A self-supplying NO coating coupled with HA@CS nanoparticles on ZE21B Mg alloy for accelerating re-endothelialization

Poly(TA-Arg) coating with self-supplying NO fabricated via ethanol-water system. • Poly(TA-Arg) sample possesses a low degradation rate. • HA@CS nanoparticles synthesized with optimal HA:CS ratio. • HA@CS sample promotes endothelialization via PI3K-Akt-eNOS and Nrf2 pathways. Rapid degradation and inadequate re-endothelialization hinder the clinical application of biodegradable magnesium (Mg) alloy stents, while thrombosis and bacterial colonization further compromise early implant performance. To address these challenges, a hierarchical bilayer coating, consisting of an inner poly(α-thioctic acid)-L-arginine (Poly(TA-Arg)) layer and an outer hyaluronic acid/chitosan (HA@CS) nanoparticle layer (particle size, ∼240 nm), was fabricated on a fluorinated ZE21B Mg alloy. The Poly(TA-Arg) layer supported endothelial cell (EC)-mediated endogenous nitric oxide (NO) production. It also provided strong interfacial adhesion and corrosion protection, reducing the corrosion current density to 5.60 × 10 −8 A cm −2 . The HA@CS layer exhibited antioxidant activity, prolonged clotting time, low hemolysis, and > 99% antibacterial efficacy, as determined by plate counting. The bilayer coating promoted EC proliferation while inhibiting smooth muscle cell growth. RNA sequencing suggested that the pro-endothelialization effect was associated with PI3K-Akt- endothelial nitric oxide synthase-related signaling and an Nrf2-related antioxidant response. In a rat abdominal aorta model, the coated wire was surrounded by a thin, well-organized neointima with endothelial coverage, minimal inflammation, and no evident thrombosis. No obvious histopathological abnormalities were observed in major organs, and hematological parameters remained within normal ranges. This multifunctional coating provides a potential strategy for improving the vascular compatibility of biodegradable Mg stents. Download: Download high-res image (332KB) Download: Download full-size image