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1.  The Use of 2D Ultrasound Elastography for Measuring Tendon Motion and Strain 
Journal of biomechanics  2013;47(3):750-754.
The goal of the current study was to investigate the fidelity of a 2D ultrasound elastography method for the measurement of tendon motion and strain. Ultrasound phantoms and ex vivo porcine flexor tendons were cyclically stretched to 4% strain while cine ultrasound radiofrequency (RF) data and video data were simultaneously collected. 2D ultrasound elastography was used to estimate tissue motion and strain from RF data, and surface tissue motion and strain were separately estimated using digital image correlation (DIC). There were strong correlations (R2 > 0.97) between DIC and RF measurements of phantom displacement and strain, and good agreement in estimates of peak phantom strain (DIC: 3.5 ± 0.2%; RF: 3.7 ± 0.1%). For tendon, elastographic estimates of displacement profiles also correlated well with DIC measurements (R2 > 0.92), and exhibited similar estimated peak tendon strain (DIC: 2.6 ± 1.4%; RF: 2.2 ± 1.3%). Elastographic tracking with B-Mode images tended to under-predict peak strain for both the phantom and tendon. This study demonstrates the capacity to use quantitative elastographic techniques to measure tendon displacement and strain within an ultrasound image window. The approach may be extendible to in vivo use on humans, which would allow for the non-invasive analysis of tendon deformation in both normal and pathological states.
doi:10.1016/j.jbiomech.2013.11.023
PMCID: PMC3904451  PMID: 24388164
Tendon mechanics; ultrasound elastography
2.  Multiscale analysis of morphology and mechanics in tail tendon from the ZDSD rat model of type 2 diabetes 
Journal of biomechanics  2013;47(3):681-686.
Type 2 diabetes (T2D) impacts multiple organ systems including the circulatory, renal, nervous and musculoskeletal systems. In collagen-based tissues, one mechanism that may be responsible for detrimental mechanical impacts of T2D is the formation of advanced glycation end products (AGEs) leading to increased collagen stiffness and decreased toughness, resulting in brittle tissue behavior. The purpose of this study was to investigate tendon mechanical properties from normal and diabetic rats at two distinct length scales, testing the hypothesis that increased stiffness and strength and decreased toughness at the fiber level would be associated with alterations in nanoscale morphology and mechanics. Individual fascicles from female Zucker diabetic Sprague-Dawley (ZDSD) rats had no differences in fascicle-level mechanical properties but had increased material-level strength and stiffness versus control rats (CD). At the nanoscale, collagen fibril D-spacing was shifted towards higher spacing values in diabetic ZDSD fibrils. The distribution of nanoscale modulus values was also shifted to higher values. Material-level strength and stiffness from whole fiber tests were increased in ZDSD tails. Correlations between nanoscale and microscale properties indicate a direct positive relationship between the two length scales, most notably in the relationship between nanoscale and microscale modulus. These findings indicate that diabetes-induced changes in material strength and modulus were driven by alterations at the nanoscale.
doi:10.1016/j.jbiomech.2013.11.045
PMCID: PMC3918737  PMID: 24360194
AFM; Tension; Nanoscale; Ultrastructure; Modulus
3.  Interaction of Lubricin with Collagen II Surfaces: Adsorption, Friction, and Normal Forces 
Journal of biomechanics  2013;47(3):659-666.
One of the major constituents of the synovial fluid that is thought to be responsible for chondroprotection and boundary lubrication is the glycoprotein lubricin (PRG4); however, the molecular mechanisms by which lubricin carries out its critical functions still remain largely unknown. We hypothesized that the interaction of lubricin with type II collagen, the main component of the cartilage extracellular matrix, results in enhanced tribological and wear properties. In this study, we examined: i) the molecular details by which lubricin interacts with type II collagen and how binding is related to boundary lubrication and adhesive interactions; and, ii) whether collagen structure can affect lubricin adsorption and its chondroprotective properties. We found that lubricin adsorbs strongly onto denatured, amorphous, and fibrillar collagen surfaces. Furthermore, we found large repulsive interactions between the collagen surfaces in presence of lubricin, which increased with increasing lubricin concentration. Lubricin attenuated the large friction and also the long-range adhesion between fibrillar collagen surfaces. Interestingly, lubricin adsorbed onto and mediated the frictional response between the denatured and native amorphous collagen surfaces equally and showed no preference on the supramolecular architecture of collagen. However, the coefficient of friction was lowest on fibrillar collagen in the presence of lubricin. We speculate that an important role of lubricin in mediating interactions at the cartilage surface is to attach to the cartilage surface and provide a protective coating that maintains the contacting surfaces in a sterically repulsive state.
doi:10.1016/j.jbiomech.2013.11.048
PMCID: PMC3925751  PMID: 24406099
Colloidal Probe Microscopy; Lateral Force Microscopy; Atomic Force Microscope; Friction; Tribology; PRG4; Wear; Glycoproteins; Collagen; Type II Collagen Lubricin; SAMs; Boundary Lubrication
4.  THE PASSIVE PROPERTIES OF MUSCLE FIBERS ARE VELOCITY DEPENDENT 
Journal of biomechanics  2013;47(3):687-693.
