Multi-functional plant flavonoids regulate pathological microenvironments for vascular stent surface engineering.

Abstract

In-stent restenosis (ISR) and late thrombosis, usually caused by excessive smooth muscle cell (SMC) proliferation and delayed endothelial layer repair, respectively, are the main risks for the failure of vascular stent implantation. For years, modification of stents with biomolecules that could selectively inhibit SMC proliferation and support endothelial cell (EC) growth had drawn extensive attention. However, the modulatory effect of these biomolecules faces the impact of oxidative stress, inflammation, and hyperlipidemia of the pathological vascular microenvironment, which is caused by the stent implantation injury and atherosclerosis lesions. Here, we modified stents with a natural and multi-functional flavonoid, baicalin (BCL), using poly-dopamine (PDA) coating technology to combat the harmful impact of the pathological microenvironment. Stent with an appropriate BCL immobilization density (approximately 2.03μg/cm2) successfully supported ECs growth while inhibited SMC proliferation. Furthermore, baicalin-modified surfaces regulated the oxidative stress, inflammation, and high-lipid of the pathological microenvironment to inhibit endothelial dysfunction and the oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cells formation. In vivo results showed that baicalin-modified stents exhibited significant anti-ISR, anti-inflammatory, and endothelialization-promoting functions. Our study suggests that the multi-functional baicalin with pathological microenvironment-regulation (PMR) effect has potential use in the surface engineering of cardiovascular devices. STATEMENT OF SIGNIFICANCE: Empowering vascular stents with selective modulation of smooth muscle cells and endothelial cells by surface technology has become an important research direction for stent surface engineering. However, stent coatings that can furthermodulate the pathological microenvironment of blood vessels have been rarely reported. In this study, we constructed a multifunctional coating based on a flavonoid, baicalin, which can selectively modulate vascular wall cells and improve the pathological microenvironment. This study may provide a reference for developing advanced vascular stents.