Visible light induced cross-linked sulfonated hyaluronic acid microspheres for directing multicellular behaviors on Mg alloy

Ischemic stroke remains a leading global cause of mortality and disability, creating an urgent need for improved treatments. Biodegradable magnesium (Mg) alloy stents represent a promising advancement for cerebrovascular applications due to their inherent biocompatibility, mechanical suitability, and unique neuroprotective properties conferred by Mg ions. However, the clinical translation of Mg alloy stents, particularly for sensitive cerebral vasculature, is hindered by two major bottlenecks: uncontrolled rapid degradation leading to premature structural failure and delayed endothelialization contributing to restenosis and thrombosis. Addressing the critical issue of biological functionality, this study develops a novel sulfonated hyaluronic acid-tyrosine microsphere (S-HA-Tyr@microsphere) coating on ZE21B Mg alloy. Monodisperse S-HA-Tyr microspheres were precisely fabricated using microfluidics and stabilized via a visible-light catalyzed tris(2,2-bipyridyl)-dichlororuthenium(II)/Sodium persulfate (Ru/SPS) system, forming a robust dityrosine bond network. This multifunctional coating integrates corrosion resistance (primarily achieved through an established MgF 2 interlayer), strong anchoring (PDA layer), and enhanced bioactivity (S-HA-Tyr@microspheres). The S-HA-Tyr@microsphere coating significantly improved hemocompatibility, reducing hemolysis to 0.35% ( p < 0.01) and platelet adhesion by 83.7% ( p < 0.001). Crucially, it promoted endothelial cells (ECs) migration and proliferation ( p < 0.01) while inhibiting smooth muscle cells (SMCs) overgrowth ( p < 0.05) and inducing macrophage M2 polarization ( p < 0.01), demonstrating excellent cell-specific regulation. In vivo evaluation confirmed the efficacy: abdominal aortic implantation in rats for 28 d revealed a superior diameter retention for the coated implants compared to bare alloy ( p < 0.05) and showed continuous endothelium with reduced neointimal formation ( p < 0.01). This innovative coating strategy facilitates both degradation control and accelerated endothelialization, overcoming key biological barriers for the clinical application of biodegradable Mg alloy cerebrovascular stents.