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Research Papers

J Biomech Eng. 2011;133(10):101001-101001-8. doi:10.1115/1.4005173.

It is well known that pore design is an important determinant of both the quantity and distribution of regenerated bone in artificial bone tissue scaffolds. A requisite feature is that scaffolds must contain pore interconnections on the order of 100–1000 μm (termed macroporosity). Within this range, there is not a definitive optimal interconnection size. Recent results suggest that pore interconnections permeating the scaffold build material on the order of 2–20 μm (termed microporosity) drive bone growth into the macropore space at a faster rate and also provide a new space for bone growth, proliferating throughout the interconnected microporous network. The effects of microstructural features on bone growth has yet to be fully understood. This work presents the manufacture and characterization of novel combinatorial test scaffolds, scaffolds that test multiple microporosity and macroporosity designs within a single scaffold. Scaffolds such as this can efficiently evaluate multiple mechanical designs, with the advantage of having the designs colocated within a single defect site and therefore less susceptible to experimental variation. This paper provides the manufacturing platform, manufacturing control method, and demonstrates the manufacturing capabilities with three representative scaffolds.

Topics: Manufacturing , Bone , Design
Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):101002-101002-10. doi:10.1115/1.4005001.

Although left ventricular assist devices (LVADs) have had success in supporting severe heart failure patients, thrombus formation within these devices still limits their long term use. Research has shown that thrombosis in the Penn State pulsatile LVAD, on a polyurethane blood sac, is largely a function of the underlying fluid mechanics and may be correlated to wall shear rates below 500 s−1 . Given the large range of heart rate and systolic durations employed, in vivo it is useful to study the fluid mechanics of pulsatile LVADs under these conditions. Particle image velocimetry (PIV) was used to capture planar flow in the pump body of a Penn State 50 cubic centimeters (cc) LVAD for heart rates of 75–150 bpm and respective systolic durations of 38–50%. Shear rates were calculated along the lower device wall with attention given to the uncertainty of the shear rate measurement as a function of pixel magnification. Spatial and temporal shear rate changes associated with data collection frequency were also investigated. The accuracy of the shear rate calculation improved by approximately 40% as the resolution increased from 35 to 12 μm/pixel. In addition, data collection in 10 ms, rather than 50 ms, intervals was found to be preferable. Increasing heart rate and systolic duration showed little change in wall shear rate patterns, with wall shear rate magnitude scaling by approximately the kinematic viscosity divided by the square of the average inlet velocity, which is essentially half the friction coefficient. Changes in in vivo operating conditions strongly influence wall shear rates within our device, and likely play a significant role in thrombus deposition. Refinement of PIV techniques at higher magnifications can be useful in moving towards better prediction of thrombosis in LVADs.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):101003-101003-10. doi:10.1115/1.4005169.

Changes in muscle fiber orientation across the wall of the left ventricle (LV) cause the apex of the heart to turn 10–15 deg in opposition to its base during systole and are believed to increase stroke volume and lower wall stress in healthy hearts. Studies show that cardiac torsion is sensitive to various disease states, which suggests that it may be an important aspect of cardiac function. Modern imaging techniques have sparked renewed interest in cardiac torsion dynamics, but no work has been done to determine whether mechanically augmented apical torsion can be used to restore function to failing hearts. In this report, we discuss the potential advantages of this approach and present evidence that turning the cardiac apex by mechanical means can displace a clinically significant volume of blood from failing hearts. Computational models of normal and reduced-function LVs were created to predict the effects of applied apical torsion on ventricular stroke work and wall stress. These same conditions were reproduced in anesthetized pigs with drug-induced heart failure using a custom apical torsion device programmed to rotate over various angles during cardiac systole. Simulations of applied 90 deg torsion in a prolate spheroidal computational model of a reduced-function pig heart produced significant increases in stroke work (25%) and stroke volume with reduced fiber stress in the epicardial region. These calculations were in substantial agreement with corresponding in vivo measurements. Specifically, the computer model predicted torsion-induced stroke volume increases from 13.1 to 14.4 mL (9.9%) while actual stroke volume in a pig heart of similar size and degree of dysfunction increased from 11.1 to 13.0 mL (17.1%). Likewise, peak LV pressures in the computer model rose from 85 to 95 mm Hg (11.7%) with torsion while maximum ventricular pressures in vivo increased in similar proportion, from 55 to 61 mm Hg (10.9%). These data suggest that: (a) the computer model of apical torsion developed for this work is a fair and accurate predictor of experimental outcomes, and (b) supra-physiologic apical torsion may be a viable means to boost cardiac output while avoiding blood contact that occurs with other assist methods.

