Journal of Biomechanics - Articles in Press

Micro CT-based multiscale elasticity of double-porous (pre-cracked) hydroxyapatite granules for regenerative medicine - Corrected Proof

2012-02-01

Abstract: Hundred micrometers-sized porous hydroxyapatite globules have proved as a successful tissue engineering strategy for bone defects in vivo, as was shown in studies on human mandibles. These granules need to provide enough porous space for bone ingrowth, while maintaining sufficient mechanical competence (stiffness and strength) in this highly load-bearing organ. This double challenge motivates us to scrutinize more deeply the micro- and nanomechanical characteristics of such globules, as to identify possible optimization routes. Therefore, we imaged such a (pre-cracked) granule in a microCT scanner, transformed the attenuation coefficients into voxel-specific nanoporosities, from which we determined, via polycrystal micromechanics, voxel-specific (heterogeneous) elastic properties. The importance of the latter and of the presence of one to several hundred micrometers-sized cracks for realistically estimating the load-carrying behavior of the globule under a typical two-point compressive loading (as in a “splitting” test) is shown through results of large-scale Finite Element analyses, in comparison to analytical results for a sphere loaded at its poles: Use of homogeneous instead of heterogeneous elastic properties would overestimate the structure's stiffness by 5% (when employing a micromechanics-based process as to attain homogeneous properties)—the cracks, in comparison, weaken the structure by one to two orders of magnitudes.

Gait asymmetry: Composite scores for mechanical analyses of sprint running - Corrected Proof

T.A. Exell, M.J.R. Gittoes, G. Irwin, D.G. Kerwin — 2012-02-01

Abstract: Gait asymmetry analyses are beneficial from clinical, coaching and technology perspectives. Quantifying overall athlete asymmetry would be useful in allowing comparisons between participants, or between asymmetry and other factors, such as sprint running performance. The aim of this study was to develop composite kinematic and kinetic asymmetry scores to quantify athlete asymmetry during maximal speed sprint running. Eight male sprint trained athletes (age 22±5 years, mass 74.0±8.7kg and stature 1.79±0.07m) participated in this study. Synchronised sagittal plane kinematic and kinetic data were collected via a CODA motion analysis system, synchronised to two Kistler force plates. Bilateral, lower limb data were collected during the maximal velocity phase of sprint running (velocity=9.05±0.37ms−1). Kinematic and kinetic composite asymmetry scores were developed using the previously established symmetry angle for discrete variables associated with successful sprint performance and comparisons of continuous joint power data. Unlike previous studies quantifying gait asymmetry, the scores incorporated intra-limb variability by excluding variables from the composite scores that did not display significantly larger (p<0.05) asymmetry than intra-limb variability. The variables that contributed to the composite scores and the magnitude of asymmetry observed for each measure varied on an individual participant basis. The new composite scores indicated the inter-participant differences that exist in asymmetry during sprint running and may serve to allow comparisons between overall athlete asymmetry with other important factors such as performance.

Fluid load support during localized indentation of cartilage with a spherical probe - Corrected Proof

E.D. Bonnevie, V.J. Baro, L. Wang, D.L. Burris — 2012-01-30

Abstract: Interstitial fluid pressurization, a consequence of a biphasic tissue structure, is essential to the load bearing and lubrication properties of articular cartilage. Focal tissue degradation may interfere with this protective mechanism, eventually leading to gross degeneration and osteoarthritis. Our long-term goal is to determine whether local contacts can be used as a means to probe local tissue integrity and functionality. In the present work, Hertzian rate-controlled microindentation was used as a model of the more complicated sliding system to directly determine the effects of contact radius and deformation rate on interstitial load support. During localized contact between a steel spherical probe and bovine articular cartilage, the equilibrium and non-equilibrium responses were well-fit by the Hertz model (R2>0.998) with a mean equilibrium contact modulus of 0.93MPa. The effective contact modulus and fluid load fraction were independent of indentation depth, contact radius, and normal force; both increased monotonically with indentation rate. At 21μm/s indentation rate, the cartilage was effectively stiffened by 6-fold with the fluid pressure supporting 85% of the contact force. The results motivated a simple analytical model that directly links the tribomechanical response (including fluid load support) and the Peclet number to measurable material properties and controllable experimental variables. This paper demonstrates that tribological contacts can be used to probe local functional properties. Such measurements can add important insights into the roles of focal tissue damage and impaired local functionality in the pathogenesis of osteoarthritis.

Comparison of different camera calibration approaches for underwater applications - Corrected Proof

2012-01-30

Abstract: The purpose of this study was to compare three camera calibration approaches applied to underwater applications: (1) static control points with nonlinear DLT; (2) moving wand with nonlinear camera model and bundle adjustment; (3) moving plate with nonlinear camera model. The DVideo kinematic analysis system was used for underwater data acquisition. The system consisted of two gen-locked Basler cameras working at 100Hz, with wide angle lenses that were enclosed in housings. The accuracy of the methods was compared in a dynamic rigid bar test (acquisition volume—4.5×1×1.5m3). The mean absolute errors were 6.19mm for the nonlinear DLT, 1.16mm for the wand calibration, 1.20mm for the 2D plate calibration using 8 control points and 0.73mm for the 2D plane calibration using 16 control points. The results of the wand and 2D plate camera calibration methods were less associated to the rigid body position in the working volume and provided better accuracy than the nonlinear DLT. Wand and 2D plate camera calibration methods presented similar and highly accurate results, being alternatives for underwater 3D motion analysis.

Calculating the axes of rotation for the subtalar and talocrural joints using 3D bone reconstructions - Corrected Proof

Parr W.C.H., Chatterjee H.J., Soligo C. — 2012-01-30

Abstract: Orientation of the subtalar joint axis dictates inversion and eversion movements of the foot and has been the focus of evolutionary and clinical studies for a number of years. Previous studies have measured the subtalar joint axis against the axis of the whole foot, the talocrural joint axis and, recently, the principal axes of the talus. The present study introduces a new method for estimating average joint axes from 3D reconstructions of bones and applies the method to the talus to calculate the subtalar and talocrural joint axes. The study also assesses the validity of the principal axes as a reference coordinate system against which to measure the subtalar joint axis. In order to define the angle of the subtalar joint axis relative to that of another axis in the talus, we suggest measuring the subtalar joint axis against the talocrural joint axis. We present corresponding 3D vector angles calculated from a modern human skeletal sample. This method is applicable to virtual 3D models acquired through surface-scanning of disarticulated ‘dry’ osteological samples, as well as to 3D models created from CT or MRI scans.

Direct comparison of measured and calculated total knee replacement force envelopes during walking in the presence of normal and abnormal gait patterns - Corrected Proof

Hannah J. Lundberg, Kharma C. Foucher, Thomas P. Andriacchi, Markus A. Wimmer — 2012-01-30

Abstract: Knee joint forces measured from instrumented implants provide important information for testing the validity of computational models that predict knee joint forces. The purpose of this study was to validate a parametric numerical model for predicting knee joint contact forces against measurements from four subjects with instrumented TKRs during the stance phase of gait. Model sensitivity to abnormal gait patterns was also investigated. The results demonstrated good agreement for three subjects with relatively normal gait patterns, where the difference between the mean measured and calculated forces ranged from 0.05 to 0.45 body weights, and the envelopes of measured and calculated forces (from three walking trials) overlapped. The fourth subject, who had a “quadriceps avoidance” external moment pattern, initially had little overlap between the measured and calculated force envelopes. When additional constraints were added, tailored to the subject’s gait pattern, the model predictions improved to complete force envelope overlap. Coefficient of multiple determination analysis indicated that the shape of the measured and calculated force waveforms were similar for all subjects (adjusted coefficient of multiple correlation values between 0.88 and 0.92). The parametric model was accurate in predicting both the magnitude and waveform of the contact force, and the accuracy of model predictions was affected by deviations from normal gait patterns. Equally important, the envelope of forces generated by the range of solutions substantially overlapped with the corresponding measured envelope from multiple gait trials for a given subject, suggesting that the variable strategic processes of in vivo force generation are covered by the solution range of this parametric model.

