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Considering that extracellular vesicles (EVs) show promising effects in wound healing, we developed a split-type microneedle (MN-EVs@miR) loaded with miR-125b-enriched engineered EVs (EVs@miR) to treat NM-induced skin injury. EVs were isolated from human umbilical cord mesenchymal stem cells (hUMSCs), loaded with miR-125b via transfection, and then conjugated to hyaluronic acid methacryloyl (HAMA) hydrogel using acrylic acid-polyethylene glycol-N-hydroxysuccinimide (AC-PEG-NHS) to prepare microneedle tips, with polyvinyl alcohol (PVA) and sodium thiosulfate constituting the substrate. The prepared MN-EVs@miR exhibited sufficient mechanical strength (0.34 N\/needle), sustained EVs@miR release over 21 days, and long-term in vivo retention (&amp;gt;21 days) with excellent biocompatibility. In vitro, EVs@miR enhanced cell viability, inhibited apoptosis, regulated inflammation (downregulating TNF-\u03b1, IL-1\u03b2, and IL-6; upregulating IL-10), and promoted angiogenesis. In vivo, MN-EVs@miR significantly mitigated NM-induced skin blistering and necrosis, with superior wound healing efficacy compared to that of EVs@miR injection and blank MNs. In conclusion, the split-type MN-EVs@miR provides a promising preventive and therapeutic strategy for NM-induced skin injuries with potential battlefield and clinical applications.<\/jats:p>","DOI":"10.1021\/acsami.6c12383","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:02:00Z","timestamp":1790629320000},"page":"54503-54514","source":"Crossref","is-referenced-by-count":0,"title":["Split-Type Microneedles Loaded with miR-125b-Enriched Extracellular Vesicles: A Sustained Preventive and Therapeutic Platform for Nitrogen Mustard-Induced Skin Injuries"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0239-7940","authenticated-orcid":true,"given":"Weiqian","family":"Jiang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Naval Medical University , , ,","place":["Shanghai, People's Republic of China, 200433"]},{"name":"The Fourth Medical Center of Chinese PLA General Hospital , , ,","place":["Beijing, People's Republic of China, 100048"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghe","family":"Meng","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Naval Medical University , , ,","place":["Shanghai, People's Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketong","family":"Liu","sequence":"additional","affiliation":[{"name":"Naval Medical University , ,","place":["Shanghai, People's Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Naval Medical University , , ,","place":["Shanghai, People's Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoying","family":"Jin","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Naval Medical University , , ,","place":["Shanghai, People's Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Naval Medical University , , ,","place":["Shanghai, People's Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Zhu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Naval Medical University , , ,","place":["Shanghai, People's Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minliang","family":"Wu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Naval Medical University , , ,","place":["Shanghai, People's Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Naval Medical University , , ,","place":["Shanghai, People's Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3467-3564","authenticated-orcid":true,"given":"Chunyu","family":"Xue","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Naval Medical University , , ,","place":["Shanghai, People's Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"2026101404065744600_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109209","article-title":"Research models of sulfur mustard- and nitrogen mustard-induced ocular injuries and potential therapeutics","volume":"223","author":"Mishra","year":"2022","journal-title":"Exp. 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