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1.  A mechanistic model on the role of “radially-running” collagen fibers on dissection properties of human ascending thoracic aorta 
Journal of biomechanics  2014;47(5):981-988.
Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovaular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fiber microarchitecture, obtained in a parallel study from multi-photon microopy, in a predictive mechanistic framework to characterize the delamination strength. We then validate our model against peel test experiments on human aortic strips and utilize the model to predict the delamination strength of separate aortic strips and compare with experimental findings. We observe that the number density and failure energy of the radially-running collagen fibers control the peel strength. Furthermore, our model suggests that the lower delamination strength previously found for the circumferential direction in human aorta is related to a lower number density of radially-running collagen fibers in that direction. Our model sets the stage for an expanded future study that could predict AoD propagation in patient-specific aortic geometries and better understand factors that may influence propensity for occurrence.
doi:10.1016/j.jbiomech.2014.01.005
PMCID: PMC4082402  PMID: 24484644
Peel force; Aorta; Dissection; Collagen fibers; Fiber bridge failure model
2.  TORSIONAL STIFFNESS AND STRENGTH OF THE PROXIMAL TIBIA ARE BETTER PREDICTED BY FINITE ELEMENT MODELS THAN DXA OR QCT 
Journal of biomechanics  2013;46(10):1655-1662.
Individuals with spinal cord injury experience a rapid loss of bone mineral below the neurological lesion. The clinical consequence of this bone loss is a high rate of fracture around regions of the knee. The ability to predict the mechanical competence of bones at this location may serve as an important clinical tool to assess fracture risk in the spinal cord injury population. The purpose of this study was to develop, and statistically compare, non-invasive methods to predict torsional stiffness (K) and strength (Tult) of the proximal tibia. Twenty-two human tibiae were assigned to either a “training set” or a “test set” (11 specimens each) and mechanically loaded to failure. The training set was used to develop subject-specific finite element (FE) models, and statistical models based on dual energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT), to predict K and Tult; the test set was used for cross-validation. Mechanical testing produced clinically relevant spiral fractures in all specimens. All methods were accurate and reliable predictors of K (cross-validation r2 ≥ 0.91; error ≤ 13%), however FE models explained an additional 15% of the variance in measured Tult and illustrated 12–16% less error than DXA and QCT models. Given the strong correlations between measured and FE predicted K (cross-validation r2= 0.95; error = 10%) and Tult (cross-validation r2= 0.91; error = 9%), we believe the FE modeling procedure has reached a level of accuracy necessary to answer clinically relevant questions.
doi:10.1016/j.jbiomech.2013.04.016
PMCID: PMC3676700  PMID: 23680350
finite element analysis; quantitative computed tomography; mechanical testing; experimental validation; bone fracture; spinal cord injury
3.  In Vitro Spine Testing Using a Robot-Based Testing System: Comparison of Displacement Control and “Hybrid Control” 
Journal of biomechanics  2013;46(10):1663-1669.
The two leading control algorithms for in-vitro spine biomechanical testing—“load control” and “displacement control”— are limited in their lack of adaptation to changes in the load-displacement response of a spine specimen—pointing to the need for sufficiently sophisticated control algorithms that are able to govern the application of loads/motions to a spine specimen in a more realistic, adaptive manner. A robotics-based spine testing system was programmed with a novel hybrid control algorithm combining “load control” and “displacement control” into a single, robust algorithm. Prior to in-vitro cadaveric testing, preliminary testing of the new algorithm was performed using a rigid-body-spring model with known structural properties. The present study also offers a direct comparison between “hybrid control” and “displacement control”.
The hybrid control algorithm enabled the robotics-based spine testing system to apply pure moments to an FSU (in flexion/extension, lateral bending, or axial rotation) in an unconstrained manner through active control of secondary translational/rotational degrees-of-freedom—successfully minimizing coupled forces/moments. The characteristic nonlinear S-shaped curves of the primary moment-rotation responses were consistent with previous reports of the FSU having a region of low stiffness (neutral zone) bounded by regions of increasing stiffness (elastic zone). Direct comparison of “displacement control” and “hybrid control” showed that hybrid control was able to actively minimize off-axis forces and resulted in larger neutral zone and range of motion.
doi:10.1016/j.jbiomech.2013.04.007
PMCID: PMC3718291  PMID: 23702044
Spinal biomechanics; osteoligamentous cervical spine; load control; displacement control; hybrid control; robotics
4.  Presence of Intervertebral Discs Alters Observed Stiffness and Failure Mechanisms in the Vertebra 
Journal of biomechanics  2013;46(10):1683-1688.
