Enabling topical and long-term anti-radical properties for percutaneous coronary intervention-related complications by i
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Published online 15 October 2020 | https://doi.org/10.1007/s40843-020-1445-x
Enabling topical and long-term anti-radical properties for percutaneous coronary intervention-related complications by incorporating TEMPOL into electrospun nanofibers 1†
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Jian Lu , Rui Wang , Li Shen , Jiasheng Yin , Guilian Liu , Han Chen , Fei Xu , Qilin Wu , 1 1* 2* 1* Changhuai Ye , Xiang Fei , Junbo Ge and Meifang Zhu ABSTRACT Scavenging reactive oxygen species (ROS) by antioxidants has been demonstrated as the most effective strategy for preventing percutaneous coronary intervention (PCI)-related complications. However, topical and long-term delivery of ROS antioxidants to a specific vascular tissue is proven to be a great challenge. Herein, an ROS scavenger of 4hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) is incorporated into electrospun nanofibers with a tunable loading amount to achieve its topical applicability and long-term antiradical capability. Biological functions of such TEMPOL-loaded electrospun membranes are evaluated by cell proliferation, ROS-scavenging capability, monocyte adhesion, cell migration, inflammatory molecule secretion and mRNA expression in vitro. After optimizing the loading amount of TEMPOL, such an electrospun membrane presents a superior ROS-scavenging and anti-inflammation performance for both endothelial cells and macrophages. The expression of endothelial prothrombogenic molecules and the migration of vascular smooth muscle cells (VSMCs) are also effectively inhibited. Thus, it is bravely predicted that the topical use of such a TEMPOL-loaded electrospun system will be a promising pathway for the anti-restenosis therapy, especially when used as a novel coating on stent for long-term and topical delivery of antioxidant drugs. Keywords: percutaneous coronary interventions, reactive oxygen species, TEMPOL, electrospinning, topical release
INTRODUCTION Cardiovascular diseases (CVDs) remain the primary
cause of morbidity and mortality globally [1], resulting in approximately 18 million CVD deaths annually [2]. Until now, percutaneous coronary interventions (PCI), including percutaneous transluminal coronary angioplasty (PTCA) and coronary stent implantation, have been widely applied for coronary artery revascularization as a non-surgical approach [3–5]. However, PCI-related complications, such as restenosis and stent thrombosis still occur at a fairly high rate and continue to limit the long-term success of the procedure. The excessive reactive oxygen species (ROS) production induced by PCI operations is recognized as a key role on the pathophysiological changes of vascular cells [6,7]. A high level of ROS would break the balance of the antioxidant defense system in human body, trigger the proliferation and migration of vascular smooth muscle cells (VSMCs) and promote monocyte/macrophage inflammation followed by endothelial dysfunction [8], thus resulting in the instent restenosis and/or thrombosis towards the stent failure [9]. Therefore, referring to such a mechanism,
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