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Research Papers

J Biomech Eng. 2011;133(2):021001-021001-12. doi:10.1115/1.4003130.

In this work, a fluid-solid interaction (FSI) analysis of a healthy and a stenotic human trachea was studied to evaluate flow patterns, wall stresses, and deformations under physiological and pathological conditions. The two analyzed tracheal geometries, which include the first bifurcation after the carina, were obtained from computed tomography images of healthy and diseased patients, respectively. A finite element-based commercial software code was used to perform the simulations. The tracheal wall was modeled as a fiber reinforced hyperelastic solid material in which the anisotropy due to the orientation of the fibers was introduced. Impedance-based pressure waveforms were computed using a method developed for the cardiovascular system, where the resistance of the respiratory system was calculated taking into account the entire bronchial tree, modeled as binary fractal network. Intratracheal flow patterns and tracheal wall deformation were analyzed under different scenarios. The simulations show the possibility of predicting, with FSI computations, flow and wall behavior for healthy and pathological tracheas. The computational modeling procedure presented herein can be a useful tool capable of evaluating quantities that cannot be assessed in vivo, such as wall stresses, pressure drop, and flow patterns, and to derive parameters that could help clinical decisions and improve surgical outcomes.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021002-021002-12. doi:10.1115/1.4003309.

The endothelial surface glycocalyx layer (SGL) and the basement membrane (BM) are two important components of the blood-brain barrier (BBB). They provide large resistance to solute transport across the BBB in addition to the tight junctions in the cleft between adjacent endothelial cells. Due to their glycosaminoglycan compositions, they carry negative charge under physiological conditions. To investigate the charge effect of the SGL and BM on the BBB permeability to charged solutes, we developed an electrodiffusion model for the transport of charged molecules across the BBB. In this model, constant charge densities were assumed in the SGL and in the BM. Both electrostatic and steric interaction and exclusion to charged molecules were considered within the SGL and the BM and at their interfaces with noncharged regions of the BBB. On the basis of permeability data for the positively charged ribonuclease (+4,radius=2.01nm) and negatively charged α-lactalbumin (10,radius=2.08nm) measured in intact rat mesenteric and pial microvessels, our model predicted that the charge density in both SGL and BM would be 30mEq/L, which is comparable to that in the SGL of mesenteric microvessels. Interestingly, our model also revealed that due to the largest concentration drop in the BM, there is a region with a higher concentration of negatively charged α-lactalbumin in the uncharged inter-endothelial cleft, although the concentration of α-lactalbumin is always lower than that of positively charged ribonuclease and that of a neutral solute in the charged SGL and BM.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021003-021003-9. doi:10.1115/1.4003310.

Maintaining vascular access (VA) patency continues to be the greatest challenge for dialysis patients. VA dysfunction, primarily due to venous neointimal hyperplasia development and stenotic lesion formation, is mainly attributed to complex hemodynamics within the arteriovenous fistula (AVF). The effect of VA creation and the subsequent geometrical remodeling on the hemodynamics and shear forces within a mature patient-specific AVF is investigated. A 3D reconstructed geometry of a healthy vein and a fully mature patient-specific AVF was developed from a series of 2D magnetic resonance image scans. A previously validated thresholding technique for region segmentation and lumen cross section contour creation was conducted in MIMICS 10.01 , allowing for the creation of a 3D reconstructed geometry. The healthy vein and AVF computational models were built, subdivided, and meshed in GAMBIT 2.3 . The computational fluid dynamic (CFD) code FLUENT 6.3.2 (Fluent Inc., Lebanon, NH) was employed as the finite volume solver to determine the hemodynamics and shear forces within the healthy vein and patient-specific AVF. Geometrical alterations were evaluated and a CFD analysis was conducted. Substantial geometrical remodeling was observed, following VA creation with an increase in cross-sectional area, out of plane curvature (maximum angle of curvature in AVF=30deg), and angle of blood flow entry. The mean flow velocity entering the vein of the AVF is dramatically increased. These factors result in complex three-dimensional hemodynamics within VA junction (VAJ) and efferent vein of the AVF. Complex flow patterns were observed and the maximum and mean wall shear stress (WSS) magnitudes are significantly elevated. Flow reversal was found within the VAJ and efferent vein. Extensive geometrical remodeling during AVF maturation does not restore physiological hemodynamics to the VAJ and venous conduit of the AVF, and high WSS and WSS gradients, and flow reversal persist. It is theorized that the vessel remodelling and the continued non-physiological hemodynamics within the AVF compound to result in stenotic lesion development.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021004-021004-7. doi:10.1115/1.4003312.