Ex vivo mechanical testing is an essential tool for study of vertebral mechanics. However, the common method of testing vertebral bodies in the absence of adjacent intervertebral discs (IVDs) may limit the physiological relevance of the results. The goal of this study was to determine the influence of IVDs on vertebral mechanical properties and failure mechanisms. Rabbit thoracic vertebral bodies were tested with and without IVDs in a stepwise fashion that incorporated a micro-computed tomography scan at each loading step. The image sequences were analyzed using digital volume correlation to quantify deformations throughout the vertebral body. The observed deformation patterns differed substantially between the groups. Specimens tested with IVDs exhibited a slow increase in strain in the inferior and posterior regions, followed by a sudden increase in strain in the anterior cortex right at the yield point. In contrast, the highest strains in the isolated vertebral bodies were in the posterior regions throughout the test. Specimens tested with IVDs had lower stiffness (507.49 ± 184.73 N/mm vs. 845.61 ± 296.09 N/mm; p = 0.044), higher ultimate displacement (2.00 ± 0.68 mm vs. 1.17 ± 0.54 mm; p = 0.043), and higher maximum shear strains (e.g. top 25th percentile: 0.19 ± 0.11 vs. 0.06 ± 0.07mm/mm; p < 0.0458), and tended to have lower ultimate force (690.28 ± 160.25 N vs. 873.81 ± 131.48 N; p = 0.056). Similar work to failure (648.15 ± 317.86 N-mm vs. 603.49 ± 437.95 N-mm; p = 0.844) was observed between the two groups. These results indicate that testing vertebral bodies in the absence of IVDs can elicit artifactual failure mechanisms. These artifacts may be more prominent than the effects on vertebral strength and toughness.
doi:10.1016/j.jbiomech.2013.04.004
PMCID: PMC3733079  PMID: 23683319
Vertebral body; mechanical testing; failure patterns; strength; load distribution
5.  Influence of Neuromuscular Noise and Walking Speed on Fall Risk and Dynamic Stability in a 3D Dynamic Walking Model 
Journal of biomechanics  2013;46(10):1722-1728.
Older adults and those with increased fall risk tend to walk slower. They may do this voluntarily to reduce their fall risk. However, both slower and faster walking speeds can predict increased risk of different types of falls. The mechanisms that contribute to fall risk across speeds are not well known. Faster walking requires greater forward propulsion, generated by larger muscle forces. However, greater muscle activation induces increased signal-dependent neuromuscular noise. These speed-related increases in neuromuscular noise may contribute to the increased fall risk observed at faster walking speeds. Using a 3D dynamic walking model, we systematically varied walking speed without and with physiologically-appropriate neuromuscular noise. We quantified how actual fall risk changed with gait speed, how neuromuscular noise affected speed-related changes in fall risk, and how well orbital and local dynamic stability measures predicted changes in fall risk across speeds. When we included physiologically-appropriate noise to the ‘push-off’ force in our model, fall risk increased with increasing walking speed. Changes in kinematic variability, orbital, and local dynamic stability did not predict these speed-related changes in fall risk. Thus, the increased neuromuscular variability that results from increased signal-dependent noise that is necessitated by the greater muscular force requirements of faster walking may contribute to the increased fall risk observed at faster walking speeds. The lower fall risk observed at slower speeds supports experimental evidence that slowing down can be an effective strategy to reduce fall risk. This may help explain the slower walking speeds observed in older adults and others.
doi:10.1016/j.jbiomech.2013.03.032
PMCID: PMC3738439  PMID: 23659911
dynamic walking; gait; stability; falling; elderly; local instability; orbital stability; walking speed
6.  Spatial periodicity in growth plate shear mechanical properties is disrupted by vitamin D deficiency 
Journal of biomechanics  2013;46(10):1597-1603.
The growth plate is a highly organized section of cartilage in the long bones of growing children that is susceptible to mechanical failure as well as structural and functional disruption caused by a dietary deficiency of vitamin D. The shear mechanical properties of the proximal tibial growth plate of rats raised either on normal or vitamin D and calcium deficient diets were measured. A sinusoidal oscillating shear load was applied to small excised growth plate specimens perpendicular to the direction of growth while imaging the deformation in real time with a fast confocal microscope. Local deformations and shear strains were quantified using image correlation. The proliferative zone of the growth plate bores the majority of the shear strain and the resting, hypertrophic and calcification zones deformed less. Surprisingly, we regularly observed discontinuous deformations in the proliferative zone in both groups that resembled cell columns sliding past one another in the direction of growth. These discontinuities manifested as regions of concentrated longitudinal shear strain. Furthermore, these shear strain concentrations were spaced evenly in the proliferative zone and the spacing between them was similar across growth plate regions and across control specimens. In contrast to the healthy controls, the vitamin D deficient growth plate exhibited larger variations in the size and orientation of cellular columns in the proliferative and hypertrophic zones. High strains were observed between columns, much as they were in the controls. However, the regular spacing of shear strain concentrations was not preserved, echoing the observation of decreased structural organization.
doi:10.1016/j.jbiomech.2013.04.023
PMCID: PMC3782304  PMID: 23706979
Growth plate; Cartilage; Shear modulus; Vitamin D
7.  A rolling constraint reproduces ground reaction forces and moments in dynamic simulations of walking, running, and crouch gait 
Journal of biomechanics  2013;46(10):1772-1776.
Recent advances in computational technology have dramatically increased the use of muscle-driven simulation to study accelerations produced by muscles during gait. Accelerations computed from muscle-driven simulations are sensitive to the model used to represent contact between the foot and ground. A foot-ground contact model must be able to calculate ground reaction forces and moments that are consistent with experimentally measured ground reaction forces and moments. We show here that a rolling constraint can model foot-ground contact and reproduce measured ground reaction forces and moments in an induced acceleration analysis of muscle-driven simulations of walking, running, and crouch gait. We also illustrate that a point constraint and a weld constraint used to model foot-ground contact in previous studies produce inaccurate reaction moments and lead to contradictory interpretations of muscle function. To enable others to use and test these different constraint types (i.e., rolling, point, and weld constraints) we have included them as part of an induced acceleration analysis in OpenSim, a freely-available biomechanics simulation package.
doi:10.1016/j.jbiomech.2013.03.030
PMCID: PMC3993009  PMID: 23702045
Biomechanics; Musculoskeletal; Dynamic simulation; Induced acceleration analysis; Contact model; Muscle function; Foot-ground constraints
8.  EFFECT OF DYNAMIC LOADING ON THE FRICTIONAL RESPONSE OF BOVINE ARTICULAR CARTILAGE 
Journal of biomechanics  2005;38(8):1665-1673.
