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    Poly(2-methacryloyloxyethyl phosphorylcholine) Grafted Bioprosthetic Heart Valve Exhibited Improved Antithrombogenicity and Anticalcification Properties

    Journal: ACS Appl. Polym. Mater.

    Authors: Huang, Xueyu; Zheng, Cheng; Ding, Kailei; Zhang, Shumang; Wei, Qingrong; Yang, Li; Wang, Yunbing

    Organizations: CAMS Innovation Fund for Medical Sciences [2021-I2M-5-013]; Chengdu Major Science and Technology Innovation Programs [2019-YF08-00235-GX]; National Natural Science Foundation of China [32071357]; Sichuan Science and Technology Program [2021YFH0011]; National Key Research and Development Programs, China [2020YFC1107802]; 111 Project of Introducing Talents of Discipline to Universities, China [B16033]

    Keywords: bioprosthetic heart valves; 2-methacryloyloxyethyl phosphorylcholine; copolymerization; anticalcification; antithrombogenicity

    Replacing diseased valves with bioprosthetic heart valves (BHVs) is an increasingly recognized treatment for valvular heart disease (VHD) due to the increasing application of transcatheter aortic valve replacement (TAVR) techniques. However, the dysfunction and structural valvular degeneration (SVD) of BHVs caused by the drawbacks of the traditional glutaraldehyde cross linking strategy including thrombosis, cytotoxicity, and calcification could shorten the lifespan of BHVs. In this study, a modification strategy for BHVs based on cocrosslinking and copolymerization was developed. Decellularized porcine pericardium and partially methacrylated poly-epsilon-lysine were first cocrosslinked by glutaraldehyde to achieve the cross-linking and methacrylation of porcine pericardium simultaneously, and then methacrylated modified pericardium was copolymerized with zwitterionic monomer 2methacryloyloxyethyl phosphorylcholine (MPC) to prepare poly-MPC grafted porcine pericardium (GM). GM exhibited improved endothelialial cells' proliferation compared with traditional glutaraldehyde cross-linked pericardium (GA) (3.67-fold higher than GA after a 3-day incubation). The platelets' adhesion test demonstrated the superiority of GM in resistance of platelet adhesion, where the platelet adhered on the surface of GM decreased by levels of approximately 75% compared with GA. Meanwhile, the results of 60-day and 150-day rat subcutaneous implantation demonstrated that GM exhibited improved anticalcification property than GA (1.6 +/- 0.4 mu g/mg versus 224 +/- 15 mu g/mg and 3.1 +/- 0.5 mu g/mg versus 252 +/- 15 mu g/mg respectively). All the results show that our modification strategy may have the potential for clinical application.
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