The passive properties of skeletal muscle play an important role in muscle function. While the passive quasi-static elastic properties of muscle fibers have been well characterized, the dynamic visco-elastic passive behavior of fibers has garnered less attention. In particular, it is unclear how the visco-elastic properties are influenced by lengthening velocity, in particular for the range of physiologically relevant velocities. The goals of this work were to: (i) measure the effects of lengthening velocity on the peak stresses within single muscle fibers to determine how passive behavior changes over a range of physiologically relevant lengthening rates (0.1–10 Lo/s), and (ii) develop a mathematical model of fiber viscoelasticity based on these measurements. We found that passive properties depend on strain rate, in particular at the low loading rates (0.1–3 Lo/s), and that the measured behavior can be predicted across a range of loading rates and time histories with a quasi-linear viscoelastic model. In the future, these results can be used to determine the impact of viscoelastic behavior on intramuscular stresses and forces during a variety of dynamic movements.
doi:10.1016/j.jbiomech.2013.11.044
PMCID: PMC3925397  PMID: 24360198
muscle fiber mechanics; viscoelasticity; QLV model
5.  An In Vitro Model for the Pathological Degradation of Articular Cartilage in Osteoarthritis 
Journal of biomechanics  2013;47(3):645-652.
The objective of this study was to develop an in vitro cartilage degradation model that emulates the damage seen in early-stage osteoarthritis. To this end, cartilage explants were collagenase-treated to induce enzymatic degradation of collagen fibers and proteoglycans at the articular surface. To assess changes in mechanical properties, intact and degraded cartilage explants were subjected to a series of confined compression creep tests. Changes in extracellular matrix structure and composition were determined using biochemical and histological approaches. Our results show that collagenase-induced degradation increased the amount of deformation experienced by the cartilage explants under compression. An increase in apparent permeability as well as a decrease in instantaneous and aggregate moduli were measured following collagenase treatment. Histological analysis of degraded explants revealed the presence of surface fibrillation, proteoglycan depletion in the superficial and intermediate zones and loss of the lamina splendens. Collagen cleavage was confirmed by the Col II–¾Cshort antibody. Degraded specimens experienced a significant decrease in proteoglycan content but maintained total collagen content. Repetitive testing of degraded samples resulted in the gradual collapse of the articular surface and the compaction of the superficial zone. Taken together, our data demonstrates that enzymatic degradation with collagenase can be used to emulate changes seen in early-stage osteoarthritis. Further, our in vitro model provides information on cartilage mechanics and insights on how matrix changes can affect cartilage’s functional properties. More importantly, our model can be applied to develop and test treatment options for tissue repair.
doi:10.1016/j.jbiomech.2013.11.050
PMCID: PMC3938093  PMID: 24360770
osteoarthritis; articular cartilage; collagenase; mechanical properties
6.  Dependence of Mechanical Properties of Trabecular Bone on Plate-Rod Microstructure Determined by Individual Trabecula Segmentation (ITS) 
Journal of biomechanics  2013;47(3):702-708.
Individual trabecula segmentation (ITS) technique can decompose the trabecular bone network into individual trabecular plates and rods and is capable of quantifying the plate/rod-related microstructural characteristics of trabecular bone. This novel technique has been shown to be able to provide in-depth insights into micromechanics and failure mechanisms of human trabecular bone, as well as to distinguish the fracture status independent of area bone mineral density in clinical applications. However, the plate/rod microstructural parameters from ITS have never been correlated to experimentally determined mechanical properties of human trabecular bone. In this study, on-axis cylindrical trabecular bone samples from human proximal tibia (n=30), vertebral body (n=10), and proximal femur (n=30) were harvested, prepared, scanned using micro computed-tomography (μCT), analyzed with ITS and mechanically tested. Regression analyses showed that the plate bone volume fraction (pBV/TV) and axial bone volume fraction (aBV/TV) calculated by ITS analysis correlated the best with elastic modulus (R2=0.96-0.97) and yield strength (R2=0.95-0.96). Trabecular plate-related microstructural parameters correlated highly with elastic modulus and yield strength, while most rod-related parameters were found inversely and only moderately correlated with the mechanical properties. In addition, ITS analysis also identified that trabecular bone at human femoral neck has the highest trabecular plate-related parameters while the other sites are similar with each other in terms of plate-rod microstructure.
doi:10.1016/j.jbiomech.2013.11.039
PMCID: PMC3925244  PMID: 24360196
7.  Effect of Glutaraldehyde Fixation on the Frictional Response of Immature Bovine Articular Cartilage Explants 
Journal of biomechanics  2013;47(3):694-701.