The current understanding of the tolerance of the frontal bone to blunt impact is limited. Previous studies have utilized vastly different methods, which limits the use of statistical analyses to determine the tolerance of the frontal bone. The purpose of this study is to determine the tolerance of the frontal bone to blunt impact. Acoustic emission sensors were used to provide a noncensored measure of the frontal bone tolerance and were essential due to the increase in impactor force after fracture onset. In this study, risk functions for fracture were developed using parametric and nonparametric techniques. The results of the statistical analyses suggest that a 50% risk of frontal bone fracture occurs at a force between 1885 N and 2405 N. Subjects that were found to have a frontal sinus present within the impacted region had a significantly higher risk of sustaining a fracture. There was no association between subject age and fracture force. The results of the current study suggest that utilizing peak force as an estimate of fracture tolerance will overestimate the force necessary to create a frontal bone fracture.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021005-021005-11. doi:10.1115/1.4003315.

The kinematics of the human ankle is commonly modeled as a biaxial hinge joint model. However, significant variations in axis orientations have been found between different individuals and also between different foot configurations. For ankle rehabilitation robots, information regarding the ankle kinematic parameters can be used to estimate the ankle and subtalar joint displacements. This can in turn be used as auxiliary variables in adaptive control schemes to allow modification of the robot stiffness and damping parameters to reduce the forces applied at stiffer foot configurations. Due to the large variations observed in the ankle kinematic parameters, an online identification algorithm is required to provide estimates of the model parameters. An online parameter estimation routine based on the recursive least-squares (RLS) algorithm was therefore developed in this research. An extension of the conventional biaxial ankle kinematic model, which allows variation in axis orientations with different foot configurations had also been developed and utilized in the estimation algorithm. Simulation results showed that use of the extended model in the online algorithm is effective in capturing the foot orientation of a biaxial ankle model with variable joint axis orientations. Experimental results had also shown that a modified RLS algorithm that penalizes a deviation of model parameters from their nominal values can be used to obtain more realistic parameter estimates while maintaining a level of estimation accuracy comparable to that of the conventional RLS routine.

Topics: Algorithms , Errors
Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021006-021006-6. doi:10.1115/1.4003131.

The evolution of implant stability in bone tissue remains difficult to assess because remodeling phenomena at the bone-implant interface are still poorly understood. The characterization of the biomechanical properties of newly formed bone tissue in the vicinity of implants at the microscopic scale is of importance in order to better understand the osseointegration process. The objective of this study is to investigate the potentiality of micro-Brillouin scattering techniques to differentiate mature and newly formed bone elastic properties following a multimodality approach using histological analysis. Coin-shaped Ti–6Al–4V implants were placed in vivo at a distance of 200μm from rabbit tibia leveled cortical bone surface, leading to an initially empty cavity of 200μm×4.4mm. After 7 weeks of implantation, the bone samples were removed, fixed, dehydrated, embedded in methyl methacrylate, and sliced into 190μm thick sections. Ultrasonic velocity measurements were performed using a micro-Brillouin scattering device within regions of interest (ROIs) of 10μm diameter. The ROIs were located in newly formed bone tissue (within the 200μm gap) and in mature bone tissue (in the cortical layer of the bone sample). The same section was then stained for histological analysis of the mineral content of the bone sample. The mean values of the ultrasonic velocities were equal to 4.97×103m/s in newly formed bone tissue and 5.31×103m/s in mature bone. Analysis of variance (p=2.42×104) tests revealed significant differences between the two groups of measurements. The standard deviation of the velocities was significantly higher in newly formed bone than in mature bone. Histological observations allow to confirm the accurate locations of the velocity measurements and showed a lower degree of mineralization in newly formed bone than in the mature cortical bone. The higher ultrasonic velocity measured in newly formed bone tissue compared with mature bone might be explained by the higher mineral content in mature bone, which was confirmed by histology. The heterogeneity of biomechanical properties of newly formed bone at the micrometer scale may explain the higher standard deviation of velocity measurements in newly formed bone compared with mature bone. The results demonstrate the feasibility of micro-Brillouin scattering technique to investigate the elastic properties of newly formed bone tissue.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021007-021007-7. doi:10.1115/1.4003317.

