Integrated hydrogel of fucoidan and rhCol III for bioprosthetic heart valves to promote the antithrombosis, anti-inflammatory, and anti-calcification properties

Glutaraldehyde cross-linked bioprosthetic heart valves (BHVs) have been widely used in clinical practice for its superior hemodynamic properties and significantly reduced requirement on anticoagulant therapy. However, the lifespan and biocompatibility of BHVs remain limited due to thrombus accumulation, poor endothelialization, inflammation, and progressive calcification. In this study, we introduced heparin-like fucoidan and recombinant humanized type III collagen (rhCol III) into glutaraldehyde cross-linked BHVs (GLUT) through photoinduced polymerization, thereby preparing an integrated hydrogel functionalized BHV (Fu-rhCol III). This multifunctional hydrogel formed a biocompatible barrier, providing robust protection for internal valve fibers and exhibiting strong resistance to platelet adhesion and thrombus formation in vitro. The Fu-rhCol III effectively reduced the cytotoxicity of GLUT, accelerating the endothelialization process. Fu-rhCol III maintained the structural stability and mechanical properties brought by glutaraldehyde cross-linking. This composite hydrogel demonstrated the significant suppression of acute inflammatory responses and satisfactory anti-calcification effect in subcutaneous implantation test. 60-day implantation results indicated that calcium deposition of Fu-rhCol III decreased by 96% compared with GLUT. In summary, this integrated hydrogel modification provides a promising strategy for future design of BHVs.