This study examined functional properties and biocompatibility of glutaraldehyde-fixed bovine articular cartilage over several weeks of incubation at body temperature to investigate its potential use as a resurfacing material in joint arthroplasty. In the first experiment, treated cartilage disks were fixed using 0.02, 0.20 and 0.60 percent glutaraldehyde for 24 h then incubated, along with an untreated control group, in saline for up to 28 days at 37 °C. Both the equilibrium compressive and tensile moduli increased nearly twofold in treated samples compared to day 0 control, and remained at that level from day 1 to 28; the equilibrium friction coefficient against glass rose nearly twofold immediately after fixation (day 1) but returned to control values after day 7. Live explants co-cultured with fixed explants showed no quantitative difference in cell viability over 28 days. In general, no significant differences were observed between 0.20 and 0.60 percent groups, so 0.20 percent was deemed sufficient for complete fixation. In the second experiment, cartilage-on-cartilage frictional measurements were performed under a migrating contact configuration. In the treated group, one explant was fixed using 0.20 percent glutaraldehyde while the apposing explant was left untreated; in the control group both explants were left untreated. From day 1 to 28, the treated group exhibited either no significant difference or slightly lower friction coefficient than the untreated group. These results suggest that a properly titrated glutaraldehyde treatment can reproduce the desired functional properties of native articular cartilage and maintain these properties for at least 28 days at body temperature.
doi:10.1016/j.jbiomech.2013.11.043
PMCID: PMC3913559  PMID: 24332617
Cartilage; Osteoarthritis; Friction; Wear; Damage
8.  Mechanical analysis of arterial plaques in native geometry with OCT wall motion analysis 
Journal of biomechanics  2013;47(3):755-758.
The mechanical behavior of an atherosclerotic plaque may encode information about the type, composition, and vulnerability to rupture. Human arterial segments with varying plaque burden were analyzed ex vivo with optical coherence tomography (OCT) to determine plaque type and to determine compliance during pulsatile inflation in their native geometry. Calcifications and lipid filled plaques showed markedly different compliance when analyzed with OCT wall motion analysis. There was also a trend towards increased circumferential variation in arterial compliance with increasing plaque burden.
doi:10.1016/j.jbiomech.2013.11.010
PMCID: PMC3914757  PMID: 24388166
Atherosclerotic plaque; Compliance; Optical coherence tomography
9.  A novel in vitro loading system to produce supraphysiologic oscillatory fluid shear stress 
Journal of biomechanics  2013;47(2):518-525.
A multi-well fluid loading (MFL) system was developed to deliver oscillatory subphysiologic to supraphysiologic fluid shear stresses to cell monolayers in vitro using standard multi-well culture plates. Computational fluid dynamics modeling with fluid-structure interactions was used to quantify the squeeze film fluid flow between an axially displaced piston and the well plate surface. Adjusting the cone angle of the piston base modulated the fluid pressure, velocity, and shear stress magnitudes. Modeling results showed that there was near uniform fluid shear stress across the well with a linear drop in pressure across the radius of the well. Using the MFL system, RAW 264.7 osteoclastic cells were exposed to oscillatory fluid shear stresses of 0, 0.5, 1.5, 4, 6, and 17 Pa. Cells were loaded 1 h per day at 1 Hz for two days. Compared to sub-physiologic and physiologic levels, supraphysiologic oscillatory fluid shear induced upregulation of osteoclastic activity as measured by tartrate-resistant acid phosphatase activity and formation of mineral resorption pits. Cell number remained constant across all treatment groups.
doi:10.1016/j.jbiomech.2013.10.036
PMCID: PMC3901248  PMID: 24275439
Fluid shear stress; Osteoclast; Mechanoregulation; Supraphysiologic fluid shear stress
10.  Experimental and finite element analysis of strains induced by axial tibial compression in young-adult and old female C57Bl/6 mice 
Journal of biomechanics  2013;47(2):451-457.
Axial compression of the mouse tibia is used to study strain-adaptive bone (re)modeling. In some studies, comparisons between mice of different ages are of interest. We characterized the tibial deformation and force–strain relationships in female C57Bl/6 mice at 5-, 12- and 22-months age. A three-gauge experimental method was used to determine the strain distribution at the mid-diaphysis, while specimen-specific finite element analysis was used to examine strain distribution along the tibial length. The peak strains in the tibial mid-diaphyseal cross-section are compressive and occur at the postero-lateral apex. The magnitudes of these peak compressive strains are 1.5 to 2 times those on the opposite, antero-medial face (a site often used for strain gauge placement). For example, −10 N force applied to a 5-months old mouse engenders a peak compressive strain of −2800 με and a tensile strain on the antero-medial face of +1450 με. The orientation of the neutral axis at the mid-diaphysis did not differ with age (p=0.46), indicating a similar deformation mode in young and old tibiae. On the other hand, from 5- to 22-months there is a 25% reduction in cortical thickness and moment of inertia (p < 0.05), resulting in significantly greater tibial strain magnitudes in older mice for equivalent applied force (p < 0.05). We conclude that comparisons of tibial loading responses in young-adult and old C57Bl/6 tibiae are facilitated by similar deformation pattern across ages, but that modest adjustment of force levels is required to engender matching peak strains.
doi:10.1016/j.jbiomech.2013.10.052
PMCID: PMC3902696  PMID: 24268312
Bone adaptation; Tibial compression; Aging; In vivo loading; Mouse tibia
11.  Impaired Varus-Valgus Proprioception and Neuromuscular Stabilization in Medial Knee Osteoarthritis 
Journal of biomechanics  2013;47(2):360-366.
