Modern view on calcification of xenogenic bioprosthetic heart valves and their anti-calcification treatment strategies

Abstract

Aim. The aim of this review was to analyze publications describing studies focusing on the pathophysiological mechanisms of calcification of bioprosthetic heart valves, and to substantiate new and promising methods of calcification prevention for the implantable medical devices. Material and methods. Databases and electronic libraries such as PubMed, Google Scholar and eLibrary were used for searching relevant articles. Search queries included the following word combinations: “bioprosthetic heart valves”, “structural valve degeneration”, “calcification”, “cyclic loading”, “inflammation”, “proteolysis”, “proteolytic enzymes”, “decellularization”, “anticalcification treatment”. The references in relevant articles were used for the search as well. Preference was given to works published from January 2013 to January 2023. Results. We have considered the key aspects of bioprosthetic heart valves calcification and the main strategies of calcification prevention. Calcification of bioprosthetic heart valves incorporates a complex set of mechanisms that includes, but is not limited to: 1) binding of calcium in chemically stabilized biomaterial by free groups of the preservative; 2) precipitation of calcium on residual donor cells and cell debris; 3) pro-calcifying changes in biological material due to proteolysis, mechanical and oxidative stress; 4) cell-mediated biomineralization. Despite modern advances in biopreservation, such as treatment with chemical agents that prevent the deposition of calcium, the problem of bioprosthetic heart valves calcification still prevails. The cause of it lies in the heterogeneity of the pathophysiological mechanisms behind the mineralization of biomaterial: the currently developed methods of calcification prevention cannot block all ways of bioprosthetic heart valves calcification. Conclusion. Calcification of bioprosthetic heart valves leaflets is a complex process that underlies the main cause of dysfunction of the medical devices. Supposedly, a new innovative approach that involves polymer hydrogel filler in biomaterials can completely prevent its calcification.