Bioinspired hydrogel-engineered bioprosthetic valve via metal-polyphenol-polysaccharide coordinated assembly for thromboresistance, accelerated endothelialization, and immunoregulation

Valvular heart disease (VHD) presents a growing global health burden, with bioprosthetic heart valves (BHVs) emerging as preferred clinical solutions due to superior hemodynamics and reduced anticoagulation requirements. However, BHVs suffer from structural valvular degeneration caused by cytotoxic glutaraldehyde residuals, thrombogenicity of exposed collagenous matrices, poor endothelialization and immune responses. To address these limitations, a metal-polyphenol-polysaccharide composited glycocalyx-mimetic hydrogel-engineered BHV (AACE-PP) was engineered through integrated hierarchical biomimetic design. A glycocalyx-mimetic hydrogel layer was welded onto BHVs via UV-initiated polymerization of methacrylated alginate, providing a hydrophilic barrier to shield thrombogenic surfaces, while EGCG-Cu metal-phenolic networks (MPNs) were incorporated to confer enzyme-mimetic and immunoregulation functionality. This dual-interfacial architecture synergistically combines physical shielding with biochemical regulation: the hydrogel coating effectively resists plasma protein adsorption, platelet adhesion and thrombosis, whereas the MPNs enable reactive oxygen species (ROS) scavenging, sustained nitric oxide release and immunoregulation. Biological evaluations demonstrated that AACE-PP significantly enhanced endothelialization, suppressed inflammatory activation, and reduced calcification compared to conventional BHVs. By emulating vascular homeostasis mechanisms through coordinated material integration, this biomimetic strategy establishes a multifunctional platform to improve BHV hemocompatibility and mitigate structural valvular degeneration.