Impaired proprioception and poor muscular stabilization in the frontal plane may lead to knee instability during functional activities, a common complaint in persons with knee osteoarthritis (KOA). Understanding these frontal plane neuromechanical properties in KOA will help elucidate the factors contributing to knee instability and aid in the development of targeted intervention strategies. The study objectives were to compare knee varus-valgus proprioception, isometric muscle strength, and active muscular contribution to stability between persons with medial KOA and healthy controls. We evaluated knee frontal plane neuromechanical parameters in 14 participants with medial KOA and 14 age- and gender-matched controls, using a joint driving device (JDD) with a customized motor and a 6-axis force sensor. Analysis of covariance with BMI as a covariate was used to test the differences in varus-valgus neuromechanical parameters between these two groups. The KOA group had impaired varus proprioception acuity (1.08 ± 0.59° vs. 0.69 ± 0.49°, p < 0.05), decreased normalized varus muscle strength (1.31 ± 0.75% vs. 1.79 ± 0.84% body weight, p < 0.05), a trend toward decreased valgus strength (1.29 ± 0.67% vs. 1.88 ± 0.99%, p = 0.054), and impaired ability to actively stabilize the knee in the frontal plane during external perturbation (4.67 ± 2.86 vs. 8.26 ± 5.95 Nm/degree, p < 0.05). The knee frontal plane sensorimotor control system is compromised in persons with medial KOA. Our findings suggest varus-valgus control deficits in both the afferent input (proprioceptive acuity) and muscular effectors (muscle strength and capacity to stabilize the joint).
doi:10.1016/j.jbiomech.2013.11.024
PMCID: PMC3929588  PMID: 24321442
Knee osteoarthritis; Proprioception; Instability; Varus-valgus motion
12.  Dynamic Contact Stress Patterns on the Tibial Plateaus during Simulated Gait: A Novel Application of Normalized Cross Correlation 
Journal of biomechanics  2013;47(2):568-574.
The spatial distribution and pattern of local contact stresses within the knee joint during activities of daily living have not been fully investigated. The objective of this study was to determine if common contact stress patterns exist on the tibial plateaus of human knees during simulated gait. To test this hypothesis, we developed a novel normalized cross-correlation (NCC) algorithm and applied it to the contact stresses on the tibial plateaus of twelve human cadaveric knees subjected to multi-directional loads mimicking gait. The contact stress profiles at different locations on the tibial plateaus were compared, where regions with similar contact stress patterns were identified across specimens. Three consistent regional patterns were found, among them two most prominent contact stress patterns were shared by 9 to 12 of all the knees and the third pattern was shared by 6 to 8 knees. The first pattern was located at the posterior aspect of the medial tibial plateau and had a single peak stress that occurred during the early stance phase. The second pattern was located at the central-posterior aspects of the lateral plateau and consisted of two peak stresses coincident with the timing of peak axial force at early and late stance. The third pattern was found on the anterior aspect of cartilage-to-cartilage contact region on the medial plateau consisted of double peak stresses. The differences in the location and profile of the contact stress patterns suggest that the medial and lateral menisci function to carry load at different points in the gait cycle: with the posterior aspect of the medial meniscus consistently distributing load only during the early phase of stance, and the posterior aspect of the lateral meniscus consistently distributing load during both the early and late phases of stance. This novel approach can help identify abnormalities in knee contact mechanics and provide a better understanding of the mechanical pathways leading to post-traumatic osteoarthritis.
doi:10.1016/j.jbiomech.2013.11.042
PMCID: PMC3936672  PMID: 24342497
Contact mechanics; cadaveric model; meniscus function; knee simulator; pressure sensor
13.  Higher critical plaque wall stress in patients who died of coronary artery disease compared with those who died of other causes: a 3D FSI study based on ex vivo MRI of coronary plaques 
Journal of biomechanics  2013;47(2):432-437.
Mechanical forces play an important role in the rupture of vulnerable plaques. This process is often associated with cardiovascular syndromes, such as heart attack and stroke. In this study, magnetic resonance imaging (MRI)-based models were used to investigate the association between plaque wall stress (PWS) and coronary artery disease (CAD).
