Investigation into the collagen fibre-mediated fatigue mechanics of bovine pericardium for use in bioprosthetic heart valves

Abstract

Bioprosthetic heart valve replacements have long been associated with inadequate durability in vivo, owing primarily to mechanical damage and calcification of the glutaraldehyde-fixed bovine pericardial leaflets (GLBP). Collagen fibres are the dominant load bearing constituent of GLBP, yet, there is no standardised pre-screening of GLBP leaflet fibre patterns for commercial devices. The aim of this thesis was to further understand how the fibrous structural parameters of GLBP influence its fatigue and damage behaviour, to aid in improving the manufacture and design of next generation leaflets. To achieve this, both mechanical testing and computational investigations were conducted. Of note, it was found that collagen fibre alignment, in addition to orientation, is a key structural feature of GLBP, where samples with fibres highly dispersed (HD) in multiple orientations, were found to have an inherently increased collagen content in comparison to GLBP with highly aligned fibres. A novel testing system was built to investigate the response of GLBP under low-strain fatigue bulge loading conditions at 150 mmHg, where samples with HD fibres accumulated significantly greater levels of permanent strain up to 60 million cycles, than GLBP with highly aligned fibres. This illustrated that the matrix-driven permanent set phenomenon of GLBP, which dominates its early-stage response in vivo, is mediated by underlying collagen fibre patterns. Moreover, experimental and computational studies revealed that highly crimped fibres were responsible for increased permanent strains in HD GLBP. Characteristically high levels of crimp protected fibres from load bearing; increasing the mechanical burden on the matrix, and consequently, tissue-level permanent strains in HD GLBP. Investigation of the variable fibre structures present in a GLBP patch in this thesis demonstrated that several fibre parameters must be controlled for in the manufacture of leaflets. Furthermore, the heterogenous delivery sites for these devices, in addition to the complex leaflet loading patterns in vivo, perhaps make GLBP unsuited to application in BHV leaflets. Leaflets with fibre patterns aligned to localised principal strain directions in vivo will likely provide improved outcomes, where leaflets made from GLBP are constrained to native pericardial fibre patterns.