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Because ferroptosis inhibition alone may not restore compromised myogenic capacity, we developed a combined stem cell\u2010conditioning strategy integrating fullerol priming with the stem cell screen\u2010enrich\u2010combine(\u2010biomaterials) circulating system (SECCS). This integrated three\u2010dimensional culture platform uses porous \u03b2\u2010TCP granules and intermittent medium circulation to generate BMSCs\u2010derived extracellular vesicles (EVs). Among 2D\u2010EVs, F\u20102D\u2010EVs, SECCS\u2010EVs, and F\u2010SECCS\u2010EVs, F\u2010SECCS\u2010EVs exhibited the strongest anti\u2010ferroptotic and pro\u2010regenerative effects. In glucolipotoxicity\u2010challenged myoblasts, F\u2010SECCS\u2010EVs attenuated ferroptotic injury and enhanced proliferation and myogenic differentiation. Transcriptomic and functional experiments identified FOXO3 as an important mediator linking antioxidant defense with myogenic programs. In diabetic mice, F\u2010SECCS\u2010EVs improved motor function, muscle strength, myofiber cross\u2010sectional area, and myogenic marker expression while modulating macrophage polarization. Free fullerol, 2D\u2010EVs, and F\u20102D\u2010EVs produced limited recovery, whereas SECCS\u2010EVs were less effective than F\u2010SECCS\u2010EVs. These muscle benefits were accompanied by favorable changes in tibial bone structure. Collectively, these findings support fullerol\u2010primed SECCS culture as a strategy for coordinating ferroptosis control with myogenic recovery in diabetes\u2010associated musculoskeletal degeneration.<\/jats:p>","DOI":"10.1002\/adhm.71868","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T02:15:50Z","timestamp":1792376150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multimodal Programming of Extracellular Vesicles via Nano\u2010Primed SECCS\u2010Based 3D Microenvironments for Coordinated Ferroptosis Suppression and Myogenic Regeneration in Diabetes"],"prefix":"10.1002","author":[{"given":"Zengguang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine  Shanghai P. R. 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