Topics: Torsion , Rotation , Fibers
Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):101004-101004-7. doi:10.1115/1.4005171.

The objective of this study was to validate the MRI-based joint contact modeling methodology in the radiocarpal joints by comparison of model results with invasive specimen-specific radiocarpal contact measurements from four cadaver experiments. We used a single validation criterion for multiple outcome measures to characterize the utility and overall validity of the modeling approach. For each experiment, a Pressurex film and a Tekscan sensor were sequentially placed into the radiocarpal joints during simulated grasp. Computer models were constructed based on MRI visualization of the cadaver specimens without load. Images were also acquired during the loaded configuration used with the direct experimental measurements. Geometric surface models of the radius, scaphoid and lunate (including cartilage) were constructed from the images acquired without the load. The carpal bone motions from the unloaded state to the loaded state were determined using a series of 3D image registrations. Cartilage thickness was assumed uniform at 1.0 mm with an effective compressive modulus of 4 MPa. Validation was based on experimental versus model contact area, contact force, average contact pressure and peak contact pressure for the radioscaphoid and radiolunate articulations. Contact area was also measured directly from images acquired under load and compared to the experimental and model data. Qualitatively, there was good correspondence between the MRI-based model data and experimental data, with consistent relative size, shape and location of radioscaphoid and radiolunate contact regions. Quantitative data from the model generally compared well with the experimental data for all specimens. Contact area from the MRI-based model was very similar to the contact area measured directly from the images. For all outcome measures except average and peak pressures, at least two specimen models met the validation criteria with respect to experimental measurements for both articulations. Only the model for one specimen met the validation criteria for average and peak pressure of both articulations; however the experimental measures for peak pressure also exhibited high variability. MRI-based modeling can reliably be used for evaluating the contact area and contact force with similar confidence as in currently available experimental techniques. Average contact pressure, and peak contact pressure were more variable from all measurement techniques, and these measures from MRI-based modeling should be used with some caution.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):101005-101005-8. doi:10.1115/1.4005175.

We report an image segmentation and registration method for studying joint morphology and kinematics from in vivo magnetic resonance imaging (MRI) scans and its application to the analysis of foot and ankle joint motion. Using an MRI-compatible positioning device, a foot was scanned in a single neutral and seven other positions ranging from maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation. A segmentation method combining graph cuts and level set was developed. In the subsequent registration step, a separate rigid body transformation for each bone was obtained by registering the neutral position dataset to each of the other ones, which produced an accurate description of the motion between them. The segmentation algorithm allowed a user to interactively delineate 14 foot bones in the neutral position volume in less than 30 min total (user and computer processing unit [CPU]) time. Registration to the seven other positions took approximately 10 additional minutes of user time and 5.25 h of CPU time. For validation, our results were compared with those obtained from 3DViewnix, a semiautomatic segmentation program. We achieved excellent agreement, with volume overlap ratios greater than 88% for all bones excluding the intermediate cuneiform and the lesser metatarsals. For the registration of the neutral scan to the seven other positions, the average overlap ratio is 94.25%, while the minimum overlap ratio is 89.49% for the tibia between the neutral position and position 1, which might be due to different fields of view (FOV). To process a single foot in eight positions, our tool requires only minimal user interaction time (less than 30 min total), a level of improvement that has the potential to make joint motion analysis from MRI practical in research and clinical applications.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):101006-101006-9. doi:10.1115/1.4005223.

