releases\/korea-approves-the-worlds-first-cell-and-gene-therapy-for-knee-osteoarthritis-300486969.html."},{"key":"ref_75","unstructured":"Won Shin, J. (2021, March 01). Invossa Approval Revoked As Korea Confirms False Data Submission. Available online: https:\/\/pink.pharmaintelligence.informa.com\/PS125369."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"979","DOI":"10.2106\/JBJS.K.00533","article-title":"NeoCart, an Autologous Cartilage Tissue Implant, Compared with Microfracture for Treatment of Distal Femoral Cartilage Lesions","volume":"94","author":"Crawford","year":"2012","journal-title":"J. Bone Jt. Surg."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/bit.25008","article-title":"Allogeneic Cell Therapy Bioprocess Economics and Optimization: Single-Use Cell Expansion Technologies","volume":"111","author":"Simaria","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Heathman, T.R., Nienow, A.W., McCall, M.J., Coopman, K., Kara, B., and Hewitt, C.J. (2015). The Translation of Cell-Based Therapies: Clinical Landscape and Manufacturing Challenges. Regen. Med., 49\u201364.","DOI":"10.2217\/rme.14.73"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Trounson, A., and McDonald, C. (2015). Stem Cell Therapies in Clinical Trials: Progress and Challenges. Cell Stem Cell, 17.","DOI":"10.1016\/j.stem.2015.06.007"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Mekhileri, N.V., Lim, K.S., Brown, G.C.J., Mutreja, I., Schon, B.S., Hooper, G.J., and Woodfield, T.B.F. (2018). Automated 3D Bioassembly of Micro-Tissues for Biofabrication of Hybrid Tissue Engineered Constructs. Biofabrication, 10.","DOI":"10.1088\/1758-5090\/aa9ef1"},{"key":"ref_81","first-page":"189","article-title":"Current Concepts in the Treatment of Cartilage Damage. A Review","volume":"118","author":"Musumeci","year":"2013","journal-title":"Ital. J. Anat. Embryol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1177\/0363546517729152","article-title":"Stem Cell Therapy for Articular Cartilage Repair: Review of the Entity of Cell Populations Used and the Result of the Clinical Application of Each Entity","volume":"46","author":"Park","year":"2018","journal-title":"Am. J. Sports Med."},{"key":"ref_83","first-page":"1","article-title":"Human Mesenchymal Stem Cell Sheets in Xeno-Free Media for Possible Allogenic Applications","volume":"9","author":"Kim","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1302\/0301-620X.101B1.BJJ-2018-0407.R1","article-title":"Long-Term Results of Fresh Osteochondral Allografts and Realignment Osteotomy for Cartilage Repair in the Knee","volume":"101-B","author":"Mei","year":"2019","journal-title":"Bone Jt. J."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kot, M., Baj-Krzyworzeka, M., Szatanek, R., Musia\u0142-Wysocka, A., Suda-Szczurek, M., and Majka, M. (2019). The Importance of HLA Assessment in \u201coff-the-Shelf\u201d Allogeneic Mesenchymal Stem Cells Based-Therapies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225680"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e205","DOI":"10.1097\/TXD.0000000000000724","article-title":"Influence of HLA Matching on the Efficacy of Allogeneic Mesenchymal Stromal Cell Therapies for Osteoarthritis and Degenerative Disc Disease","volume":"3","author":"Vega","year":"2017","journal-title":"Transplant. Direct"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/jor.1100090504","article-title":"Mesenchymal Stem Cells","volume":"9","author":"Caplan","year":"1991","journal-title":"J. Orthop. Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Caplan, A.I., and Sorrell, J.M. (2015). The MSC Curtain That Stops the Immune System. Immunol. Lett.","DOI":"10.1016\/j.imlet.2015.06.005"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal Criteria for Defining Multipotent Mesenchymal Stromal Cells. The International Society for Cellular Therapy Position Statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1016\/j.biopha.2018.11.099","article-title":"Mesenchymal Stem Cell-Based Therapy of Osteoarthritis: Current Knowledge and Future Perspectives","volume":"109","author":"Harrell","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Lee, W.Y., and Wang, B. (2017). Cartilage Repair by Mesenchymal Stem Cells: Clinical Trial Update and Perspectives. J. Orthop. Transl., 76\u201388.","DOI":"10.1016\/j.jot.2017.03.005"},{"key":"ref_92","unstructured":"Schachtele, S., Clouser, C., and Aho, J. (2018). Markers and Methods to Validate Mesenchymal Stem Cell Identity, Potency, and Quality. R&D Syst. White Pap., Available online: https:\/\/www.rndsystems.com\/resources\/articles\/markers-and-methods-verify-mesenchymal-stem-cell-identity-potency-and-quality."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.procbio.2016.04.017","article-title":"Revisiting MSC Expansion from Critical Quality Attributes to Critical Culture Process Parameters","volume":"59","author":"Martin","year":"2017","journal-title":"Process Biochem."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Bravery, C.A., Carmen, J., Fong, T., Oprea, W., Hoogendoorn, K.H., Woda, J., Burger, S.R., Rowley, J.A., Bonyhadi, M.L., and Van\u2019T Hof, W. (2013). Potency Assay Development for Cellular Therapy Products: An ISCT* Review of the Requirements and Experiences in the Industry. Cytotherapy, 9\u201319.e9.","DOI":"10.1016\/j.jcyt.2012.10.008"},{"key":"ref_95","unstructured":"(2011). 95. FDA.; CBER. Draft Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products. Biotechnol. Law Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3727\/096368915X689622","article-title":"Clinical Trials with Mesenchymal Stem Cells: An Update","volume":"25","author":"Squillaro","year":"2016","journal-title":"Cell Transplant."},{"key":"ref_97","first-page":"1","article-title":"Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures","volume":"2018","author":"Merckx","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1089\/ten.teb.2019.0250","article-title":"Lineage Commitment, Signaling Pathways, and the Cytoskeleton Systems in Mesenchymal Stem Cells","volume":"26","author":"Saidova","year":"2019","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e10998","DOI":"10.1371\/journal.pone.0010998","article-title":"Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells","volume":"5","author":"Yamashita","year":"2010","journal-title":"PLoS ONE"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1634\/stemcells.2007-0374","article-title":"Chondrogenic Differentiation of Human Bone Marrow Stem Cells in Transwell Cultures: Generation of Scaffold-Free Cartilage","volume":"25","author":"Murdoch","year":"2007","journal-title":"Stem Cells"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1089\/tea.2007.0272","article-title":"Chondrogenic Differentiation of Human Mesenchymal Stem Cells in Three-Dimensional Alginate Gels","volume":"14","author":"Xu","year":"2008","journal-title":"Tissue Eng. Part A"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1002\/stem.764","article-title":"Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential","volume":"29","author":"Liu","year":"2011","journal-title":"Stem Cells"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000313399","article-title":"Hypertrophy in Mesenchymal Stem Cell Chondrogenesis: Effect of TGF-\u03b2 Isoforms and Chondrogenic Conditioning","volume":"192","author":"Mueller","year":"2010","journal-title":"Cells Tissues Organs"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.biomaterials.2018.11.036","article-title":"Engineering Hyaline Cartilage from Mesenchymal Stem Cells with Low Hypertrophy Potential via Modulation of Culture Conditions and Wnt\/\u03b2-Catenin Pathway","volume":"192","author":"Deng","year":"2019","journal-title":"Biomaterials"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1053\/joca.1999.0306","article-title":"Cellular Interactions and Signaling in Cartilage Development","volume":"8","author":"DeLise","year":"2000","journal-title":"Osteoarthr. Cartil."