VEGF combined with DAPT promotes tissue regeneration and remodeling in vascular grafts  

作　　者：Tao Yang Guangxu Li Xifeng Li Boyang Wei Hengxian Su Wenchao Liu Shenquan Guo Nan Yang Tao Xu Chuanzhi Duan 

机构地区：[1]Neurosurgery Center,Department of Cerebrovascular Surgery,The National Key Clinical Specialty,The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease,Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration,The Neurosurgery Institute of Guangdong Province,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China [2]Department of Neurosurgery,The First Affiliated Hospital of Jinan University,Guangzhou,Guangdong,510630,China [3]Department of Bio-intelligent Manufacturing and Living Matter Bioprinting Center,Research Institute of Tsinghua University in Shenzhen,Tsinghua University,Shenzhen 518057,People’s Republic of China [4]Department of Tsinghua Shenzhen International Graduate School,Tsinghua University,Shenzhen 518055,People’s Republic of China

出　　处：《Regenerative Biomaterials》2023年第1期1577-1591,共15页再生生物材料（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant No.81974178);Introduced and Jointly Built High-end R&D Institute of Jiangxi.(Grant No.20203CCH45008);Science and Technology Program of Guangzhou,China(Grant No.202201010969).

摘　　要：Previous research on tissue-engineered blood vessels(TEBVs)has mainly focused on the intima or adventitia unilaterally,neglecting the equal importance of both layers.Meanwhile,the efficacy of grafts modified with vascular endothelial growth factor(VEGF)merely has been limited.Here,we developed a small-diameter graft that can gradually release VEGF andγsecretase inhibitor IX(DAPT)to enhance tissue regeneration and remodeling in both the intima and adventitia.In vitro,experiments revealed that the combination of VEGF and DAPT had superior pro-proliferation and pro-migration effects on endothelial cells.In vivo,the sustained release of VEGF and DAPT from the grafts resulted in improved regeneration and remodeling.Specifically,in the intima,faster endothelialization and regeneration of smooth muscle cells led to higher patency rates and better remodeling.In the adventitia,a higher density of neovascularization,M2 macrophages and fibroblasts promoted cellular ingrowth and replacement of the implant with autologous neo-tissue.Furthermore,western blot analysis confirmed that the regenerated ECs were functional and the effect of DAPT was associated with increased expression of vascular endothelial growth factor receptor 2.Our study demonstrated that the sustained release of VEGF and DAPT from the graft can effectively promote tissue regeneration and remodeling in both the intima and adventitia.This development has the potential to significantly accelerate the clinical application of small-diameter TEBVs.

关 键 词：VEGF NOTCH GRAFT regeneration REMODELING 

分 类 号：R318[医药卫生—生物医学工程]