Modifying Biological Heart Valve Leaflets using Anti-fouling Polymer Incorporated with Metal-Phenolic Networks for Enhanced Anti-Thrombosis, Anti-Calcification and Endothelialization

Abstract

Promoting the endothelialization of the bioprosthetic valve is necessary to improve the performance of the valve, and good hemocompatibility ensures an adequate time for the endothelialization process. In this work, metal-phenolic networks (MPNs), formed by the coordination interactions between (-)-Epigallocatechin gallate (EGCG) and copper ions (Cu 2+ ), were incorporated into the zwitterionic polymer modified glutaraldehyde crosslinked leaflets. The modified valve leaflets can prevent thrombosis and calcification mainly due to the antifouling zwitterionic polymer, and meanwhile can induce enhanced endothelialization potential via the generation of nitric oxide.Bioprosthetic leaflets incorporating EGCG and Cu 2+ as well as zwitterionic copolymers contributed to the growth of endothelial cells in co-culture experiments, achieving a proliferation improvement of up to 50% compared to glutaraldehyde-crosslinked valves.Subcutaneous implantation confirmed that the modified leaflets exhibit great anticalcification ability (with a 90% reduction in calcium deposition relative to glutaraldehyde-crosslinked valves) and reduced inflammatory response. The valve leaflets modified by EGCG, Cu 2+ and zwitterionic polymer have antithrombosis, anticalcification properties and pro-endothelialization potential.