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

• Published in: Bioactive materials Vol. 19; pp. 666 - 677
• Main Authors: Wang, Rui, Lu, Jian, Yin, Jiasheng, Chen, Han, Liu, Hongmei, Xu, Fei, Zang, Tongtong, Xu, Rende, Li, Chenguang, Wu, Yizhe, Wu, Qilin, Fei, Xiang, Zhu, Meifang, Shen, Li, Ge, Junbo
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.01.2023; KeAi Publishing; KeAi Communications Co., Ltd
• Subjects: Electrospun nanofiber membrane; In-stent restenosis; Re-endothelialization; Reactive oxygen species; In-stent restenosis; Reactive oxygen species; Electrospun nanofiber membrane; Re-endothelialization
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2022.04.033

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. [Display omitted] •A bioactive rapamycin and ROS scavenger TEMPOL loaded nanofibrous membrane constructed through coaxial electrospinning.•Ideal stent coating for inhibiting VSMCs while sparing ECs.•Rapamycin/TEMPOL act synergistically in anti-inflammatory effect of ECs and maintaining contractile phenotype of VSMCs.•Rapid endothelialization and anti-stenotic effect achieved in porcine model.