The finite element (FE) model of the pelvic joint is helpful for clinical diagnosis and treatment of pelvic injuries. However, the effect of an FE model boundary condition on the biomechanical behavior of a pelvic joint has not been well studied. The objective of this study was to study the effect of boundary condition on the pelvic biomechanics predictions. A 3D FE model of a pelvis using subject-specific estimates of intact bone structures, main ligaments and bone material anisotropy by computed tomography (CT) gray value was developed and validated by bone surface strains obtained from rosette strain gauges in an in vitro pelvic experiment. Then three FE pelvic models were constructed to analyze the effect of boundary condition, corresponding to an intact pelvic joint, a pelvic joint without sacroiliac ligaments and a pelvic joint without proximal femurs, respectively. Vertical load was applied to the same pelvis with a fixed prosthetic femoral stem and the same load was simulated in the FE model. A strong correlation coefficient (R2=0.9657) was calculated, which indicated a strong correlation between the FE analysis and experimental results. The effect of boundary condition changes on the biomechanical response depended on the anatomical location and structure of the pelvic joint. It was found that acetabulum fixed in all directions with the femur removed can increase the stress distribution on the acetabular inner plate (approximately double the original values) and decrease that on the superior of pubis (from 7 MPa to 0.6 MPa). Taking sacrum and ilium as a whole, instead of sacroiliac and iliolumber ligaments, can influence the stress distribution on ilium and pubis bone vastly. These findings suggest pelvic biomechanics is very dependent on the boundary condition in the FE model.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):101007-101007-10. doi:10.1115/1.4005224.

Under fast dynamic loading conditions (e.g. high-energy impact), the load rate dependency of the intervertebral disc (IVD) material properties may play a crucial role in the biomechanics of spinal trauma. However, most finite element models (FEM) of dynamic spinal trauma uses material properties derived from quasi-static experiments, thus neglecting this load rate dependency. The aim of this study was to identify hyperelastic material properties that ensure a more biofidelic simulation of the IVD under a fast dynamic compressive load. A hyperelastic material law based on a first-order Mooney-Rivlin formulation was implemented in a detailed FEM of a L2-L3 functional spinal unit (FSU) to represent the mechanical behavior of the IVD. Bony structures were modeled using an elasto-plastic Johnson-Cook material law that simulates bone fracture while ligaments were governed by a viscoelastic material law. To mimic experimental studies performed in fast dynamic compression, a compressive loading velocity of 1 m/s was applied to the superior half of L2, while the inferior half of L3 was fixed. An exploratory technique was used to simulate dynamic compression of the FSU using 34 sets of hyperelastic material constants randomly selected using an optimal Latin hypercube algorithm and a set of material constants derived from quasi-static experiments. Selection or rejection of the sets of material constants was based on compressive stiffness and failure parameters criteria measured experimentally. The two simulations performed with calibrated hyperelastic constants resulted in nonlinear load-displacement curves with compressive stiffness (7335 and 7079 N/mm), load (12,488 and 12,473 N), displacement (1.95 and 2.09 mm) and energy at failure (13.5 and 14.7 J) in agreement with experimental results (6551 ± 2017 N/mm, 12,411 ± 829 N, 2.1 ± 0.2 mm and 13.0 ± 1.5 J respectively). The fracture pattern and location also agreed with experimental results. The simulation performed with constants derived from quasi-static experiments showed a failure energy (13.2 J) and a fracture pattern and location in agreement with experimental results, but a compressive stiffness (1580 N/mm), a failure load (5976 N) and a displacement to failure (4.8 mm) outside the experimental corridors. The proposed method offers an innovative way to calibrate the hyperelastic material properties of the IVD and to offer a more realistic simulation of the FSU in fast dynamic compression.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):101008-101008-9. doi:10.1115/1.4005251.

