@article{Cong2025, 
author = {Yan Cong and Sheng Meng and Xiaoye Xie and Yiqi Chen and Yucong Li and Yingqian Zhou and Wandi Li and Lipeng Zhang and Guoqing Yang and Qian Wei and Chuan’an Shen},
title = {Engineered sEVs encapsulated in GelMA facilitated diabetic wound healing by promoting angiogenesis via targeting thrombospondin-1},
year = {2025},
journal = {Burns & Trauma},
volume = {13},
number = {10},
pages = {tkaf036},
keywords = {Thrombospondin-1, Angiogenesis, miR-221-3p, Diabetic wounds, Small extracellular vesicles},
url = {https://www.sciopen.com/article/10.1093/burnst/tkaf036},
doi = {10.1093/burnst/tkaf036},
abstract = {BackgroundChronic nonhealing wounds are major complications in diabetic patients, with impaired angiogenesis playing a critical role in the delayed healing process. Current treatments for diabetic wounds are inadequate. The dysregulation of endothelial cell genes, particularly thrombospondin-1 (TSP-1), impairs neovascularization and delays wound repair. In recent years, hydrogel-based wound dressings have gained widespread application in biomedicine. The study introduced a new therapeutic approach, embedding miR-221-3p-loaded small extracellular vesicles (miR-221OE-sEVs) within gelatin methacryloyl (GelMA) hydrogels to reduce TSP-1 levels and improve healing in diabetic wounds.MethodsFirst, we observed upregulated TSP-1 expression in human umbilical vein endothelial cells (HUVECs) when cultured in a high-glucose (HG) environment. We employed small interfering RNA (siRNA) and miR-221-3p to suppress TSP-1 expression and then evaluate the functional effects on HUVECs. Subsequently, miR-221-3p was encapsulated in sEVs via lentiviral transfection. The effects of miR-221OE-sEVs on HUVECs under HG conditions were evaluated. Finally, miR-221OE-sEVs were incorporated into a GelMA hydrogel (G-miR-221OE-sEVs) and applied to a diabetic murine wound model to evaluate their effects on wound closure and angiogenesis.ResultsUnder HG conditions, the use of siTSP-1 to silence TSP-1 enhanced the proliferation, migration, and tube formation capabilities of HUVECs. Similarly, miR-221-3p treatment exerted proregenerative effects via the targeting of TSP-1. We successfully generated miR-221OE-sEVs that exhibited a 28-fold increase in miR-221-3p expression, which significantly enhanced HUVEC functionality under HG conditions. Encapsulation within the GelMA hydrogel enabled G-miR-221OE-sEVs to significantly accelerate diabetic wound healing via increased angiogenesis.ConclusionsThis study demonstrated the successful fabrication of a novel bioactive wound dressing (G-miR-221OE-sEVs), which promotes diabetic wound healing by promoting angiogenesis through the regulation of TSP-1. This approach offers a potential therapeutic option for enhancing the management of diabetic wounds.}
}