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Here, micelle\u2010microfluidic hydrogel microspheres, featuring keto\u2010enol\u2010thiol bridged nano\u2010sized secondary structures that disintegrate within the intracellular peroxidative environment to reveal \u03b2\u2010diketone groups with metal chelation capabilities, are utilized for the in situ removal of reactive iron, thereby facilitating cartilage repair through the restoration of mitochondrial homeostasis. The relevant experiments demonstrate that the microspheres reduce iron influx by downregulating transferrin receptor (TfR1) expression and decrease mitochondrial iron uptake by upregulating mitochondrial outer membrane iron\u2010sulfur cluster protein (CISD1), thus restoring intracellular mitochondrial iron homeostasis. Furthermore, the antioxidant properties of the ketone\u2010thioether segments synergistically mitigate chondrocyte phospholipid peroxidation via Nrf2\/SLC7A11\/GPX4 axis, inhibiting ferroptosis and slowing OA progression. In summary, this system that in situ sustainably chelates reactive iron via metal coordination exhibits great potential in the minimally invasive treatment of OA and other ferroptosis\u2010mediated diseases.<\/jats:p>","DOI":"10.1002\/adhm.202403933","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:46:18Z","timestamp":1741743978000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["\u03b2\u2010Diketone Functionalized Microspheres Chelate Reactive Iron via Metal Coordination for Cartilage Repair"],"prefix":"10.1002","volume":"14","author":[{"given":"Yong","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery Center for Spinal Minimally Invasive Research Tongren Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200336 China"},{"name":"Department of Spinal Surgery Qinghai University Affiliated Hospital  29 Tongren Road Xi Ning Qinghai 810006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery Center for Spinal Minimally Invasive Research Tongren Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200336 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin 2nd Road Shanghai 200025 P. 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