Step-wise CAG@PLys@PDA-Cu^(2+)modification on micropatterned nanofibers for programmed endothelial healing  

作　　者：Bingcheng Yi Boya Zhou Zhenfeng Song Lei Yu Wenbo Wang Wei Liu 

机构地区：[1]Department of Plastic and Reconstructive Surgery,Shanghai Key Laboratory of Tissue Engineering,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200011,China [2]Department of Vascular Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200011,China

出　　处：《Bioactive Materials》2023年第7期657-676,共20页生物活性材料（英文）

基　　金：This work was supported by National Key Research and Development Program of China(2018YFC1105800 to WL);China Postdoctoral Science Foundation(2020M681322 to BY);National Natural Science Foundation of China(31870967 to WL and 81701841 to WW).

摘　　要：Native-like endothelium regeneration is a prerequisite for material-guided small-diameter vascular regeneration.In this study,a novel strategy is proposed to achieve phase-adjusted endothelial healing by step-wise modification of parallel-microgroove-patterned(i.e.,micropatterned)nanofibers with polydopamine-copper ion(PDA-Cu^(2+))complexes,polylysine(PLys)molecules,and Cys-Ala-Gly(CAG)peptides(CAG@PLys@PDA-Cu^(2+)).Using electrospun poly(L-lactide-co-caprolactone)random nanofibers as the demonstrating biomaterial,step-wise modification of CAG@PLys@PDA-Cu^(2+)significantly enhanced substrate wettability and protein adsorption,exhibited an excellent antithrombotic surface and outstanding phase-adjusted capacity of endothelium regeneration involving cell adhesion,endothelial monolayer formation,and the regenerated endothelium maturation.Upon in vivo implantation for segmental replacement of rabbit carotid arteries,CAG@PLys@PDA-Cu^(2+)modified grafts(2 mm inner diameter)with micropatterns on inner surface effectively accelerated native-like endothelium regeneration within 1 week,with less platelet aggregates and inflammatory response compared to those on non-modified grafts.Prolonged observations at 6-and 12-weeks post-implantation demonstrated a positive vascular remodeling with almost fully covered endothelium and mature smooth muscle layer in the modified vascular grafts,accompanied with well-organized extracellular matrix.By contrast,non-modified vascular grafts induced a disorganized tissue formation with a high risk of thrombogenesis.In summary,step-wise modification of CAG@PLys@PDA-Cu^(2+)on micropatterned nanofibers can significantly promote endothelial healing without inflicting thrombosis,thus confirming a novel strategy for developing functional vascular grafts or other blood-contacting materials/devices.

关 键 词：Surface chemistry Anisotropic topography Step-wise modification Endothelial healing Functional vascular grafts 

分 类 号：R318.08[医药卫生—生物医学工程]