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Here, integration of diabetic\u2010wound single\u2010cell transcriptomic datasets identifies a neutrophil subpopulation enriched in cluster of differentiation 55 (CD55) with complement\u2010regulatory and reparative features. Guided by this atlas\u2010derived signature, activated neutrophil\u2010derived extracellular vesicles (aNEVs) enriched in CD55 are generated under high\u2010glucose and lipopolysaccharide stimulation and incorporated into a microbial transglutaminase\u2010crosslinked gelatin hydrogel for localized delivery and protease\u2010sensitive matrix remodeling. The resulting gelatin\/aNEV composite hydrogel (Gel\/aNEV) attenuates complement\u2010associated inflammatory signaling, C3a production, oxidative stress, and pro\u2010inflammatory cytokine expression, while promoting reparative macrophage reprogramming and endothelial migration. In diabetic wounds, a single application of Gel\/aNEV accelerates wound closure and enhances angiogenesis, collagen remodeling, and tissue regeneration. Integrated transcriptomic\u2013proteomic analyses further reveal coordinated changes in complement, inflammatory, redox, extracellular\u2010matrix, and regenerative programs, supporting a multicomponent therapeutic model. Collectively, this study establishes an atlas\u2010to\u2010therapy framework that uses disease\u2010associated neutrophil states to guide extracellular\u2010vesicle engineering, integrating complement regulation, immune reprogramming, and biomaterial\u2010assisted delivery for diabetic wound repair.<\/jats:p>","DOI":"10.1002\/advs.78320","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:51:43Z","timestamp":1792122703000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Atlas\u2010Guided CD55\u2010Enriched Neutrophil Extracellular Vesicles for Complement\u2013Macrophage Modulation in Diabetic Wounds"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2467-9488","authenticated-orcid":false,"given":"Tairong","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao 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