Cross-Linking Methacrylated Porcine Pericardium by Radical Polymerization Confers Enhanced Extracellular Matrix Stability, Reduced Calcification, and Mitigated Immune Response to Bioprosthetic Heart Valves

The aging population and the development of transcatheter aortic valve replacement (TAVR) technology largely expand the usage of bioprosthetic heart valves (BHVs) in patients. Almost all of the commercial BHVs are treated with glutaraldehyde (GA). However, the GA-treated BHVs display the drawbacks such as extracellular matrix (ECM) degradation, cytotoxicity, immune response, and calcification. In this study, radical polymerization reaction, a powerful tool commonly used in preparing polymers and hydrogels, has been developed to fix decellularized ECM instead of GA treatment. Porcine pericardium (PP) is taken as an example of ECM for BHVs fabrication to investigate the impact of radical polymerization on the tissue properties. The radical polymerization method better stabilizes collagen and elastin of PP than GA treatment and produces a soft biomaterial more like the native heart valve. Furthermore, radical polymerization cross-linked PP exhibits excellent cytocompatibility. After implanted subcutaneously in rats for 30 days, radical polymerization cross-linked PP shows better elastin stability, mitigated immune response, and reduced calcification than GA-PP. All these results suggest that radical polymerization is an ideal cross-linking method for BHVs or tissue engineering heart valve scaffolds and it also has the potential for creating a variety of ECM-polymer hybrid biomaterials in the future.