Ex vivo MRI data of coronary plaques from 12 patients were used to construct 12 three-dimensional (3D) fluid-structure interaction (FSI) computational models. Six of the patients had died from CAD and six had died from non-CAD causes. PWS was assessed using all nodal points on the lumen surface of each plaque. The maximum PWS from all possible vulnerable sites of each plaque was defined as the 3D critical plaque wall stress (CPWS).
Mean 3D CPWS in the CAD group was 94.3% higher than that in the non-CAD group (265.6 vs. 136.7 kPa, P=0.0029). There was no statistically significant difference in global maximum plaque wall stress (GMPWS) between the two groups (P=0.347). There was also no statistically significant difference in plaque burden between the CAD group (84.4 ± 5%) and the non-CAD group (82.0 ± 8%, P=0.552). The results indicate that plaques from patients who died from CAD were associated with higher CPWS compared with those from patients who died from non-CAD causes. With further validation, analysis of CPWS may prove to be an important component in assessment of plaque vulnerability.
doi:10.1016/j.jbiomech.2013.11.007
PMCID: PMC3988129  PMID: 24345380
coronary artery disease; fluid structure interactions; magnetic resonance imaging; vulnerable plaque; stress
14.  Straightening of curved pattern of collagen fibers under load controls aortic valve shape 
Journal of biomechanics  2013;47(2):341-346.
The network of collagen fibers in the aortic valve leaflet is believed to play an important role in the strength and durability of the valve. However, in addition to its stress-bearing role, such a fiber network has the potential to produce functionally important shape changes in the closed valve under pressure load. We measured the average pattern of the collagen network in porcine aortic valve leaflets after staining for collagen. We then used finite element simulation to explore how this collagen pattern influences the shape of the closed valve. We observed a curved or bent pattern, with collagen fibers angled downward from the commissures toward the center of the leaflet to form a pattern that is concave toward the leaflet free edge. Simulations showed that these curved fiber trajectories straighten under pressure load, leading to functionally important changes in closed valve shape. Relative to a pattern of straight collagen fibers running parallel to the leaflet free edge, the concave pattern of curved fibers produces a closed valve with a 40% increase in central leaflet coaptation height and with decreased leaflet billow, resulting in a more physiological closed valve shape. Furthermore, simulations show that these changes in loaded leaflet shape reflect changes in leaflet curvature due to modulation of in-plane membrane stress resulting from straightening of the curved fibers. This effect appears to play an important role in normal valve function and may have important implications for the design of prosthetic and tissue engineered replacement valves.
doi:10.1016/j.jbiomech.2013.11.032
PMCID: PMC4002177  PMID: 24315286
Finite element model; Aortic valve; Collagen pattern
15.  Reliability of assessing trunk motor control using position and force tracking and stabilization tasks 
Journal of biomechanics  2013;47(1):44-49.
System-based methods have been applied to assess trunk motor control in people with and without back pain, although the reliability of these methods has yet to be established. Therefore, the goal of this study was to quantify within- and between-day reliability of assessing trunk motor control using systems-based methods involving position and force tracking and stabilization tasks. Ten healthy subjects performed six tasks, involving tracking and stabilizing of trunk angular position in the sagittal plane, and trunk flexion and extension force. Tracking tasks involved following a one-dimensional, time-varying input signal displayed on a screen by changing trunk position (position tracking) or trunk force (force tracking). Stabilization tasks involved maintaining a constant trunk position (position stabilization) or constant trunk force (force stabilization) while a sagittal plane disturbance input was applied to the pelvis using a robotic platform. Time and frequency domain assessments of error (root mean square and H2 norm, respectively) were computed for each task on two separate days. Intra-class correlation coefficients (ICC) for error and coefficients of multiple correlations (CMC) for frequency response curves were used to quantify reliability of each task. Reliability for all tasks was excellent (between-day ICC ≥ 0.8 and CMC > 0.75, within-day CMC > 0.85). Therefore, position and force control tasks used for assessing trunk motor control can be deemed reliable.
doi:10.1016/j.jbiomech.2013.10.018
PMCID: PMC3898167  PMID: 24262851
Trunk Position Control; Trunk Force Control; H2 Norm; Disturbance Rejection; Systems Approach
16.  An analytical model to predict interstitial lubrication of cartilage in migrating contact areas 
Journal of biomechanics  2013;47(1):148-153.