Mechanical forces are key regulators of cell function with varying loads capable of modulating behaviors such as alignment, migration, phenotype modulation, and others. Historically, cell-stretching experiments have employed mechanically simple environments (e.g., uniform uniaxial or equibiaxial stretches). However, stretch distributions in vivo can be highly non-uniform, particularly in cases of disease or subsequent to interventional treatments. Herein, we present a cell-stretching device capable of subjecting cells to controllable gradients in biaxial stretch via radial deformation of circular elastomeric membranes. By including either a defect or a rigid fixation at the center of the membrane, various gradients are generated. Capabilities of the device were quantified by tracking marked positions of the membrane while applying various loads, and experimental feasibility was assessed by conducting preliminary experiments with 3T3 fibroblasts and 10T1/2 cells subjected to 24 h of cyclic stretch. Quantitative real-time PCR was used to measure changes in mRNA expression of a profile of genes representing the major smooth muscle phenotypes. Genes associated with the contractile state were both upregulated (e.g., calponin) and downregulated (e.g., α-2-actin), and genes associated with the synthetic state were likewise both upregulated (e.g., SKI-like oncogene) and downregulated (e.g., collagen III). In addition, cells aligned with an orientation perpendicular to the maximal stretch direction. We have developed an in vitro cell culture device that can produce non-uniform stretch environments similar to in vivo mechanics. Cells stretched with this device showed alignment and altered mRNA expression indicative of phenotype modulation. Understanding these processes as they relate to in vivo pathologies could enable a more accurately targeted treatment to heal or inhibit disease, either through implantable device design or pharmaceutical approaches.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):101009-101009-9. doi:10.1115/1.4005286.

The expansive growth and differentiation potential of human embryonic stem cells (hESCs) make them a promising source of cells for regenerative medicine. However, this promise is off set by the propensity for spontaneous or uncontrolled differentiation to result in heterogeneous cell populations. Cell elasticity has recently been shown to characterize particular cell phenotypes, with undifferentiated and differentiated cells sometimes showing significant differences in their elasticities. In this study, we determined the Young’s modulus of hESCs by atomic force microscopy using a pyramidal tip. Using this method we are able to take point measurements of elasticity at multiple locations on a single cell, allowing local variations due to cell structure to be identified. We found considerable differences in the elasticity of the analyzed hESCs, reflected by a broad range of Young’s modulus (0.05-10 kPa). This surprisingly high variation suggests that elasticity could serve as the basis of a simple and efficient large scale purification/separation technique to discriminate subpopulations of hESCs.

Commentary by Dr. Valentin Fuster

Technical Briefs

J Biomech Eng. 2011;133(10):104501-104501-6. doi:10.1115/1.4005176.

The purpose of this study is to evaluate the potential correlation between peak wall stress (PWS) and abdominal aortic aneurysm (AAA) morphology and how it relates to aneurysm rupture potential. Using in-house segmentation and meshing software, six 3-dimensional (3D) AAA models from a single patient followed for 28 months were generated for finite element analysis. For the AAA wall, both isotropic and anisotropic materials were used, while an isotropic material was used for the intraluminal thrombus (ILT). These models were also used to calculate 36 geometric indices characteristic of the aneurysm morphology. Using least squares regression, seven significant geometric features (p < 0.05) were found to characterize the AAA morphology during the surveillance period. By means of nonlinear regression, PWS estimated with the anisotropic material was found to be highly correlated with three of these features: maximum diameter (r = 0.992, p = 0.002), sac volume (r = 0.989, p = 0.003) and diameter to diameter ratio (r = 0.947, p = 0.033). The correlation of wall mechanics with geometry is nonlinear and reveals that PWS does not increase concomitantly with aneurysm diameter. This suggests that a quantitative characterization of AAA morphology may be advantageous in assessing rupture risk.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):104502-104502-7. doi:10.1115/1.4005177.

