Zwitterionic hydrogel-coated heart valves with improved endothelialization and anti-calcification properties

Abstract

Valve replacement surgery is the golden standard for end-stage valvular disease due to the lack of self-repair ability. Currently, bioprosthetic heart valves (BHVs) crosslinked by glutaraldehyde (GA) have been the most popular choice in clinic, especially after the emerge of transcatheter aortic valve replacement (TAVR). Nevertheless, the lifespan of BHVs is limited due to severe calcification and deterioration. In this study, to improve the anti-calcification property of BHVs, decellularized heart valves were modified by methacrylic anhydride to introduce double bonds (MADHVs), and a hybrid hydrogel made of sulfobetaine methacrylate (SBMA) and methacrylated hyaluronic acid (MAHA) was then coated onto the surface of MADHVs. Followed by grafting of Arg-Glu-Asp-Val (REDV), an endothelial cell-affinity peptide, the BHVs with improved affinity to endothelial cell (SMHVs-REDV) was obtained. SMHVs-REDV exhibited excellent collagen stability, reliable mechanical property and superior hemocompatibility. Moreover, enhanced biocompatibility and endothelialization potential compared with GA-crosslinked BHVs were achieved. After subcutaneous implantation for 30 days, SMHVs-REDV showed significantly reduced immune response and calcification compared with GA-crosslinked BHVs. Overall, simultaneous endothelialization and anti-calcification can be realized by this strategy, which was supposed to be benefit for improving the main drawbacks for available commercial BHVs products.