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1089\/ten.tea.2012.0479","article-title":"A Comparison of Three-Dimensional Culture Systems to Evaluate in Vitro Chondrogenesis of Equine Bone Marrow-Derived Mesenchymal Stem Cells","volume":"19","author":"Watts","year":"2013","journal-title":"Tissue Eng. Part A"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.biomaterials.2015.02.037","article-title":"Scaffold Composition Affects Cytoskeleton Organization, Cell-Matrix Interaction and the Cellular Fate of Human Mesenchymal Stem Cells upon Chondrogenic Differentiation","volume":"52","author":"Li","year":"2015","journal-title":"Biomaterials"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/rheumatology\/ken341","article-title":"Morphology of the Bovine Chondrocyte and of Its Cytoskeleton in Isolation and in Situ: Are Chondrocytes Ubiquitously Paired through the Entire Layer of Articular Cartilage?","volume":"47","author":"Sasazaki","year":"2008","journal-title":"Rheumatology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1089\/ten.tec.2015.0375","article-title":"Analytic Models of Oxygen and Nutrient Diffusion, Metabolism Dynamics, and Architecture Optimization in Three-Dimensional Tissue Constructs with Applications and Insights in Cerebral Organoids","volume":"22","author":"McMurtrey","year":"2016","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Samal, J.R.K., Rangasami, V.K., Samanta, S., Varghese, O.P., and Oommen, O.P. (2021). Discrepancies on the Role of Oxygen Gradient and Culture Condition on Mesenchymal Stem Cell Fate. Adv. Healthc. Mater., 2002058.","DOI":"10.1002\/adhm.202002058"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"141","DOI":"10.2174\/1574888X09666131230142459","article-title":"Roles of Hypoxia During the Chondrogenic Differentiation of Mesenchymal Stem Cells","volume":"9","author":"Shang","year":"2014","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40824-018-0134-x","article-title":"Hypoxic Condition Enhances Chondrogenesis in Synovium-Derived Mesenchymal Stem Cells","volume":"22","author":"Bae","year":"2018","journal-title":"Biomater. Res."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Malladi, P., Xu, Y., Chiou, M., Giaccia, A.J., and Longaker, M.T. (2006). Effect of Reduced Oxygen Tension on Chondrogenesis and Osteogenesis in Adipose-Derived Mesenchymal Cells. Am. J. Physiol. Cell Physiol., 290.","DOI":"10.1152\/ajpcell.00415.2005"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1074\/jbc.M707729200","article-title":"Hypoxia Promotes the Differentiated Human Articular Chondrocyte Phenotype through SOX9-Dependent and -Independent Pathways","volume":"283","author":"Lafont","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Vater, C., Kasten, P., and Stiehler, M. (2011). Culture Media for the Differentiation of Mesenchymal Stromal Cells. Acta Biomater., 463\u2013477.","DOI":"10.1016\/j.actbio.2010.07.037"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Achilli, T.M., Meyer, J., and Morgan, J.R. (2012). Advances in the Formation, Use and Understanding of Multi-Cellular Spheroids. Expert Opin. Biol. Ther., 1347\u20131360.","DOI":"10.1517\/14712598.2012.707181"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1073\/pnas.052716199","article-title":"In Vitro Cartilage Formation by Human Adult Stem Cells from Bone Marrow Stroma Defines the Sequence of Cellular and Molecular Events during Chondrogenesis","volume":"99","author":"Sekiya","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s10529-010-0293-x","article-title":"Chondrogenic Differentiation of Human Mesenchymal Stem Cells: A Comparison between Micromass and Pellet Culture Systems","volume":"32","author":"Zhang","year":"2010","journal-title":"Biotechnol. Lett."