Investigation of whiplash injuries in the upper cervical spine using a detailed neck model - Corrected Proof

Jason B. Fice, Duane S. Cronin — 2012-01-30

Abstract: Whiplash injuries continue to have significant societal cost; however, the mechanism and location of whiplash injury is still under investigation. Recently, the upper cervical spine ligaments, particularly the alar ligament, have been identified as a potential whiplash injury location. In this study, a detailed and validated explicit finite element model of a 50th percentile male cervical spine in a seated posture was used to investigate upper cervical spine response and the potential for whiplash injury resulting from vehicle crash scenarios. This model was previously validated at the segment and whole spine levels for both kinematics and soft tissue strains in frontal and rear impact scenarios.The model predicted increasing upper cervical spine ligament strain with increasing impact severity. Considering all upper cervical spine ligaments, the distractions in the apical and alar ligaments were the largest relative to their failure strains, in agreement with the clinical findings. The model predicted the potential for injury to the apical ligament for 15.2g frontal or 11.7g rear impacts, and to the alar ligament for a 20.7g frontal or 14.4g rear impact based on the ligament distractions. Future studies should consider the effect of initial occupant position on ligament distraction.

Characterization of a hyper-viscoelastic phantom mimicking biological soft tissue using an abdominal pneumatic driver with magnetic resonance elastography (MRE) - Corrected Proof

2012-01-30

Abstract: The purpose of this study was to create a polymer phantom mimicking the mechanical properties of soft tissues using experimental tests and rheological models.Multifrequency Magnetic Resonance Elastography (MMRE) tests were performed on the present phantom with a pneumatic driver to characterize the viscoelastic (μ, η) properties using Voigt, Maxwell, Zener and Springpot models. To optimize the MMRE protocol, the driver behavior was analyzed with a vibrometer. Moreover, the hyperelastic properties of the phantom were determined using compressive tests and Mooney–Rivlin model.The range of frequency to be used with the round driver was found between 60Hz and 100Hz as it exhibits one type of vibration mode for the membrane. MRE analysis revealed an increase in the shear modulus with frequency reflecting the viscoelastic properties of the phantom showing similar characteristic of soft tissues. Rheological results demonstrated that Springpot model better revealed the viscoelastic properties (μ=3.45kPa, η=6.17Pas) of the phantom and the Mooney–Rivlin coefficients were C10=1.09.10−2MPa and C01=−8.96.10−3MPa corresponding to μ=3.95kPa.These studies suggest that the phantom, mimicking soft tissue, could be used for preliminary MRE tests to identify the optimal parameters necessary for in vivo investigations. Further developments of the phantom may allow clinicians to more accurately mimic healthy and pathological soft tissues using MRE.

Electromechanical wave imaging for noninvasive mapping of the 3D electrical activation sequence in canines and humans in vivo - Corrected Proof

Elisa E. Konofagou, Jean Provost — 2012-01-27

Abstract: 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.

Semi-automated mitral valve morphometry and computational stress analysis using 3D ultrasound - Corrected Proof

2012-01-27

Abstract: In vivo human mitral valves (MV) were imaged using real-time 3D transesophageal echocardiography (rt-3DTEE), and volumetric images of the MV at mid-systole were analyzed by user-initialized segmentation and 3D deformable modeling with continuous medial representation, a compact representation of shape. The resulting MV models were loaded with physiologic pressures using finite element analysis (FEA). We present the regional leaflet stress distributions predicted in normal and diseased (regurgitant) MVs. Rt-3DTEE, semi-automated leaflet segmentation, 3D deformable modeling, and FEA modeling of the in vivo human MV is tenable and useful for evaluation of MV pathology.

Measurement of strut chordal forces of the tricuspid valve using miniature C ring transducers - Corrected Proof

Lauren G. Troxler, Erin M. Spinner, Ajit P. Yoganathan — 2012-01-27

Abstract: Tricuspid valve (TV) leaflets, papillary muscles (PM), and tendinous chords must work together to ensure proper coaptation. Alterations in valvular mechanics, including chordal forces, may lead to improper coaptation resulting in tricuspid regurgitation. Little is known about TV mechanics as right-sided heart diseases have been overlooked. We sought to fill this gap by understanding the role of TV strut chords with the objective to understand how strut chordal force varies depending on papillary muscle (PM) origin and leaflet attachment in the normal state. Additionally we investigated how these forces are altered with abnormal geometry. Porcine TVs (n=18) were studied in a right-heart simulator capable of reproducing physiological and pathological conditions. Miniature force transducers were placed on strut chords to measure forces throughout the cardiac cycle. In the normal state, chordal force depended upon PM attachment in which chords branching from the septal PM (SPM) carried significantly less force compared to those branching from the anterior PM (APM) (p≤0.05). Annular dilatation resulted in significant increase in chordal force (p≤0.05) on all strut chords. Severe PM displacement led to increased chordal force in chords attaching the APM to the posterior leaflet as well as chords attaching the PPM to the septal leaflet. Elevated chordal force due to isolated annular dilatation was further increased only with addition of apical displacement of the APM. These results provide initial knowledge of TV chordal force mechanics and may be applied to future studies on TV repair techniques.

Modeling and experimentation of bone drilling forces - Corrected Proof

JuEun Lee, B. Arda Gozen, O. Burak Ozdoganlar — 2012-01-27

Abstract: Prediction and control of bone drilling forces are critical to the success of many orthopaedic operations. Uncontrolled and large forces can cause drill-bit breakage, drill breakthrough, excessive heat generation, and mechanical damage to the bone. This paper presents a mechanistic model for prediction of thrust forces and torques experienced during bone drilling. The model incorporates the radially varying drill-bit geometry and cutting conditions analytically, while capturing the material and friction properties empirically through a specific energy formulation. The forces from the chisel edge are modeled by considering the indentation process that occurs in the vicinity of the drill-bit axis. A procedure is outlined to calibrate the specific energies, where only a small number of calibration experiments are required for a wide range of drilling conditions and drill-bit geometry. The calibration parameters for the cortical portions of bovine tibia are identified through drilling tests. Subsequently, a series of validation tests are conducted under different feed rates and spindle speeds. The thrust forces and torques were observed to vary considerably between bones from different animals. The forces from the model were seen to match well with those from the experimentation within the inherent variations from the bone characteristics. The model can be used to select favorable drilling conditions, to assist in robotic surgeries, and to design optimal orthopaedic drill bits.

Solute transport across a contact interface in deformable porous media - Corrected Proof

Gerard A. G.A. Ateshian, Steve Maas, Jeffrey A. J.A. Weiss — 2012-01-27

Abstract: A finite element formulation of neutral solute transport across a contact interface between deformable porous media is implemented and validated against analytical solutions. By reducing the integral statements of external virtual work on the two contacting surfaces into a single contact integral, the algorithm automatically enforces continuity of solute molar flux across the contact interface, whereas continuity of the effective solute concentration (a measure of the solute mechano-chemical potential) is achieved using a penalty method. This novel formulation facilitates the analysis of problems in biomechanics where the transport of metabolites across contact interfaces of deformable tissues may be of interest. This contact algorithm is the first to address solute transport across deformable interfaces, and is made available in the public domain, open-source finite element code FEBio (http://www.febio.org).

Constitutive model for brain tissue under finite compression - Corrected Proof

Kaveh Laksari, Mehdi Shafieian, Kurosh Darvish — 2012-01-27

Abstract: While advances in computational models of mechanical phenomena have made it possible to simulate dynamically complex problems in biomechanics, accurate material models for soft tissues, particularly brain tissue, have proven to be very challenging. Most studies in the literature on material properties of brain tissue are performed in shear loading and very few tackle the behavior of brain in compression. In this study, a viscoelastic constitutive model of bovine brain tissue under finite step-and-hold uniaxial compression with 10s–1 ramp rate and 20s hold time has been developed. The assumption of quasi-linear viscoelasticity (QLV) was validated for strain levels of up to 35%. A generalized Rivlin model was used for the isochoric part of the deformation and it was shown that at least three terms (C10, C01 and C11) are needed to accurately capture the material behavior. Furthermore, for the volumetric deformation, a two parameter Ogden model was used and the extent of material incompressibility was studied. The hyperelastic material parameters were determined through extracting and fitting to two isochronous curves (0.06s and 14s) approximating the instantaneous and steady-state elastic responses. Viscoelastic relaxation was characterized at five decay rates (100, 10, 1, 0.1, 0s−1) and the results in compression and their extrapolation to tension were compared against previous models.

