Calcification and structural damage together accelerate porcine pericardium failure

Aortic stenosis (AS) is characterised by the narrowing and stiffening of the aortic valve, which restricts blood flow from the heart to the rest of the body. Severe AS is a life-threatening condition which affects 1.48 % of individuals aged 55 and older, with a four-year mortality rate of 44.9 % if left untreated. Minimally invasive treatment for AS involves the implantation of a bioprosthetic valve with porcine or bovine pericardium leaflets, which frequently succumb to failure due to regurgitation or stenosis caused in part by calcification and structural damage. The relationship between these two durability-limiting processes is debated, and the influence of device crimping on both factors is not comprehensively understood. This study aims to explore the relationship between calcification and structural damage and determine if device crimping affects these processes. First, porcine pericardium (PP) tissue was exposed to either in vitro calcification in unloaded conditions (calcification) or cyclic bulge loading in saline, without calcification (structural damage). Subsequently, PP was simultaneously calcified and cyclically loaded for 30 million cycles. Simultaneous calcification and loading led to dramatically increased calcification and structural damage, including tissue rupture. Device crimping was not found to have a significant impact on calcification or structural damage. However, fibre architecture was found to affect rupture location, and dramatically affect the rate of rupture of PP. This finding has implications for future bioprosthetic valve leaflet anti-calcification strategies, where tissue mechanics influenced by the underlying tissue fibre architecture should be considered to minimise both structural damage and calcification. STATEMENT OF SIGNIFICANCE: Porcine pericardium (PP) is a commonly used biomaterial, most frequently in the leaflets of bioprosthetic valves. These devices frequently succumb to failure due to regurgitation or stenosis caused in part by calcification and structural damage of their leaflets. This work shows that calcification and structural damage work together to accelerate failure of PP, with dramatically increased calcification and structural damage of PP, including rupture, when the tissue is exposed to both simultaneously. Fibre architecture of PP was found to affect rupture location, and dramatically affect rate of rupture. This finding has implications for bioprosthetic leaflet durability, where tissue mechanics influenced by the underlying tissue fibre architecture should be considered to minimise both structural damage and calcification and maximise valve durability.