Summary
The objective of this study was to test the hypotheses that (1) the steady-state friction coefficient of articular cartilage is significantly smaller under cyclical compressive loading than the equilibrium friction coefficient under static loading, and decreases as a function of loading frequency; (2) the steady-state cartilage interstitial fluid load support remains significantly greater than zero under cyclical compressive loading and increases as a function of loading frequency. Unconfined compression tests with sliding of bovine shoulder cartilage against glass in saline were carried out on fresh cylindrical plugs (n=12), under three sinusoidal loading frequencies (0.05 Hz, 0.5 Hz and 1 Hz) and under static loading; the time-dependent friction coefficient μeff was measured. The interstitial fluid load support was also predicted theoretically. Under static loading μeff increased from a minimum value (μmin=0.005±0.003) to an equilibrium value (μeq=0.153±0.032). In cyclical compressive loading tests μeff similarly rose from a minimum value (μmin=0.004±0.002, 0.003±0.001 and 0.003±0.001 at 0.05, 0.5 and 1 Hz) and reached a steady-state response oscillating between a lower-bound (μlb=0.092±0.016, 0.083±0.019 and 0.084±0.020) and upper bound (μub=0.382±0.057, 0.358±0.059, and 0.298±0.061). For all frequencies it was found that and μub> μeq and μlb < μeq (p<0.05). Under cyclical compressive loading the interstitial fluid load support was found to oscillate above and below the static loading response, with suction occurring over a portion of the loading cycle at steady-state conditions. All theoretical predictions and most experimental results demonstrated little sensitivity to loading frequency. On the basis of these results, both hypotheses were rejected. Cyclical compressive loading is not found to promote lower frictional coefficients or higher interstitial fluid load support than static loading.
doi:10.1016/j.jbiomech.2004.07.025
PMCID: PMC4059373  PMID: 15958224
Cartilage; dynamic loading; friction coefficient; interstitial fluid pressurization
9.  In-vivo transducer to measure dynamic mitral annular forces 
Journal of biomechanics  2012;45(8):1514-1516.
Limited knowledge exists regarding the forces which act on devices implanted to the heart’s mitral valve. Developing a transducer to measure the peak force magnitudes, time rates of change, and relationship with left ventricular pressure will aid in device development. A novel force transducer was developed and implanted in the mitral valve annulus of an ovine subject. In the post-cardioplegic heart, septal-lateral and transverse forces were continuously measured for cardiac cycles reaching a peak left ventricular pressure of 90 mmHg. Each force was seen to increase from ventricular diastole and found to peak at mid-systole. The mean change in septal-lateral and transverse forces throughout the cardiac cycle was 4.4 ± 0.2 N and 1.9 ± 0.1 N respectively. During isovolumetric contraction, the septal-lateral and transverse forces were found to increase at peak rate of 143 ± 8 N/s and 34 ± 9 N/s, respectively. Combined, this study provides the first quantitative assessment of septal-lateral and transverse forces within the contractile mitral annulus. The developed transducer was successful in measuring these forces whose methods may be extended to future studies. Upon additional investigation, these data may contribute to the safer development and evaluation of devices aimed to repair or replace mitral valve function.
doi:10.1016/j.jbiomech.2012.03.009
PMCID: PMC4046323  PMID: 22483226
Mitral valve; Ischemic mitral regurgitation; Force; Strain gage; Transducer
10.  In Vivo Kinematics of the Knee during Weight Bearing in High Flexion 
Journal of biomechanics  2013;46(9):1576-1582.
Achieving high flexion is an objective of contemporary total knee arthoplasty, however little is known on the knee biomechanics at high flexion under weight-bearing conditions. This study is to investigate the 6DOF kinematics and tibiofemoral cartilage contact biomechanics of the knee during weight-bearing flexion from full extension to maximal flexion. Eight knees from seven healthy subjects with no history of injuries or chronic pain were recruited. The knees were MRI scanned to create 3D models of the tibia and femur, including their articular cartilage surfaces. The subjects were then imaged using a dual fluoroscopic image system while performing a weight-bearing quasi-static single-legged lunge from full extension to maximal flexion. The 6DOF kinematics and the articular cartilage contact locations were measured along the flexion path of the knee. The result indicated that the internal tibial rotation increased sharply at low flexion angles (full extension to 30°), maintained a small variation in the middle range of flexion (30° to 120°), and then sharply increased again at high flexion angles (120° to maximal flexion). The contact point moved similarly in the medial and lateral compartments before 120° of flexion, but less on the medial compartment at high flexion angles. The results indicated that the knee motion couldn’t be described using one character in the entire range of flexion, especially in high flexion. The knee kinematic data in the entire range of flexion of the knee could be instrumental for designing new knee prostheses to achieve physical high flexion and improving rehabilitation protocols after knee injuries.
doi:10.1016/j.jbiomech.2013.03.014
PMCID: PMC3660465  PMID: 23591448
In vivo knee kinematics; Cartilage contact; High flexion
11.  EFFECTIVENESS OF SURGICAL RECONSTRUCTION TO RESTORE RADIOCARPAL JOINT MECHANICS AFTER SCAPHOLUNATE LIGAMENT INJURY. AN IN VIVO MODELING STUDY 
Journal of biomechanics  2013;46(9):1548-1553.
