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Here, we develop injectable hydrogel microspheres featuring an interpenetrating polymer network (IPN) and the capability to anchor in situ to the cartilage matrix for OA treatment. Using microfluidics, we fabricate platelet\u2010derived growth factor\u2010BB (PDGF\u2010BB)\u2010loaded IPN microspheres (GS\/GF) and apply a polydopamine (PDA) coating via self\u2010polymerization to form core\u2013shell GS\/GF\u2010PDA\/DS microspheres loaded with diclofenac sodium (DS). Upon intra\u2010articular injection, the PDA shell enabled targeted adhesion to cartilage defects through catechol\u2010mediated bioadhesion, while released DS and PDA collectively alleviate inflammation by scavenging reactive oxygen species, suppressing pro\u2010inflammatory cytokines, and modulating macrophage polarization. Concurrently, PDGF\u2010BB release enhances endogenous mesenchymal stem cell (MSC) recruitment. The IPN structure improves mechanical robustness and provides a dynamic microenvironment conducive to chondrogenic differentiation of recruited MSCs. In vitro, the GS\/GF\u2010PDA\/DS microspheres exhibit good injectability and cartilage\u2010anchoring ability. In addition, they modulate macrophage polarization, attenuate chondrocyte inflammation, and facilitate both the migration and chondrogenic differentiation of MSCs. In vivo, the GS\/GF\u2010PDA\/DS microspheres significantly reduce synovial inflammation and accelerate cartilage regeneration in rats. This study presents a biofunctional material system that integrates immunomodulation, stem cell recruitment, and cartilage repair for comprehensive OA therapy.<\/jats:p>","DOI":"10.1002\/adhm.202504727","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:20:42Z","timestamp":1764332442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Injectable Hydrogel Microspheres for Osteoarthritis Therapy via Endogenous Mesenchymal Stem Cells Homing and Chondrogenic Differentiation Enhancement"],"prefix":"10.1002","volume":"15","author":[{"given":"Longhui","family":"Chen","sequence":"first","affiliation":[{"name":"Academy of Integrative Medicine Fujian University of Traditional Chinese Medicine  Fuzhou China"},{"name":"College of Biological Science and Engineering Fuzhou University  Fuzhou 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