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

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 2.03 μg/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: Baicalin, a plant flavonoid, was covalently immobilized on the surface of the cardiovascular material. 1. The baicalin-modified surfaces selectively inhibit excessive growth of SMCs while supporting the healthy growth of ECs. 2. The baicalin-modified surfaces regulate the pathological microenvironments by reducing the oxidative stress, inflammatory, and ox-LDL induced macrophage to foam cell transition. 3. The baicalin-modified stent showed excellent in vivo biocompatibility.