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Here, inspired by meniscal natural maturational and regenerative process, we developed an effective and translational strategy to facilitate meniscal regeneration by three-dimensionally printing biomimetic meniscal scaffold combining autologous synovium transplant, which contained abundant intrinsic MSCs. We verified that this facilitated anisotropic meniscus\u2013like tissue regeneration and protected cartilage from degeneration in large animal model. Mechanistically, the biomechanics and matrix stiffness up-regulated Piezo1 expression, facilitating concerted activation of calcineurin and NFATc1, further activated YAP-pSmad2\/3-SOX9 axis, and consequently facilitated fibrochondrogenesis of MSCs during meniscal regeneration. In addition, Piezo1 induced by biomechanics and matrix stiffness up-regulated collagen cross-link enzyme expression, which catalyzed collagen cross-link and thereby enhanced mechanical properties of regenerated tissue.<\/jats:p>","DOI":"10.1126\/sciadv.adg8138","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T18:58:31Z","timestamp":1699469911000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":45,"title":["Meniscal fibrocartilage regeneration inspired by meniscal maturational and regenerative process"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3948-4060","authenticated-orcid":true,"given":"Wenqiang","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, China."},{"name":"Beijing Key Laboratory of Sports Injuries, Beijing, 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