In-Stent Re-Endothelialization Strategies: Cells, Extracellular Matrix, and Extracellular Vesicles

Abstract

Arterial stenosis caused by atherosclerosis often requires stent implantation to increase the patency of target artery. However, such external devices often lead to in-stent restenosis due to inadequate re-endothelialization and subsequent inflammatory responses. Therefore, re-endothelialization strategies after stent implantation have been developed to enhance endothelial cell recruitment or to capture circulating endothelial progenitor cells. Notably, recent research indicates that coating stent surfaces with biogenic materials enhances the long-term safety of implantation, markedly diminishing the risk of in-stent restenosis. In this review, we begin by describing the pathophysiology of coronary artery disease and in-stent restenosis. Then, we review the characteristics and materials of existing stents used in clinical practice. Lastly, we explore biogenic materials aimed at accelerating re-endothelialization, including extracellular matrix, cells, and extracellular vesicles. This review helps overcome the limitations of current stents for cardiovascular disease and outlines the next phase of research and development. Impact Statement Due to the potential risk of restenosis in all types of vascular stents, re-endothelialization strategies should be considered in stent development. This review discusses the use of biogenic materials, including extracellular matrix, cells, and extracellular vesicles, on stent surfaces to induce endothelial cell recruitment and suppress inflammatory responses, thereby preventing neointimal hyperplasia. Compared with other strategies, biogenic materials offer greater stability and safety with fewer side effects, addressing current unmet needs. Consequently, this review offers a novel perspective on the development of a new generation of stents.