Disruption of the scapholunate ligament can cause a loss of normal scapholunate mechanics and eventually lead to osteoarthritis. Surgical reconstruction attempts to restore scapholunate relationship and shows improvement in functional outcomes, but postoperative effectiveness in restoring normal radiocarpal mechanics still remains a question. The objective of this study was to investigate the benefits of surgical repair by observing changes in contact mechanics on the cartilage surface before and after surgical treatment. Six patients with unilateral scapholunate dissociation were enrolled in the study, and displacement driven magnetic resonance image based-surface contact modeling was used to investigate normal, injured and postoperative radiocarpal mechanics. Model geometry was acquired from images of wrists taken in a relaxed position. Kinematics were acquired from image registration between the relaxed images, and images taken during functional loading. Results showed a trend for increase in radiocarpal contact parameters with injury. Peak and mean contact pressures significantly decreased after surgery in the radiolunate articulation and there were no significant differences between normal and postoperative wrists. Results indicated surgical repair improves contact mechanics after injury and that contact mechanics can be surgically restored to be similar to normal. This study provides novel contact mechanics data on the effects of surgical repair after scapholunate ligament injury. With further work, it may be possible to more effectively differentiate between treatments and degenerative changes based on in vivo contact mechanics data.
doi:10.1016/j.jbiomech.2013.03.020
PMCID: PMC3711862  PMID: 23618131
Scapholunate Dissociation; Modeling; Contact Pressure; Magnetic Resonance Imaging; Posttraumatic Osteoarthritis
12.  Cervical spine intervertebral kinematics with respect to the head are different during flexion and extension motions 
Journal of biomechanics  2013;46(8):1471-1475.
Previous dynamic imaging studies of the cervical spine have focused entirely on intervertebral kinematics while neglecting to investigate the relationship between head motion and intervertebral motion. Specifically, it is unknown if the relationship between head and intervertebral kinematics is affected by movement direction. We tested the hypothesis that there would be no difference in sagittal plane intervertebral angles at identical head orientations during the flexion and extension movements. Nineteen asymptomatic subjects performed continuous head flexion-extension movements while biplane radiographs were collected at 30 images per second. A previously validated model-based volumetric tracking process determined three-dimensional vertebral position with sub-millimeter accuracy throughout the flexion–extension motion. Head movement was recorded at 60 Hz using conventional motion analysis and reflective markers. Intervertebral angles were determined at identical head orientations during the flexion and extension movements. Cervical motion segments were in a more extended orientation during flexion and in a more flexed orientation during extension for any given head orientation. The results suggest that static radiographs cannot accurately represent vertebral orientation during dynamic motion. Further, data should be collected during both flexion and extension movements when investigating intervertebral kinematics with respect to global head orientation. Also, in vitro protocols that use intervertebral total range of motion as validation criteria may be improved by assessing model fidelity using continuous intervertebral kinematics in flexion and in extension. Finally, musculoskeletal models of the head and cervical spine should account for the direction of head motion when determining muscle moment arms because vertebral orientations (and therefore muscle attachment sites) are dependent on the direction of head motion.
doi:10.1016/j.jbiomech.2013.03.004
PMCID: PMC3767970  PMID: 23540377
In vivo; Dynamic kinematics; Disc degeneration; Movement direction
13.  Dynamic Mechanical Compression of Devitalized Articular Cartilage Does Not Activate Latent TGF-β 
Journal of biomechanics  2013;46(8):10.1016/j.jbiomech.2013.03.006.
A growing body of research has highlighted the role that mechanical forces play in the activation of the latent TGF-β in biological tissues. In synovial joints, it has recently been demonstrated that the mechanical shearing of synovial fluid, induced during joint motion, rapidly activates a large fraction of its soluble latent TGF-β content. Based on this observation, the primary hypothesis of the current study is that the mechanical deformation of articular cartilage, induced by dynamic joint motion, can similarly activate the large stores of latent TGF-β bound to the tissue extracellular matrix (ECM).
Here, devitalized deep zone articular cartilage cylindrical explants (n=84) were subjected to continuous dynamic mechanical loading (low strain: ±2% or high strain: ±7.5% at 0.5 Hz) for up to 15 h or maintained unloaded. TGF-β activation was measured in these samples over time while accounting for the active TGF-β that remains bound to the cartilage ECM. Results indicate that TGF-β1 is present in cartilage at high levels (68.5±20.6 ng/mL) and resides predominantly in the latent form (>98% of total). Under dynamic loading, active TGF-β1 levels did not statistically increase from the initial value nor the corresponding unloaded control values for any test, indicating that physiologic dynamic compression of cartilage is unable to directly activate ECM-bound latent TGF-β purely mechanical pathways and leading us to reject the hypothesis of this study.
