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TECHNICAL PAPERS: Cell

J Biomech Eng. 2004;126(5):545-551. doi:10.1115/1.1798053.

Recent results demonstrate the exquisite sensitivity of cell orientation responses to the pattern of imposed deformation. Cells undergoing pure in-plane uniaxial stretching orient differently than cells that are simply elongated—likely because the latter stimulus produces simultaneous compression in the unstretched direction. It is not known, however, if cells respond differently to pure stretching than to pure compression. This study was performed to address this issue. Human aortic endothelial cells were seeded on deformable silicone membranes and subjected to various magnitudes and rates of pure stretching or compression. The cell orientation and cytoskeletal stress fiber organization responses were examined. Both stretching and compression resulted in magnitude-dependent but not rate-dependent orientation responses away from the deforming direction. Compression produced a slower temporal response than stretching. However, stress fiber reorganization responses–early disruption followed by reassembly into parallel arrays along the cells’ long axes were similar between the two stimuli. Moreover, the cell orientation and stress fiber responses appeared to be uncoupled since disruption of stress fibers was not required for the cell orientation. Moreover, parallel actin stress fibers were observed at oblique angles to the deforming direction indicating that stress fibers can reassemble when undergoing deformation.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):552-558. doi:10.1115/1.1800559.

We investigated the mechanotransduction pathway in endothelial cells between their nucleus and adhesions to the extracellular matrix. First, we measured nuclear deformations in response to alterations of cell shape as cells detach from a flat surface. We found that the nuclear deformation appeared to be in direct and immediate response to alterations of the cell adhesion area. The nucleus was then treated as a neo-Hookean compressible material, and we estimated the stress associated with the cytoskeleton and acting on the nucleus during cell rounding. With the obtained stress field, we estimated the magnitude of the forces deforming the nucleus. Considering the initial and final components of this adhesion-cytoskeleton-nucleus force transmission pathway, we found our estimate for the internal forces acting on the nucleus to be on the same order of magnitude as previously measured traction forces, suggesting a direct mechanical link between adhesions and the nucleus.

Commentary by Dr. Valentin Fuster

TECHNICAL PAPERS: Fluids/Heat/Transport

J Biomech Eng. 2004;126(5):559-566. doi:10.1115/1.1797904.

Vascular stents influence the post-procedural hemodynamic environment in ways that may encourage restenosis. Understanding how stents influence flow patterns may lead to more hemodynamically compatible stent designs that alleviate thrombus formation and promote endothelialization. This study employed time-resolved Digital Particle Image Velocimetry (DPIV) to compare the hemodynamic performance of two stents in a compliant vessel. The first stent was a rigid insert, representing an extreme compliance mismatch. The second stent was a commercially available nitinol stent with some flexural characteristics. DPIV showed that compliance mismatch promotes the formation of a ring vortex in the vicinity of the stent. Larger compliance mismatch increased both the size and residence time of the ring vortex, and introduced in-flow stagnation points. These results provide detailed quantitative evidence of the hemodynamic effect of stent mechanical properties. Better understanding of these characteristics will provide valuable information for modifying stent design in order to promote long-term patency.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):567-577. doi:10.1115/1.1798051.

In this study, we investigate the steady propagation of a liquid plug within a two-dimensional channel lined by a uniform, thin liquid film. The Navier-Stokes equations with free-surface boundary conditions are solved using the finite volume numerical scheme. We examine the effect of varying plug propagation speed and plug length in both the Stokes flow limit and for finite Reynolds number (Re). For a fixed plug length, the trailing film thickness increases with plug propagation speed. If the plug length is greater than the channel width, the trailing film thickness agrees with previous theories for semi-infinite bubble propagation. As the plug length decreases below the channel width, the trailing film thickness decreases, and for finite Re there is significant interaction between the leading and trailing menisci and their local flow effects. A recirculation flow forms inside the plug core and is skewed towards the rear meniscus as Re increases. The recirculation velocity between both tips decreases with the plug length. The macroscopic pressure gradient, which is the pressure drop between the leading and trailing gas phases divided by the plug length, is a function of U and U2, where U is the plug propagation speed, when the fluid property and the channel geometry are fixed. The U2 term becomes dominant at small values of the plug length. A capillary wave develops at the front meniscus, with an amplitude that increases with Re, and this causes large local changes in wall shear stresses and pressures.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):578-584. doi:10.1115/1.1798032.

