Incorporating Copper to Biodegradable Magnesium Alloy Vascular Stents via a Cu(II)‐Eluting Coating for Synergistic Enhancement in Prolonged Durability and Rapid Re‐Endothelialization

Abstract

Biodegradable magnesium-based scaffolds present outstanding potential to revolutionize the treatment of coronary artery diseases, in which full recovery of arteries without long-term irritation of implants is anticipated for averting adverse events associated with the permanent stents. However, overfast degradation of magnesium (Mg) alloys obstructs their extensive applications in terms of early structural failure and impaired biocompatibility. Herein, a facile copper-incorporated coating system through nonaqueous phase synthesis of polydopamine is developed to facilitate Cu(II) capture along with robust film deposited on easily corrodible Mg, which subsequently enables sustained Cu(II) elution. It remarkably enhances corrosion resistance and impedes Mg degradation, which also contributes to improved, superior cytocompatibility, and abolished hemolysis. Moreover, through simultaneous control of Cu(II) and Mg(II) release to modulate the local microenvironment, a synergistic biochemical effect on desirable vascular cell selectivity is triggered for boosted endothelial cell viability and suppressed smooth muscle cell. Stent implantation into rabbit abdominal aorta thus exhibits accelerated re-endothelialization completed in a week, and enhanced biological outcomes, alleviated complications and prolonged structural durability in 3-month follow-up. Collectively, this study opens up an alternative route of deploying a multifunctional surface modification strategy tailoring active interplay with the Mg matrix for better outcomes of next-generation bio resorbable vascular stents.

3D-printed, Citrate-based Bioresorbable Vascular Scaffolds for Coronary Artery Angioplasty

“…Endothelium regeneration is an important step toward vascular healing. Given the vital roles played by endothelium in vascular biology 29 , it has been widely recognized that the rapid and functional regeneration of endothelium is critical for achieving long-term patency and biocompatibility of vascular scaffolds/stents [30][31][32] . In this study, immunohistochemical assessments indicated that the 70-80% coverage of endothelium occurs on day 28 post-implantation for almost all scaffolded/stented arteries.…”

“…Previous studies have shown poor endothelium recovery with the Absorb BVS than with metallic DES in a rabbit model 33 . Despite the significant efforts made to facilitate endothelium adhesion, proliferation, and migration through a variety of strategies 31,32 , the mechanism of endothelium regeneration on vascular scaffolds/stent is still unclear 30,34 . A recent study found that blood circulating monocytes would adhere to the luminal surfaces of acellular vascular graft, differentiate into a mixed endothelial (CD144 + ) and macrophage (CD163 + ) phenotype, and further develop into mature endothelial cells in vitro and in the ovine model 35 .…”