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Stromal vascular fraction (SVF) transplantation has demonstrated potential for regenerating damaged joint tissue; however, the pathological microenvironment impairs SVF stemness, thereby limiting therapeutic efficacy. Herein, we developed a bioinspired hydrogel formed via the cross\u2010linking of hyaluronic acid\u2010grafted dopamine and a fibroblast growth factor 2\u2010mimetic peptide\u2010modified RADA16\u2010I. This injectable hydrogel combined excellent gelation performance with multifunctionality, particularly in enhancing SVF proliferation and chondrogenic differentiation. The hydrogel activated forkhead box M1 (FOXM1) \u2013 mediated epigenetic reprogramming, enhancing DNA repair capacity and increasing chromatin accessibility at pluripotency loci. In a rat OA model, combined hydrogel and SVF transplantation significantly enhanced articular cartilage regeneration and ameliorated OA symptoms. This study provides preliminary evidence showing that a biomaterial\u2010mediated epigenetic reprogramming strategy improves recovery in OA, highlighting the therapeutic potential of the novel hydrogel for stem cell\u2010based regenerative medicine.<\/jats:p>","DOI":"10.1002\/advs.202517297","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:37:22Z","timestamp":1776681442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Self\u2010Assembling Hybrid Hydrogel Reprograms the Stromal Vascular Fraction to Treat Osteoarthritis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7734-1229","authenticated-orcid":false,"given":"Waifang","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Xijing Hospital The Fourth Military Medical University  Xi'an P. R. 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