The effect of local bending on gating of MscL using a representative volume element and finite element simulation

Many physiological processes such as cell division, endocytosis and exocytosis cause severe local curvature of the cell membrane. Local curvature has been shown experimentally to modulate numerous mechanosensitive (MS) ion channels. In order to quantify the effects of local curvature we introduced a coarse grain representative volume element for the bacterial mechanosensitive ion channel of large conductance (MscL) using continuum elasticity. Our model is designed to be consistent with the channel conformation in the closed and open states to capture its major continuum rheological behavior in response to the local membrane curvature. Herein we show that change in the local curvature of the lipid bilayer can modulate MscL activity considerably by changing both bilayer thickness and lateral pressure profile. Intriguingly, although bending in any direction results in almost the same free-energy cost, inward (cytoplasmic) bending favors channel opening, whereas outward (periplasmic) bending facilitates closing of the narrowest part of the MscL pore. This quantitative study using MscL as a model channel may have wide reaching consequences for the effect of local curvature on the physiological function of other types of prokaryotic and eukaryotic membrane proteins.     

A lower extremity model for muscle-driven simulation of activity using explicit finite element modeling

A key strength of computational modeling is that it can provide estimates of muscle, ligament, and joint loads, stresses, and strains through non-invasive means. However, simulations that can predict the forces in the muscles during activity while maintaining sufficient complexity to realistically represent the muscles and joint structures can be computationally challenging. For this reason, the current state of the art is to apply separate rigid-body dynamic and finite-element (FE) analyses in series. However, the use of two or more disconnected models often fails to capture key interactions between the joint-level and whole-body scales. Single framework MSFE models have the potential to overcome the limitations associated with disconnected models in series. The objectives of the current study were to create a multi-scale FE model of the human lower extremity that combines optimization, dynamic muscle modeling, and structural FE analysis in a single framework and to apply this framework to evaluate the mechanics of healthy knee specimens during two activities. Two subject-specific FE models (Model 1, Model 2) of the lower extremity were developed in ABAQUS/Explicit including detailed representations of the muscles. Muscle forces, knee joint loading, and articular contact were calculated for two activities using an inverse dynamics approach and static optimization. Quadriceps muscle forces peaked at the onset of chair rise (2174 N, 1962 N) and in early stance phase (510 N, 525 N), while gait saw peak forces in the hamstrings (851 N, 868 N) in midstance. Joint forces were similar in magnitude to available telemetric patient data. This study demonstrates the feasibility of detailed quasi-static, muscle-driven simulations in an FE framework.     

Long-term study of bone remodelling after femoral stem: a comparison between dexa and finite element simulation

A hip replacement with a cemented or cementless femoral stem produces an effect on the bone called adaptive remodelling, attributable to mechanical and biological factors. The objective of all of cementless prostheses designs has been to achieve a perfect transfer of loads in order to avoid stress-shielding, which produces an osteopenia. In order to quantify this, the long term and mass-produced study with dual energy X-ray absorptiometry (DEXA) is necessary. Finite element (FE) simulation makes possible the explanation of the biomechanical changes which are produced in the femur after stem implantation. The good correlation obtained between the results of the FE simulation and the densitometric study allow, on one hand, to explain from the point of view of biomechanical performance the changes observed in bone density in the long-term, where it is clear that these are due to a different transfer of load in the implanted model compared to the healthy femur; on the other hand, it validates the simulation model, in a way that it can be used in different conditions and at different time periods, to carry out a sufficiently precise prediction of the evolution of the bone density from the biomechanical behaviour in the interaction between the prosthesis and femur.     

