Multilayer surface coating for enhanced anti-inflammation, anti-restenosis, and re-endothelialization in advanced biodegradable vascular stents

Coronary artery disease (CAD) remains a leading cause of mortality worldwide, while conventional drug-eluting stents (DES) face limitations in long-term safety and controlled drug release. Here, we developed a poly (L-lactic acid) (PLLA)-based biodegradable vascular scaffold (BVS) with a three-layer coating using distinct technologies for spatiotemporal drug delivery. The luminal surface was selectively coated via electrospraying with alpha-lipoic acid (ALA) to promote endothelialization. The abluminal surface was treated using ultrasonic spray coating with magnesium hydroxide (MH) and everolimus (EVL) to suppress smooth muscle cell proliferation and inflammation. Finally, a precision dot-printing method was employed to deliver doxorubicin (DOX) for early inhibition of restenosis. This strategy enabled time- and site-specific drug release, achieving antioxidant, anti-inflammatory, and <i>anti</i>-restenotic effects while facilitating re-endothelialization. <i>In vivo</i> studies in a porcine model confirmed that the BVS-AEMD significantly reduced thrombosis and inflammation, underscoring its potential as a next-generation cardiovascular therapeutic platform.