A TEMPOL and rapamycin loaded nanofiber-covered stent favors endothelialization and mitigates neointimal hyperplasia and local inflammation  

作　　者：Rui Wang Jian Lu Jiasheng Yin Han Chen Hongmei Liu Fei Xu Tongtong Zang Rende Xu Chenguang Li Yizhe Wu Qilin Wu Xiang Fei Meifang Zhu Li Shen Junbo Ge 

机构地区：[1]Department of Cardiology,Zhongshan Hospital,Fudan University,Shanghai Institute of Cardiovascular Diseases,National Clinical Research Center for Interventional Medicine,Shanghai,China [2]State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,College of Materials Science and Engineering,International Joint Laboratory for Advanced Fiber and Low-dimension Materials,Donghua University,Shanghai,201620,China [3]Research Unit of Cardiovascular Techniques and Devices,Chinese Academy of Medical Sciences,Shanghai,China [4]Shanghai Engineering Research Center of Interventional Medicine,Shanghai,China

出　　处：《Bioactive Materials》2023年第1期666-677,共12页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(No.82170342);the Shanghai Engineering Research Center of Interventional Medicine(No.19DZ2250300);the National Key R&D Program of China(No.2021YFA1201300 and No.2020YFC1316703);the Chinese Academy of Medical Sciences(2019-I2M-5-060,2020-JKCS-0154020);the Shanghai Shenkang Hospital Development Center(SHDC2020CR3023B).

摘　　要：An increased level of reactive oxygen species(ROS)plays a major role in endothelial dysfunction and vascular smooth muscle cell(VSMC)proliferation during in-stent thrombosis and restenosis after coronary artery stenting.Herein,we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl(TEMPOL)and rapamycin(RAPA)that correspondingly serves as an ROS scavenger and VSMC inhibitor.This system has the potential to improve the biocompatibility of current drug-eluting stent(DES)coatings with the long-term and continuous release of TEMPOL and rapamycin.Moreover,the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells(ECs).This membrane demonstrated superior ROS-scavenging,anti-inflammatory and antithrombogenic effects in ECs.In addition,the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB(PDGF-BB)-induced proliferation of VSMCs.In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.

关 键 词：Electrospun nanofiber membrane In-stent restenosis RE-ENDOTHELIALIZATION Reactive oxygen species 

分 类 号：R318.08[医药卫生—生物医学工程]