Injectable hydrogel harnessing foreskin mesenchymal stem cell-derived extracellular vesicles for treatment of chronic diabetic skin wounds

利用包皮间充质干细胞衍生的细胞外囊泡的可注射水凝胶治疗慢性糖尿病皮肤伤口

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作者:Chang Xu, Jin-Feng Cao, Yue Pei, Yujin Kim, Huiyeon Moon, Chui-Qin Fan, Mao-Chuan Liao, Xing-Yu Wang, Fei Yao, Yu-Jun Zhang, Shao-Hui Zhang, Jian Zhang, Jian-Zhang Li, Jong Seung Kim, Lian Ma, Zhong-Jian Xie

Abstract

Chronic skin wounds are a serious complication of diabetes with a high incidence rate, which can lead to disability or even death. Previous studies have shown that mesenchymal stem cells derived extracellular vesicles (EVs) have beneficial effects on wound healing. However, the human foreskin mesenchymal stem cell (FSMSCs)-derived extracellular vesicle (FM-EV) has not yet been isolated and characterized. Furthermore, the limited supply and short lifespan of EVs also hinder their practical use. In this study, we developed an injectable dual-physical cross-linking hydrogel (PSiW) with self-healing, adhesive, and antibacterial properties, using polyvinylpyrrolidone and silicotungstic acid to load FM-EV. The EVs were evenly distributed in the hydrogel and continuously released. In vivo and vitro tests demonstrated that the synergistic effect of EVs and hydrogel could significantly promote the repair of diabetic wounds by regulating macrophage polarization, promoting angiogenesis, and improving the microenvironment. Overall, the obtained EVs-loaded hydrogels developed in this work exhibited promising applicability for the repair of chronic skin wounds in diabetes patients.

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