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bioRxiv · 10.1101/2020.10.21.347047

Collagen fibre-mediated mechanical damage increases calcification of bovine pericardium for use in bioprosthetic heart valves

Whelan, A.·Williams, E.·Fitzpatrick, E.·Murphy, B.·Gunning, P. S.·O'Reilly, D.·Lally, C.
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Abstract

In cases of aortic stenosis, bioprosthetic heart valves (BHVs), with leaflets made from glutaraldehyde fixed bovine pericardium (GLBP), are often implanted to replace the native diseased valve. Widespread use of these devices, however, is restricted due to inadequate long-term durability owing specifically to premature leaflet failure. Mechanical fatigue damage and calcification remain the primary leaflet failure modes, where glutaraldehyde treatment is known to accelerate calcification. The literature in this area is limited, with some studies suggesting mechanical damage increases calcification and others that they are independent degenerative mechanisms. In this study, specimens which were non-destructively pre-sorted according to collagen fibre architecture and then uniaxially cyclically loaded until failure or 1 million cycles, were placed in an in-vitro calcification solution. Measurements of percentage volume calcification demonstrated that the weakest specimen group (those with fibres aligned perpendicular to the load) had statistically significantly higher volumes of calcification when compared to those with a high fatigue life. Moreover, SEM imaging revealed that ruptured and damaged fibres presented binding sites for calcium to attach; resulting in more than 4 times the volume of calcification in fractured samples when compared to those which did not fail by fatigue. To the authors knowledge, this study quantifies for the first time, that mechanical damage drives calcification in commercial-grade GLBP and that this calcification varies spatially according to localised levels of damage. These findings illustrate that not only is calcification potential in GLBP exacerbated by fatigue damage, but that both failure phenomena are underpinned by the unloaded collagen fibre organisation. Consequently, controlling for GLBP collagen fibre architecture in leaflets could minimise the progression of these prevalent primary failure modes in patient BHVs.

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Whelan, A., Williams, E., Fitzpatrick, E., Murphy, B., Gunning, P. S., O'Reilly, D., Lally, C.. 2020-10-21. Collagen fibre-mediated mechanical damage increases calcification of bovine pericardium for use in bioprosthetic heart valves. https://doi.org/10.1101/2020.10.21.347047

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