Accommodation of the human lens capsule using a finite element model based on nonlinear regionally anisotropic biomembranes

Accommodation of the eyes, the mechanism that allows humans to focus their vision on near objects, naturally diminishes with age via presbyopia. People who have undergone cataract surgery, using current surgical methods and artificial lens implants, are also left without the ability to accommodate. The process of accommodation is generally well known; however the specific mechanical details have not been adequately explained due to difficulties and consequences of performing in vivo studies. Most studies have modeled the mechanics of accommodation under assumptions of a linearly elastic, isotropic, homogenous lens and lens capsule. Recent experimental and numerical studies showed that the lens capsule exhibits nonlinear elasticity and regional anisotropy. In this paper we present a numerical model of human accommodation using a membrane theory based finite element approach, incorporating recent findings on capsular properties. This study seeks to provide a novel perspective of the mechanics of accommodation. Such findings may prove significant in seeking biomedical solutions to restoring loss of visual power.     

Cervical spine morphology and ligament property variations: A finite element study of their influence on sagittal bending characteristics

Cervical spine finite element models reported in biomechanical literature usually represent a static morphology. Not considering morphology as a model parameter limits the predictive capabilities for applications in personalized medicine, a growing trend in modern clinical practice. The objective of the study was to investigate the influence of variations in spinal morphology on the flexion-extension responses, utilizing mesh-morphing-based parametrization and metamodel-based sensitivity analysis. A C5-C6 segment was used as the baseline model. Variations of intervertebral disc height, facet joint slope, facet joint articular processes height, vertebral body anterior-posterior depth, and segment size were parametrized. In addition, material property variations of ligaments were considered for sensitivity analysis. The influence of these variations on vertebral rotation and forces in the ligaments were analyzed. The disc height, segmental size, and body depth were found to be the most influential (in the cited order) morphology variations; while among the ligament material property variations, capsular ligament and ligamentum flavum influenced vertebral rotation the most. Changes in disc height influenced forces in the posterior ligaments, indicating that changes in the anterior load-bearing column of the spine could have consequences on the posterior column. A method to identify influential morphology variations is presented in this work, which will help automation efforts in modeling to focus on variations that matter. This study underscores the importance of incorporating influential morphology parameters, easily obtained through computed tomography/magnetic resonance images, to better predict subject-specific biomechanical responses for applications in personalized medicine.     

Three-dimensional finite element simulations of the mechanical response of the fingertip to static and dynamic compressions

The analysis of the mechanics of the contact interactions of fingers/handle and the stress/strain distributions in the soft tissues in the fingertip is essential to optimize design of tools to reduce many occupation-related hand disorders. In the present study, a three-dimensional (3D) finite element (FE) model for the fingertip is proposed to simulate the nonlinear and time-dependent responses of a fingertip to static and dynamic loadings. The proposed FE model incorporates the essential anatomical structures of a finger: skin layers (outer and inner skins), subcutaneous tissue, bone and nail. The soft tissues (inner skin and subcutaneous tissue) are considered to be nonlinearly viscoelastic, while the hard tissues (outer skin, bone and nail) are considered to be linearly elastic. The proposed model has been used to simulate two loading scenarios: (a) the contact interactions between the fingertip and a flat surface and (b) the indentation of the fingerpad via a sharp wedge. For case (a), the predicted force/displacement relationships and time-dependent force responses are compared with the published experimental data; for case (b), the skin surface deflection profiles were predicted and compared with the published experimental observations. Furthermore, for both cases, the time-dependent stress/strain distributions within the tissues of the fingertip were calculated. The good agreement between the model predictions and the experimental observations indicates that the present model is capable of predicting realistic time-dependent force/displacement responses and stress/strain distributions in the soft tissues for dynamic loading conditions.     