The discrete nature of trabecular bone microarchitecture affects implant stability - Corrected Proof

Andreas J. Wirth, Ralph Müller, G. Harry van Lenthe — 2012-01-27

Abstract: Small endosseous implants, such as screws, are important components of modern orthopedics and dentistry. Hence they have to reliably fulfill a variety of requirements, which makes the development of such implants challenging. Finite element analysis is a widely used computational tool used to analyze and optimize implant stability in bone. For these purposes, bone is generally modeled as a continuum material. However, bone failure and bone adaptation processes are occurring at the discrete level of individual trabeculae; hence the assessment of stresses and strains at this level is relevant. Therefore, the aim of the present study was to investigate how peri-implant strain distribution and load transfer between implant and bone are affected by the continuum assumption. We performed a computational study in which cancellous screws were inserted in continuum and discrete models of trabecular bone; axial loading was simulated. We found strong differences in bone-implant stiffness between the discrete and continuum bone model. They depended on bone density and applied boundary conditions. Furthermore, load transfer from the screw to the surrounding bone differed strongly between the continuum and discrete models, especially for low-density bone. Based on our findings we conclude that continuum bone models are of limited use for finite element analysis of peri-implant mechanical loading in trabecular bone when a precise quantification of peri-implant stresses and strains is required. Therefore, for the assessment and improvement of trabecular bone implants, finite element models which accurately represent trabecular microarchitecture should be used.

A methodology to accurately quantify patellofemoral cartilage contact kinematics by combining 3D image shape registration and cine-PC MRI velocity data - Corrected Proof

Bhushan S. Borotikar, William H. Sipprell, Emily E. Wible, Frances T. Sheehan — 2012-01-27

Abstract: Patellofemoral osteoarthritis and its potential precursor patellofemoral pain syndrome (PFPS) are common, costly, and debilitating diseases. PFPS has been shown to be associated with altered patellofemoral joint mechanics; however, an actual variation in joint contact stresses has not been established due to challenges in accurately quantifying in vivo contact kinematics (area and location). This study developed and validated a method for tracking dynamic, in vivo cartilage contact kinematics by combining three magnetic resonance imaging (MRI) techniques, cine-phase contrast (CPC), multi-plane cine (MPC), and 3D high-resolution static imaging. CPC and MPC data were acquired from 12 healthy volunteers while they actively extended/flexed their knee within the MRI scanner. Since no gold standard exists for the quantification of in vivo dynamic cartilage contact kinematics, the accuracy of tracking a single point (patellar origin relative to the femur) represented the accuracy of tracking the kinematics of an entire surface. The accuracy was determined by the average absolute error between the PF kinematics derived through registration of MPC images to a static model and those derived through integration of the CPC velocity data. The accuracy ranged from 0.47mm to 0.77mm for the patella and femur and from 0.68mm to 0.86mm for the patellofemoral joint. For purely quantifying joint kinematics, CPC remains an analytically simpler and more accurate (accuracy <0.33mm) technique. However, for application requiring the tracking of an entire surface, such as quantifying cartilage contact kinematics, this combined imaging approach produces accurate results with minimal operator intervention.

Hand breakaway strength model—Effects of glove use and handle shapes on a person's hand strength to hold onto handles to prevent fall from elevation - Corrected Proof

Pilwon Hur, Binal Motawar, Na Jin Seo — 2012-01-27

Abstract: This study developed biomechanical models for hand breakaway strength that account for not only grip force but also hand–handle frictional coupling in generation of breakaway strength. Specifically, models for predicting breakaway strength for two commonly-used handle shapes (circular and rectangular handles) and varying coefficients of friction (COF) between the hand and handle were proposed. The models predict that (i) breakaway strength increases with increasing COF and (ii) a circular handle with a 50.8mm-diameter results in greater mean breakaway strength than a handle with a rectangular cross-section of 38.1 by 38.1mm for COFs greater than 0.42. To test these model predictions, breakaway strengths of thirteen healthy young adults were measured for three frequently-encountered COF conditions (represented by three glove types of polyester (COF=0.32), bare hand (COF=0.50), and latex (COF=0.74) against an aluminum handle) and for the two handle shapes. Consistent with the model predictions, mean breakaway strength increased with increasing COF and was greater for the circular than rectangular handle for COFs of 0.50 and 0.74. Examination of breakaway strength normalized to body weight reveals that modification of COF and handle shapes could influence whether one can hold his/her body using the hands or not (thus must fall), highlighting the importance of considering these parameters for fall prevention. The biomechanical models developed herein have the potential to be applied to general handle shapes and COF conditions. These models can be used to optimize handle design to maximize breakaway strength and minimize injuries due to falls from ladders or scaffolds.

Replicating a Colles fracture in an excised radius: Revisiting testing protocols - Corrected Proof

David W. Wagner, Derek P. Lindsey, Gary S. Beaupre — 2012-01-27

Abstract: A distal radius fracture in middle-age and older adults is often considered a sentinel indicator of osteoporosis. Mechanical testing of cadaveric specimens is often used to quantify bone strength and develop insight for relating in-vivo measures to fracture force. Mechanical testing protocols using an intact forearm have been successful at replicating a Colles fracture, however, excised isolated radius protocols based on the intact forearm testing protocol have not been as successful. One protocol originally designed to replicate the physiological condition of a fall on an outstretched hand was reproduced in our laboratory, yet surprisingly the produced distal radius fracture patterns were not consistent among specimens nor was dorsal angulation of the distal fragment that is characteristic of a Colles fracture observed. The purpose of this study was to perform a mechanics-based analysis of the excised radius loading protocol in order to quantify the imposed and internal forces on the radius. An idealized beam model of the excised radius revealed that in the area of the distal radius where Colles fractures occur, 99.99% of the maximum strain on the bone outer surface was the result of pure compressive loading. This loading condition is in direct contrast to the accepted mechanics of a Colles fracture, which is characterized as a metaphyseal bending fracture with the volar cortex failing due to tensile stresses and the dorsal cortex exhibiting compression and comminution. The results suggest that additional research, particularly related to overcoming the difficulties of reliably supporting and applying a force to the distal end of the radius, is necessary for clinical fracture patterns to be reliably reproduced with an excised radius mechanical testing protocol.

Pure moment testing for spinal biomechanics applications: Fixed versus 3D floating ring cable-driven test designs - Corrected Proof

Jessica A. Tang, Justin K. Scheer, Christopher P. Ames, Jenni M. Buckley — 2012-01-25

Abstract: Pure moment testing has become a standard protocol for in vitro assessment of the effect of surgical techniques or devices on the bending rigidity of the spine. Of the methods used for pure moment testing, cable-driven set-ups are popular due to their low requirements and simple design. Fixed loading rings are traditionally used in conjunction with these cable-driven systems. However, the accuracy and validity of the loading conditions applied with fixed ring designs have raised some concern, and discrepancies have been found between intended and prescribed loading conditions for flexion–extension. This study extends this prior work to include lateral bending and axial torsion, and compares this fixed ring design with a novel “3D floating ring” design. A complete battery of multi-axial bending tests was conducted with both rings in multiple different configurations using an artificial lumbar spine. Applied moments were monitored and recorded by a multi-axial load cell at the base of the specimen. Results indicate that the fixed ring design deviates as much as 77% from intended moments and induces non-trivial shear forces (up to 18N) when loaded to a non-destructive maximum of 4.5Nm. The novel 3D floating ring design largely corrects the inherent errors in the fixed ring design by allowing additional directions of unconstrained motion and producing uniform loading conditions along the length of the specimen. In light of the results, it is suggested that the 3D floating ring set-up be used for future pure moment spine biomechanics applications using a cable-driven apparatus.