In most cryopreservation applications, the final concentrations of cryoprotective agents (CPAs) must be reduced to biocompatible levels. However, traditional methods for removing CPAs usually have disadvantages of operation complexity, time consumption, and ease of contamination, especially for the applications involving large volumes of cell suspensions. A dilution-filtration system, which involves pure ultrafiltration for separation, was developed for continuous, automatic, and closed process of removing CPAs. To predict the optimal protocols under given experimental conditions, a theoretical model was established first. Cell-free experiments were then conducted to investigate the variation in CPA concentration during the process, and the experimental data were compared with the theoretical values for the validation of the model. Finally, ten units (212.9ml/unit±9.5ml/unit) of thawed human red blood cells (cryopreserved with 40% (w/v) glycerol) were deglycerolized using the theoretically optimal operation protocols to further validate the effectiveness and advantage of the system. In the cell-free experiments, glycerol was continuously removed and the concentration variations fitted the simulated results quite well. In the in-vitro experiments, glycerol concentration in RBC suspension was reduced to 5.57g/l±2.81g/l within an hour, and the cell count recovery rate was 91.19%±3.57%, (n=10), which proves that the system is not only safe for removing CPAs, but also particularly efficient for processing large-scale samples. However, the operation parameters must be carefully controlled and the optimal protocols should be specialized and various from case to case. The presented theoretical model provides an effective approach to find out the optimal operation protocols under given experimental conditions and constrains.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021008-021008-11. doi:10.1115/1.4003319.

Cardiovascular diseases are the number one cause of death in the world, making the understanding of hemodynamics and development of treatment options imperative. The most common modality for treatment of occlusive coronary artery diseases is the use of stents. Stent design profoundly influences the postprocedural hemodynamic and solid mechanical environment of the stented artery. However, despite their wide acceptance, the incidence of stent late restenosis is still high (Zwart, 2010, “Coronary Stent Thrombosis in the Current Era: Challenges and Opportunities for Treatment,” Current Treatment Options in Cardiovascular Medicine, 12(1), pp. 46–57), and it is most prevailing at the proximal and distal ends of the stent. In this work, we focus our investigation on the localized hemodynamic effects of compliance mismatch due to the presence of a stent in an artery. The compliance mismatch in a stented artery is maximized at the proximal and distal ends of the stent. Hence, it is our objective to understand and reveal the mechanism by which changes in compliance contribute to the generation of nonphysiological wall shear stress (WSS). Such adverse hemodynamic conditions could have an effect on the onset of restenosis. Three-dimensional, spatiotemporally resolved computational fluid dynamics simulations of pulsatile flow with fluid-structure interaction were carried out for a simplified coronary artery with physiologically relevant flow parameters. A model with uniform elastic modulus is used as the baseline control case. In order to study the effect of compliance variation on local hemodynamics, this baseline model is compared with models where the elastic modulus was increased by two-, five-, and tenfold in the middle of the vessel. The simulations provided detailed information regarding the recirculation zone dynamics formed during flow reversals. The results suggest that discontinuities in compliance cause critical changes in local hemodynamics, namely, altering the local pressure and velocity gradients. The change in pressure gradient at the discontinuity was as high as 90%. The corresponding changes in WSS and oscillatory shear index calculated were 9% and 15%, respectively. We demonstrate that these changes are attributed to the physical mechanism associating the pressure gradient discontinuities to the production of vorticity (vorticity flux) due to the presence of the stent. The pressure gradient discontinuities and augmented vorticity flux are affecting the wall shear stresses. As a result, this work reveals how compliance variations act to modify the near wall hemodynamics of stented arteries.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021009-021009-9. doi:10.1115/1.4003321.

The energy produced during the ramming of bighorn sheep (Ovis canadensis) would be expected to result in undesirable stresses in their frontal skull, which in turn would cause brain injury; yet, this animal seems to suffer no ill effects. In general, horn is made of an α-keratin sheath covering a bone. Despite volumes of data on the ramming behavior of Ovis canadensis, the extent to which structural components of horn and horn-associated structure or tissue absorb the impact energy generated by the ramming event is still unknown. This study investigates the hypothesis that there is a mechanical relationship present among the ramming event, the structural constituents of the horn, and the horn-associated structure. The three-dimensional complex structure of the bighorn sheep horn was successfully constructed and modeled using a computed tomography (CT) scan and finite element (FE) method, respectively. Three different three-dimensional quasi-static models, including a horn model with trabecular bone, a horn model with compact bone that instead of trabecular bone, and a horn model with trabecular bone as well as frontal sinuses, were studied. FE simulations were used to compare distributions of principal stress in the horn and the frontal sinuses and the strain energy under quasi-static loading conditions. It was noticed that strain energy due to elastic deformation of the complex structure of horn modeled with trabecular bone and with trabecular bone and frontal sinus was different. In addition, trabecular bone in the horn distributes the stresses over a larger volume, suggesting a mechanical link between the structural constituents and the ramming event. This phenomenon was elucidated through the principal stress distribution in the structure. This study will help designers in choosing appropriate material combinations for the successful design of protective structures against a similar impact.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021010-021010-9. doi:10.1115/1.4003322.

