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Here, we identify excessive neutrophil extracellular traps (NETs) as a key mediator linking sleep deprivation to delayed oral wound closure. NETs-associated proteases compromise epithelial barrier function and suppress repair cell migration. To address this, we developed a melatonin-loaded niosome-incorporated silk fibroin methacrylate (SilMA)\/gelatin methacryloyl (GelMA) composite hydrogel microneedle (Nio-MT@S-G MN) for localized melatonin delivery and regulation of the NET-associated inflammatory microenvironment. Niosomes achieve efficient encapsulation and sustained melatonin release, while SilMA\/GelMA microneedles enable transmucosal administration with favorable mechanical strength. In vitro, Nio-MT@S-G MN promotes keratinocyte migration, reduces NETs marker expression and extracellular DNA release in neutrophils, and alleviates NETs-mediated inhibition of tight junction Zonula occludens-1 (ZO-1) expression. In mice combining sleep deprivation and oral ulcers, local Nio-MT@S-G MN application attenuates NETs deposition and inflammation, restores epithelial barrier proteins and significantly accelerates ulcer closure. By integrating controlled drug delivery with immune microenvironment regulation, this microneedle provides a translational strategy for treating sleep disorder-aggravated mucosal injuries. It may also be applicable to other chronic wounds characterized by dysregulated neutrophil responses.<\/jats:p>","DOI":"10.1093\/rb\/rbag180","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:14:57Z","timestamp":1786965297000},"source":"Crossref","is-referenced-by-count":0,"title":["Niosome-mediated melatonin delivery via SilMA\/GelMA microneedles promotes healing of sleep deprivation-aggravated oral ulcers"],"prefix":"10.1093","volume":"13","author":[{"given":"Ying","family":"Xie","sequence":"first","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhi","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehao","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamoran","family":"Tuerhong","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengji","family":"Shi","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Tang","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehui","family":"Hu","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Orthodontics, , Chongqing 401147 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youchun","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingcong","family":"Yang","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Periodontology, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"He","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Dang","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danfeng","family":"Shen","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Yang","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices . Beijing 100081,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1768-1140","authenticated-orcid":false,"given":"Yuzhou","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Stomatological Hospital of Chongqing Medical-University Department of Prosthodontics, , Chongqing 401147,","place":["China"]},{"name":"Chongqing Key Laboratory of Oral Diseases & Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education & Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering , Chongqing 401147,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"2026100515061585600_rbag180-B1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12105-018-0981-8","article-title":"Ulcerated lesions of the oral mucosa: clinical and histologic 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