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In this study, we identified miR\u2010197\u20103p as a previously unrecognized, cartilage\u2010protective miRNA significantly downregulated in both aged and osteoarthritic cartilage. Functional studies revealed that miR\u2010197\u20103p restores ECM anabolism, suppresses senescence and directly targets G3BP1, a stress granule protein linked to redox imbalance and inflammatory signaling. To enable effective intra\u2010articular delivery, we engineered a multifunctional microsphere platform (miR\/PBNP@Gel) by co\u2010encapsulating miR\u2010197\u20103p and ultrasmall Prussian blue nanozymes (PBNPs) into GelMA hydrogel microspheres. This composite design synergistically enhances miRNA stability, facilitates cellular internalization and provides continuous reactive oxygen species (ROS) scavenging to protect mitochondrial function. miR\/PBNP@Gel reversed mitochondrial dysfunction and senescence in OA chondrocytes, while promoting cartilage repair and joint function in vivo. Metabolomic profiling further revealed reprogramming of TCA cycle and antioxidant pathways. This work established miR\u2010197\u20103p as a novel therapeutic regulator in OA and introduced a bioinstructive, injectable, and cell\u2010free strategy that integrates miRNA therapy and redox modulation for disease modification and cartilage regeneration.<\/jats:p>","DOI":"10.1002\/advs.76364","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T17:39:56Z","timestamp":1783186796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanozyme\u2010Reinforced miR\u2010197\u20103p Delivery Resets Metabolic and Senescence Pathways to Rejuvenate Osteoarthritic Cartilage"],"prefix":"10.1002","volume":"13","author":[{"given":"Xuejie","family":"Cai","sequence":"first","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College  Beijing China"},{"name":"Department of Orthopedic Surgery State Key Laboratory of Complex 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