Heart valve disease is generally treated by surgical replacement with either a mechanical or bioprosthetic valve. While prosthetic valves perform remarkably well, having significantly reduced patient mortality since their inception in 1960, each type exhibits specific drawbacks. Specifically, thrombosis and anticoagulation in the case of mechanical valves; calcific and fatigue-related degeneration in bioprosthetic heart valve (BHV). In attempt to improve the durability of BHV, recent studies have focused on quantifying the biomechanical interactions between the organ, tissue, and cellular-level components in native heart valve and BHV tissues. Such data is considered fundamental to designing improved BHV, and ultimately may be useful in the design of tissue engineered heart valves (TEHV).The goals of this research were two-fold: (1) to simulate layer-specific mechanical property changes incurred by the porcine BHV with fatigue, and (2) to simulate the cellular-level deformation of valve interstitial cells (VIC) nuclei under organ-level transvalvular pressures. For the first goal, parametric studies were conducted to isolate the effective modulii of the individual layers using finite element simulations of native and BHV tissues in flexure. The finite element simulations isolated fatigue-related changes in the overall effective modulus of BHV tissues specifically to the collagen-rich fibrosa layer. These results may be useful in designing improved BHV, as novel fixatives and fixation methods may have the capacity to target specific layers of the BHV tissue. For the second goal, cellular-level VIC nuclei deformations were quantified experimentally by analyzing images of histological sections prepared from native porcine aortic valves subjected to transvalvular pressures. Finite element simulations were conducted to quantify the relationship between organ-level transvalvular pressure, concomitant tissue-level strain, and ultimate cellular-level VIC nuclei deformation. The cellular-level image analysis studies uncovered layer-specific, positive relationships between VIC nuclei deformations and transvalvular pressure. These data were found to correlate with previously published data on the associated collagen fiber architecture, providing insight into the tissue-to-cellular level mechanical coupling predicted by the finite element simulations. These results may be useful in designing TEHV, as evidence suggests that the secretion and organization of extracellular matrix (ECM) (e.g., collagen) by the constituent cells of a TEHV can be modulated by mechanical deformation.To the best of our knowledge, the simulations presented herein represent the first attempt to quantify layer-specific changes in porcine BHV tissue mechanical properties with fatigue. Moreover, we report the first information on the cellular-level deformation of VIC nuclei under transvalvular pressures, including experimental analysis of the native porcine aortic valve, as well as rigorous finite element simulations. These micromechanical simulations thus offer new data on the biomechanical behavior of heart valve tissues, and may contribute to the design of improved BHV and TEHV.
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