Mechanistic insights into ultraviolet-crosslinked sulfonated hyaluronic acid microspheres for stable biointerfaces on biodegradable cerebrovascular magnesium implants

Abstract

Ischemic stroke remains a leading cause of death and disability worldwide, highlighting the urgent need to develop safer and more effective cerebrovascular implants. Biodegradable magnesium (Mg) alloys offer advantages such as high mechanical strength and the presence of neuroprotective Mg 2 ⁺ ions, but their rapid corrosion and delayed endothelialization limit their clinical application. Monodisperse sulfonated hyaluronic acid-tyramine (S-HA-Tyr) microspheres were prepared using microfluidic technology. The microspheres were subsequently stabilized through tris(2,2′-bipyridine)ruthenium(II) chloride/sodium persulfate (Ru/SPS)-mediated ultraviolet (UV) crosslinking, forming a dense and highly stable dityrosine network. The UV-cured microspheres are then integrated into a hierarchical magnesium fluoride (MgF 2 )/polydopamine (PDA)/S-HA-Tyr coating on ZE21B Mg alloy, achieving simultaneous corrosion resistance, interfacial strengthening, and vascular bioactivity. In contrast to conventional Mg alloy coatings that typically provide a single function, this hierarchical MgF 2 /PDA/S-HA-Tyr system integrates corrosion protection, interfacial adhesion, and vascular bioactivity within one platform. This coating significantly reduced corrosion current density (nearly two orders of magnitude), shifted corrosion potential by 330 mV, and decreased corrosion rate by >85%, while exhibiting excellent blood compatibility with extremely low hemolysis (0.19%). Nanoindentation revealed a marked increase in elastic modulus (18–58 GPa) and hardness (0.9–3.2 GPa), with reduced creep deformation, indicating robust interfacial reinforcement of the coating. Importantly, in vitro co-culture studies of endothelial cells (ECs) and smooth muscle cells (SMCs) demonstrated selective cellular regulation: the coating enhanced EC proliferation and migration (∼18%), suppressed SMC overgrowth while inducing a contractile phenotype, and promoted macrophage (MA) polarization toward the anti-inflammatory M2 phenotype. In vivo subcutaneous implantation showed improved tissue response. These results demonstrate that UV-crosslinked S-HA-Tyr@microspheres provide a robust, multifunctional surface strategy that can simultaneously accelerate endothelial repair and control Mg alloy degradation, offering a promising platform for next-generation cerebrovascular implants.