Salidroside-Loaded Stem Cell-derived Artificial Nanovesicles in Hydrogel Microneedles Alleviate Inflammation and Enhance Diabetic Wound Regeneration

Diabetic wounds often arise from a dysregulated wound microenvironment characterized by persistent inflammation, impaired angiogenesis, and aberrant macrophage polarization, leading to delayed healing and severe disability. In this study, we fabricated a stem cell-derived artificial nanovesicles-salidroside@gelatin methacryloyl/polyvinyl alcohol composite microneedle system (CNV-Sa@GelMA/PVA-MN) composed of a GelMA/PVA hydrogel matrix integrated with salidroside loaded stem cell-derived artificial nanovesicles to achieve efficient therapy for diabetic wound. The system penetrated the skin barrier for precise delivery, with stem cell-derived artificial nanovesicles enabling sustained salidroside release and collectively enhancing its anti-inflammatory and pro-angiogenic activities in vitro. Mechanistically, network pharmacology, molecular dynamics simulations, and proteomics revealed the system suppressed the NF-κB pathway, promoted macrophage M1 to M2 polarization, and alleviated inflammatory responses. In vivo experiments confirmed it significantly accelerated wound closure and inhibited inflammatory factor release. These findings highlighted a promising strategy for diabetic wound therapy through inflammatory microenvironment regulation and coordinated tissue repair.