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In this study, nanoflow cytometry to detect EVs in DFU skin tissues is used and found a significant increase in the Translocase of Outer Mitochondrial Membrane 20 (TOM20)\n                    <jats:sup>+<\/jats:sup>\n                    mitochondrial\u2010derived vesicles (MDVs). The role of MDVs in DFU is yet to be reported. Using single\u2010cell datasets, it is discovered that the increase in MDVs may be regulated by Sorting Nexin 9 (SNX9). In vitro experiments revealed that MDVs secreted by fibroblasts cultured in high glucose medium exhibited similar composition and protein enrichment results to those in DFU tissues, suggesting their potential as an ideal in vitro surrogate. These MDVs promoted apoptosis and intracellular oxidative stress, disrupted mitochondrial structure, and reduced aerobic metabolism in target cells. In vivo experiments also showed that MDV drops hindered wound healing in diabetic mice; however, this effect is rescued by SNX9 inhibitors, restoring mitochondrial dynamics and balance. Under high glucose conditions, MDVs significantly upregulated oxidative stress levels and induced mitochondrial dysfunction. This study proposes targeting MDVs as a potential therapeutic strategy for DFU.\n                  <\/jats:p>","DOI":"10.1002\/advs.202407574","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T06:44:13Z","timestamp":1737441853000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Extracellular Mitochondrial\u2010Derived Vesicles Affect the Progression of Diabetic Foot Ulcer by Regulating Oxidative Stress and Mitochondrial Dysfunction"],"prefix":"10.1002","volume":"12","author":[{"given":"Huihui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Burns Nanfang Hospital Southern Medical University  Guangzhou 510515 China"},{"name":"Guangdong Engineering Research Center for Translation of Medical 3D Printing Application Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics National Key Discipline of Human Anatomy School of Basic Medical 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