Dual Exosome Coating for Modulating Endothelial Function and Inflammation.

Abstract

Conventional drug-eluting stents can lead to complications such as in-stent restenosis and late thrombosis due to the lack of a well-functioning endothelium and inadequate inflammatory regulation. In this study, a dual exosome coating was fabricated to promote endothelial function and macrophage efferocytosis via a synergistic effect by endothelial cell-sourced and mesenchymal stem cell-sourced exosomes. By the biotin-avidin interaction, the dual exosomes were proportionally grafted onto the substrate and evenly distributed. The coating facilitated the formation of a functionally intact endothelial layer, inhibited macrophage adhesion, and suppressed inflammation. The dual exosomes on the coating acted through upregulating the expression of eNOS and downregulating NOX1 and NOX4 to reduce oxidative stress and effectively repair endothelial function. The dual exosomes also upregulated the expression of SLC29a1 and SLC2a1 and downregulated CD300a, CD36, and Lp-PLA2 to promote efferocytosis and inhibit inflammation. Additionally, it promoted smooth muscle cell phenotypic transformation, reduced thrombosis, and decreased the neointima thickness. Overall, this coating loaded with dual exosomes provided a potential and universal strategy for vascular stent surface modification.