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"19185","DOI":"10.1074\/jbc.M414275200","article-title":"Developmental Regulation of Wnt\/\u03b2-Catenin Signals Is Required for Growth Plate Assembly, Cartilage Integrity, and Endochondral Ossification","volume":"280","author":"Tamamura","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/2470351","article-title":"The Signaling Pathways Involved in Chondrocyte Differentiation and Hypertrophic Differentiation","volume":"2016","author":"Li","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/jcp.20656","article-title":"Wnt Induction of Chondrocyte Hypertrophy through the Runx2 Transcription Factor","volume":"208","author":"Dong","year":"2006","journal-title":"J. Cell. Physiol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Madeira, C., Santhagunam, A., Salgueiro, J.B., and Cabral, J.M.S. (2015). Advanced Cell Therapies for Articular Cartilage Regeneration. Trends Biotechnol., 35\u201342.","DOI":"10.1016\/j.tibtech.2014.11.003"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Vinatier, C., Mrugala, D., Jorgensen, C., Guicheux, J., and No\u00ebl, D. (2009). Cartilage Engineering: A Crucial Combination of Cells, Biomaterials and Biofactors. Trends Biotechnol., 307\u2013314.","DOI":"10.1016\/j.tibtech.2009.02.005"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1089\/ten.teb.2015.0142","article-title":"Multiscale Biofabrication of Articular Cartilage: Bioinspired and Biomimetic Approaches","volume":"21","author":"Tatman","year":"2015","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.biomaterials.2017.05.021","article-title":"Selective Laser Sintering Scaffold with Hierarchical Architecture and Gradient Composition for Osteochondral Repair in Rabbits","volume":"137","author":"Du","year":"2017","journal-title":"Biomaterials"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/term.2476","article-title":"In Situ Handheld Three-Dimensional Bioprinting for Cartilage Regeneration","volume":"12","author":"Duchi","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s42242-018-0031-0","article-title":"Biomaterials for Repair and Regeneration of the Cartilage Tissue","volume":"2","author":"Ansari","year":"2019","journal-title":"Bio-Des. Manuf."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Bernhard, J.C., and Vunjak-Novakovic, G. (2016). Should We Use Cells, Biomaterials, or Tissue Engineering for Cartilage Regeneration?. Stem Cell Res. Ther., 56.","DOI":"10.1186\/s13287-016-0314-3"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Campos, Y., Almirall, A., Fuentes, G., Bloem, H.L., Kaijzel, E.L., and Cruz, L.J. (2019). Tissue Engineering: An Alternative to Repair Cartilage. Tissue Eng. Part B Rev., 357\u2013373.","DOI":"10.1089\/ten.teb.2018.0330"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1136\/ard.2002.002162","article-title":"Chondrocyte Number and Proteoglycan Synthesis in the Aging and Osteoarthritic Human Articular Cartilage","volume":"63","author":"Bobacz","year":"2004","journal-title":"Ann. Rheum. Dis."},{"key":"ref_131","first-page":"7","article-title":"Comparison between High Cell-Density Culture Systems for Chondrogenic Differentiation and Articular Cartilage Reconstruction of Human Mesenchymal Stem Cells: A Literature Review","volume":"2","author":"Mahboudi","year":"2017","journal-title":"Regen. Reconstr. Restor."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S1534-5807(04)00075-9","article-title":"Cell Shape, Cytoskeletal Tension, and RhoA Regulate Stem Cell Lineage Commitment","volume":"6","author":"Mcbeath","year":"2004","journal-title":"Dev. Cell"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1177\/0363546508321474","article-title":"Transplantation of de Novo Scaffold-Free Cartilage Implants into Sheep Knee Chondral Defects","volume":"36","author":"Jubel","year":"2008","journal-title":"Am. J. Sports Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1007\/s13770-016-9065-6","article-title":"Disc-Type Hyaline Cartilage Reconstruction Using 3D-Cell Sheet Culture of Human Bone Marrow Stromal Cells and Human Costal Chondrocytes and Maintenance of Its Shape and Phenotype after Transplantation","volume":"13","author":"Jang","year":"2016","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1177\/1947603515627342","article-title":"Transplantation of Scaffold-Free Cartilage-Like Cell-Sheets Made from Human Bone Marrow Mesenchymal Stem Cells for Cartilage Repair: A Preclinical