Chemical bonding of biological valve leaflets with an aminated zwitterionic copolymer for long-term anticoagulation and improved anti-calcification

Abstract

Glutaraldehyde cross-linked pericardium (GLUT), mostly used in Bioprosthetic heart valves (BHVs) clinically, still has problems of valve thrombus, cytotoxicity, and calcification. Although many new crosslinking approaches have been explored to obtain certain biological achievements, their clinical applications are still some way off, which might be ascribed to the limitations of preservation and sterilization. In this study, a novel post-crosslinking of GLUT was developed using a zwitterionic copolymer. The copolymer imitating the molecular structure of phospholipids was composed of the copolymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC), N-(3-Aminopropyl) methacrylamide hydrochloride (APMA), and Lauryl methacrylate (LMA). With the introduction of primary amines, the zwitterionic copolymer could be effectively utilized in the post-crosslinking of GLUT. Meanwhile, the anticoagulation properties of valve leaflets could be adjusted by combining aminated zwitterionic copolymers with different molecular weights. The valve leaflets modified with aminated zwitterionic copolymer not only maintained original mechanical property and structural integrity, but also significantly improved the long-term anti-coagulation and stability in vitro and ex vivo. The subcutaneous implantation confirmed that the modified leaflets possessed great resistance to calcification along with reduced inflammatory response. Besides, the modified leaflets could be further stored in glutaraldehyde solution (a storage formula for commercial valves) and still retained great anti-coagulant and anti-calcification properties. The study demonstrated a better clinical potential of the modified leaflets via the post-crosslinking of glutaraldehyde treated leaflets with the aminated zwitterionic copolymer.