Spatiotemporally Orchestrated H2S/NO-Releasing Stent for Synergistic Vascular Healing

Cardiovascular stents persistently struggle to reconcile rapid endothelialization with long-term prevention of thrombosis and restenosis. This study develops a spatiotemporally orchestrated dual-gas-releasing hydrogel coating that synchronizes H 2 S and NO delivery with the dynamic phases of vascular healing. The coating is fabricated by covalently grafting an alginate coating onto poly(L-lactic acid) stents via a benzophenone-mediated two-step surface photopolymerization. A thiol‑activated H 2 S donor is anchored within the coating, while alginate‑chelated Cu 2 ⁺ catalyzes NO generation from endogenous S‑nitrosothiols. An early H 2 S burst synergizes with NO to suppress thromboinflammation and prime a regenerative niche, while sustained NO release maintains vascular homeostasis and directs long-term remodeling. The coating reduces platelet adhesion by over 90%, virtually eliminates thrombosis in an arteriovenous shunt model, triples endothelial coverage, and suppresses smooth muscle cell proliferation by ≈73%. It also reprograms macrophage polarization, increasing the M2/M1 ratio tenfold, and reduces intracellular ROS levels by >90%. In a rabbit abdominal aorta model, the coating promotes flow-aligned endothelialization, achieving CD31⁺/eNOS⁺ coverage comparable to native tissue within 3 months, while decreasing neointimal thickness by 66% versus controls. This spatiotemporally tailored gasotransmitter delivery resolves the healing dichotomy of stents, providing a clinically translatable platform for next-generation vascular implants.