Difficulties in predicting the behavior of some high Reynolds number flows in the circulatory system stem in part from the severe requirements placed on the turbulence model chosen to close the time-averaged equations of fluid motion. In particular, the successful turbulence model is required to (a) correctly capture the “nonequilibrium” effects wrought by the interactions of the organized mean-flow unsteadiness with the random turbulence, (b) correctly reproduce the effects of the laminar-turbulent transitional behavior that occurs at various phases of the cardiac cycle, and (c) yield good predictions of the near-wall flow behavior in conditions where the universal logarithmic law of the wall is known to be not valid. These requirements are not immediately met by standard models of turbulence that have been developed largely with reference to data from steady, fully turbulent flows in approximate local equilibrium. The purpose of this paper is to report on the development of a turbulence model suited for use in arterial flows. The model is of the two-equation eddy-viscosity variety with dependent variables that are zero-valued at a solid wall and vary linearly with distance from it. The effects of transition are introduced by coupling this model to the local value of the intermittency and obtaining the latter from the solution of a modeled transport equation. Comparisons with measurements obtained in oscillatory transitional flows in circular tubes show that the model produces substantial improvements over existing closures. Further pulsatile-flow predictions, driven by a mean-flow wave form obtained in a diseased human carotid artery, indicate that the intermittency-modified model yields much reduced levels of wall shear stress compared to the original, unmodified model. This result, which is attributed to the rapid growth in the thickness of the viscous sublayer arising from the severe acceleration of systole, argues in favor of the use of the model for the prediction of arterial flows.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):585-593. doi:10.1115/1.1798056.

In order to bridge the gap of existing artificial heart technology to the diverse needs of the patient population, we have been investigating the viability of a scaled-down design of the current 70 cc Penn State artificial heart. The issues of clot formation and hemolysis may become magnified within a 50 cc chamber compared to the existing 70 cc one. Particle image velocimetry (PIV) was employed to map the entire 50 cc Penn State artificial heart chamber. Flow fields constructed from PIV data indicate a rotational flow pattern that provides washout during diastole. In addition, shear rate maps were constructed for the inner walls of the heart chamber. The lateral walls of the mitral and aortic ports experience high shear rates while the upper and bottom walls undergo low shear rates, with sufficiently long exposure times to potentially induce platelet activation or thrombus formation. In this study, we have demonstrated that PIV may adequately map the flow fields accurately in a reasonable amount of time. Therefore, the potential exists of employing PIV as a design tool.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):594-603. doi:10.1115/1.1800553.

The flow field and energetic efficiency of total cavopulmonary connection (TCPC) models have been studied by both in vitro experiment and computational fluid dynamics (CFD). All the previous CFD studies have employed the structured mesh generation method to create the TCPC simulation model. In this study, a realistic TCPC model with complete anatomical features was numerically simulated using both structured and unstructured mesh generation methods. The flow fields and energy losses were compared in these two meshes. Two different energy loss calculation methods, the control volume and viscous dissipation methods, were investigated. The energy losses were also compared to the in vitro experimental results. The results demonstrated that: (1) the flow fields in the structured model were qualitatively similar to the unstructured model; (2) more vortices were present in the structured model than in the unstructured model; (3) both models had the least energy loss when flow was equally distributed to the left and right pulmonary arteries, while high losses occurred for extreme pulmonary arterial flow splits; (4) the energy loss results calculated using the same method were significantly different for different meshes; and (5) the energy loss results calculated using different methods were significantly different for the same mesh.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):604-613. doi:10.1115/1.1800554.