A continuous description of intervertebral motion by means of spline interpolation of kinematic data extracted by videofluoroscopy - Corrected Proof

Paolo Bifulco, Mario Cesarelli, Tommaso Cerciello, Maria Romano — 2012-01-25

Abstract: In vivo analysis of intervertebral kinematics provides useful information about spinal disorders and performance of disk prostheses. Diagnosis of intervertebral instability is based on measurement of abnormal range of segmental motion in sagittal plane through functional flexion–extension radiography; however, this concise measure does not take into account the progression of segmental motion in between flexion and extension extremes. Fluoroscopy can support analysis of intervertebral kinematics during patient's motion with an acceptable X-ray dose. A spline-based method designed for a continuous-time description of intervertebral motion extracted by videofluoroscopy is proposed. Fluoroscopic sagittal sequences of lumbar spine were processed by an automated method based on template matching to track vertebrae. A smoothing spline interpolation of the estimated intervertebral kinematic data was performed and a continuous-time description of segmental rotation and translation was obtained; the smoothing parameter was chosen both to preserve motion and to reduce noise. Concise measurements were extracted by the continuous-time kinematics and compared with standard clinical measurements of intervertebral sagittal rotation and translation. The trajectory of instantaneous center of rotation, never presented before for in vivo spinal segments, was provided and compared with standard measurements of the finite center of rotation. Results showed a good agreement with standard clinical measurements: on average, absolute differences resulted 0.74degree for sagittal rotation, 0.59mm for translation and 1.02mm for the x- and y-position of center of rotation. The proposed method offers an effective technique for the continuous-time description of intervertebral motion, maintaining standard clinical measurements for diagnosis of lumbar instability.

Corrigendum to “Patient-specific finite element analysis of the human femur—A double-blinded biomechanical validation” [J. Biomech. 44 (2011) 1666–1672] - Corrected Proof

Nir Trabelsi, Zohar Yosibash, Christof Wutte, Peter Augat, Sebastian Eberle — 2012-01-24

In our paper patient-specific finite element (PSFE) models based on quantitative computer tomography (qCT) were validated by biomechanical in-vitro experiments, which determined strains and local displacements on the bone surface and the axial stiffness of the specimens. Although an excellent match was observed for the strains and displacements, the PSFE analysis did not match well the measured axial stiffness in the experiments. The reason for this discrepancy was discovered to be associated with the measured testing setup as follows:

A neural network model to predict knee adduction moment during walking based on ground reaction force and anthropometric measurements - Corrected Proof

Julien Favre, Matthieu Hayoz, Jennifer C. Erhart-Hledik, Thomas P. Andriacchi — 2012-01-18

Abstract: The external knee adduction moment (KAM) is a major variable for the evaluation of knee loading during walking, specifically in patients with knee osteoarthritis. However, assessment of the KAM is limited to locations where full motion laboratories are available. The purpose of this study was to develop and test a simple method to predict the KAM using only force plate and anthropometric measurements. Three groups of 28 knees (asymptomatic, mild osteoarthritis, and severe osteoarthritis) were studied. Walking trials were collected at different speeds using a motion capture system and a force plate. The reference KAM was calculated by inverse dynamics. For the prediction, inter-subject artificial neural networks were designed using 11 inputs coming from the ground reaction force and the mechanical axis alignment. The predicted KAM curves were similar to the reference curves with median mean absolute deviation (MAD) of 0.36%BW⁎Ht and median correlation coefficient of 0.966 over 756 individual trials. When comparing mean group curves, the median MAD was 0.09%BW⁎Ht and the median correlation coefficient 0.998. The peak values and the angular impulses extracted from the predicted and reference curves were significantly correlated, and the same significant differences were obtained among the three groups when the predicted or when the reference curves were used for 95% of the comparisons. In conclusion, this study demonstrated that a simple method using a generic artificial neural network can predict the KAM curve during walking with a high level of significance and provides a practical option for a broader evaluation of the KAM.

The speed of sound through trabecular bone predicted by Biot theory - Corrected Proof

Young June Yoon, Jae-Pil Chung, Chul-Soo Bae, Seog-Young Han — 2012-01-16

Abstract: Cancellous bone is a highly porous material filled with fluid. The mechanical properties of cancellous bone determine whether the bone is normal or osteoporotic. Wave propagation can be used to measure the elastic constants of cancellous bone. Recently, poroelasticity theory has been used to predict the elastic constants of cancellous bone from the wave velocities. In this study, it is shown that the fast wave, predicted by the Biot theory, corresponds to the wave penetrating the trabeculae, while the slow wave is determined by the interaction between the trabeculae and the fluid. The trabecular shape does not affect the wave velocity significantly when using the variable, which is determined by the microstructure, and the slow wave velocity decreases after the porosity reaches 80%.

Variability of gait is dependent on direction of progression: Implications for active control - Corrected Proof

Shane R. Wurdeman, Neil B. Huben, Nicholas Stergiou — 2012-01-16

Abstract: Typical healthy walking displays greater variability in the mediolateral direction compared to the anteroposterior direction. This greater variability is thought to represent increased uncertainty in movement. As a result, it has been postulated that the mediolateral direction of gait requires more active control by the central nervous system while the anteroposterior direction is controlled through passive actions. However, this theory has only been tested on gait where progression occurs in the anteroposterior direction. Therefore, the purpose of this study was to investigate how the amount of variability is affected if progression occurs in the mediolateral direction using a lateral stepping gait. Results showed the anteroposterior direction had a significantly greater amount of variability than the mediolateral direction (p<0.001). The results do not support current models of a partition of active control to different anatomical planes. Rather, it seems that other physical entities involved in motion, such as momentum and inertia, are able to decrease the dependence on active control from the central nervous system. In a lateral stepping gait, such physical entities were no longer assisting in the anteroposterior direction but had a larger impact in the mediolateral direction as it was the direction of progression. As a result variability in the anteroposterior direction increased. Thus, it is possible to infer increased reliance on active control from the central nervous system in the direction orthogonal to progression.

Finite element analysis of the effect of loading curve shape on brain injury predictors - Corrected Proof

Andrew Post, Blaine Hoshizaki, Michael D. Gilchrist — 2012-01-13

Abstract: Prediction of traumatic and mild traumatic brain injury is an important factor in managing their prevention. Currently, the prediction of these injuries is limited to peak linear and angular acceleration loading curves derived from laboratory reconstructions. However it remains unclear as to what aspect of these loading curves contributes to brain tissue damage. This research uses the University College Dublin Brain Trauma Model (UCDBTM) to analyse three distinct loading curve shapes meant to represent different helmet loading scenarios. The loading curves were applied independently in each axis of linear and angular acceleration and their effect on currently used predictors of TBI and mTBI was examined. Loading curve shape A had a late time to peak, B an early time to peak and C had a consistent plateau. The areas under the curve for all three loading curve shapes were identical. The results indicate that loading curve A produced consistently higher maximum principal strains and Von Mises stress than the other two loading curve types. Loading curve C consistently produced the lowest values of maximum principal strain and Von Mises stress, with loading curve B being lowest in only 2 cases. The areas of peak Von Mises stress and Principal strain also varied depending on loading curve shape and acceleration input.

Modeling of cardiac muscle thin films: Pre-stretch, passive and active behavior - Corrected Proof

2012-01-12

Abstract: Recent progress in tissue engineering has made it possible to build contractile bio-hybrid materials that undergo conformational changes by growing a layer of cardiac muscle on elastic polymeric membranes. Further development of such muscular thin films for building actuators and powering devices requires exploring several design parameters, which include the alignment of the cardiac myocytes and the thickness/Young's modulus of elastomeric film. To more efficiently explore these design parameters, we propose a 3-D phenomenological constitutive model, which accounts for both the passive deformation including pre-stretch and the active behavior of the cardiomyocytes. The proposed 3-D constitutive model is implemented within a finite element framework, and can be used to improve the current design of bio-hybrid thin films and help developing bio-hybrid constructs capable of complex conformational changes.

Acute mechanical effects of elastase on the infrarenal mouse aorta: Implications for models of aneurysms - Corrected Proof

M.J. Collins, J.F. Eberth, E. Wilson, J.D. Humphrey — 2012-01-12

Abstract: Intraluminal exposure of the infrarenal aorta to porcine pancreatic elastase represents one of the most commonly used experimental models of the development and progression of abdominal aortic aneurysms. Morphological and histological effects of elastase on the aortic wall have been well documented in multiple rodent models, but there has been little attention to the associated effects on mechanical properties. In this paper, we present the first biaxial mechanical data on, and associated nonlinear constitutive descriptors of, the effects of elastase on the infrarenal aorta in mice. Quantification of the dramatic, acute effects of elastase on wall behavior in vitro is an essential first step toward understanding the growth and remodeling of aneurysms in vivo, which depends on both the initial changes in the mechanics and the subsequent inflammation-mediated turnover of cells and extracellular matrix that contributes to the evolving mechanics.

