{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:29:11Z","timestamp":1789586951170,"version":"build-2803163510"},"reference-count":55,"publisher":"SAGE Publications","issue":"3-4","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tissue Engineering Part A"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>\n                    Osteoarthritis, a degenerative disease of articular cartilage and the leading cause of disability, is preceded by acute cartilage injury in a significant proportion of cases. Current auto- and allograft interventions are limited by supply and variability in therapeutic efficacy, prompting interest in tissue engineering solutions. Cell sheet tissue engineering, a scaffold-free regenerative technique, has shown promise in preclinical and clinical trials across various cell types and diseases. Polydactyly-derived juvenile cartilage-derived chondrocyte (JCC) sheets from juvenile patients are a potent cell source for developing allogeneic therapies. JCC sheets have proven safe and effective in animal models and as an add-on therapy in a recent clinical cartilage repair study. However, JCC\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    expansion leads to de-differentiation, contributing to long healing times. This study hypothesized that\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    differentiation of JCC sheets into hyaline-like cartilage constructs could accelerate cartilage regeneration without compromising implant integration. To this end, sheet integration, maturation, and healing of conventionally prepared vs. differentiated JCC sheets were compared in an established nude rat focal chondral defect model. Differentiated JCC sheets exhibit mature cartilage phenotypes prior to transplant. Both conventional and differentiated JCC sheets are reliably transplanted without additional fixation. Histological evaluation reveals that both transplant groups produced equivalent neocartilage regeneration, filling defects with mature hyaline cartilage at 2- and 4-weeks post-transplant. Notably, differentiated JCC sheets respond to\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    signals, undergoing matrix remodeling and integration with adjacent and subchondral tissue. Given equivalent healing outcomes, the future utility of\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    JCC sheet predifferentiation from other JCC donors with different healing capacities should be balanced against their increased culture costs over conventional sheets.\n                  <\/jats:p>","DOI":"10.1089\/ten.tea.2024.0208","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T11:19:04Z","timestamp":1731928744000},"page":"184-194","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Differentiated and Untreated Juvenile Chondrocyte Sheets Regenerate Cartilage Similarly\n                    <i>In Vivo<\/i>"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6519-640X","authenticated-orcid":false,"given":"Nicol\u00e1s F.","family":"Metzler","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmaceutics, Health Sciences, Cell Sheet Tissue Engineering Center (CSTEC), University of Utah, Salt Lake City, Utah, USA."},{"name":"Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmaceutics, Health Sciences, Cell Sheet Tissue Engineering Center (CSTEC), University of Utah, Salt Lake City, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Matsukura","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmaceutics, Health Sciences, Cell Sheet Tissue Engineering Center (CSTEC), University of Utah, Salt Lake City, Utah, USA."},{"name":"Department of Orthopaedic Surgery, Asahikawa Medical University, Asahikawa, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5859-5225","authenticated-orcid":false,"given":"Adam J.","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmaceutics, Health Sciences, Cell Sheet Tissue Engineering Center (CSTEC), University of Utah, Salt Lake City, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Grainger","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmaceutics, Health Sciences, Cell Sheet Tissue Engineering Center (CSTEC), University of Utah, Salt Lake City, Utah, USA."},{"name":"Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruo","family":"Okano","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmaceutics, Health Sciences, Cell Sheet Tissue Engineering Center (CSTEC), University of Utah, Salt Lake City, Utah, USA."},{"name":"Institute of Advanced Biomedical Engineering and Science, Tokyo Women\u2019s Medical University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"e_1_3_5_2_2","unstructured":"March L Cross M Lo C et al. Osteoarthritis: A Serious Disease. 2016. Available from: https:\/\/oarsi.org\/sites\/oarsi\/files\/docs\/2016\/oarsi_white_paper_oa_serious_disease_121416_1.pdf [Last accessed: February8 2023]."},{"key":"e_1_3_5_3_2","volume-title":"United States Bone and Joint Initative","author":"Hochberg MC","year":"2020","unstructured":"Hochberg MC, , Cisternas MG, , Watkins-Castillo SI. Osteoarthritis. In: United States Bone and Joint Initative. The Burden of Musculoskeletal Diseases in the United States (BMUS): Rosemont, IL; 2020."},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32279-7"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.bot.0000246468.80635.ef"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12178-019-09595-x"},{"key":"e_1_3_5_7_2","first-page":"263","article-title":"Osteochondral allografts in knee surgery: Narrative review of evidence to date","volume":"14","author":"Lai WC","year":"2022","unstructured":"Lai WC, , Bohlen HL, , Fackler NP, et al. Osteochondral allografts in knee surgery: Narrative review of evidence to date. 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