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Uncontrollable bleeding and coagulation disorders following severe trauma present major challenges for existing hemostatic agents. To address these issues, a multifunctional nucleic acid hydrogel (TR21@TS) is developed by integrating microRNA\u201021\u20105p\u2010loaded tetrahedral framework nucleic acids (tFNAs) with tannic acid (TA) and tetra\u2010polyethylene glycol (4\u2010PEG) derivatives, and the hybrid hydrogel exhibited wet adhesiveness, mechanical robustness, sprayability, and injectability. Compared to commercial products, the hydrogel showed superior hemostatic performance in a rat acute liver hemorrhage model and accelerated wound closure in full\u2010thickness DWs. Both in vitro and in vivo studies revealed that the hydrogel reprogrammed macrophage polarization, attenuated oxidative stress and inflammation via nuclear factor kappa B (NF\u2010\u03baB) inhibition, and enhanced angiogenesis through protein kinase B (AKT) pathway activation, thereby facilitating tissue regeneration. This functionalized nucleic acid hydrogel represents a promising therapeutic strategy for addressing uncontrolled hemorrhage and chronic diabetic wound healing.<\/jats:p>","DOI":"10.1002\/smll.202506587","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T09:25:22Z","timestamp":1754558722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Sprayable Nucleic Acid Hydrogel for Diabetic Wound Healing via Immunomodulation and Angiogenesis"],"prefix":"10.1002","volume":"21","author":[{"given":"Mei","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu 610041 P. R. 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