Osmotic swelling and residual stress in cardiovascular tissues - Corrected Proof

Yoram Lanir — 2012-01-11

Abstract: Osmotic swelling (OS) and residual stress (RS) significantly affect the function of cardiovascular (CVS) tissues and organs. The physical mechanisms of OS and RS are reviewed and analyzed with focus on the theoretical background and related experimental evidence. It will be shown that swelling of CVS tissues stems from the presence of charged proteoglycan macro-molecules in these tissues, and that this swelling is a key determinant of RS. In view of OS and RS functional significance in mechanical function, modeling attempts which incorporate them in CVS stress analysis will be presented and discussed.

Planar biaxial characterization of diseased human coronary and carotid arteries for computational modeling - Corrected Proof

2012-01-11

Abstract: Computational models have the potential to provide precise estimates of stresses and strains associated with sites of coronary plaque rupture. However, lack of adequate mathematical description of diseased human vessel wall mechanical properties is hindering computational accuracy. The goal of this study is to characterize the behavior of diseased human coronary and carotid arteries using planar biaxial testing. Diseased coronary specimens exhibit relatively high stiffness (50–210kPa) and low extensibility (1–10%) at maximum equibiaxial stress (250kPa) compared to human carotid specimens and values commonly reported for porcine coronary arteries. A thick neointimal layer observed histologically appears to be associated with heightened stiffness and the direction of anisotropy of the specimens. Fung, Choi–Vito and modified Mooney–Rivlin constitutive equations fit the multiaxial data from multiple stress protocols well, and parameters from representative coronary specimens were utilized in a finite element model with fluid–solid interactions. Computed locations of maximal stress and strain are substantially altered, and magnitudes of maximum principal stress (48–65kPa) and strain (6.5–8%) in the vessel wall are lower than previously predicted using parameters from uniaxial tests. Taken together, the results demonstrate the importance of utilizing disease-matched multiaxial constitutive relationships within patient-specific computational models to accurately predict stress and strain within diseased coronary arteries.

Considerations for reporting finite element analysis studies in biomechanics - Corrected Proof

2012-01-11

Abstract: Simulation-based medicine and the development of complex computer models of biological structures is becoming ubiquitous for advancing biomedical engineering and clinical research. Finite element analysis (FEA) has been widely used in the last few decades to understand and predict biomechanical phenomena. Modeling and simulation approaches in biomechanics are highly interdisciplinary, involving novice and skilled developers in all areas of biomedical engineering and biology. While recent advances in model development and simulation platforms offer a wide range of tools to investigators, the decision making process during modeling and simulation has become more opaque. Hence, reliability of such models used for medical decision making and for driving multiscale analysis comes into question. Establishing guidelines for model development and dissemination is a daunting task, particularly with the complex and convoluted models used in FEA. Nonetheless, if better reporting can be established, researchers will have a better understanding of a model's value and the potential for reusability through sharing will be bolstered. Thus, the goal of this document is to identify resources and considerate reporting parameters for FEA studies in biomechanics. These entail various levels of reporting parameters for model identification, model structure, simulation structure, verification, validation, and availability. While we recognize that it may not be possible to provide and detail all of the reporting considerations presented, it is possible to establish a level of confidence with selective use of these parameters. More detailed reporting, however, can establish an explicit outline of the decision-making process in simulation-based analysis for enhanced reproducibility, reusability, and sharing.

The influence of acetabular cup material on pelvis cortex surface strains, measured using digital image correlation - Corrected Proof

A.S. Dickinson, A.C. Taylor, M. Browne — 2012-01-11

Abstract: Acetabular cup loosening is a late failure mode of total hip replacements, and peri-prosthetic bone deterioration may promote earlier failure. Preservation of supporting bone quality is a goal for implant design and materials selection, to avoid stress shielding and bone resorption. Advanced polymer composite materials have closer stiffness to bone than metals, ceramics or polymers, and have been hypothesised to promote less adverse bone adaptation. Computer simulations have supported this hypothesis, and the present study aimed to verify this experimentally.A composite hemi-pelvis was implanted with Cobalt Chromium (CoCr), polyethylene (UHMWPE) and MOTIS®carbon-fibre-reinforced polyether etherketone (CFR-PEEK) acetabular cups. In each case, load was applied to the implanted pelvis and Digital Image Correlation (DIC) was used for surface strain measurement. The test was repeated for an intact hemi-pelvis. Trends in implanted vs. intact bone principal strains were inspected to assess the average principal strain magnitude change, allowing comparison of the potential bone responses to implantation with the three cups.The CFR-PEEK cup was observed to produce the closest bone strain to the intact hip in the main load path, the superior peri-acetabular cortex (+12% on average, R2=0.84), in comparison to CoCr (+40%, R2=0.91) and UHWMPE cups (−26%, R2=0.94). Clinical observations have indicated that increased periacetabular cortex loading may result in reduced polar cancellous bone loading, leading to longer term losses in periprosthetic bone mineral density. This study provides experimental evidence to verify previous computational studies, indicating that cups produced using materials with stiffness closer to cortical bone recreate physiological cortical bone strains more closely and could, therefore, potentially promote less adverse bone adaptation than stiffer press-fitted implants in current use.

The minimum required muscle force for a sit-to-stand task - Corrected Proof

Shinsuke Yoshioka, Akinori Nagano, Dean C. Hay, Senshi Fukashiro — 2012-01-11

Abstract: The purpose of this study was to reveal the minimum required muscle force for a sit-to-stand task. Combining experimental procedures and computational processing, movements of various sit-to-stand patterns were obtained. Muscle forces and activations during a movement were calculated with an inverse dynamics method and a static numerical optimization method. The required muscle force for each movement was calculated with peak muscle activation, muscle physiological cross sectional area and specific tension. The robustness of the results was quantitatively evaluated with sensitivity analyses. From the results, a distinct threshold was found for the total required muscle force of the hip and knee extensors. Specifically, two findings were revealed: (1) the total force of hip and knee extensors is appropriate as the index of minimum required muscle force for a sit-to-stand task and (2) the minimum required total force is within the range of 35.3–49.2N/kg. A muscle is not mechanically independent from other muscles, since each muscle has some synergetic or antagonistic muscles. This means that the mechanical threshold of one muscle varies with the force exertion abilities of other muscles and cannot be evaluated independently. At the same time, some kinds of mechanical threshold necessarily exist in the sit-to-stand task, since a muscle force is an only force to drive the body and people cannot stand up from a chair without muscles. These indicate that the existence of the distinct threshold in the result of the total required muscle force is reasonable.

Elastic modulus of hard tissues - Corrected Proof

Benny Bar-On, H. Daniel Wagner — 2012-01-11

Abstract: This work aims at evaluating the elastic modulus of hard biological tissues by considering their staggered platelet micro-structure. An analytical expression for the effective modulus along the stagger direction is formulated using three non-dimensional structural variables. Structures with a single staggered hierarchy (e.g. collagen fibril) are first studied and predictions are compared with the experimental results and finite element simulations from the literature. A more complicated configuration, such as an array of fibrils, is analyzed next. Finally, a mechanical model is proposed for tooth dentin, in which variations in the multi-scale structural hierarchy are shown to significantly affect the macroscopic mechanical properties.