These results suggest that deep zone articular chondrocytes must alternatively obtain access to active TGF-β through chemical-mediated activation and further suggest that mechanical deformation is unlikely to directly activate the ECM-bound latent TGF-β of various other tissues, such as muscle, ligament, and tendon.
doi:10.1016/j.jbiomech.2013.03.006
PMCID: PMC3810401  PMID: 23540376
TGF-β activation; articular cartilage; dynamic loading; growth factors; extracellular matrix
14.  Modulation of neonatal growth plate development by ex vivo intermittent mechanical stress 
Journal of biomechanics  2007;40(12):2686-2693.
Although growth plate response to mechanical stress has been increasingly studied, our understanding of mechanical modulation of neonatal growth plate is incomplete, especially concerning biochemical changes. This study was designed to explore the cellular and biochemical responses of the cranial base growth plate (CBGP) explant upon cyclic loading. The growth plate with subchondral bone was aseptically isolated from each of 24 neonatal rabbits and fixated in an organ culture system. Cyclic loading was applied to growth plate explants at 200 mN and 1 Hz for 60 min (N = 12), whereas control explants were immersed in organ culture for 60 min without mechanical loading (N = 12). Computerized image analysis revealed that cyclic loading induced significantly more proliferating chondrocytes than unloaded controls (p<0.001), as well as significantly higher growth plate height at 856 ± 30 μm than the unloaded controls at 830 ± 36 μm (p<0.05). Immunoblotting with monoclonal antibodies (mAb) disclosed that the average mAb binding area for chondroitin sulfate was significantly higher in the loaded specimens than the unloaded controls at (p<0.001). The average mAb binding area for keratan sulfate was also significantly higher in the loaded specimens than the unloaded controls (p<0.01). Biochemical analysis showed that the average total hyaluronan content of loaded specimens at 0.25 ± 0.06 μg/μg DNA was significantly higher than the unloaded controls at 0.09 ± 0.05 μg/μg DNA (p<0.01). Taken together, these data suggest that brief doses of cyclic, intermittent forces activate cellular and molecular responses in the CBGP ex vivo. Whether hyaluronan-mediated pathway is involved in the biological responses of growth plate to mechanical loading warrants additional investigations.
doi:10.1016/j.jbiomech.2006.12.014
PMCID: PMC4035018  PMID: 17346717
Chondrocytes; Growth plate; Cartilage; Osteoblasts; Bone; Cyclic loading
15.  Defining feasible bounds on muscle activation in a redundant biomechanical task; practical implications of redundancy 
Journal of biomechanics  2013;46(7):1363-1368.
Measured muscle activation patterns often vary significantly from musculoskeletal model predictions that use optimization to resolve redundancy. Although experimental muscle activity exhibits both inter- and intra-subject variability we lack adequate tools to quantify the biomechanical latitude that the nervous system has when selecting muscle activation patterns. Here, we identified feasible ranges of individual muscle activity during force production in a musculoskeletal model to quantify the degree to which biomechanical redundancy allows for variability in muscle activation patterns. In a detailed cat hindlimb model matched to the posture of three cats, we identified the lower and upper bounds on muscle activity in each of 31 muscles during static endpoint force production across different force directions and magnitudes. Feasible ranges of muscle activation were relatively unconstrained across force magnitudes such that only a few (0∼13%) muscles were found to be truly “necessary” (e.g. exhibited non-zero lower bounds) at physiological force ranges. Most muscles were “optional” having zero lower bounds, and frequently had “maximal” upper bounds as well. Moreover, “optional” muscles were never selected by optimization methods that either minimized muscle stress, or that scaled the pattern required for maximum force generation. Therefore, biomechanical constraints were generally insufficient to restrict or specify muscle activation levels for producing a force in a given direction, and many muscle patterns exist that could deviate substantially from one another but still achieve the task. Our approach could be extended to identify the feasible limits of variability in muscle activation patterns in dynamic tasks such as walking.
doi:10.1016/j.jbiomech.2013.01.020
PMCID: PMC4021711  PMID: 23489436
Motor control; Musculoskeletal model; Muscle redundancy; Cat hindlimb
16.  Varying whole body vibration amplitude differentially affects tendon and ligament structural and material properties 
Journal of biomechanics  2013;46(9):1496-1500.
Whole Body Vibration (WBV) is becoming increasingly popular for helping to maintain bone mass and strengthening muscle. Vibration regimens optimized for bone maintenance often operate at hypogravity levels (<1 G) and regimens for muscle strengthening often employ hypergravity (>1 G) vibrations. The effect of vibratory loads on tendon and ligament properties is unclear though excessive vibrations may be injurious. Our objective was to evaluate how tendon gene expression and the mechanical/histological properties of tendon and ligament were affected in response to WBV in the following groups: no vibration, low vibration (0.3 G peak-to-peak), and high vibration (2 G peak-to-peak). Rats were vibrated for 20 min a day, 5 days a week, for 5 weeks. Upon sacrifice, the medial collateral ligament (MCL), patellar tendon (PT), and the Achilles Tendon (AT) were isolated with insertion sites intact. All tissues were tensile tested to determine structural and material properties or used for histology. Patellar tendon was also subjected to quantitative RT-PCR to evaluate expression of anabolic and catabolic genes. No differences in biomechanical data between the control and the low vibration groups were found. There was evidence of significant weakness in the MCL with high vibration, but no significant effect on the PT or AT. Histology of the MCL and PT showed a hypercellular tissue response and some fiber disorganization with high vibration. High vibration caused an increase in collagen expression and a trend for an increase in IGF-1 expression suggesting a potential anabolic response to prevent tendon overuse injury.
doi:10.1016/j.jbiomech.2013.03.033
PMCID: PMC4020418  PMID: 23623311
Whole body vibration; Acceleration; Tendon; Ligament; Collagen expression
17.  The explosive growth of small voids in vulnerable cap rupture; cavitation and interfacial debonding 
Journal of biomechanics  2012;46(2):396-401.
