Double bond crosslinked and phosphocholinated biological heart valve with robust antithrombogenicity, durability and anticalcification property

Glutaraldehyde crosslinked biological heart valves (BHVs) are increasingly implanted with development of transcatheter heart valve implantation. While poor cytocompatibility and calcification that are associated with glutaraldehyde crosslinking may further lead to degeneration of BHVs, and post-implantation thrombosis also induces dysfunction of BHVs. Herein, porcine pericardium (PP) was firstly methacrylated by 2-Isocyanatoethyl methacrylate (ICM) to graft C--C (double bond) bonds and then copolymerized with phosphocholine-based monomer 2-methacryloyloxyethyl phosphorylcholine (MPC) to fabricate phosphocholinated BHVs (PICM-MPCPP). PICM-MPC-PP exhibited improved stability, cytocompatibility. Mitigated immune response and reduced calcification were observed in PICM-MPC-PP, after subcutaneous implantation. Owing to the introduction of biomimetic fouling-resistant poly-MPC, the antithrombotic performance was improved for PICM-MPC-PP. Moreover, PICM-MPC-PP fabricated BHV prototype was demonstrated to exhibit satisfactory durability and hydrodynamics under wide range of simulated conditions. Altogether, the proposed double bond crosslinking strategy simultaneously accomplished crosslinking and antithrombotic modification of BHVs, and PICM-MPC-PP with improved biocompatibility, antithrombogenicity, anticalcification performance as well as appropriate hydrodynamics and durability would be a promising alternative for BHVs crosslinked by glutaraldehyde.