For nearly a century, articular cartilage has been known for its exceptional tribological properties. For nearly as long, there have been research efforts to elucidate the responsible mechanisms for application toward biomimetic bearing applications. It is now widely accepted that interstitial fluid pressurization is the primary mechanism responsible for the unusual lubrication and load bearing properties of cartilage. Although the biomechanics community has developed elegant mathematical theories describing the coupling of solid and fluid (biphasic) mechanics and its role in interstitial lubrication, quantitative gaps in our understanding of cartilage tribology have inhibited our ability to predict how tribological conditions and material properties impact tissue function. This paper presents an analytical model of the interstitial lubrication of biphasic materials under migrating contact conditions. Although finite element and other numerical models of cartilage mechanics exist, they typically neglect the important role of the collagen network and are limited to a specific set of input conditions, which limits general applicability. The simplified approach taken in this work aims to capture the broader underlying physics as a starting point for further model development. In agreement with existing literature, the model indicates that a large Peclet number, Pe, is necessary for effective interstitial lubrication. It also predicts that the tensile modulus must be large relative to the compressive modulus. This explains why hydrogels and other biphasic materials do not provide significant interstitial pressure under high Pe conditions. The model quantitatively agrees with in-situ measurements of interstitial load support and the results have interesting implications for tissue engineering and osteoarthritis problems. This paper suggests that a low tensile modulus (from chondromalacia or local collagen rupture after impact, for example) may disrupt interstitial pressurization, increase shear stresses, and activate a condition of progressive surface damage as a potential precursor of osteoarthritis.
doi:10.1016/j.jbiomech.2013.09.020
PMCID: PMC3889488  PMID: 24275436
cartilage; contact mechanics; biphasic; interstitial lubrication; osteoarthritis
17.  The Effects of Femoral Graft Placement on Cartilage Thickness after Anterior Cruciate Ligament Reconstruction 
Journal of biomechanics  2013;47(1):10.1016/j.jbiomech.2013.10.003.
Altered joint motion has been thought to be a contributing factor in the long-term development of osteoarthritis after ACL reconstruction. While many studies have quantified knee kinematics after ACL injury and reconstruction, there is limited in vivo data characterizing the effects of altered knee motion on cartilage thickness distributions. Thus, the objective of this study was to compare cartilage thickness distributions in two groups of patients with ACL reconstruction: one group in which subjects received a non-anatomic reconstruction that resulted in abnormal joint motion and another group in which subjects received an anatomically placed graft that more closely restored normal knee motion. Ten patients with anatomic graft placement (mean follow-up: 20 months) and 12 patients with non-anatomic graft placement (mean follow-up: 18 months) were scanned using high-resolution MR imaging. These images were used to generate 3D mesh models of both knees of each patient. The operative and contralateral knee models were registered to each other and a grid sampling system was used to make site-specific comparisons of cartilage thickness. Patients in the non-anatomic graft placement group demonstrated a significant decrease in cartilage thickness along the medial intercondylar notch in the operative knee relative to the intact knee (8%). In the anatomic graft placement group, no significant changes were observed. These findings suggest that restoring normal knee motion after ACL injury may help to slow the progression of degeneration. Therefore, graft placement may have important implications on the development of osteoarthritis after ACL reconstruction.
doi:10.1016/j.jbiomech.2013.10.003
PMCID: PMC3874409  PMID: 24210473
Kinematics; MRI; imaging; osteoarthritis; mechanics; ACL
18.  Enhancement of neuromuscular dynamics and strength behavior using extremely low magnitude mechanical signals in mice 
Journal of biomechanics  2013;47(1):10.1016/j.jbiomech.2013.09.024.
Exercise in general, and mechanical signals in particular, help ameliorate the neuromuscular symptoms of aging and possibly other neurodegenerative disorders by enhancing muscle function. To better understand the salutary mechanisms of such physical stimuli, we evaluated the potential for low intensity mechanical signals to promote enhanced muscle dynamics. The effects of daily brief periods of low intensity vibration (LIV) on neuromuscular functions and behavioral correlates were assessed in mice. Physiological analysis revealed that LIV increased isometric force production in semitendinosus skeletal muscle. This effect was evident in both young and old mice. Isometric force recordings also showed that LIV reduced the fatiguing effects of intensive synaptic muscle stimulation. Furthermore, LIV increased evoked neurotransmitter release at neuromuscular synapses but had no effect on spontaneous end plate potential amplitude or frequency. In behavioral studies, LIV increased mouse grip strength and potentiated initial motor activity in a novel environment. These results provide evidence for the efficacy of LIV in producing changes in the neuromuscular system that translate into performance gains at a behavioral scale.
doi:10.1016/j.jbiomech.2013.09.024
PMCID: PMC3881264  PMID: 24157062
Whole body vibration; neuromuscular; quantal content; muscle strength; mechanical signals
19.  Head Impact Exposure in Male and Female Collegiate Ice Hockey Players 
Journal of biomechanics  2013;47(1):109-114.
