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

Abstract

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.

The study of dry biological valve crosslinked with a combination of carbodiimide and polyphenol

“…At present, a variety of non-glutaraldehyde crosslinking methods can be found in the literature, including chemical crosslinkers such as carbodiimide [ 2 , 5 ], epoxides [ 14 , 15 ], free radical polymerization crosslinkers [ 4 , 16 ], and natural crosslinkers such as curcumin [ 6 ], procyanidins [ 3 , 5 ], genipin [ 17 , 18 ], tannins [ 19 ], etc. However, currently, all the biological valve products in clinical use are prepared by crosslinking with glutaraldehyde, and almost no pericardial materials with non-glutaraldehyde crosslinking have been used for commercial biological valve products.…”

Crosslinking porcine aortic valve by radical polymerization for the preparation of BHVs with improved cytocompatibility, mild immune response, and reduced calcification

“…1,2 Compared with mechanical heart valves (MHVs), bioprosthetic heart valves (BHVs) don’t require lifelong anticoagulant therapy, and their better biocompatibility and superior hemodynamic properties make them the preferred choice for valve replacemen. 3,4…”

“…26,27 Radical polymerization crosslinking method has been used in the preparation of polymers and hydrogels because of its mild reaction conditions and wide application range. 3,28,29 Guo, Jin et al. 3,30 successfully modified MA and glycidyl methacrylate (GMA) monomers on porcine pericardium by radical polymerization crosslinking, thus greatly improving the biocompatibility and anticalcification performance of BHVs, demonstrating the effectiveness of such method.…”

“…3,28,29 Guo, Jin et al. 3,30 successfully modified MA and glycidyl methacrylate (GMA) monomers on porcine pericardium by radical polymerization crosslinking, thus greatly improving the biocompatibility and anticalcification performance of BHVs, demonstrating the effectiveness of such method. Porcine aortic valve (PAV) is also a commonly used xenogenic tissue material for BHVs.…”

Tissue Engineering for Mimics and Modulations of Immune Functions

“…Wang's group functionalized porcine pericardium with methacryloyl groups for radical polymerization. [ 136,140 ] The resultant graft exhibited better stability and reduced inflammation, recruiting fewer CD68‐expressing macrophages than glutaraldehyde‐treated grafts.…”