Nonlinear viscoelasticty plays an essential role in the functional behavior of spinal ligaments - Corrected Proof

Kevin L. Troyer, Christian M. Puttlitz — 2012-01-11

Abstract: Despite the significant role ligament viscoelasticity plays in functional spinal biomechanics, relatively few studies have been performed to develop constitutive models that explicitly characterize this complex behavior. Unfortunately, the application and interpretation of these previous models are limited due to the use of simplified (quasi-linear) viscoelastic formulations or characterization techniques that have been shown to affect the predictive accuracy of the fitted coefficients. In order to surmount these previous limitations, the current study presents the application of a novel fitting technique (applied to stress relaxation experiments) and nonlinear viscoelastic constitutive formulation to human cervical spine anterior longitudinal ligament (ALL), posterior longitudinal ligament (PLL) and ligamentum flavum (LF). The fitted coefficients were validated by quantifying the ability of the constitutive equation to predict an independent cyclic data set across multiple physiologic strain amplitudes and frequencies. The resulting validated constitutive formulation indicated that the strain-dependent viscoelastic behavior of the longitudinal ligaments (ALL and PLL) was dominated by both the short-term (t=0.1s) and the steady-state (as t→∞) behavior. Conversely, the LF exhibited consistent relaxation behavior across the investigated temporal spectrum. From these data, it can be hypothesized that the unique strain-dependent temporal behavior of these spinal ligaments may be a functional adaptation that minimizes muscular expenditure during quasi-static postures while maximizing structural stability of the spine during transient loading events.

Activation and aponeurosis morphology affect in vivo muscle tissue strains near the myotendinous junction - Corrected Proof

Niccolo M. Fiorentino, Frederick H. Epstein, Silvia S. Blemker — 2012-01-11

Abstract: Hamstring strain injury is one of the most common injuries in athletes, particularly for sports that involve high speed running. The aims of this study were to determine whether muscle activation and internal morphology influence in vivo muscle behavior and strain injury susceptibility. We measured tissue displacement and strains in the hamstring muscle injured most often, the biceps femoris long head muscle (BFLH), using cine DENSE dynamic magnetic resonance imaging. Strain measurements were used to test whether strain magnitudes are (i) larger during active lengthening than during passive lengthening and (ii) larger for subjects with a relatively narrow proximal aponeurosis than a wide proximal aponeurosis. Displacement color maps showed higher tissue displacement with increasing lateral distance from the proximal aponeurosis for both active lengthening and passive lengthening, and higher tissue displacement for active lengthening than passive lengthening. First principal strain magnitudes were averaged in a 1cm region near the myotendinous junction, where injury is most frequently observed. It was found that strains are significantly larger during active lengthening (0.19SD0.09) than passive lengthening (0.13SD0.06) (p<0.05), which suggests that elevated localized strains may be a mechanism for increased injury risk during active as opposed to passive lengthening. First principal strains were higher for subjects with a relatively narrow aponeurosis width (0.26SD 0.15) than wide (0.14SD 0.04) (p<0.05). This result suggests that athletes who have BFLH muscles with narrow proximal aponeuroses may have an increased risk for BFLH strain injuries.

Critical role of cardiac t-tubule system for the maintenance of contractile function revealed by a 3D integrated model of cardiomyocytes - Corrected Proof

Asuka Hatano, Jun-ichi Okada, Toshiaki Hisada, Seiryo Sugiura — 2012-01-09

Abstract: T-tubules in mammalian ventricular myocytes constitute an elaborate system for coupling membrane depolarization with intracellular Ca2+ signaling to control cardiac contraction. Deletion of t-tubules (detubulation) has been reported in heart diseases, although the complex nature of the cardiac excitation–contraction (E–C) coupling process makes it difficult to experimentally establish causal relationships between detubulation and cardiac dysfunction. Alternatively, numerical simulations incorporating the t-tubule system have been proposed to elucidate its functional role. However, the majority of models treat the subcellular spaces as lumped compartments, and are thus unable to dissect the impact of morphological changes in t-tubules. We developed a 3D finite element model of cardiomyocytes in which subcellular components including t-tubules, myofibrils, sarcoplasmic reticulum, and mitochondria were modeled and realistically arranged. Based on this framework, physiological E–C coupling was simulated by simultaneously solving the reaction-diffusion equation and the mechanical equilibrium for the mathematical models of electrophysiology and contraction distributed among these subcellular components. We then examined the effect of detubulation in this model by comparing with and without the t-tubule system. This model reproduced the Ca2+ transients and contraction observed in experimental studies, including the response to beta-adrenergic stimulation, and provided detailed information beyond the limits of experimental approaches. In particular, the analysis of sarcomere dynamics revealed that the asynchronous contraction caused by a large detubulated region can lead to impairment of myocyte contractile efficiency. These data clearly demonstrate the importance of the t-tubule system for the maintenance of contractile function.

A new approach to quantify trabecular resorption adjacent to cemented knee arthroplasty - Corrected Proof

2012-01-09

Abstract: A new micro-computed tomography (μCT) image processing approach to estimate the loss of cement–bone interlock was developed using the concept that PMMA cement flows and cures around trabeculae during the total knee arthroplasty procedure. The initial mold shape of PMMA cement was used to estimate the amount of interdigitated bone at the time of implantation and following in vivo service using enbloc human postmortem retrievals. Laboratory prepared specimens, where there would be no biological bone resorption, were used as controls to validate the approach and estimate errors. The image processing technique consisted of identifying bone and cement from the μCT scan set, dilation of the cement to identify the cement cavity space, and Boolean operations to identify the different components of the interdigitated cement–bone regions. For laboratory prepared specimens, there were small errors in the estimated resorbed bone volume fraction (reBVfr=0.11±0.09) and loss in contact area fraction (CAfr=0.06±0.15). These values would be zero if there were no error in the method. For the postmortem specimens, the resorbed volume fraction (reBVfr=0.85±0.16) was large, meaning that only 15% of the cement mold shape was still filled with bone. The loss of contact area fraction (CAfr=0.84±0.17) was similarly large. This new approach provides a convenient method to visualize and quantify trabecular bone loss from interdigitated regions from postmortem retrievals. The technique also illustrates for the first time that there are dramatic changes in how bone is fixed to cement following in vivo service.

Effect of low pass filtering on joint moments from inverse dynamics: Implications for injury prevention - Corrected Proof

Eirik Kristianslund, Tron Krosshaug, Antonie J. van den Bogert — 2012-01-09

Abstract: Analyses of joint moments are important in the study of human motion, and are crucial for our understanding of e.g. how and why ACL injuries occur. Such analyses may be affected by artifacts due to inconsistencies in the equations of motion when force and movement data are filtered with different cut-off frequencies. The purpose of this study was to quantify the effect of these artifacts, and compare joint moments calculated with the same or different cut-off frequency for the filtering of force and movement data. 123 elite handball players performed sidestep cutting while the movement was recorded by eight 240Hz cameras and the ground reaction forces were recorded by a 960Hz force plate. Knee and hip joint moments were calculated through inverse dynamics, with four different combinations of cut-off frequencies for signal filtering: movement 10Hz, force 10Hz, (10–10); movement 15Hz, force 15Hz; movement 10Hz, force 50Hz (10–50); movement 15Hz, force 50Hz. The results revealed significant differences, especially between conditions with different filtering of force and movement. Mean (SD) peak knee abduction moment for the 10–10 and 10–50 condition were 1.27 (0.53) and 1.64 (0.68) Nm/kg, respectively. Ranking of players based on knee abduction moments were affected by filtering condition. Out of 20 players with peak knee abduction moment higher than mean+1SD with the 10–50 condition, only 11 were still above mean+1SD when the 10–10 condition was applied. Hip moments were very sensitive to filtering cut-off. Mean (SD) peak hip flexion moment was 3.64 (0.75) and 5.92 (1.80) under the 10–10 and 10–50 conditions, respectively. Based on these findings, force and movement data should be processed with the same filter. Conclusions from previous inverse dynamics studies, where this was not the case, should be treated with caution.

Mechanical changes in the rat right ventricle with decellularization - Corrected Proof

2012-01-03

Abstract: The stiffness, anisotropy, and heterogeneity of freshly dissected (control) and perfusion-decellularized rat right ventricles were compared using an anisotropic inverse mechanics method. Cruciform tissue samples were speckled and then tested under a series of different biaxial loading configurations with simultaneous force measurement on all four arms and displacement mapping via image correlation. Based on the displacement and force data, the sample was segmented into piecewise homogeneous partitions. Tissue stiffness and anisotropy were characterized for each partition using a large-deformation extension of the general linear elastic model. The perfusion-decellularized tissue had significantly higher stiffness than the control, suggesting that the cellular contribution to stiffness, at least under the conditions used, was relatively small. Neither anisotropy nor heterogeneity (measured by the partition standard deviation of the modulus and anisotropy) varied significantly between control and decellularized samples. We thus conclude that although decellularization produces quantitative differences in modulus, decellularized tissue can provide a useful model of the native tissue extracellular matrix. Further, the large-deformation inverse method presented herein can be used to characterize complex soft tissue behaviors.

