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In this study, a novel therapeutic approach is proposed utilizing mesenchymal stem cell\u2010derived extracellular vesicles (EVs) coating on ruthenium\u2010loaded metal\u2010organic frameworks (Ru@ZrMOF), which exhibit catalase mimetic activities. The EVs coating enhances the biocompatibility and targeting efficiency of the Ru@ZrMOF, while also promoting cartilage protection. Through reactive oxygen species (ROS) scavenging and oxygen production, Ru@ZrMOF\/EVs significantly alleviate joint inflammation, promote cartilage protection, and inhibit pannus formation. The therapeutic mechanism involves polarization of macrophages from the M1 pro\u2010inflammatory phenotype to the M2 anti\u2010inflammatory phenotype, facilitating a shift in cytokine profiles from pro\u2010inflammatory to anti\u2010inflammatory, and downregulation of hypoxia inducible factor\u20101\u03b1. These findings demonstrate that Ru@ZrMOF\/EVs offer a promising strategy for RA treatment by addressing both inflammation and tissue protection through targeted ROS regulation and immune modulation.<\/jats:p>","DOI":"10.1002\/advs.202502894","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T21:33:56Z","timestamp":1768426436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Biocatalytic Nanoregulators Restore Joint Redox\u2010Immune Homeostasis in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"13","author":[{"given":"Xingheng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ultrasound National Clinical Research Center for Geriatrics Med\u2010X Center for Materials West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound National Clinical Research Center for Geriatrics Med\u2010X Center for Materials West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound National Clinical Research Center for Geriatrics Med\u2010X Center for Materials West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujiao","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Ultrasound National Clinical Research Center for Geriatrics Med\u2010X Center for Materials West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangxue","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Ultrasound National Clinical Research Center for Geriatrics Med\u2010X Center for Materials West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1184-4036","authenticated-orcid":false,"given":"Liqiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"MOE Frontiers Science Center for Precision Oncology Faculty of Health Sciences University of Macau  Macau SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound National Clinical Research Center for Geriatrics Med\u2010X Center for Materials West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjiao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound National Clinical Research Center for Geriatrics Med\u2010X Center for Materials West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102776"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31472-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01661"},{"key":"e_1_2_9_4_1","first-page":"591","volume":"18","author":"Finckh A.","year":"2022","journal-title":"Nat. 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