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This study discovers the novel roles of three\u2010way crosstalk between meniscus, synovial membrane, and fat in the regulation of meniscus injury, degeneration, and healing. A novel meniscus\u2010on\u2010a\u2010chip (MoC) model is developed, equipped with a bioprinted synovial membrane, engineered fat tissue, and a meniscus explant healing model, treated with bioactive glue and synovial mesenchymal stem cells (syMSCs). Our MoC integrated with a meniscus\u2010specific bioreactor enables a comprehensive investigation into the combinational effects of inflammation and physiological\/pathological loading on meniscus healing and degeneration. The MoC successfully replicates not only meniscus healing induced by bioactive glue but also the OA initiation and progression from meniscus injury. Comprehensive scRNA\u2010seq with CellChat analysis suggests how communications between adipocytes, macrophages, fibrochondrocytes, and syMSCs regulate the fate of meniscus injury in response to exogenous stimulation. This study represents the first identification of cell\u2010cell communication signals between meniscus, synovial membrane, fat, and syMSCs, which are potentially responsible for regulating meniscus healing under inflammation and mechanical loading. These novel findings may have significant implications for developing next\u2010generation therapeutics for meniscus injury and prevention of joint degeneration through regulating multi\u2010tissue crosstalk in the joint.<\/jats:p>","DOI":"10.1002\/advs.77758","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:33:17Z","timestamp":1789619597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Tissue Crosstalk Regulating Meniscus Healing Under Inflammation and Physiological Loading"],"prefix":"10.1002","author":[{"given":"Hun Jin","family":"Jeong","sequence":"first","affiliation":[{"name":"Biomedical Engineering University of Maryland East Shore  Princess Anne Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elen","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Dental Medicine Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Seo","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Dental Medicine Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Dental Medicine Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Comito","sequence":"additional","affiliation":[{"name":"College of Dental Medicine Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-1191","authenticated-orcid":false,"given":"Chang H.","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Dental Medicine Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-031-02576-1","volume-title":"Engineering the Knee Meniscus","author":"Athanasiou K. 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