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Exosome/metformin-loaded self-healing conductive hydrogel rescues microvascular dysfunction and promotes chronic diabetic wound healing by inhibiting mitochondrial fission

引用

Bioactive Materials 2023年第8期26卷 323-336页

作者： Yue Zhang Meng Li Yunchuan Wang Fei Han Kuo Shen Liang Luo Yan Li Yanhui Jia Jian Zhang Weixia Cai Kejia Wang Ming Zhao Jing Wang Xiaowen Gao Chenyang Tian Baolin Guo Dahai Hu Department of Burns and Cutaneous Surgery Xijing HospitalFourth Military Medical University127 Changle West RoadXi’anShaanxi710032China State Key Laboratory for Mechanical Behavior of Materials And Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an710049China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an710049China

Chronic diabetic wounds remain a globally recognized clinical *** occur due to high concentrations of reactive oxygen species and vascular function disorders.A promising strategy for diabetic wound healing is the delivery of exosomes,comprising bioactive *** activates the vascular endothelial growth factor pathway,thereby improving angiogenesis in hyperglycemic ***,multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported,and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains ***,we engineered dual-loaded hydrogels possessing tissue adhesive,antioxidant,self-healing and electrical conductivity properties,wherein 4-armed SH-PEG cross-links with Ag^(+),which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound *** carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group,creating a stable three-dimensional structure for exosome and metformin *** diabetic wound model of the present study suggests that the PEG/Ag/CNT-M+E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular *** mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission,thereby protecting F-actin homeostasis and alleviating microvascular ***,we propose a drug-bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.

关键词： dual-loaded hydrogels Adipose-derived mesenchymal stem cell exosomes Metformin Angiogenesis Mitochondrial fission Chronic diabetic wound Wound healing

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