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However, current strategies hardly generate sufficient grafts, as tissues cannot maintain size growth and cartilaginous phenotypes simultaneously. Herein, a step\u2010wise strategy is developed for fabricating expandable human macromass cartilage (macro\u2010cartilage) in a 3D condition by employing human polydactyly chondrocytes and a screen\u2010defined serum\u2010free customized culture (CC). CC\u2010induced chondrocytes demonstrate improved cell plasticity, expressing chondrogenic biomarkers after a 14.59\u2010times expansion. Crucially, CC\u2010chondrocytes form large\u2010size cartilage tissues with average diameters of 3.25 \u00b1 0.05\u00a0mm, exhibiting abundant homogenous matrix and intact structure without a necrotic core. Compared with typical culture, the cell yield in CC increases 2.57 times, and the expression of cartilage marker collagen type II increases 4.70 times. Transcriptomics reveal that this step\u2010wise culture drives a proliferation\u2010to\u2010differentiation process through an intermediate plastic stage, and CC\u2010chondrocytes undergo a chondral lineage\u2010specific differentiation with an activated metabolism. Animal studies show that CC macro\u2010cartilage maintains a hyaline\u2010like cartilage phenotype in vivo and significantly promotes the healing of large cartilage defects. Overall, an efficient expansion of human macro\u2010cartilage with superior regenerative plasticity is achieved, providing a promising strategy for joint regeneration.<\/jats:p>","DOI":"10.1002\/advs.202301833","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T07:22:06Z","timestamp":1688368926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Hyperplastic Human Macromass Cartilage for Joint Regeneration"],"prefix":"10.1002","volume":"10","author":[{"given":"Ya","family":"Wen","sequence":"first","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310058 China"},{"name":"Department of Sports Medicine Zhejiang University School of Medicine  Hangzhou 310058 China"},{"name":"Zhejiang University\u2010University of Edinburgh Institute Zhejiang University School of Medicine and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishan","family":"Chen","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; 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