Study","volume":"7","author":"Itokazu","year":"2016","journal-title":"Cartilage"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1089\/ten.tea.2008.0617","article-title":"Production of Hyaline-like Cartilage by Bone Marrow Mesenchymal Stem Cells in a Self-Assembly Model","volume":"15","author":"Elder","year":"2009","journal-title":"Tissue Eng. Part A"},{"key":"ref_137","first-page":"503","article-title":"Autologous Cultured Chondrocytes: Adverse Events Reported to the United States Food and Drug Administration","volume":"88","author":"Wood","year":"2006","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1002\/jor.23535","article-title":"Mechanical Properties and Structure-Function Relationships of Human Chondrocyte-Seeded Cartilage Constructs after in Vitro Culture","volume":"35","author":"Middendorf","year":"2017","journal-title":"J. Orthop. Res."},{"key":"ref_139","first-page":"251","article-title":"Cartilage Defect Regeneration by Ex Vivo Engineered Autologous Microtissue-Preliminary Results","volume":"26","author":"Meyer","year":"2012","journal-title":"In Vivo"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s00167-008-0663-2","article-title":"Clinical Application of Scaffolds for Cartilage Tissue Engineering","volume":"17","author":"Iwasa","year":"2009","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1053\/joca.1999.0324","article-title":"Articular Cartilage Nutrition Is Mediated by Subchondral Bone: A Long-Term Autograft Study in Baboons","volume":"8","author":"Malinin","year":"2000","journal-title":"Osteoarthr. Cartil."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Chu, C.R., Szczodry, M., and Bruno, S. (2010). Animal Models for Cartilage Regeneration and Repair. Tissue Eng. Part B Rev., 16.","DOI":"10.1089\/ten.teb.2009.0452"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"310re9","DOI":"10.1126\/scitranslmed.aac7019","article-title":"Impact of Guidance Documents on Translational Large Animal Studies of Cartilage Repair","volume":"7","author":"Pfeifer","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Gregory, M.H., Capito, N., Kuroki, K., Stoker, A.M., Cook, J.L., and Sherman, S.L. (2012). A Review of Translational Animal Models for Knee Osteoarthritis. Arthritis.","DOI":"10.1155\/2012\/764621"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Goetz, J.E., Fredericks, D., Petersen, E., Rudert, M.J., Baer, T., Swanson, E., Roberts, N., Martin, J., and Tochigi, Y. (2015). A Clinically Realistic Large Animal Model of Intra-Articular Fracture That Progresses to Post-Traumatic Osteoarthritis. Osteoarthr. Cartil.","DOI":"10.1016\/j.joca.2015.05.022"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Ahern, B.J., Parvizi, J., Boston, R., and Schaer, T.P. (2009). Preclinical Animal Models in Single Site Cartilage Defect Testing: A Systematic Review. Osteoarthr. Cartil., 17.","DOI":"10.1016\/j.joca.2008.11.008"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1177\/1947603510397535","article-title":"International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials","volume":"2","author":"Hoemann","year":"2011","journal-title":"Cartilage"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1126\/science.1166753","article-title":"Chemistry: Repair or Replacement\u2013A Joint Perspective","volume":"323","author":"Klein","year":"2009","journal-title":"Science"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/art.23548","article-title":"Biomechanics of Cartilage Articulation: Effects of Lubrication and Degeneration on Shear Deformation","volume":"58","author":"Wong","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1115\/1.3452605","article-title":"The Frictional Behavior of Human Synovial Joints\u2013Part 1: Natural Joints","volume":"97","author":"Unsworth","year":"1975","journal-title":"J. Lubr. Technol."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Patel, J.M., Wise, B.C., Bonnevie, E.D., and Mauck, R.L. (2019). A Systematic Review and Guide to Mechanical Testing for Articular Cartilage Tissue Engineering. Tissue Eng. Part C Methods, 593\u2013608.","DOI":"10.1089\/ten.tec.2019.0116"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Nakagawa, Y., Muneta, T., Otabe, K., Ozeki, N., Mizuno, M., Udo, M., Saito, R., Yanagisawa, K., Ichinose, S., and Koga, H. (2016). Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin in Vitro and in Vivo. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148777"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1126\/science.aay8276","article-title":"Cartilage-Inspired, Lipid-Based Boundary-Lubricated Hydrogels","volume":"370","author":"Lin","year":"2020","journal-title":"Science"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1756-185X.2011.01599.x","article-title":"Mesenchymal Stem Cell Therapy for Knee Osteoarthritis. Preliminary Report of Four Patients","volume":"14","author":"Davatchi","year":"2011","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"136","DOI":"10.5966\/sctm.2012-0030","article-title":"Concise Review: Cell Therapy and Tissue Engineering for Cardiovascular Disease","volume":"1","author":"Haraguchi","year":"2012","journal-title":"Stem Cells Transl. Med."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Yang, J., Yamato, M., Shimizu, T., Sekine, H., Ohashi, K., Kanzaki, M., Ohki, T., Nishida, K., and Okano, T. (2007). Reconstruction of Functional Tissues with Cell Sheet Engineering. Biomaterials, 5033\u20135043.","DOI":"10.1016\/j.biomaterials.2007.07.052"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Yang, J., Yamato, M., Kohno, C., Nishimoto, A., Sekine, H., Fukai, F., and Okano, T. (2005). Cell Sheet Engineering: Recreating Tissues without Biodegradable Scaffolds. Biomaterials, 26.","DOI":"10.1016\/j.biomaterials.2005.04.061"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jcyt.2018.10.013","article-title":"Cell Sheet Technology: A Promising Strategy in Regenerative Medicine","volume":"21","author":"Li","year":"2019","journal-title":"Cytotherapy"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Owaki, T., Shimizu, T., Yamato, M., and Okano, T. (2014). Cell Sheet Engineering for Regenerative Medicine: Current Challenges and Strategies. Biotechnol. J., 904\u2013914.","DOI":"10.1002\/biot.201300432"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/marc.1990.030111109","article-title":"Thermo-responsive Polymeric Surfaces; Control of Attachment and Detachment of Cultured Cells","volume":"11","author":"Yamada","year":"1990","journal-title":"Die Makromol. Chem. Rapid Commun."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1002\/jbm.a.36627","article-title":"Cell Sheet Tissue Engineering: Cell Sheet Preparation, Harvesting\/Manipulation, and Transplantation","volume":"107","author":"Kobayashi","year":"2019","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/(SICI)1097-4636(19990615)45:4<355::AID-JBM10>3.0.CO;2-7","article-title":"Decrease in Culture Temperature Releases Monolayer Endothelial Cell Sheets Together with Deposited Fibronectin Matrix from Temperature-Responsive Culture Surfaces","volume":"45","author":"Kushida","year":"1999","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1002\/adma.200701978","article-title":"Tissue Engineering Based on Cell Sheet Technology","volume":"19","author":"Matsuda","year":"2007","journal-title":"Adv. Mater."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1186\/s13287-019-1431-6","article-title":"Phenotypic Traits of Mesenchymal Stem Cell Sheets Fabricated by Temperature-Responsive Cell Culture Plate: Structural Characteristics of MSC Sheets","volume":"10","author":"Nakao","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0074-7696(08)61542-9","article-title":"Cellular Tensegrity: Exploring How Mechanical Changes in the Cytoskeleton Regulate Cell Growth, Migration, and Tissue Pattern during Morphogenesis","volume":"150","author":"Ingber","year":"1994","journal-title":"Int. Rev. Cytol."