ADSC‐Derived Extracellular Vesicles Loaded with VEGF mRNA Delivered by Antibacterial Hydrogel Promote Angiogenesis and Reconstruction of Prefabricated Flaps

Abstract Prefabricated flaps often suffer from distal necrosis due to ischemia, with no clinically effective prevention or treatment currently available. Although extracellular vesicles (EVs) derived from adipose‐derived stem cells (ADSCs) have shown pro‐angiogenic potential, their therapeutic efficacy alone remains limited. In this study, VEGF mRNA is successfully encapsulated within ADSCs‐derived EVs, which subsequently exhibit pro‐angiogenic effects on cultured human umbilical vein endothelial cells (HUVECs). To enable sustained release, a biocompatible tannic acid‐based hydrogel (TA‐Gel) is developed with tunable mechanical properties and antimicrobial activity. This hydrogel significantly enhances both flap viability and vascular regeneration in vivo when combined with VEGF‐EVs. Transcriptome sequencing reveals that VEGF‐EVs@TA‐Gel upregulates differentially expressed genes (DEGs) involved in VEGF‐related pro‐angiogenesis, collagen response, and anti‐oxidative stress pathways. Moreover, 16S rRNA sequencing confirms that VEGF‐EVs@TA‐Gel inhibits the growth of common pathogenic bacteria, including Escherichia coli and Pseudomona . Collectively, these findings indicate that VEGF‐EVs@TA‐Gel promotes the survival and quality of prefabricated flaps through the sustainable release of VEGF mRNA‐loaded EVs.