A self-supplying nitric oxide coating on Mg alloy for vascular stents promotes re-endothelialization

Mimicking the function of healthy endothelial cells (ECs) to catalyze NO release from endogenous donors represents an effective strategy for repairing the inevitable endothelial injury following stent implantation. However, insufficient levels of endogenous NO donors often limit catalytic NO generation, challenging the maintenance of cardiovascular homeostasis. To address this, a poly(thioctic acid)-arginine (TA-Arg) coating on a fluorinated magnesium (Mg) alloy for in-situ NO supply to address delayed endothelialization. The coating adhered firmly to the MgF₂ surface via hydrogen bonding, with TA and Arg connected through salt-bridge hydrogen bond interactions. The immobilized Arg acted as a precursor for NO synthesis, which was catalytically generated in situ by ECs via endothelial nitric oxide synthase (eNOS). Meanwhile, TA served as an eNOS enhancer, boosting intracellular eNOS activity and facilitating the conversion of Arg to NO, enabling sustained and stable localized NO release. In vitro tests showed that the coating significantly decelerated Mg alloy degradation and exhibited high hemocompatibility with pronounced pro-endothelial potential. RNA-seq analyses further revealed that the coating promoted activation of NO-associated PI3K-Akt and MAPK pathways and activated the core antioxidant transcription factor Nrf2 (evidenced by the coordinated upregulation of HMOX1 and NQO1), while concurrently suppressing ferroptosis through genes such as SLC7A11 and FTH1. In vivo implantation confirmed reduced inflammation, enhanced endothelial repair, and inhibited hyperplasia, highlighting the dual role of NO release and antioxidative activity in promoting rapid endothelialization with good biosafety. STATEMENT OF SIGNIFICANCE: Magnesium (Mg) alloys hold significant promise as next-generation materials for cardiovascular stents owing to their complete biodegradability and excellent biocompatibility. However, their rapid degradation rate and delayed endothelialization remain major obstacles to clinical applications. To address these challenges, this study developed a nitric oxide (NO)-self-supplying poly(thioctic acid)-arginine (TA-Arg) coating on a fluorinated Mg alloy substrate. Both in vitro and in vivo results demonstrated that the TA-Arg sample not only markedly decelerated the degradation of the Mg alloy but also regulated vascular cell behavior, showing considerable potential to promote rapid endothelialization. Overall, this endogenous NO‑supplying strategy is highly straightforward, cost-effective, and scalable, offering a versatile and practical approach for surface modification to facilitate real-world applications of Mg-based stents.