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Conventional intra\u2010articular therapies provide limited relief and fail to address its multifactorial pathogenesis. Here, we present an injectable hydrogel microsphere platform that integrates antioxidative, anti\u2010inflammatory, and regenerative functions for localized OA management. Uniform (\u223c125\u00a0\u00b5m) chondroitin sulfate methacrylate (ChSMA)\u2010based microspheres are fabricated via microfluidic photocross\u2010linking. Manganese dioxide nanoparticles provided catalytic reactive oxygen species (ROS) scavenging, while dexamethasone sodium phosphate enabled sustained release, reducing TNF\u2010\u03b1 and IL\u20106 levels by \u223c30%. Bone marrow mesenchymal stem cells (BMSCs) are co\u2010delivered to promote cartilage repair. In vitro, the microspheres reduce intracellular ROS, induce M2 macrophage polarization, and suppress inflammatory cytokines by 60\u201370%, with IL\u201010 levels increased by \u223c90%. 3D co\u2010culture supports chondrocyte\/BMSC viability and matrix production. In vivo, intra\u2010articular injection in a rat OA model markedly reduces cartilage erosion, decreases osteophyte volume by 80%, and improves subchondral bone microarchitecture. Histological staining confirms matrix restoration and structural preservation, with Osteoarthritis Research Society International (OARSI) scores reduced by 88%. Collectively, this injectable hydrogel microsphere system offers a minimally invasive and integrated strategy, simultaneously delivering antioxidative, anti\u2010inflammatory, and regenerative effects for comprehensive OA management.<\/jats:p>","DOI":"10.1002\/advs.202517083","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T12:27:59Z","timestamp":1769776079000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Injectable Chondroitin Sulfate Methacrylate Hydrogel Microspheres Co\u2010Loaded with GLPM Nanozyme, Dexamethasone, and Stem Cells for Synergistic Osteoarthritis Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaochen","family":"Feng","sequence":"first","affiliation":[{"name":"Institute of Biomaterials and Tissue Engineering &amp; Fujian Provincial Key Laboratory of Biochemical Technology Huaqiao University  Xiamen Fujian 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