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Despite the availability of various therapeutics and medications, a complete resolution of OA remains elusive. In this study, novel functional hydrogels are developed by integrating natural bioactive molecules for OA treatment. Specifically, baicalin (Bai) is combined with 2\u2010hydroxyethyl acrylate (HEA) to form a polymerizable monomer (HEA\u2010Bai) through esterification, which is subjected to reversible addition\u2010fragmentation chain transfer (RAFT) polymerization to produce Bai\u2010based polymer (P<jats:sub>m<\/jats:sub>). These macromolecules are incorporated into Schiff\u2010base hydrogels, which demonstrate excellent mechanical properties and self\u2010healing performance. Notably, the Bai\u2010based formulations are taken up by fibroblast\u2010like synoviocytes (FLSs), where they regulate glycolysis. Mechanistically, inhibition of yes\u2010associated protein 1 (YAP1) by the formulations suppressed the FLSs glycolysis and reduced the secretion of inflammatory factors, including interleukin 1\u03b2 (IL\u20101\u03b2), IL\u20106, and IL\u20108. Furthermore, the functional hydrogel (AG\u2010P<jats:sub>m<\/jats:sub>)\u2010OC, severing as a lubricant and nutrient, prolonged joint retention of Bai, thereby reducing cartilage degradation and synovial inflammation. Meanwhile, (AG\u2010P<jats:sub>m<\/jats:sub>)\u2010OC alleviated joint pain by targeting the YAP1 signaling and inhibiting macrophage recruitment and polarization. Taken together, this flavonoid\u2010based injectable hydrogel exhibits enhanced biocompatibility and efficacy against OA.<\/jats:p>","DOI":"10.1002\/advs.202410951","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T05:15:09Z","timestamp":1737522909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A Baicalin\u2010Based Functional Polymer in Dynamic Reversible Networks Alleviates Osteoarthritis by Cellular Interactions"],"prefix":"10.1002","volume":"12","author":[{"given":"Yili","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Bone and Joint Surgery the First Affiliated Hospital of Jinan University Key Laboratory of Regenerative Medicine of Ministry of Education Jinan University  Guangzhou Guangdong 510630 China"},{"name":"Department of Immunobiology, College of Life Science and Technology Jinan University  Guangzhou 510632 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