While it is generally accepted that ruptures in fibrous cap atheromas cause most acute coronary deaths, and that plaque rupture occurs in the fibrous cap at the location where the tissue stress exceeds a certain critical peak circumferential stress, the exact mechanism of rupture initiation remains unclear. We recently reported the presence of multiple microcalcifications (μCalcs) < 50μm diameter embedded within the fibrous cap, μCalcs that could greatly increase cap instability by introducing up to a 5-fold increase in local tissue stress. Here, we explore the hypothesis that, aside from cap thickness, μCalc size and interparticle spacing are principal determinants of cap rupture risk. Also, we propose that cap rupture is initiated near the poles of the μCalcs due to the presence of tiny voids that explosively grow at a critical tissue stress and then propagate across the fibrous cap. We develop a theoretical model based on classic studies in polymeric materials by Gent (1980), which indicates that cavitation as opposed to interfacial debonding is the more likely mechanism for cap rupture produced by μCalcs < 65μm diameter. This analysis suggests that there is a critical μCalc size range, from 5μm to 65μm, in which cavitation should be prevalent. This hypothesis for cap rupture is strongly supported by our latest μCT studies in which we have observed trapped voids in the vicinity of μCalcs within fibrous caps in human coronaries.
doi:10.1016/j.jbiomech.2012.10.040
PMCID: PMC4019735  PMID: 23218838
cavitation; vulnerable plaque; microcalcifications; fibrous cap rupture
18.  Difference in hemodynamic and wall stress of ascending thoracic aortic aneurysms with bicuspid and tricuspid aortic valve 
Journal of biomechanics  2013;46(10):1729-1738.
The aortic dissection (AoD) of an ascending thoracic aortic aneurysm (ATAA) initiates when the hemodynamic loads exerted on the aneurysmal wall overcome the adhesive forces holding the elastic layers together. Parallel coupled, two-way fluid–structure interaction (FSI) analyses were performed on patient-specific ATAAs obtained from patients with either bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) to evaluate hemodynamic predictors and wall stresses imparting aneurysm enlargement and AoD. Results showed a left-handed circumferential flow with slower-moving helical pattern in the aneurysm's center for BAV ATAAs whereas a slight deviation of the blood flow toward the anterolateral region of the ascending aorta was observed for TAV ATAAs. Blood pressure and wall shear stress were found key hemodynamic predictors of aneurysm dilatation, and their dissimilarities are likely associated to the morphological anatomy of the aortic valve. We also observed discontinues, wall stresses on aneurysmal aorta, which was modeled as a composite with two elastic layers (i.e., inhomogeneity of vessel structural organization). This stress distribution was caused by differences on elastic material properties of aortic layers. Wall stress distribution suggests AoD just above sinotubular junction. Moreover, abnormal flow and lower elastic material properties that are likely intrinsic in BAV individuals render the aneurysm susceptible to the initiation of AoD.
doi:10.1016/j.jbiomech.2013.03.029
PMCID: PMC4016719  PMID: 23664314
Fluid–structure interaction; Aortic dissection; Ascending thoracic aortic aneurysm; Bicuspid aortic valve
19.  A numerical study of the flow-induced vibration characteristics of a voice-producing element for laryngectomized patients 
Journal of biomechanics  2007;40(16):3598-3606.
A computational model for exploring the design of a voice-producing voice prosthesis, or voice-producing element (VPE), is presented. The VPE is intended for use by laryngectomized patients who cannot benefit from current speech rehabilitation techniques. Previous experiments have focused on the design of a double-membrane voice generator as a VPE. For optimization studies, a numerical model has been developed. The numerical model introduced incorporates the finite element (FE) method to solve for the flow-induced vibrations of the VPE system, including airflow coupled with a mass-loaded membrane. The FE model includes distinct but coupled fluid and solid domains. The flow solver is governed by the incompressible, laminar, unsteady Navier–Stokes equations. The solid solver allows for large deformation, large strain, and collision. It is first shown that the model satisfactorily represents previously published experimental results in terms of frequency and flow rate, enabling the model for use as a design tool. The model is then used to study the influence of geometric scaling, membrane thickness, membrane stiffness, and slightly convergent or divergent channel geometry on the model response. It is shown that physiological allowable changes in the latter three device parameters alone will not be sufficient to generate the desired reduction in fundamental frequency. However, their effects are quantified and it is shown that membrane stiffness and included angle should be considered in future designs.
doi:10.1016/j.jbiomech.2007.06.007
PMCID: PMC4010319  PMID: 17662296
Voice-producing element; Voice prosthesis; Flow-induced vibrations; Finite element model; Total laryngectomy
20.  Electromechanical wave imaging for noninvasive mapping of the 3D electrical activation sequence in canines and humans in vivo 
Journal of biomechanics  2012;45(5):856-864.