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Wei, Q., Reidler, D., Shen, M.Y., and Huang, H. (2013). Keratinocyte Cytoskeletal Roles in Cell Sheet Engineering. BMC Biotechnol., 13.","DOI":"10.1186\/1472-6750-13-17"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Tsuda, Y., Shimizu, T., Yamato, M., Kikuchi, A., Sasagawa, T., Sekiya, S., Kobayashi, J., Chen, G., and Okano, T. (2007). Cellular Control of Tissue Architectures Using a Three-Dimensional Tissue Fabrication Technique. Biomaterials, 28.","DOI":"10.1016\/j.biomaterials.2007.08.002"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Kikuchi, T., Shimizu, T., Wada, M., Yamato, M., and Okano, T. (2014). Automatic Fabrication of 3-Dimensional Tissues Using Cell Sheet Manipulator Technique. Biomaterials, 35.","DOI":"10.1016\/j.biomaterials.2013.12.014"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"5625","DOI":"10.1016\/j.biomaterials.2011.04.050","article-title":"Stacking of Aligned Cell Sheets for Layer-by-Layer Control of Complex Tissue Structure","volume":"32","author":"Williams","year":"2011","journal-title":"Biomaterials"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/nprot.2012.027","article-title":"Fabrication of Functional Three-Dimensional Tissues by Stacking Cell Sheets in Vitro","volume":"7","author":"Haraguchi","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Sekine, W., Haraguchi, Y., Shimizu, T., Yamato, M., Umezawa, A., and Okano, T. (2013). Chondrocyte Differentiation of Human Endometrial Gland-Derived MSCs in Layered Cell Sheets. Sci. World J., 2013.","DOI":"10.1155\/2013\/359109"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Mitani, G., Sato, M., Lee, J.I., Kaneshiro, N., Ishihara, M., Ota, N., Kokubo, M., Sakai, H., Kikuchi, T., and Mochida, J. (2009). The Properties of Bioengineered Chondrocyte Sheets for Cartilage Regeneration. BMC Biotechnol., 9.","DOI":"10.1186\/1472-6750-9-17"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.bbrc.2006.08.096","article-title":"Bioengineered Chondrocyte Sheets May Be Potentially Useful for the Treatment of Partial Thickness Defects of Articular Cartilage","volume":"349","author":"Kaneshiro","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1089\/ten.tea.2010.0659","article-title":"Cardiac Cell Sheet Transplantation Improves Damaged Heart Function via Superior Cell Survival in Comparison with Dissociated Cell Injection","volume":"17","author":"Sekine","year":"2011","journal-title":"Tissue Eng. Part A"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1089\/ten.tea.2014.0310","article-title":"Repair Mechanism of Osteochondral Defect Promoted by Bioengineered Chondrocyte Sheet","volume":"21","author":"Shimizu","year":"2014","journal-title":"Tissue Eng. Part A"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"5278","DOI":"10.1016\/j.biomaterials.2012.03.073","article-title":"Repair of Articular Cartilage Defect with Layered Chondrocyte Sheets and Cultured Synovial Cells","volume":"33","author":"Ito","year":"2012","journal-title":"Biomaterials"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1016\/j.biomaterials.2012.01.056","article-title":"Cartilage Repair in Transplanted Scaffold-Free Chondrocyte Sheets Using a Minipig Model","volume":"33","author":"Ebihara","year":"2012","journal-title":"Biomaterials"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/term.1610","article-title":"Studies of the Humoral Factors Produced by Layered Chondrocyte Sheets","volume":"9","author":"Hamahashi","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/term.1764","article-title":"Characterization of Chondrocyte Sheets Prepared Using a Co-Culture Method with Temperature-Responsive Culture Inserts","volume":"10","author":"Kokubo","year":"2016","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_180","first-page":"2067","article-title":"Rabbit Xenogeneic Transplantation Model for Evaluating Human Chondrocyte Sheets Used in Articular Cartilage Repair","volume":"12","author":"Takahashi","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_181","first-page":"1296","article-title":"Regenerative Effects of Human Chondrocyte Sheets in a Xenogeneic Transplantation Model Using Immune-Deficient