In order to understand mechanisms of gas and aerosol transport in the human respiratory system airflow in the upper airways of a pediatric subject (male aged 5) was calculated using Computational Fluid Dynamic techniques. An in vitro reconstruction of the subject’s anatomy was produced from MRI images. Flow fields were solved for steady inhalation at 6.4 and 8 LPM. For validation of the numerical solution, airflow in an adult cadaver based trachea was solved using identical numerical methods. Comparisons were made between experimental results and computational data of the adult model to determine solution validity. It was found that numerical simulations can provide an accurate representation of axial velocities and turbulence intensity. Data on flow resistance, axial velocities, secondary velocity vectors, and turbulent kinetic energy are presented for the pediatric case. Turbulent kinetic energy and axial velocities were heavily dependant on flow rate, whereas turbulence intensity varied less over the flow rates studied. The laryngeal jet from an adult model was compared to the laryngeal jet in the pediatric model based on Tracheal Reynolds number. The pediatric case indicated that children show axial velocities in the laryngeal jet comparable to adults, who have much higher tracheal Reynolds numbers than children due to larger characteristic dimensions. The intensity of turbulence follows a similar trend, with higher turbulent kinetic energy levels in the pediatric model than would be expected from measurements in adults at similar tracheal Reynolds numbers. There was reasonable agreement between the location of flow structures between adults and children, suggesting that an unknown length scale correlation factor could exist that would produce acceptable predictions of pediatric velocimetry based off of adult data sets. A combined scale for turbulent intensity as well may not exist due to the complex nature of turbulence production and dissipation.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):614-624. doi:10.1115/1.1800571.

Endothelial surface glycocalyx plays an important role in the regulation of microvessel permeability by possibly changing its charge and configuration. To investigate the mechanisms by which surface properties of the endothelial cells control the changes in microvessel permeability, we extended the electrodiffusion model developed by Fu et al. [Am. J. Physiol. 284 , H1240–1250 (2003)], which is for the interendothelial cleft with a negatively charged surface glycocalyx layer, to include the filtration due to hydrostatic and oncotic pressures across the microvessel wall as well as the electrical potential across the glycocalyx layer. On the basis of the hypotheses proposed by Curry [Microcirculation 1 (1): 11–26 (1994)], the predictions from this electrodiffusion-filtration model provide a good agreement with experimental data for permeability of negatively charged α-lactalbumin summarized in Curry [Microcirculation 1 (1), 11–26 (1994)] under various conditions. In addition, we applied this new model to describe the transport of negatively charged macromolecules, bovine serum albumin (BSA), across venular microvessels in frog mesentery. According to the model, the convective component of the albumin transport is greatly diminished by the presence of a negatively charged glycocalyx under both normal and increased permeability conditions.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):625-635. doi:10.1115/1.1798055.

The study of pulsatile flow in stenosed vessels is of particular importance because of its significance in relation to blood flow in human pathophysiology. To date, however, there have been few comprehensive publications detailing systematic numerical simulations of turbulent pulsatile flow through stenotic tubes evaluated against comparable experiments. In this paper, two-equation turbulence modeling has been explored for sinusoidally pulsatile flow in 75% and 90% area reduction stenosed vessels, which undergoes a transition from laminar to turbulent flow as well as relaminarization. Wilcox’s standard k-ω model and a transitional variant of the same model are employed for the numerical simulations. Steady flow through the stenosed tubes was considered first to establish the grid resolution and the correct inlet conditions on the basis of comprehensive comparisons of the detailed velocity and turbulence fields to experimental data. Inlet conditions based on Womersley flow were imposed at the inlet for all pulsatile cases and the results were compared to experimental data from the literature. In general, the transitional version of the k-ω model is shown to give a better overall representation of both steady and pulsatile flow. The standard model consistently over predicts turbulence at and downstream of the stenosis, which leads to premature recovery of the flow. While the transitional model often under-predicts the magnitude of the turbulence, the trends are well-described and the velocity field is superior to that predicted using the standard model. On the basis of this study, there appears to be some promise for simulating physiological pulsatile flows using a relatively simple two-equation turbulence model.

Commentary by Dr. Valentin Fuster

TECHNICAL PAPERS: Joint/Whole Body

J Biomech Eng. 2004;126(5):636-640. doi:10.1115/1.1798011.

A finite element model of a semiconstrained ankle implant with the tibia and fibula was constructed so that the stresses in the polyethylene liner could be computed. Two different widths of talar components were studied and proximal boundary conditions were computed from an inverse process providing a load of five times body weight appropriately distributed across the osseous structures. von Mises stresses indicated small regions of localized yielding and contact stresses that were similar to those in acetabular cup liners. A wider talar component with 36% more surface area reduced contact stress and von Mises stresses at the center of the polyethylene component by 17%.

Topics: Stress
Commentary by Dr. Valentin Fuster

TECHNICAL PAPERS: Soft Tissue

J Biomech Eng. 2004;126(5):641-650. doi:10.1115/1.1800556.