Cardiovascular diseases rank as America’s primary killer, claiming the lives of over 41% of more than 2.4 million Americans. One of the main reasons for this high death toll is the severe lack of effective imaging techniques for screening, early detection and localization of an abnormality detected on the electrocardiogram (ECG). The two most widely used imaging techniques in the clinic are CT angiography and echocardiography with limitations in speed of application and reliability, respectively. It has been established that the mechanical and electrical properties of the myocardium change dramatically as a result of ischemia, infarction or arrhythmia; both at their onset and after survival. Despite these findings, no imaging technique currently exists that is routinely used in the clinic and can provide reliable, non-invasive, quantitative mapping of the regional, mechanical and electrical function of the myocardium. Electromechanical Wave Imaging (EWI) is an ultrasound-based technique that utilizes the electromechanical coupling and its associated resulting strain to infer to the underlying electrical function of the myocardium. The methodology of EWI is first described and its fundamental performance is presented. Subsequent in vivo canine and human applications are provided that demonstrate the applicability of Electromechanical Wave Imaging in differentiating between sinus rhythm and induced pacing schemes as well as mapping arrhythmias. Preliminary validation with catheter mapping is also provided and transthoracic electromechanical mapping in all four chambers of the human heart is also presented demonstrating the potential of this novel methodology to noninvasively infer to both the normal and pathological electrical conduction of the heart.
doi:10.1016/j.jbiomech.2011.11.027
PMCID: PMC4005422  PMID: 22284425
Cardiac; Displacement; Echocardiography; Elasticity Imaging; Electromechanical; Ischemia; Myocardial; Radio-Frequency; Stiffness; Strain; Ultrasound; Wave
21.  HETEROGENEITY OF BONE MINERAL DENSITY AND FATIGUE FAILURE OF HUMAN VERTEBRAE 
Journal of biomechanics  2013;46(7):1396-1399.
There is increasing interest in using the heterogeneity of tissue properties in a bone for predicting its fracture risk. Heterogeneity of volum etric bone mineral density (BMD) as measured from quantitative computed tomography (QCT) is of particular interest as these measurements are clinically feasible. Previous examinations of the relationship between the BMD heterogeneity and the mechanical behavior of human vertebrae considered quasistatic strength only and were with limited number of samples. McCubbrey et al. studied the value of regional BMDs for predicting vertebral fatigue life, determined from short-cycle tests at force levels scaled with the estimated strength of the vertebra, but the focus of that work was in best predictor subsets without a specific focus on the heterogeneity of BMD or the positive vs negative direction of the relationships. The previous analysis also did not take into account the censored nature of the fatigue life data. As such, whether BMD heterogeneity is positively or negatively associated with fatigue life and whether this is independent from the average or minimum BMD are not clear. In the present work, we revisite d the McCubbrey data for a preliminary examination of the relationship between BMD heterogeneity and fatigue life using survival analysis. The analysis suggests that BMD heterogeneity measured as the intra-vertebral standard deviation of BMDs in a vertebra is negatively associated with short cycle (high-amplitude) fatigue life independent from the average BMD. The results motivate further studies on the role of BMD heterogeneity in fatigue failure and clinical fracture risk of human vertebrae.
doi:10.1016/j.jbiomech.2013.02.015
PMCID: PMC3628284  PMID: 23538003
Fatigue life; failure analysis; quantitative computed tomography; regional bone mineral density; intra-vertebral variability
22.  A NEW FRACTURE ASSESSMENT APPROACH COUPLING HR-pQCT IMAGING AND FRACTURE MECHANICS-BASED FINITE ELEMENT MODELING 
Journal of biomechanics  2013;46(7):1305-1311.
A new fracture assessment approach that combines HR-pQCT imaging with fracture mechanics-based finite element modeling was developed to evaluate distal radius fracture load. Twenty distal radius images obtained from postmenopausal women (fracture, n = 10; nonfracture, n = 10) were processed to obtain a cortical and a whole bone model for each subject. The geometrical properties of each model were evaluated and the corresponding fracture load was determined under realistic fall conditions using cohesive finite element modeling. The results showed that the whole bone fracture load can be estimated based on the cortical fracture load for nonfracture (R2 = 0.58, p = 0.01) and pooled data (R2 = 0.48, p < 0.001) but not for the fracture group. The portion of the whole bone fracture load carried by the cortical bone increased with increasing cortical fracture load (R2 ≥ 0.5, p < 0.05) indicating that a more robust cortical bone carries a larger percentage of whole bone fracture load. Cortical thickness was found to be the best predictor of both cortical and whole bone fracture load for all groups (R2 range: 0.49–0.96, p < 0.02) with the exception of fracture group whole bone fracture load showing the predictive capability of cortical geometrical properties in determining whole bone fracture load. Fracture group whole bone fracture load was correlated with trabecular thickness (R2 = 0.4, p < 0.05) whereas the nonfracture and the pooled group did not show any correlation with the trabecular parameters. In summary, this study introduced a new modeling approach that coupled HR-pQCT imaging with fracture mechanics-based finite element simulations, incorporated fracture toughness and realistic fall loading conditions in the models, and showed the significant contribution of the cortical compartment to the overall fracture load of bone. Our results provide more insight into the fracture process in bone and may lead to improved fracture load predictions.
doi:10.1016/j.jbiomech.2013.02.009
PMCID: PMC3641900  PMID: 23497802
High resolution peripheral computed tomography (HR-pQCT); cortical bone; cohesive finite element modeling; distal radius; fracture
23.  Impact Differences in Ground Reaction Force and Center of Mass Between the First and Second Landing Phases of a Drop Vertical Jump and their Implications for Injury Risk Assessment 
Journal of biomechanics  2013;46(7):1237-1241.
