Radical Polymerization-crosslinking Method for Improving Extracellular Matrix Stability in Bioprosthetic Heart Valves with Reduced Potential for Calcification and Inflammatory Response

In recent years, the number of heart valve replacements has multiplied with valve diseases because of aging populations and the surge in rheumatic heart disease in young people. Among them, bioprosthetic heart valves (BHVs) have become increasingly popular. Transcatheter aortic valve implantation (TAVI) valve as an emerging BHV has been increasingly applied to patients. However, the current commercially used BHVs treated with glutaraldehyde (Glut) still face the problem of durability. BHVs derived from Glut-treated xenogenetic tissues would undergo structural degeneration and calcification sometimes even as short as less than 10 years. This issue has already become a big challenge considering more and more young patients at the age of 50-60 s are receiving the BHV replacement. In our study, an approach that is totally different from the previous techniques named by us as the radical polymerization-crosslinking (RPC) method was developed to improve extracellular matrix stability, prevent calcification, and reduce inflammatory response in BHVs. The porcine pericardium (PP) tissue was decellularized, functionalized with methacryloyl groups, and subsequently crosslinked by radical polymerization. We found that high-density RPC treatment remarkably improved the stability of collagen and elastin of PP, enhanced its endothelialization potential, and provided reliable biomechanical performance as compared to Glut treatment. The in vivo rat model also confirmed the increased componential stability and the reduced inflammatory response of RPC-treated PP. Moreover, the RPC-treated PP showed better in vivo anticalcification potential than Glut-treated PP. STATEMENT OF SIGNIFICANCE: Bioprosthetic heart valves (BHVs) manufactured from glutaraldehyde (Glut)-treated xenogeneic tissues have been used to treat valve-related diseases for several decades. However, the durability of BHVs remains unresolved and becomes more pronounced particularly in younger patients. Although a number of new alternative methods for Glut crosslinking have been proposed, their overall performance is still far from ready to use in humans. In this study, radical polymerization was investigated for crosslinking the porcine pericardium (PP). This treatment was found to have advantages compared to Glut-treated PP in terms of stability, biocompatibility, and anticalcification potential with the hope of addressing the needs of more robust biomaterials for the fabrication of BHVs.