Activities of daily living (ADLs) generate complex, multidirectional forces in the anterior cruciate ligament (ACL). While calibration problems preclude direct measurement in patients, ACL forces can conceivably be measured in animals after technical challenges are overcome. For example, motion and force sensors can be implanted in the animal but investigators must determine the extent to which these sensors and surgery affect normal gait. Our objectives in this study were to determine (1) if surgically implanting knee motion sensors and an ACL force sensor significantly alter normal ovine gait and (2) how increasing gait speed and grade on a treadmill affect ovine gait before and after surgery. Ten skeletally mature, female sheep were used to test four hypotheses: (1) surgical implantation of sensors would significantly decrease average and peak vertical ground reaction forces (VGRFs) in the operated limb, (2) surgical implantation would significantly decrease single limb stance duration for the operated limb, (3) increasing treadmill speed would increase VGRFs pre- and post operatively, and (4) increasing treadmill grade would increase the hind limb VGRFs pre- and post operatively. An instrumented treadmill with two force plates was used to record fore and hind limb VGRFs during four combinations of two speeds (1.0 m/s and 1.3 m/s) and two grades (0 deg and 6 deg). Sensor implantation decreased average and peak VGRFs less than 10% and 20%, respectively, across all combinations of speed and grade. Sensor implantation significantly decreased the single limb stance duration in the operated hind limb during inclined walking at 1.3 m/s but had no effect on single limb stance duration in the operated limb during other activities. Increasing treadmill speed increased hind limb peak (but not average) VGRFs before surgery and peak VGRF only in the unoperated hind limb during level walking after surgery. Increasing treadmill grade (at 1 m/s) significantly increased hind limb average and peak VGRFs before surgery but increasing treadmill grade post op did not significantly affect any response measure. Since VGRF values exceeded 80% of presurgery levels, we conclude that animal gait post op is near normal. Thus, we can assume normal gait when conducting experiments following sensor implantation. Ultimately, we seek to measure ACL forces for ADLs to provide design criteria and evaluation benchmarks for traditional and tissue engineered ACL repairs and reconstructions.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):021011-021011-12. doi:10.1115/1.4003325.

Sitting-acquired deep tissue injury (DTI) is a severe form of pressure ulcer (PU) often affecting patients with spinal cord injury (SCI) who also tend to suffer from intramuscular fat infiltration, soft tissue scarring (due to previous PU), and/or muscle spasticity in their buttocks. We previously used finite element (FE) modeling to evaluate whether abnormal bodyweight is a risk factor for sitting-acquired DTI. Here we hypothesize that fat infiltration, scarring, or spasms increase internal loads in the gluteus muscles in the vicinity of the ischial tuberosities during sitting, which consequently put SCI patients with these conditions at a higher risk for DTI. Our objective was to determine changes in gluteal strains and stresses and tissue volumes exposed to elevated strains/stresses associated with these factors. Thirty-five FE models of coronal slices through the seated buttocks, simulating these conditions at different severities, were developed. We calculated peak strains and stresses in glutei and percentage volumes of muscle tissue exposed to above-critical strains/stresses (compression strain50%, compression/von Mises stress2kPa, and strain energy density0.5kPa). Progressive intramuscular fat infiltration increased all the aforementioned outcome measures. Increase in size of scar patterns that were contained in both muscle and fat tissues similarly elevated the outcome measures. Spasms increased muscle stresses and volumetric exposures to stress, but tissue volumes at risk were 12% and increases due to spasticity were slight. We conclude that the above potential risk factors can be listed according to the following order of importance: (i) fat infiltration, (ii) scars contained in both muscle and fat tissues, and (iii) spasms. This information should be considered when prioritizing prevention means and resources for patients with SCI.

Commentary by Dr. Valentin Fuster

Technical Briefs

J Biomech Eng. 2011;133(2):024501-024501-6. doi:10.1115/1.4003311.

