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Nanozymes, which exhibit catalytic activity similar to natural enzymes, is able to promote OA repair through antioxidant, hypoxia alleviation, and regulation of the inflammatory microenvironment, demonstrating significant application potential in OA treatment. In this study, ultra\u2010small binary hybridized Se\u2010doped Pt nanoparticles (PS NPs) are loaded into Zr\u2010based metal\u2010organic frameworks (MOFs) and further encapsulated with oxidized chondroitin sulfate (OCS), ultimately yielding a novel nano\u2010platform (OCS@MOF@PS) for effective OA repair. Due to the bimetallic synergistic catalytic effect, PS NPs exhibited multi\u2010enzyme mimetic activities. In vitro and in vivo studies have demonstrated that OCS@MOF@PS effectively scavenged intracellular ROS, alleviated hypoxia in macrophages, and induced their polarization toward the M2 phenotype. This effect may be associated with the regulation of the PI3K\/Akt\/mTOR signaling pathway. In OA rat model, OCS@MOF@PS significantly attenuated OA joint damage, achieving 78.25 \u00b1 0.28% and 75.70 \u00b1 0.55% reductions in international cartilage repair society (ICRS) score and Mankin score, respectively, at day 56 post\u2010treatment. In conclusion, this nano\u2010platform, with efficient ROS scavenging activity, hypoxia\u2010alleviating capability and excellent biocompatibility, represents a promising therapeutic strategy for OA and other inflammatory diseases fueled by oxidative stress.<\/jats:p>","DOI":"10.1002\/adhm.202504802","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T05:25:25Z","timestamp":1767763525000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Functionalized Metal\u2010Organic Frameworks Loaded with Ultra\u2010Small Pt\u2010Se Nanoenzymes Promote Osteoarthritis Repair via Efficient ROS Scavenging and Macrophage Polarization Modulation"],"prefix":"10.1002","volume":"15","author":[{"given":"Jiang","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Sports Medicine and Rehabilitation Peking University Shenzhen Hospital  Shenzhen 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