Background: Experiments on the fatigue of tendons have shown that cyclic loading induces failure at stresses lower than the ultimate tensile strength (UTS) of the tendons. The number of cycles to failure (Nf) has been shown to be dependent upon the magnitude of the applied cyclic stress. Method of approach: Utilizing data collected by Schechtman (1995), we demonstrate that the principles of Linear Elastic Fracture Mechanics (LEFM) can be used to predict the fatigue behavior of tendons under cyclic loading for maximum stress levels that are higher than 10% of the ultimate tensile strength (UTS) of the tendon (the experimental results at 10% UTS did not fit with our equations). Conclusions: LEFM and other FM approaches may prove to be very valuable in advancing our understanding of damage accumulation in soft connective tissues.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):651-656. doi:10.1115/1.1800573.

The redistribution of water in response to static tensile loading was investigated in rabbit Achilles tendons in vitro. The distribution of water was measured along a radially oriented line, using a one-dimensional proton-density map created from fits to diffusion-weighted magnetic resonance (MR) data. Water movements were measured during application of tensile loads of 5N (N=7) and 10N (N=6). Water distribution along the line was measured before loading and up to 42 min after load application. Static loading with either 5 or 10N loads caused a steady increase in proton density in the outside edge (rim) of the tendon. The 10N load lowered the proton density in the core of the tendon, but did so in a single step that was observed when the load was applied. The 5N load caused no change in proton density in the core region. The immediate redistribution from the core was statistically significant for the 10N load, but not the 5N load application. Statistically significant within-group proton-density increases were observed in the rim after 42 min postload for all tendons irrespective of load condition. The rate of proton-density postload increase at the rim region did not depend upon load. The rate for the 5N load case was 0.010±0.002 min−1 and 0.007±0.002 min−1 in the 10N case. Thus, while generally consistent with an extrusion model, the data show other features that argue for a more complex model.

Topics: Stress , Water , Tendons
Commentary by Dr. Valentin Fuster
J Biomech Eng. 2004;126(5):657-665. doi:10.1115/1.1800557.

Knowledge of the biomechanical properties of human atherosclerotic plaques is of essential importance for developing more insights in the pathophysiology of the cardiovascular system and for better predicting the outcome of interventional treatments such as balloon angioplasty. Available data are mainly based on uniaxial tests, and most of the studies investigate the mechanical response of fibrous plaque caps only. However, stress distributions during, for example, balloon angioplasty are strongly influenced by all components of atherosclerotic lesions. A total number of 107 samples from nine human high-grade stenotic iliac arteries were tested; associated anamnesis of donors reported. Magnetic resonance imaging was employed to test the usability of the harvested arteries. Histological analyses has served to characterize the different tissue types. Prepared strips of 7 different tissue types underwent cyclic quasistatic uniaxial tension tests in axial and circumferential directions; ultimate tensile stresses and stretches were documented. Experimental data of individual samples indicated anisotropic and highly nonlinear tissue properties as well as considerable interspecimen differences. The calcification showed, however, a linear property, with about the same stiffness as observed for the adventitia in high stress regions. The stress and stretch values at calcification fracture are smaller (179±56 kPa and 1.02±0.005) than for each of the other tissue components. Of all intimal tissues investigated, the lowest fracture stress occurred in the circumferential direction of the fibrous cap (254.8±79.8 kPa at stretch 1.182±0.1). The adventitia demonstrated the highest and the nondiseased media the lowest mechanical strength on average.

Commentary by Dr. Valentin Fuster

TECHNICAL PAPERS: Other

J Biomech Eng. 2004;126(5):666-671. doi:10.1115/1.1797991.

The complex modulus (E*) and elastic modulus (E) of agarose gels (2% to 4%) are measured with a dynamic mechanical analyzer in frequency sweep shear sandwich mode between 0.1 and 20 Hz. The data showed that E* and E increase with frequency according to a power law which can be described by a fractional derivative model to characterize the dynamic viscoelasticity of the gel. The functions between the model parameters including storage modulus coefficient (H) and the power law exponent (β) and the agarose concentration are established. A molecular basis for the application of the fractional derivative model to gel polymers is also discussed. Such an approach can be useful in tissue culture studies employing dynamic pressurization or for validation of magnetic resonance elastography.

Commentary by Dr. Valentin Fuster

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