Different approaches to heart valve decellularization: A comprehensive overview of the past 30 years

Xenogeneic decellularized heart valve scaffolds have the potential to overcome the limitations of existing bioprosthetic heart valves that have limited duration due to calcification and tissue degeneration phenomena. This article presents a review of 30 years of decellularization approaches adopted in cardiovascular tissue engineering, with a focus on the use, either individually or in combination, of different detergents. The safety and efficacy of cell-removal procedures are specifically reported and discussed, as well as the structure and biomechanics of the treated extracellular matrix (ECM). Detergent residues within the ECM, production of hyaluronan fragments, safe removal of cellular debris, and the persistence of the alpha-Gal epitope after the decellularization treatments are of particular interest as parameters for the identification of the best tissue for the manufacture of bioprostheses. Special attention has also been given to key factors that should be considered in the manufacture of the next generation of xenogeneic bioprostheses, where tissues must retain the ability to be remodeled and to grow in weight along with body reshaping.