The purpose of this study was to quantify head impact exposure (frequency, location and magnitude of head impacts) for individual male and female collegiate ice hockey players and to investigate differences in exposure by sex, player position, session type, and team. Ninety-nine (41 male, 58 female) players were enrolled and 37,411 impacts were recorded over three seasons. Frequency of impacts varied significantly by sex (males: 287 per season, females: 170, p<0.001) and helmet impact location (p<0.001), but not by player position (p=0.088). Head impact frequency also varied by session type; both male and female players sustained more impacts in games than in practices (p<0.001), however the magnitude of impacts did not differ between session types. There was no difference in 95th percentile peak linear acceleration between sexes (males: 41.6g, females: 40.8g), but 95th percentile peak rotational acceleration and HITsp (a composite severity measure) were greater for males than females (4424, 3409 rad/s2, and 25.6, 22.3, respectively). Impacts to the back of the helmet resulted in the greatest 95th percentile peak linear accelerations for males (45.2g) and females (50.4g), while impacts to the side and back of the head were associated with the greatest 95th percentile peak rotational accelerations (males: 4719, 4256 rad/sec2, females: 3567, 3784 rad/sec2 respectively). It has been proposed that reducing an individual’s head impact exposure is a practical approach for reducing the risk of brain injuries. Strategies to decrease an individual athlete’s exposure need to be sport and gender specific, with considerations for team and session type.
doi:10.1016/j.jbiomech.2013.10.004
PMCID: PMC3902856  PMID: 24210478
impact biomechanics; hockey; gender; concussion
20.  Compressive and tensile mechanical properties of the porcine nasal septum 
Journal of biomechanics  2013;47(1):154-161.
The expanding nasal septal cartilage is believed to create a force that powers midfacial growth. In addition, the nasal septum is postulated to act as a mechanical strut that prevents the structural collapse of the face under masticatory loads. Both roles imply that the septum is subject to complex biomechanical loads during growth and mastication. The purpose of this study was to measure the mechanical properties of the nasal septum to determine (1) whether the cartilage is mechanically capable of playing an active role in midfacial growth and in maintaining facial structural integrity and (2) if regional variation in mechanical properties is present that could support any of the postulated loading regimens. Porcine septal samples were loaded along the horizontal or vertical axes in compression and tension, using different loading rates that approximate the in vivo situation. Samples were loaded in random order to predefined strain points (2–10%) and strain was held for 30 or 120 seconds while relaxation stress was measured. Subsequently, samples were loaded until failure. Stiffness, relaxation stress and ultimate stress and strain were recorded. Results showed that the septum was stiffer, stronger and displayed a greater drop in relaxation stress in compression compared to tension. Under compression, the septum displayed non-linear behavior with greater stiffness and stress relaxation under faster loading rates and higher strain levels. Under tension, stiffness was not affected by strain level. Although regional variation was present, it did not strongly support any of the suggested loading patterns. Overall, results suggest that the septum might be mechanically capable of playing an active role in midfacial growth as evidenced by increased compressive residual stress with decreased loading rates. However, the low stiffness of the septum compared to surrounding bone does not support a strut role. The relatively low stiffness combined with high stress relaxation under fast loading rates suggests that the nasal septum is a stress dampener, helping to absorb and dissipate loads generated during mastication.
doi:10.1016/j.jbiomech.2013.09.026
PMCID: PMC3910320  PMID: 24268797
21.  Evaluation of automated statistical shape model based knee kinematics from biplane fluoroscopy 
Journal of biomechanics  2013;47(1):122-129.
State-of-the-art fluoroscopic knee kinematic analysis methods require the patient-specific bone shapes segmented from CT or MRI. Substituting the patient-specific bone shapes with personalizable models, such as statistical shape models (SSM), could eliminate the CT/MRI acquisitions, and thereby decrease costs and radiation dose (when eliminating CT). SSM based kinematics, however, have not yet been evaluated on clinically relevant joint motion parameters.
Therefore, in this work the applicability of SSM-s for computing knee kinematics from biplane fluoroscopic sequences was explored. Kinematic precision with an edge based automated bone tracking method using SSM-s was evaluated on 6 cadaver and 10 in-vivo fluoroscopic sequences. The SSMs of the femur and the tibia-fibula were created using 61 training datasets. Kinematic precision was determined for medial-lateral tibial shift, anterior-posterior tibial drawer, joint distraction-contraction, flexion, tibial rotation and adduction. The relationship between kinematic precision and bone shape accuracy was also investigated.
The SSM based kinematics resulted in sub-millimeter (0.48–0.81 mm) and approximately one degree (0.69–0.99°) median precision on the cadaveric knees compared to bone-marker-based kinematics. The precision on the in-vivo datasets was comparable to the cadaveric sequences when evaluated with a semi-automatic reference method. These results are promising, though further work is necessary to reach the accuracy of CT-based kinematics. We also demonstrated that a better shape reconstruction accuracy does not automatically imply a better kinematic precision. This result suggests that the ability of accurately fitting the edges in the fluoroscopic sequences has a larger role in determining the kinematic precision than the overall 3D shape accuracy.
doi:10.1016/j.jbiomech.2013.09.022
PMCID: PMC4033785  PMID: 24207131
Ttracking; SSM; Femur; Tibia; 2D/3D reconstruction
22.  Embryonic Mechanical and Soluble Cues Regulate Tendon Progenitor Cell Gene Expression as a Function of Developmental Stage and Anatomical Origin 
Journal of biomechanics  2013;47(1):214-222.
