Investigation of Structure-Mechanics-Property Relations in Heart Valve Tissues

The microstructure and the mechanical property of the heart valve are physically critical factors in modeling the valve tissue equivalent. The heart valve tissue has a complex microstructure primarily containing collagen fibers and valve interstitial cells (VICs). The extracellular matrix (ECM) of the heart valve tissue, where collagen is the main component, provides strength to support the structure of the tissue. The inhomogeneity of the collagen fiber architecture gives rise to the nonlinear anisotropic material property of the tissue. Besides, to respond mechanical loads, VICs mediate a series of bioregulations for ECM remodeling such as homeostasis, collagen synthesis, and collagen degradation through collagen fibers, which further result in changes of the material behavior corresponding to mechanical stimulation. Due to the inhomogeneous architecture of collagen fibers and randomly distributed cell population, the mechanical behavior of the heart valve tissue becomes more complicated during cardiac cycles.;Heart valves open and close correctly and persistently during cardiac systole and diastole for blood circulation. It is a widely acknowledged health concern that heart valve diseases lead to defective structures and improper functions of heart valves to directly influence the blood circulation and the heart workload. To date, at least 250,000 people are suffering heart valve diseases in the United States, and the population keeps rising. Studies have indicated that heart valve diseases are caused by the disrupted tissue homeostasis under a variety of pathological conditions, resulting in alterations in heart valve microstructures, mechanical properties, and other biomechanical regulations.;Severe collagen depletion is one of disordered tissue remodeling caused by matrix metalloproteinases (MMPs) that pathologically induces matrix destruction, changes the viscoelastic property of the heart valve tissue, further affects cellular regulations mediated by VICs, and even leads to heart valve diseases. With application of collagenase simulating collagen degradation by MMPs, this study focuses on characterizing stress-relaxation behaviors of fresh porcine heart valve tissues and collagenase-treated ones under different stretching conditions. Moreover, the collagen concentration is measured to provide biochemical information related to the mechanical stress relaxation. The results reveal the sensitivity of collagen fibers to proteolytic degradation. The decrease in the stress state of the heart valve tissue is associated with the stretching level and the collagenase concentration. Stress is further decreased after applying collagenase, and a larger stress drop results from a higher strain level and/or a higher collagenase concentration. Therefore, the current study provides important links between several factors: collagen degradation, activities of matrix metalloproteinases, collagen fiber directions, and mechanical stimulations.;It is known that heart valves constantly experience different stress states during cardiac cycles; however, how these mechanical stimuli translate into extracellular matrix remodeling, cellular mechanotransduction, cell migration, and collagen synthesis are still unclear. Although the computational simulations of heart valve tissue have been widely studied via the homogenization of collagen fiber distribution or the simplified representation of the highly heterogeneous collagen fiber network excluding the cell population, the matrix-to-cell stress transfer is underestimated. Meanwhile, VIC regulations have been investigated from cells generally isolated from the matrix prior to adhesion molecule characterization; thus, tissue-cell mechanical interactions have not been fully characterized in the native in vivo environment in which they normally operate. To demonstrate heterogeneously distributed collagen fibers responsible for transmitting forces into cells, this study introduces a virtual experiment via an image-based finite element analysis incorporating a histological photomicrograph of a porcine heart valve tissue. Furthermore, the evolution of stress fields at both the tissue and cellular levels is reported to contribute toward refining our collective understanding of valvular tissue micromechanics while a computational tool is provided to further study of valvular cell-matrix interactions.