Abstract

The unique advantages of nitric oxide (NO) in cardiovascular disease therapy have driven the development of methods to functionalize cardiovascular stents for local generation of NO. However, current NO-generating materials used for surface engineering stents have limitations such as a complex fabrication process, poor stent adhesion strength, and low control of NO release. Herein, we apply synergetic coordination and catecholamine surface chemistry to develop an adhesive NO-generating coating with a copper-catecholamine framework through a simple, one-step molecule/ion co-assembly process. The copper-catecholic-selenocystamine framework provides glutathione peroxidase (GPx)-like interfacial catalytic activity, which results in long-term, stable, adjustable NO release rates from the coating. The resulting desirable therapeutic dose and release kinetics of NO endow the vascular stent with the ability to simultaneously inhibit platelet activation and smooth muscle cell (SMC) proliferation, and enhances endothelial cell (EC) adhesion, proliferation, and migration in vitro. Vascular stent functionalized by the optimized copper-catecholic-selenocystamine coating significantly suppresses thrombosis, promotes re-endothelialization, and reduces intimal hyperplasia in vivo, and may be promising to address the clinical complications associated with restenosis and late stent thrombosis.

Highlights

  • Cardiovascular diseases (CVDs) continue to be the leading cause of death and disability all over the world[1]

  • Based on the above drawbacks of these strategies for an ideal Nitric oxide (NO)-generating stent coating, we report a one-step molecule/ion co-assembly method to form an adhesive NO-generating coating inspired by the synergetic coordination and catecholamine chemistry found in mussel byssus and adhesive plaque formation processes

  • Copper-catecholamine framework characterization To verify that the formation mechanism of the CuII

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Summary

Introduction

Cardiovascular diseases (CVDs) continue to be the leading cause of death and disability all over the world[1]. Inevitable vessel wall injury after stenting frequently complicates pathobiology processes associated with leukocyte accumulation, inflammation, smooth muscle cell migration, and proliferation, which lead to restenosis in addition to the risk of thrombus formation on the foreign surface[3,4,5]. Native endothelium consisting of a monolayer of endothelial cells is an important part of blood vessels and plays a critical role in maintaining homeostasis in the cardiovascular system. Continuous release of NO by ECs is crucial for preventing thrombosis[6], suppressing smooth muscle cell migration and proliferation[7], inhibiting leukocyte activation[8], and promoting healing of atherosclerotic lesions[9]. There is great interest in biomimetic surface modification of cardiovascular stents as delivery vehicles that locally release or generate

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