Dependence of cyclic stretch-induced stress fiber reorientation on stretch waveform - Corrected Proof

Abhishek Tondon, Hui-Ju Hsu, Roland Kaunas — 2011-12-29

Abstract: Cyclic uniaxial stretching of adherent nonmuscle cells induces the gradual reorientation of their actin stress fibers perpendicular to the stretch direction to an extent dependent on stretch frequency. By subjecting cells to various temporal waveforms of cyclic stretch, we revealed that stress fibers are much more sensitive to strain rate than strain frequency. By applying asymmetric waveforms, stress fibers were clearly much more responsive to the rate of lengthening than the rate of shortening during the stretch cycle. These observations were interpreted using a theoretical model of networks of stress fibers with sarcomeric structure. The model predicts that stretch waveforms with fast lengthening rates generate greater average stress fiber tension than that generated by fast shortening. This integrated approach of experiment and theory provides new insight into the mechanisms by which cells respond to matrix stretching to maintain tensional homeostasis.

The effects of angiotensin II on the coupled microstructural and biomechanical response of C57BL/6 mouse aorta - Corrected Proof

2011-12-26

Abstract: Rationale: Abdominal aortic aneurysm (AAA) is a complex disease that leads to a localized dilation of the infrarenal aorta, the rupture of which is associated with significant morbidity and mortality. Animal models of AAA can be used to study how changes in the microstructural and biomechanical behavior of aortic tissues develop as disease progresses in these animals. We chose here to investigate the effect of angiotensin II (AngII) in C57BL/6 mice as a first step towards understanding how such changes occur in the established ApoE−/− AngII infused mouse model of AAA.Objective: The objective of this study was to utilize a recently developed device in our laboratory to determine how the microstructural and biomechanical properties of AngII-infused C57BL/6 wildtype mouse aorta change following 14 days of AngII infusion.Methods: C57BL/6 wildtype mice were infused with either saline or AngII for 14 day. Aortas were excised and tested using a device capable of simultaneously characterizing the biaxial mechanical response and load-dependent (unfixed, unfrozen) extracellular matrix organization of mouse aorta (using multiphoton microscopy). Peak strains and stiffness values were compared across experimental groups, and both datasets were fit to a Fung-type constitutive model. The mean mode and full width at half maximum (FWHM) of fiber histograms from two photon microscopy were quantified in order to assess the preferred fiber distribution and degree of fiber splay, respectively.Results: The axial stiffness of all mouse aorta was found to be an order of magnitude larger than the circumferential stiffness. The aortic diameter was found to be significantly increased for the AngII infused mice as compared to saline infused control (p=0.026). Aneurysm, defined as a percent increase in maximum diameter of 30% (defined with respect to saline control), was found in 3 of the 6 AngII infused mice. These three mice displayed adventitial collagen that lacked characteristic fiber crimp. The biomechanical response in the AngII infused mice showed significantly reduced circumferential compliance. We also noticed that the ability of the adventitial collagen fibers in AngII infused mice to disperse in reaction to circumferential loading was suppressed.Conclusions: Collagen remodeling is present following 14 days of AngII infusion in C57BL/6 mice. Aneurysmal development occurred in 50% of our AngII infused mice, and these dilatations were accompanied with adventitial collagen remodeling and decreased circumferential compliance.

Reprogramming cardiomyocyte mechanosensing by crosstalk between integrins and hyaluronic acid receptors - Corrected Proof

2011-12-26

Abstract: The elastic modulus of bioengineered materials has a strong influence on the phenotype of many cells including cardiomyocytes. On polyacrylamide (PAA) gels that are laminated with ligands for integrins, cardiac myocytes develop well organized sarcomeres only when cultured on substrates with elastic moduli in the range 10kPa–30kPa, near those of the healthy tissue. On stiffer substrates (>60kPa) approximating the damaged heart, myocytes form stress fiber-like filament bundles but lack organized sarcomeres or an elongated shape. On soft (<1kPa) PAA gels myocytes exhibit disorganized actin networks and sarcomeres. However, when the polyacrylamide matrix is replaced by hyaluronic acid (HA) as the gel network to which integrin ligands are attached, robust development of functional neonatal rat ventricular myocytes occurs on gels with elastic moduli of 200Pa, a stiffness far below that of the neonatal heart and on which myocytes would be amorphous and dysfunctional when cultured on polyacrylamide-based gels. The HA matrix by itself is not adhesive for myocytes, and the myocyte phenotype depends on the type of integrin ligand that is incorporated within the HA gel, with fibronectin, gelatin, or fibrinogen being more effective than collagen I. These results show that HA alters the integrin-dependent stiffness response of cells in vitro and suggests that expression of HA within the extracellular matrix (ECM) in vivo might similarly alter the response of cells that bind the ECM through integrins. The integration of HA with integrin-specific ECM signaling proteins provides a rationale for engineering a new class of soft hybrid hydrogels that can be used in therapeutic strategies to reverse the remodeling of the injured myocardium.

Mechanics, mechanobiology, and modeling of human abdominal aorta and aneurysms - Corrected Proof

J.D. Humphrey, G.A. Holzapfel — 2011-12-22

Abstract: Biomechanical factors play fundamental roles in the natural history of abdominal aortic aneurysms (AAAs) and their responses to treatment. Advances during the past two decades have increased our understanding of the mechanics and biology of the human abdominal aorta and AAAs, yet there remains a pressing need for considerable new data and resulting patient-specific computational models that can better describe the current status of a lesion and better predict the evolution of lesion geometry, composition, and material properties and thereby improve interventional planning. In this paper, we briefly review data on the structure and function of the human abdominal aorta and aneurysmal wall, past models of the mechanics, and recent growth and remodeling models. We conclude by identifying open problems that we hope will motivate studies to improve our computational modeling and thus general understanding of AAAs.

The elastic properties of valve interstitial cells undergoing pathological differentiation - Corrected Proof

2011-12-21

Abstract: Increasing evidence indicates that the progression of calcific aortic valve disease (CAVD) is influenced by the mechanical forces experienced by valvular interstitial cells (VICs) embedded within the valve matrix. The ability of VICs to sense and respond to tissue-level mechanical stimuli depends in part on cellular-level biomechanical properties, which may change with disease. In this study, we used micropipette aspiration to measure the instantaneous elastic modulus of normal VICs and of VICs induced to undergo pathological differentiation in vitro to osteoblast or myofibroblast lineages on compliant and stiff collagen gels, respectively. We found that VIC elastic modulus increased after subculturing on stiff tissue culture-treated polystyrene and with pathological differentiation on the collagen gels. Fibroblast, osteoblast, and myofibroblast VICs had distinct cellular-level elastic properties that were not fully explained by substrate stiffness, but were correlated with α-smooth muscle actin expression levels. C-type natriuretic peptide, a peptide expressed in aortic valves in vivo, prevented VIC stiffening in vitro, consistent with its ability to inhibit α-smooth muscle actin expression and VIC pathological differentiation. These data demonstrate that VIC phenotypic plasticity and mechanical adaptability are linked and regulated both biomechanically and biochemically, with the potential to influence the progression of CAVD.

Tensile properties of vascular smooth muscle cells: Bridging vascular and cellular biomechanics - Corrected Proof

Takeo Matsumoto, Kazuaki Nagayama — 2011-12-19

Abstract: Vascular walls change their dimensions and mechanical properties adaptively in response to blood pressure. Because these responses are driven by the smooth muscle cells (SMCs) in the media, a detailed understanding of the mechanical environment of the SMCs should reveal the mechanism of the adaptation. As the mechanical properties of the media are highly heterogeneous at the microscopic level, the mechanical properties of the cells should be measured directly. The tensile properties of SMCs are, thus, important to reveal the microscopic mechanical environment in vascular tissues; their tensile properties have a close correlation with the distribution and arrangement of elements of the cytoskeletal networks, such as stress fibers and microtubules. In this review, we first introduce the experimental techniques used for tensile testing and discuss the various factors affecting the tensile properties of vascular SMCs. Cytoskeletal networks are particularly important for the mechanical properties of a cell and its mechanism of mechanotransduction; thus, the mechanical properties of cytoskeletal filaments and their effects on whole-cell mechanical properties are discussed with special attention to the balance of intracellular forces among the intracellular components that determines the force applied to each element of the cytoskeletal filaments, which is the key to revealing the mechanotransduction events regulating mechanical adaptation. Lastly, we suggest future directions to connect tissue and cell mechanics and to elucidate the mechanism of mechanical adaptation, one of the key issues of cardiovascular solid biomechanics.

