Affiliation:
1. Key Laboratory of Smart Drug Delivery (Ministry of Education) Department of Pharmaceutics School of Pharmacy Fudan University Shanghai 201203 China
2. Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200011 China
Abstract
AbstractTissue repair and regeneration in ischemic areas require effective strategies for angiogenesis and microcirculation reconstruction. In this research, extracellular vesicles (EVs) derived from hemangioma stem cells (HemSC) are used as bio‐functional materials for angiogenesis. In addition, a novel thermo‐sensitive hydrogel based on chitosan (CS) and modified with hyaluronic oligosaccharides (oHA), is specially developed as an ideal carrier of HemSC‐EVs. The oHA/CSgel provides a sustained‐release delivery system for EVs, enhances the angiogenic function of HemSC‐EVs, and exerts other bio‐functions to comprehensively accelerate tissue repair. The physical properties of EVs@oHA/CSgel proved to be soft, highly elastic deformable, biocompatible, and can maintain the shape and structure of EVs. In vitro co‐culture assay verifies the angiogenic effect of EVs@oHA/CSgel, and this effect is also evaluated in a diabetic wound model. Compared to untreated group, the EVs@oHA/CSgel group has only 26.9% wound area on day 14, and 226.8% blood flux mark on day 17. Pharmacological mechanisms of HemSC‐EVs are predicted by RNA‐seq, and cluster analysis of miRNAs predicted targets presents several up‐regulated biological processes involving in angiogenesis and wound healing. In conclusion, it is suggested that EVs@oHA/CSgel as a satisfying therapeutic system for microcirculation reconstruction in tissue repair.
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials