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

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

doi:10.1016/j.bioactmat.2022.04.033

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

Bioact Mater. 2022 May 11:19:666-677. doi: 10.1016/j.bioactmat.2022.04.033. eCollection 2023 Jan.

Authors

Rui Wang^{1

2}, Jian Lu³, Jiasheng Yin^{1

2}, Han Chen^{1

2}, Hongmei Liu³, Fei Xu^{1

2}, Tongtong Zang^{1

2}, Rende Xu^{1

2

4}, Chenguang Li^{1

2

4}, Yizhe Wu^{1

2

4}, Qilin Wu³, Xiang Fei³, Meifang Zhu³, Li Shen^{1

2

4}, Junbo Ge^{1

2

4}

Affiliations

¹ Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai, China.
² Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Shanghai, China.
³ 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.
⁴ Shanghai Engineering Research Center of Interventional Medicine, Shanghai, China.

Abstract

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.

Keywords: Electrospun nanofiber membrane; In-stent restenosis; Re-endothelialization; Reactive oxygen species.