Mechanisms of bioprosthetic heart valve failure: Fatigue causes collagen denaturation and glycosaminoglycan loss

Abstract

Bioprosthetic heart valve (BPHV) degeneration, characterized by extracellular matrix deterioration, remodeling, and calcification, is an important clinical problem accounting for thousands of surgeries annually. Here we report for the first time, in a series of in vitro accelerated fatigue studies (5-500 million cycles) with glutaraldehyde fixed porcine aortic valve bioprostheses, that the mechanical function of cardiac valve cusps caused progressive damage to the molecular structure of type I collagen as assessed by Fourier transform IR spectroscopy (FTIR). The cyclic fatigue caused a progressive loss of helicity of the bioprosthetic cuspal collagen, which was evident from FTIR spectral changes in the amide I carbonyl stretching region. Furthermore, cardiac valve fatigue in these studies also led to loss of glycosaminoglycans (GAGs) from the cuspal extracellular matrix. The GAG levels in glutaraldehyde crosslinked porcine aortic valve cusps were 65.2 ± 8.66 g uronic acid/10 mg of dry weight for control and 7.91 ± 1.1 g uronic acid/10 mg of dry weight for 10-300 million cycled cusps. Together, these molecular changes contribute to a significant gradual decrease in cuspal bending strength as documented in a biomechanical bending assay measuring three point deformation. We conclude that fatigue-induced damage to type I collagen and loss of GAGs are major contributing factors to material degeneration in bioprosthetic cardiac valve deterioration.

Decellularization of pericardial tissue and its impact on tensile viscoelasticity and glycosaminoglycan content

“…It is well known, that the GAG content and type have a significant role in the mechanical performance of tissues such as bovine pericardium [21,36,38] and porcine heart valves [39]. In this study, we observed a reduction in GAG content on bovine pericardial tissue and therefore it was expected that the tensile properties would be affected to different extents depending on the amount of GAG removed.…”

Cell colonization in degradable 3D porous matrices

“…Scaffolding material eventually disappears leaving only the necessary healthy tissue in a topologically required form. 8,9,11 The 3D matrix provides more space for cellular colonization and proliferation as well as provides a different set of physiological signals to the developing tissue. One option for creating tissue scaffolds is to use extracellular matrix (ECM) components derived from animal sources.…”

Animal models for the atherosclerosis research: a review

“…The electrophysiologic parameters of pigs also more closely resemble those of man than other models, except the non-human primate (Liedtke et al, 1975;Bowman and Hughes, 1984;Hughes, 1986). Moreover, cardiovascular surgical procedures using swine have been technically feasible for ventricular assist devices for patients suffering from acute myocardial infarction (Vyavahare et al, 1999;Schoen and Levy, 2009), vascular stents, and restenosis (David et al, 1998;David et al, 2009), which make swine a unique surgical model.…”