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However, current research primarily focuses on local cartilage repair and phenotype maintenance, lacking a systematic approach to subcellular mitochondrial quality control. To address this, the present study proposes a mitochondrial quality control strategy based on nanozyme hydrogel microspheres (\u201cmitochondrial inspector\u201d), constructed through electrostatic self\u2010assembly, incorporation of dynamic diselenide bonds, and microfluidic technology. The mitochondrial oxidative stress microenvironment is improved by cerium dioxide nanoparticles and combined with metformin to activate autophagy to clear persistently dysfunctional mitochondria, thereby inhibiting OA progression. In vitro results showed that \u201cmitochondrial inspector\u201d not only significantly improved the oxidative stress microenvironment of chondrocytes, but also efficiently scavenged the damaged mitochondria, increased the mitochondrial membrane potential by over 20\u2010fold, and notably improved the mitochondrial function and chondrocyte homeostasis. In a rat OA model, minimally invasive intra\u2010articular injection of the \u201cmitochondrial inspector\u201d effectively regulated mitochondrial quality, alleviated cartilage matrix degradation, reduced osteophyte formation by \u224880%, and reduced the Mankin score for cartilage damage by over 70%. In summary, this study presents a novel nanozyme microsphere\u2010based mitochondrial quality control strategy for the treatment of OA, providing new insights for subcellular therapies for other aging\u2010related diseases.<\/jats:p>","DOI":"10.1002\/adhm.202405069","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:56:58Z","timestamp":1741712218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Cerium Dioxide Nanoparticles\u2010Based Inspector Enhances Mitochondrial Quality Control to Maintain Chondrocyte Homeostasis in Osteoarthritis Therapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Li","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopedics Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine The First Affiliated Hospital of Chongqing Medical University Orthopedic Laboratory of Chongqing Medical University  Chongqing 400016 P. 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