Hsiao-Ying Shadow Huang

Application of simple biomechanical and biochemical tests to heart valve leaflets: Implications for heart valve characterization and tissue engineering:

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.

Biaxial stress relaxation of semilunar heart valve leaflets during simulated collagen catabolism: Effects of collagenase concentration and equibiaxial strain state.

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.

In Situ Imaging of Lithium-Ion Batteries Via the Secondary Ion Mass Spectrometry

To develop lithium-ion batteries with a high rate-capability and low cost, the prevention of capacity loss is one of major challenges, which needs to be tackled in the lithium-ion battery industry. During electrochemical processes, lithium ions diffuse from and insert into battery electrodes accompanied with the phase transformation, whereas ionic diffusivity and concentration are keys to the resultant battery capacity. In the current study, we compare voltage versus capacity of lithium-ion batteries at different current-rates (C-rates) discharging. Larger hysteresis and voltage fluctuations are observed in higher C-rate samples. We investigate origins of voltage fluctuations by quantifying lithium-ion intensity and distribution via a time-of-flight secondary ion mass spectrometry (ToF-SIMS). The result shows that for fully discharged samples, lithium-ion intensity and distribution are not C-rate dependent, suggesting different lithium-ion insertion mechanisms at a higher C-rate discharging might be solely responsible for the observed low frequency voltage fluctuation.

Biaxial mechanical properties of bovine jugular venous valve leaflet tissues

Venous valve incompetence has been implicated in diseases ranging from chronic venous insufficiency (CVI) to intracranial venous hypertension. However, while the mechanical properties of venous valve leaflet tissues are central to CVI biomechanics and mechanobiology, neither stress–strain curves nor tangent moduli have been reported. Here, equibiaxial tensile mechanical tests were conducted to assess the tangent modulus, strength and anisotropy of venous valve leaflet tissues from bovine jugular veins. Valvular tissues were stretched to 60% strain in both the circumferential and radial directions, and leaflet tissue stress–strain curves were generated for proximal and distal valves (i.e., valves closest and furthest from the right heart, respectively). Toward linking mechanical properties to leaflet microstructure and composition, Masson’s trichrome and Verhoeff–Van Gieson staining and collagen assays were conducted. Results showed: (1) Proximal bovine jugular vein venous valves tended to be bicuspid (i.e., have two leaflets), while distal valves tended to be tricuspid; (2) leaflet tissues from proximal valves exhibited approximately threefold higher peak tangent moduli in the circumferential direction than in the orthogonal radial direction (i.e., proximal valve leaflet tissues were anisotropic;

Virtual experiments of heart valve tissues

p<0.01

Prediction of matrix-to-cell stress transfer in heart valve tissues

p<0.01); (3) individual leaflets excised from the same valve apparatus appeared to exhibit different mechanical properties (i.e., intra-valve variability); and (4) leaflets from distal valves exhibited a trend of higher soluble collagen concentrations than proximal ones (i.e., inter-valve variability). To the best of the authors’ knowledge, this is the first study reporting biaxial mechanical properties of venous valve leaflet tissues. These results provide a baseline for studying venous valve incompetence at the tissue level and a quantitative basis for prosthetic venous valve design.

Constitutive modeling of jugular vein-derived venous valve leaflet tissues

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.

Mixed Modes Fracture and Fatigue Evaluation for Lithium-Ion Batteries

The heart valve tissue mainly contains collagen fibers and valve interstitial cells (VICs) and constantly experiences different stress states during cardiac cycles. Due to the anisotropic architecture of collagen fibers and highly inhomogeneous cell population, the mechanical behavior of the heart valve becomes more complicated. It is known that external mechanical stimuli can lead to extracellular matrix (ECM) remodeling, cellular mechanotransduction, cell migration, and collagen synthesis; however, the mechanism of matrix-to-cell stress transfer remains unclear. Current study presents heterogeneously distributed collagen fibers responsible for transmitting forces into cells by an image-based finite element analysis incorporating histological photomicrographs of porcine heart valve tissues. Besides, nonlinear and anisotropic material properties tissue models are incorporated to quantify and visualize the overall stress distributions in heart valve tissues. By establishing an effectively predictive method with new computational tools and by performing virtual experiments on the heart valves, the role of load transmission in heart valves is clarified. The current study completely illustrates the stress distribution around cells and demonstrates the force transmission and reception between cells and matrix in the heart valve tissue. Therefore, our developed image-based finite element models provide new insights not only into clarifying the role of the force transmission and reception between heterogeneously distributed collagen fibers, but also a better understanding of relationships between the mechanical stimuli, cellular mechanotransduction, cell migration, matrix synthesis, and tissue remodeling in heart valves.