Stem cell-based engineering strategies for tendons have yet to yield a normal functional tissue, due in part to a need for tenogenic factors. Additionally, the ability to evaluate differentiation has been challenged by a lack of markers for differentiation. We propose to inform tendon regeneration with developmental cues involved in normal tissue formation and with phenotypic markers that are characteristic of differentiating tendon progenitor cells (TPCs). Mechanical forces, fibroblast growth factor (FGF)-4 and transforming growth factor (TGF)-β2 are implicated in embryonic tendon development, yet the isolated effects of these factors on differentiating TPCs are unknown. Additionally, developmental mechanisms vary between limb and axial tendons, suggesting the respective cell types are programmed to respond uniquely to exogenous factors. To characterize developmental cues and benchmarks for differentiation toward limb vs. axial phenotypes, we dynamically loaded and treated TPCs with growth factors and assessed gene expression profiles as a function of developmental stage and anatomical origin. Based on scleraxis expression, TGFβ2 was tenogenic for TPCs at all stages, while loading was for late-stage cells only, and FGF4 had no effect despite regulation of other genes. When factors were combined, TGF 2 continued to be tenogenic, while FGF4 appeared anti-tenogenic. Various treatments elicited distinct responses by axial vs. limb TPCs of specific stages. These results identified tenogenic factors, suggest tendon engineering strategies should be customized for tissues by anatomical origin, and provide stage-specific gene expression profiles of limb and axial TPCs as benchmarks with which to monitor tenogenic differentiation of stem cells.
doi:10.1016/j.jbiomech.2013.09.018
PMCID: PMC4157071  PMID: 24231248
Tendon; Differentiation; Embryonic; Mechanical loading; Growth factor; Development
23.  CHANGES IN THE INTERFACIAL SHEAR RESISTANCE OF DISC ANNULUS FIBROSUS FROM GENIPIN CROSSLINKING 
Journal of biomechanics  2013;47(1):10.1016/j.jbiomech.2013.10.019.
Crosslinking soft tissue has become more common in tissue engineering applications, and recent studies have demonstrated that soft tissue mechanical behavior can be directly altered through crosslinking. Using a recently reported test method that shears adjacent disc lamella, the effect of genipin crosslinking on interlamellar shear resistance was studied using in vitro bovine disc annulus.
Specimens of adjacent lamella were dissected from 4 discs taken from 3 fresh frozen bovine tails. These specimens were paired and soaked in either 50mM EPPS Phosphate (ph9) with 20mM genipin at 37°C for 4 hours or in 50mM EPPS Phosphate (ph9) of which twelve specimens (6 per treatment) were successfully tested and analyzed.
Crosslinked specimens were noted to have significantly higher yield force per width (59%), peak force per width (70%), and resilience (69%) compared to sham treated controls, supporting the hypothesis that genipin crosslinking increases the resistance to interlamellar shear of the annulus interface. Additionally, a possible dependency may exist between the interlamellar shear strength and neighboring lamella because of the bridging fiber network previously described by other investigators.
doi:10.1016/j.jbiomech.2013.10.019
PMCID: PMC3879687  PMID: 24290138
disc; lamella; interfacial shear; lamellar shear; crosslinking; genipin
24.  [No title available] 
PMCID: PMC4295818  PMID: 25443884
25.  Mechanical stiffness as an improved single-cell indicator of osteoblastic human mesenchymal stem cell differentiation 
Journal of biomechanics  2013;47(9):2197-2204.
Although it has been established that cellular stiffness can change as a stem cell differentiates, the precise relationship between cell mechanics and other phenotypic properties remains unclear. Inherent cell heterogeneity and asynchronous differentiation complicate population analysis; therefore, single-cell analysis was employed to determine how changes in cell stiffness correlate with changes in molecular biomarkers during differentiation. Design of a custom gridded tissue culture dish facilitated single-cell comparisons between cell mechanics and other differentiation biomarkers by enabling sequential measurement of cell mechanics and protein biomarker expression at the single cell level. The Young’s modulus of mesenchymal stem cells was shown not only to decrease during chemically-induced osteoblast differentiation, but also to correlate more closely with the day of differentiation than did the relative expression of the traditional osteoblast differentiation markers, bone sialoprotein and osteocalcin. Therefore, cell stiffness, a measurable property of individual cells, may serve as an improved indicator of single-cell osteoblast differentiation compared to traditional biological markers. Revelation of additional osteoblast differentiation indicators, such as cell stiffness, can improve identification and collection of starting cell populations, with applications to mesenchymal stem cell therapies and stem cell-based tissue engineering.
doi:10.1016/j.jbiomech.2013.11.017
PMCID: PMC4024369  PMID: 24296276
MSC; Atomic force microscopy; Bone sialoprotein; Cell stiffness; Osteoblast differentiation; Osteocalcin

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