Micropatterned cell sheets with defined cell and extracellular matrix orientation exhibit anisotropic mechanical properties - Corrected Proof

2011-12-19

Abstract: For an arterial replacement graft to be effective, it must possess the appropriate strength in order to withstand long-term hemodynamic stress without failure, yet be compliant enough that the mismatch between the stiffness of the graft and the native vessel wall is minimized. The native vessel wall is a structurally complex tissue characterized by circumferentially oriented collagen fibers/cells and lamellar elastin. Besides the biochemical composition, the functional properties of the wall, including stiffness, depend critically on the structural organization. Therefore, it will be crucial to develop methods of producing tissues with defined structures in order to more closely mimic the properties of a native vessel. To this end, we sought to generate cell sheets that have specific ECM/cell organization using micropatterned polydimethylsiloxane (PDMS) substrates to guide cell organization and tissue growth. The patterns consisted of large arrays of alternating grooves and ridges. Adult bovine aortic smooth muscle cells cultured on these substrates in the presence of ascorbic acid produced ECM-rich sheets several cell layers thick in which both the cells and ECM exhibited strong alignment in the direction of the micropattern. Moreover, mechanical testing revealed that the sheets exhibited mechanical anisotropy similar to that of native vessels with both the stiffness and strength being significantly larger in the direction of alignment, demonstrating that the microscale control of ECM organization results in functional changes in macroscale material behavior.

Persistent vascular collagen accumulation alters hemodynamic recovery from chronic hypoxia - Corrected Proof

2011-12-19

Abstract: Pulmonary arterial hypertension (PAH) is caused by narrowing and stiffening of the pulmonary arteries that increase pulmonary vascular impedance (PVZ). In particular, small arteries narrow and large arteries stiffen. Large pulmonary artery (PA) stiffness is the best current predictor of mortality from PAH. We have previously shown that collagen accumulation leads to extralobar PA stiffening at high strain (). We hypothesized that collagen accumulation would increase PVZ, including total pulmonary vascular resistance (Z0), characteristic impedance (ZC), pulse wave velocity (PWV) and index of global wave reflections (Pb/Pf), which contribute to increased right ventricular afterload. We tested this hypothesis by exposing mice unable to degrade type I collagen (Col1a1R/R) to 21 days of hypoxia (hypoxia), some of which were allowed to recover for 42 days (recovery). Littermate wild-type mice (Col1a1+/+) were used as controls. In response to hypoxia, mean PA pressure (mPAP) increased in both mouse genotypes with no changes in cardiac output (CO) or PA inner diameter (ID); as a consequence, Z0 (mPAP/CO) increased by ∼100% in both genotypes (p<0.05). Contrary to our expectations, ZC, PWV and Pb/Pf did not change. However, with recovery, ZC and PWV decreased in the Col1a1+/+ mice and remained unchanged in the Col1a1R/R mice. Z0 decreased with recovery in both genotypes. Microcomputed tomography measurements of large PAs did not show evidence of stiffness changes as a function of hypoxia exposure or genotype. We conclude that hypoxia-induced PA collagen accumulation does not affect the pulsatile components of pulmonary hemodynamics but that excessive collagen accumulation does prevent normal hemodynamic recovery, which may have important consequences for right ventricular function.

External approach to in vivo force measurement on mitral valve traction suture - Corrected Proof

2011-12-19

Abstract: Background: Force measurements on the mitral valve apparatus have been reported from in vivo and in vitro studies. Recent reparative techniques for ischemic mitral valve insufficiency call for papillary muscle relocation. This study describes a device to measure forces generated on traction sutures utilized for this purpose.Methods: The transducer design was based on a modified caliper with strain gauges attached. Finite element computer simulation was employed to optimize the signal output. The system was designed to facilitate investigation of the effects of shortening GoreTex traction suture that was extended from near the fibrous trigones of the mitral valve through the papillary muscles. The suture was exteriorized out through the left ventricle in a porcine setup (n=11) and attached to the dedicated device for simultaneous papillary muscle relocation and traction suture force measurement.Results: The transducer demonstrated excellent signal strength, linearity, and durability. Peak force was seen at the onset of the systolic isovolumic contraction (p<0.001). Initial results indicated that this external approach can document force magnitudes comparable to previous internally measured forces in the mitral valve apparatus.Conclusions: It has been proven feasible to measure forces in the mitral valve papillary muscle relocation sutures with an external device. The results from using this equipment will provide insight into the biomechanical requirements of relocation traction sutures and other devices utilized for papillary muscle relocation.

Intracellular Ca2+ accumulation is strain-dependent and correlates with apoptosis in aortic valve fibroblasts - Corrected Proof

2011-12-16

Abstract: Aortic valve (AV) disease is often characterized by the formation of calcific nodules within AV leaflets that alter functional biomechanics. In vitro, formation of these nodules is associated with osteogenic differentiation and/or increased contraction and apoptosis of AV interstitial cells (AVICs), leading to growth of calcium phosphate crystal structures. In several other cell types, increased intracellular Ca2+ has been shown to be an important part in activation of osteogenic differentiability. However, elevated intracellular Ca2+ is known to mediate cell contraction, and has also been shown to lead to apoptosis in many cell types. Therefore, a rise in intracellular Ca2+ may precede cellular changes that lead to calcification, and fibroblasts similar to AVICs have been shown to exhibit increases in intracellular Ca2+ in response to mechanical strain. In this study, we hypothesized that strain induces intracellular Ca2+ accumulation through stretch-activated calcium channels. We were also interested in assessing possible correlations between intracellular Ca2+ increases and apoptosis in AVICs. To test our hypothesis, cultured porcine AVICs were used to assess correlates between strain, intracellular Ca2+, and apoptosis. Ca2+ sensitive fluorescent dyes were utilized to measure real-time intracellular Ca2+ changes in strained AVICs. Ca2+ changes were then correlated with AVIC apoptosis using flow cytometric Annexin V apoptosis assays. These data indicate that strain-dependent accumulation of intracellular Ca2+ is correlated with apoptosis in AVICs. We believe that these findings indicate early mechanotransductive events that may initiate AV calcification pathways.

Modeling of cardiac growth and remodeling of myofiber orientation - Corrected Proof

Peter H.M. Bovendeerd — 2011-12-15

Abstract: The heart has the ability to respond to long-term changes in its environment through changes in mass (growth), shape (morphogenesis) and tissue properties (remodeling). For improved quantitative understanding of cardiac growth and remodeling (G&R) experimental studies need to be complemented by mathematical models. This paper reviews models for cardiac growth and remodeling of myofiber orientation, as induced by mechanical stimuli. A distinction is made between optimization models, that focus on the end stage of G&R, and adaptation models, that aim to more closely describe the mechanistic relation between stimulus and effect. While many models demonstrate qualitatively promising results, a lot of questions remain, e.g. with respect to the choice of the stimulus for G&R or the long-term stability of the outcome of the model. A continued effort combining information on mechanotransduction at the cellular level, experimental observations on G&R at organ level, and testing of hypotheses on stimulus–effect relations in mathematical models is needed to answer these questions on cardiac G&R. Ultimately, models of cardiac G&R seem indispensable for patient-specific modeling, both to reconstruct the actual state of the heart and to assess the long-term effect of potential interventions.Highlights: ► Filtering characteristics of double-pass Mach–Zehnder interferometer were analyzed. ► Single-wavelength tunable range covered 40nm from 1064nm to 1104nm. ► Tunable multi-wavelengths lasing output was also observed. ► Main factors limiting the output power were analyzed.