Nonglutaraldehyde crosslinked bioprosthetic heart valves based on 2-isocyanatoethyl methacrylate crosslinked porcine pericardium with improved properties of stability, cytocompatibility and anti-calcification

Abstract

Valvular heart diseases (VHD) have a high incidence in the elderly, and the morbidity and fatality rate of VHD increase gradually. To save the lives of patients at the end stage of VHD, valve replacement is the most effective treatment. Owning to the good hydrodynamic performance and application of transcatheter aortic valve replacement (TAVR), bioprosthetic heart valves (BHVs) fabricated from glutaraldehyde crosslinked porcine or bovine pericardium have become a popular choice for patients. However, BHVs fail within 10–15 years of implantation due to the structural degradation and calcification which are greatly attributed to glutaraldehyde crosslinking. In this work, 2-isocyanatoethyl methacrylate (ICM) was used as crosslinking agent for the first time to stabilize porcine pericardium by radical polymerization crosslinking. The ICM-crosslinked pericardium (PICM10-PP) was demonstrated to exhibit better cytocompatibility, mechanical property, and milder immune responses compared with glutaraldehyde crosslinked porcine pericardium (GA-PP). In addition, the PICM10-PP was less calcific than GA-PP after 30 and 90 days of subcutaneous implantation. Following the guidance of ISO5840-3, the hydrodynamic performance and durability of PICM10-PP were evaluated and demonstrated to conform the requirements for BHVs. These results indicate that ICM is a potential alternative of glutaraldehyde in crosslinking BHVs. A nonglutaraldehyde crosslinked bioprosthetic heart valve based 2-isocyanatoethyl methacrylate (ICM) crosslinked porcine pericardium. Methacryloyl groups were introduced to the porcine pericardium through the reaction between collagen and ICM, and the crosslinking was achieved through subsequent radical polymerization. The crosslinked porcine pericardium exhibited enhanced stability, cytocompatibility, mechanical property, anti-calcification hemocompatibility, and its hydrodynamic performance and durability were met the requirements of ISO5840-3. • 2-isocyanatoethyl methacrylate (ICM) was used as nonglutaraldehyde crosslinking agent for the first time for porcine pericardium. • The ICM-crosslinked pericardium (PICM10-PP) exhibited improved cytocompatibility and mechanical property.. • PICM10-PP was shown to be dramatically less calcific than GA-PP. • The hydrodynamic performance and durability of PICM10-PP met the requirement of ISO5840-3 for BHVs.