A simple biomechanical test with real-time displacement and strain mapping is reported, which provides displacement vectors and principal strain directions during the mechanical characterization of heart valve tissues. The maps reported in the current study allow us to quickly identify the approximate strain imposed on a location in the samples. The biomechanical results show that the aortic valves exhibit stronger anisotropic mechanical behavior than that of the pulmonary valves before 18% strain equibiaxial stretching. In contrast, the pulmonary valves exhibit stronger anisotropic mechanical behavior than aortic valves beyond 28% strain equibiaxial stretching. Simple biochemical tests are also conducted. Collagens are extracted at different time points (24, 48, 72, and 120 h) at different locations in the samples. The results show that extraction time plays an important role in determining collagen concentration, in which a minimum of 72 h of extraction is required to obtain saturated collagen concentration. This work provides an easy approach for quantifying biomechanical and biochemical properties of semilunar heart valve tissues, and potentially facilitates the development of tissue engineered heart valves.

Heart valve leaflet collagen turnover and remodeling are innate to physiological homeostasis; valvular interstitial cells routinely catabolize damaged collagen and affect repair. Moreover, evidence indicates that leaflets can adapt to altered physiological (e.g. pregnancy) and pathological (e.g. hypertension) mechanical load states, tuning collagen structure and composition to changes in pressure and flow. However, while valvular interstitial cell-secreted matrix metalloproteinases are considered the primary effectors of collagen catabolism, the mechanisms by which damaged collagen fibers are selectively degraded remain unclear. Growing evidence suggests that the collagen fiber strain state plays a key role, with the strain-dependent configuration of the collagen molecules either masking or presenting proteolytic sites, thereby protecting or accelerating collagen proteolysis. In this study, the effects of equibiaxial strain state on collagen catabolism were investigated in porcine aortic valve and pulmonary valve tissues. Bacterial collagenase (0.2 and 0.5 mg/mL) was utilized to simulate endogenous matrix metalloproteinases, and biaxial stress relaxation and biochemical collagen concentration served as functional and compositional measures of collagen catabolism, respectively. At a collagenase concentration of 0.5 mg/mL, increasing the equibiaxial strain imposed during stress relaxation (0%, 37.5%, and 50%) yielded significantly lower median collagen concentrations in the aortic valve (p = 0.0231) and pulmonary valve (p = 0.0183), suggesting that relatively large strain magnitudes may enhance collagen catabolism. Collagen concentration decreases were paralleled by trends of accelerated normalized stress relaxation rate with equibiaxial strain in aortic valve tissues. Collectively, these in vitro results indicate that biaxial strain state is capable of affecting the susceptibility of valvular collagens to catabolism, providing a basis for further investigation of how such phenomena may manifest at different strain magnitudes or in vivo.

Skin is a multilayered composite material and composed principally of the proteins collagen, elastic fibers and fibroblasts. The direction-dependent material properties of skin tissue is important for physiological functions like skin expansion. The current study has developed methods to characterize the directional biomechanical properties of porcine skin tissues as studies have shown that pigs represent a useful animal model due to similarities between porcine and human skin. It is observed that skin tissue has a nonlinear anisotropy biomechanical behavior, where the parameters of material modulus is 378 ± 160 kPa in the preferred-fiber direction and 65.96 ± 40.49 kPa in the cross-fiber direction when stretching above 30% strain equibiaxially. The result from the study provides methods of characterizing biaxial mechanical properties of skin tissue, as the collagen fiber direction appears to be one of the primary determinants of tissue anisotropy.

Previous studies show that the collagen fiber architecture is key to the heart valves tissue mechanical property. We report a real-time strain mapping approach that provides displacement vectors and principal strain directions during the mechanical characterization of heart valve tissues. The strain maps reported in the current study allows an individual to quickly identify the approximate strain imposed on a location of the sample. The result shows that when samples are biaxially stretched under 18% strain, less anisotropy is observed in both aortic and pulmonary valve leaflet samples. Moreover, when samples are stretched from 28% to 35%, pulmonary valves leaflet samples exhibits a stronger anisotropic effect than aortic valve. Therefore, a higher degree of straightening is required for collagen fibers to be fully aligned. This work provides an easy approach to quantify mechanical properties with the corresponding strain maps of heart valve tissues and potentially facilitates the developments of tissue engineering heart valves.

This study presents an image-based finite element analysis incorporating histological photomicrographs of heart valve tissues. We report stress fields inside heart valve tissues, where heterogeneously distributed collagen fibres are responsible for transmitting forces into cells. Linear isotropic and anisotropic tissue material property models are incorporated to quantify the overall stress distributions in heart valve tissues. By establishing an effective predictive method with new computational tools and by performing virtual experiments on the heart valve tissue photomicrographs, we clarify how stresses are transferred from matrix to cell. The results clearly reveal the roles of heterogeneously distributed collagen fibres in mitigating stress developments inside heart valve tissues. Moreover, most local peak stresses occur around cell nuclei, suggesting that higher stress may be mediated by cells for biomechanical regulations.

Non-linear and anisotropic heart valve leaflet tissue mechanics manifest principally from the stratification, orientation, and inhomogeneity of their collagenous microstructures. Disturbance of the native collagen fiber network has clear consequences for valve and leaflet tissue mechanics and presumably, by virtue of their intimate embedment, on the valvular interstitial cell stress-strain state and concomitant phenotype. In the current study, a set of virtual biaxial stretch experiments were conducted on porcine pulmonary valve leaflet tissue photomicrographs via an image-based finite element approach. Stress distribution evolution during diastolic valve closure was predicted at both the tissue and cellular levels. Orthotropic material properties consistent with distinct stages of diastolic loading were applied. Virtual experiments predicted tissue-and cellular-level stress fields, providing insight into how matrix-to-cell stress transfer may be influenced by the inhomogeneous collagen fiber architecture, tissue anisotropic material properties, and the cellular distribution within the leaflet tissue. To the best of the authors' knowledge, this is the first study reporting on the evolution of stress fields at both the tissue and cellular levels in valvular tissue and thus contributes toward refining our collective understanding of valvular tissue micromechanics while providing a computational tool enabling the further study of valvular cell-matrix interactions.

Heart valves are inhomogeneous microstructure with nonlinear anisotropic properties and constantly experience different stress states during cardiac cycles. However, how tissue-level mechanical forces can translate into altered cellular stress states remains unclear, and associated biomechanical regulation in the tissue has not been fully understood. In the current study, we use an image-based finite element method to investigate factors contributing the stress distributions at both tissue- and cell-levels inside the healthy heart valve tissues. Effects of tissue microstructure, inhomogeneity, and anisotropic material property at different diastole states are discussed to provide a better understanding of structure-mechanics-property interactions, which alters tissue-to-cell stress transfer mechanisms in heart valve tissue. To the best of the authors’ knowledge, this is the first study reporting on the evolution of stress fields at both the tissue- and cellular-levels in valvular tissue, and thus contributes toward refining our collective understanding of valvular tissue micromechanics while providing a computational tool enabling further study of valvular cell-tissue interactions.

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