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

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 

作者机构：Department of Burns and Cutaneous SurgeryXijing HospitalFourth Military Medical University127 Changle West RoadXi’anShaanxi710032China State Key Laboratory for Mechanical Behavior of MaterialsAnd Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an710049China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi’an Jiaotong UniversityXi’an710049China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2023年第26卷第8期

页      面：323-336页

核心收录：

学科分类：081702[工学-化学工艺] 1002[医学-临床医学] 08[工学] 0817[工学-化学工程与技术] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by National Natural Science Foundation of China Youth Science Fund Project(No.82002039) National Natural Science Foundation of China(81530064) National Natural Science Foundation of China(81772071) National Natural Science Foundation of China(No.82172210) 

主　　题：Dual-loaded hydrogels Adipose-derived mesenchymal stem cell exosomes Metformin Angiogenesis Mitochondrial fission Chronic diabetic wound Wound healing 

摘      要：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.