Effect of Inorganic Body Mimetic Solutions and Chemical Modifications on the Calcium Phosphate Precipitation on Pericardium used in Bioprosthetic Heart Valves

Abstract

Calcific aortic valve disease (CAVD) is a leading fatal disorder caused by calcium phosphate deposits on valve leaflets, which impairs blood flow through the heart. The only existing treatment is replacement with a bioprosthetic or mechanical valve. Bioprosthetic heart valves (BHVs) calcify similarly to native valves. The mechanism for this calcification is unclear. There are currently two main theories regarding the calcification mechanism of BHVs: one preferentially biological and the other preferentially physiochemical. In this study we aim to evaluate the effect of different inorganic body mimetic solutions and valve chemical modifications on the calcification in pericardium used in BHVs. The impact of three physiochemical elements was studied in this project: the chemical modification of pericardium by acid or base treatment, simulated body fluid (SBF) with different concentrations of calcium, phosphorus and magnesium ions and mechanical damage of the pericardium. The modified bovine pericardium samples and collagen gels were incubated at 36.5°C in SBF for 7 or 14 days, then stained with Alizarin Red and analysed by fluorescence and electron microscopy (SEM). Minimal to no calcium phosphate precipitation was observed in all pericardium samples. Collagen gel controls exhibited significant precipitation depending on solution composition and treatment. The absence of observable calcium phosphate precipitation in the pericardium samples suggests that physiochemical factors alone cannot drive BHV calcification. The findings in this study challenge the hypothesis that physiochemical parameters are the main drive for calcification in BHVs, supporting growing evidence that it is an active process involving cellular and biological mechanisms.