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

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.

负载TEMPOL的静电纺丝纳米纤维实现PCI相关并发症治疗的局部长期抗自由基性能

使用抗氧剂清除活性氧(ROS)被证实是应对经皮冠状动脉介入治疗(PCI)相关并发症的有效方法,但抗氧剂向特定组织的长期局部输送不易实现.本文将抗氧剂TEMPOL可控地负载入静电纺丝纳米纤维以实现其局部应用和长期抗自由基能力,制得TEMPOL负载薄膜的生物功能通过细胞增殖、ROS清除能力、单核细胞黏附、细胞迁移、炎症因子mRNA水平的表达及分泌等体外实验进行了表征.薄膜在优化TEMPOL负载量后,对内皮细胞和巨噬细胞表现出优异的清除ROS和抗炎症能力;同时有效抑制内皮细胞促血栓形成因子的表达和血管平滑肌细胞的迁移.因此,我们预测该TEMPOL负载电纺体系的局部使用,如用作长期局部输送抗氧化药物的血管支架涂层,可以有效治疗血管再狭窄和抑制血栓形成.