Silicone implants are used for prosthetic arthroplasty of metacarpophalangeal (MCP) joints severely damaged by rheumatoid arthritis. Different silicone elastomer MCP implant designs have been developed, including the Swanson and the NeuFlex implants. The goal of this study was to compare the in vitro mechanical behavior of Swanson and NeuFlex MCP joint implants. Three-dimensional (3D) finite element (FE) models of the silicone implants were modeled using the commercial software ANSYS and subjected to angular displacement from 0 deg to 90 deg. FE models were validated using mechanical tests of implants incrementally bent from 0 deg to 90 deg in a joint simulator. Swanson size 2 and 4 implants were compared with NeuFlex size 10 and 30 implants, respectively. Good agreement was observed throughout the range of motion for the flexion bending moment derived from 3D FE models and mechanical tests. From 30 deg to 90 deg, the Swanson 2 demonstrated a greater resistance to deformation than the NeuFlex 10 and required a greater bending moment for joint flexion. For larger implant sizes, the NeuFlex 30 had a steeper moment-displacement curve, but required a lower moment than the Swanson 4, due to implant preflexion. On average, the stress generated at the implant hinge from 30 deg to 90 deg was lower in the NeuFlex than in the Swanson. On average, starting from the neutral position of 30 deg for the preflexed NeuFlex implant, higher moments were required to extend the NeuFlex implants to 0 deg compared with the Swanson implants, which returned spontaneously to resting position. Implant toggling within the medullary canals was less in the NeuFlex than in the Swanson. The differential performance of these implants may be useful in implant selection based on the preoperative condition(s) of the joint and specific patient functional needs.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):024502-024502-5. doi:10.1115/1.4003313.

The process of bone remodeling is governed by mechanical stresses and strains. Studies on the effects of mechanical stimulation on cell response are often difficult to compare as the nature of the stimuli and differences in parameters applied vary greatly. Experimental systems for the investigation of mechanical stimuli are mostly limited in throughput or flexibility and often the sum of several stimuli is applied. In this work, a flexible system that allows the investigation of cell response to isolated intermittent cyclic hydrostatic pressure (icHP) on a high throughput level is shown. Human bone derived cells were cultivated with or without mechanical stimulus in the presence or absence of chemical cues triggering osteogenesis for 7–10 days. Cell proliferation and osteogenic differentiation were evaluated by cell counting and immunohistochemical staining for bone alkaline phosphatase as well as collagen 1, respectively. In either medium, both cell proliferation and level of differentiation were increased when the cultures were mechanically stimulated. These initial results therefore qualify the present system for studies on the effects of isolated icHP on cell fate and encourage further investigations on the details behind the observed effects.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(2):024503-024503-5. doi:10.1115/1.4003327.

The annulus fibrosus of the intervertebral disk experiences multidirectional tension in vivo, yet the majority of mechanical property testing has been uniaxial. Therefore, our understanding of how this complex multilayered tissue responds to loading may be deficient. This study aimed to determine the mechanical properties of porcine annular samples under uniaxial and biaxial tensile loading. Two-layer annulus samples were isolated from porcine disks from four locations: anterior superficial, anterior deep, posterior superficial, and posterior deep. These tissues were then subjected to three deformation conditions each to a maximal stretch ratio of 1.23: uniaxial, constrained uniaxial, and biaxial. Uniaxial deformation was applied in the circumferential direction, while biaxial deformation was applied simultaneously in the circumferential and compressive directions. Constrained uniaxial consisted of a stretch ratio of 1.23 in the circumferential direction while holding the tissue stationary in the axial direction. The maximal stress and stress-stretch ratio (S-S) moduli determined from the biaxial tests were significantly higher than those observed during both the uniaxial tests (maximal stress, 97.1% higher during biaxial; p=0.002; S-S moduli, 117.9% higher during biaxial; p=0.0004) and the constrained uniaxial tests (maximal stress, 46.8% higher during biaxial; S-S moduli, 82.9% higher during biaxial). These findings suggest that the annulus is subjected to higher stresses in vivo when under multidirectional tension.

Commentary by Dr. Valentin Fuster

Design Innovation

J Biomech Eng. 2011;133(2):025001-025001-5. doi:10.1115/1.4003132.

Laser direct-write technology such as modified laser-induced forward transfer (LIFT) is emerging as a revolutionary technology for biological construct fabrication. While many modified LIFT-based cell direct writing successes have been achieved, possible process-induced cell injury and death is still a big hurdle for modified LIFT-based cell direct writing to be a viable technology. The objective of this study is to propose metallic foil-assisted LIFT using a four-layer structure to achieve better droplet size control and increase cell viability in direct writing of human colon cancer cells (HT-29). The proposed four layers include a quartz disk, a sacrificial and adhesive layer, a metallic foil, and a cell suspension layer. The bubble formation-induced stress wave is responsible for droplet formation. It is found that the proposed metallic foil-assisted LIFT approach is an effective cell direct-write technology and provides better printing resolution and high post-transfer cell viability when compared with other conventional modified LIFT technologies such as matrix-assisted pulsed-laser evaporation direct-write; at the same time, the possible contamination from the laser energy absorbing material is minimized using a metallic foil.

Commentary by Dr. Valentin Fuster

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