The foot consists of many small bones with complicated joints that guide and limit motion. A variety of invasive and noninvasive means [mechanical, X-ray stereophotogrammetry, electromagnetic sensors, retro-reflective motion analysis, computer tomography (CT), and magnetic resonance imaging (MRI)] have been used to quantify foot bone motion. In the current study we used a foot plate with an electromagnetic sensor to determine an individual subject’s foot end range of motion (ROM) from maximum plantar flexion, internal rotation, and inversion to maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation. We then used a custom built MRI-compatible device to hold each subject’s foot during scanning in eight unique positions determined from the end ROM data. The scan data were processed using software that allowed the bones to be segmented with the foot in the neutral position and the bones in the other seven positions to be registered to their base positions with minimal user intervention. Bone to bone motion was quantified using finite helical axes (FHA). FHA for the talocrural, talocalcaneal, and talonavicular joints compared well to published studies, which used a variety of technologies and input motions. This study describes a method for quantifying foot bone motion from maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation with relatively little user processing time.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):104503-104503-5. doi:10.1115/1.4005222.

The main reason for the revision of total hip replacements is aseptic loosening, caused by stress shielding and wear particle induced osteolysis. In order to detect an implant loosening early, the osseointegration of endoprosthetic implants must be measured exactly. Currently applied diagnostic methods, such as standard radiographs and clinical symptomatology, often result in an imprecise diagnosis. A novel radiation-free method to improve the diagnostic investigation of implant loosening is presented. The osseointegration of an implant can be identified using mechanical magnetic sensors (oscillators), which impinge on small membranes inside an implant component, e.g., the femoral hip stem. The maximum velocity after impingement of the oscillator depends on the osseointegration of the implant. Excitation of the oscillator is realized by a coil outside the human body. Another external coil is used to detect the velocity of the oscillator. To demonstrate the principle of the novel loosening sensor, an overdimensioned test device was designed to measure simulated loosening phases in the first experimental tests with different material layers. The overdimensioned test device of the loosening sensor showed significant differences in the various phases of fixation. Analysis of the membrane without any material layer in the case of advanced loosening resulted in a 23% higher maximum velocity compared to an attached artificial bone layer. Based on these preliminary results, the sensor system shows potential for the detection of implant loosening. Moreover, the proposed system could be used in experimental applications to determine the quality of bioactive coatings and new implant materials.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2011;133(10):104504-104504-3. doi:10.1115/1.4005174.

Articular cartilage is comprised of macromolecules, proteoglycans, with (charged) chondroitin sulfate side-chains attached to them. The proteoglycans are attached to longer hyaluronic acid chains, trapped within a network of type II collagen fibrils. As a consequence of their relatively long persistence lengths, the number of persistence lengths along the chondroitin sulfate and proteoglycan chains is relatively small, and consequently, the retraction times for these side chains are also quite short. We argue that, as a consequence of this, they will not significantly inhibit the reptation of the hyaluronic acid chains. Scaling arguments applied to this model allow us to show that the shortest of the mechanical relaxation times of cartilage, that have been determined by Fyhrie and Barone to be due to reptation of the hyaluronic acid polymers, should have a dependence on the load, i.e., force per unit interface area P, carried by the cartilage, proportional to P3/2.

Commentary by Dr. Valentin Fuster

Errata

J Biomech Eng. 2011;133(10):107001-107001-1. doi:10.1115/1.4005178.
FREE TO VIEW

It has come to our attention that Eq. 16 in our paper is incorrectly listed as identical to Eq. (13). With the thought that it is never too late to get it right, and there is always time for one last proofreading, Eq. 16 of Johnson and Tarbell [1] should read Display Formula

k1,k2=Mα2±M2α24+(β11β22+Mα)
(16)

Commentary by Dr. Valentin Fuster

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