The drop vertical jump (DVJ) task is commonly used to assess biomechanical performance measures that are associated with ACL injury risk in athletes. Previous investigations have solely assessed the first landing phase. We examined the first and second landings of a DVJ for differences in the magnitude of vertical ground reaction force (vGRF) and position of center of mass (CoM). A cohort of 239 adolescent female basketball athletes completed a series of DVJ tasks from an initial box height of 31 cm. Dual force platforms and a three dimensional motion capture system recorded force and positional data for each trial. There was no difference in peak vGRF between landings (p = 0.445), but side-to-side differences increased from the first to second landing (p = 0.007). Participants demonstrated a lower minimum CoM during stance in the first landing than the second landing (p < 0.001). The results have important implications for the future assessment of ACL injury risk behaviors in adolescent female athletes. Greater side-to-side asymmetry in vGRF and higher CoM during impact indicate the second landing of a DVJ may exhibit greater perturbation and better represent in-game mechanics associated with ACL injury risk.
doi:10.1016/j.jbiomech.2013.02.024
PMCID: PMC3644482  PMID: 23538000
Drop Jump; ACL; Reaction Force; Injury Prevention; Biomechanics
24.  Empirical Assessment of Dynamic Hamstring Function during Human Walking 
Journal of biomechanics  2013;46(7):1255-1261.
The hamstrings are often associated with the development of crouch gait, a fatiguing form of walking characterized by excessive hip flexion, knee flexion and ankle dorsiflexion during stance. However, recent studies have called into question whether abnormally active hamstrings induce the limb to move into a crouch posture. The purpose of this study was to directly measure the influence of the hamstrings on limb posture during stance. Nineteen healthy young adults walked on an instrumented treadmill at their preferred speed. A 90 ms long pulse train was used to stimulate the medial hamstrings during either terminal swing or loading response of random gait cycles. Induced motion was defined as the difference in joint angle trajectories between stimulated and non-stimulated strides. A dynamic musculoskeletal simulation of normal gait was generated and similarly perturbed by increasing hamstring excitation. The experiments show that hamstring stimulation induced a significant increase in posterior pelvic tilt, knee flexion and ankle dorsiflexion during stance, while having relatively less influence on the hip angular trajectory. The induced motion patterns were similar whether the hamstrings were stimulated during late swing or early stance, and were generally consistent with the direction of induced motion predicted by gait simulation models. Hence, we conclude that overactive hamstrings have the potential to induce the limb to move toward a crouch gait posture.
doi:10.1016/j.jbiomech.2013.02.019
PMCID: PMC3645289  PMID: 23540723
crouch gait; muscle function; electrical stimulation; forward dynamics
25.  The influence of computational strategy on prediction of mechanical stress in carotid atherosclerotic plaques: Comparison of 2D structure-only, 3D structure-only, one-way and fully coupled fluid-structure interaction analyses 
Journal of Biomechanics  2014;47(6):1465-1471.
Background
Compositional and morphological features of carotid atherosclerotic plaques provide complementary information to luminal stenosis in predicting clinical presentations. However, they alone cannot predict cerebrovascular risk. Mechanical stress within the plaque induced by cyclical changes in blood pressure has potential to assess plaque vulnerability. Various modeling strategies have been employed to predict stress, including 2D and 3D structure-only, 3D one-way and fully coupled fluid-structure interaction (FSI) simulations. However, differences in stress predictions using different strategies have not been assessed.
Methods
Maximum principal stress (Stress-P1) within 8 human carotid atherosclerotic plaques was calculated based on geometry reconstructed from in vivo computerized tomography and high resolution, multi-sequence magnetic resonance images. Stress-P1 within the diseased region predicted by 2D and 3D structure-only, and 3D one-way FSI simulations were compared to 3D fully coupled FSI analysis.
Results
Compared to 3D fully coupled FSI, 2D structure-only simulation significantly overestimated stress level (94.1 kPa [65.2, 117.3] vs. 85.5 kPa [64.4, 113.6]; median [inter-quartile range], p=0.0004). However, when slices around the bifurcation region were excluded, stresses predicted by 2D structure-only simulations showed a good correlation (R2=0.69) with values obtained from 3D fully coupled FSI analysis. 3D structure-only model produced a small yet statistically significant stress overestimation compared to 3D fully coupled FSI (86.8 kPa [66.3, 115.8] vs. 85.5 kPa [64.4, 113.6]; p<0.0001). In contrast, one-way FSI underestimated stress compared to 3D fully coupled FSI (78.8 kPa [61.1, 100.4] vs. 85.5 kPa [64.4, 113.7]; p<0.0001).
Conclusions
A 3D structure-only model seems to be a computationally inexpensive yet reasonably accurate approximation for stress within carotid atherosclerotic plaques with mild to moderate luminal stenosis as compared to fully coupled FSI analysis.
doi:10.1016/j.jbiomech.2014.01.030
PMCID: PMC3989027  PMID: 24529358
Carotid; Atherosclerosis; Stroke; Mechanics; Stress

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