Rats","volume":"14","author":"Takizawa","year":"2020","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Sato, M., Yamato, M., Mitani, G., Takagaki, T., Hamahashi, K., Nakamura, Y., Ishihara, M., Matoba, R., Kobayashi, H., and Okano, T. (2019). Combined Surgery and Chondrocyte Cell-Sheet Transplantation Improves Clinical and Structural Outcomes in Knee Osteoarthritis. NPJ Regen. Med., 4.","DOI":"10.1038\/s41536-019-0069-4"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.reth.2018.07.003","article-title":"Cartilage Repair and Inhibition of the Progression of Cartilage Degeneration after Transplantation of Allogeneic Chondrocyte Sheets in a Nontraumatic Early Arthritis Model","volume":"9","author":"Takatori","year":"2018","journal-title":"Regen. Ther."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Toyoda, E., Sato, M., Takahashi, T., Maehara, M., Okada, E., Wasai, S., Watanabe, M., Iijima, H., Nonaka, K., and Kawaguchi, Y. (2020). Transcriptomic and Proteomic Analyses Reveal the Potential Mode of Action of Chondrocyte Sheets in Hyaline Cartilage Regeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010149"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1089\/ten.tec.2015.0254","article-title":"Assessment of the Safety of Chondrocyte Sheet Implantation for Cartilage Regeneration","volume":"22","author":"Yokoyama","year":"2016","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/bs.mcb.2019.11.020","article-title":"Cell Sheet Tissue Engineering for Scaffold-Free Three-Dimensional (3D) Tissue Reconstruction","volume":"Volume 157","author":"Kim","year":"2020","journal-title":"Methods in Cell Biology"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"170","DOI":"10.4161\/org.28990","article-title":"Stacked Stem Cell Sheets Enhance Cell-Matrix Interactions","volume":"10","author":"Patel","year":"2014","journal-title":"Organogenesis"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1002\/term.2102","article-title":"Fabrication of Functional 3D Hepatic Tissues with Polarized Hepatocytes by Stacking Endothelial Cell Sheets in Vitro","volume":"11","author":"Kim","year":"2017","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41232-017-0053-6","article-title":"Characterization of Polydactyly-Derived Chondrocyte Sheets versus Adult Chondrocyte Sheets for Articular Cartilage Repair","volume":"37","author":"Maehara","year":"2017","journal-title":"Inflamm. Regen."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/sj.gt.3302515","article-title":"Enhanced Repair of Articular Cartilage Defects in Vivo by Transplanted Chondrocytes Overexpressing Insulin-like Growth Factor I (IGF-I)","volume":"12","author":"Madry","year":"2005","journal-title":"Gene Ther."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Alkaya, D., Gurcan, C., Kilic, P., Yilmazer, A., and Gurman, G. (2020). Where Is Human-Based Cellular Pharmaceutical R&D Taking Us in Cartilage Regeneration?. 3 Biotech, 1\u201313.","DOI":"10.1007\/s13205-020-2134-5"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1089\/ten.tea.2020.0062","article-title":"Synergistic CRISPRa-Regulated Chondrogenic Extracellular Matrix Deposition without Exogenous Growth Factors","volume":"26","author":"Farhang","year":"2020","journal-title":"Tissue Eng. Part A"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1089\/ten.teb.2015.0147","article-title":"A Road Map to Commercialization of Cartilage Therapy in the United States of America","volume":"22","author":"Sridharan","year":"2015","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40169-019-0244-7","article-title":"From Fiction to Science: Clinical Potentials and Regulatory Considerations of Gene Editing","volume":"8","author":"Schacker","year":"2019","journal-title":"Clin. Transl. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/643\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:35:17Z","timestamp":1760160917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,13]]},"references-count":194,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["cells10030643"],"URL":"https:\/\/doi.org\/10.3390\/cells10030643","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,13]]}}}