Discretization error when using finite element models: Analysis and evaluation of an underestimated problem

Mesh convergence tests are often insufficiently performed in finite element analyses. There are many parameters which may have an effect on the mesh convergence behavior. The aim of this study was to identify the influence of different parameters on the mesh convergence behavior.For this purpose we used a simplified axis-symmetrical model of a single pedicle screw flank with surrounding bone to simulate a pull-out test. In parameter studies, the flank radii and the contact conditions at the bone–screw interface were varied. These parameter studies were carried out using an implicit and explicit solver. Thereby, the convergence criteria and the number of the substeps for the implicit nonlinear iteration process as well as the velocity and the material density for the explicit approach were considered.The mesh convergence behavior was influenced by varying the flank radii and the contact conditions. The implicit calculations led to a reaction force, which converged rapidly to a certain value with increasing mesh density, whereas the maximum von-Mises stress showed substantial convergence problems. The number of substeps and the convergence criteria of the iteration process strongly influenced the implicit solutions. In contrast, the maximum von-Mises stresses resulting from explicit calculations converged to a certain value after only a few refinement steps. Different pull-out velocities substantially affected the mesh convergence behavior, while the material density showed only a negligible influence.The results indicated the need to perform an appropriate mesh convergence test when using finite element methods. We were able to show that different parameters strongly influence the mesh convergence behavior and we demonstrated that convergence tests do not always lead to a satisfactory or acceptable solution.     

Development and experimental validation of a finite element model of total ankle replacement

Total ankle replacement remains a less satisfactory solution compared to other joint replacements. The goal of this study was to develop and validate a finite element model of total ankle replacement, for future testing of hypotheses related to clinical issues. To validate the finite element model, an experimental setup was specifically developed and applied on 8 cadaveric tibias. A non-cemented press fit tibial component of a mobile bearing prosthesis was inserted into the tibias. Two extreme anterior and posterior positions of the mobile bearing insert were considered, as well as a centered one. An axial force of 2 kN was applied for each insert position. Strains were measured on the bone surface using digital image correlation. Tibias were CT scanned before implantation, after implantation, and after mechanical tests and removal of the prosthesis. The finite element model replicated the experimental setup. The first CT was used to build the geometry and evaluate the mechanical properties of the tibias. The second CT was used to set the implant position. The third CT was used to assess the bone-implant interface conditions. The coefficient of determination (R-squared) between the measured and predicted strains was 0.91. Predicted bone strains were maximal around the implant keel, especially at the anterior and posterior ends. The finite element model presented here is validated for future tests using more physiological loading conditions.     

Estimation of in vivo inter-vertebral loading during motion using fluoroscopic and magnetic resonance image informed finite element models

Finite element (FE) models driven by medical image data can be used to estimate subject-specific spinal biomechanics. This study aimed to combine magnetic resonance (MR) imaging and quantitative fluoroscopy (QF) in subject-specific FE models of upright standing, flexion and extension. Supine MR images of the lumbar spine were acquired from healthy participants using a 0.5 T MR scanner. Nine 3D quasi-static linear FE models of L3 to L5 were created with an elastic nucleus and orthotropic annulus. QF data was acquired from the same participants who performed trunk flexion to 60° and trunk extension to 20°. The displacements and rotations of the vertebrae were calculated and applied to the FE model. Stresses were averaged across the nucleus region and transformed to the disc co-ordinate system (S1 = mediolateral, S2 = anteroposterior, S3 = axial). In upright standing S3 was predicted to be −0.7 ± 0.6 MPa (L3L4) and −0.6 ± 0.5 MPa (L4L5). S3 increased to −2.0 ± 1.3 MPa (L3L4) and −1.2 ± 0.6 MPa (L4L5) in full flexion and to −1.1 ± 0.8 MPa (L3L4) and −0.7 ± 0.5 MPa (L4L5) in full extension. S1 and S2 followed similar patterns; shear was small apart from S23. Disc stresses correlated to disc orientation and wedging. The results demonstrate that MR and QF data can be combined in a participant-specific FE model to investigate spinal biomechanics in vivo and that predicted stresses are within ranges reported in the literature.     

Modeling and simulation of novel antenna for the treatment of hepatocellular carcinoma using finite element method

In this article, new interstitial antenna operating at a frequency of 2.45 GHz for the treatment of hepatocellular carcinoma (HCC) using microwave ablation has been investigated. This antenna is basically an asymmetrical miniaturized choke dipole antenna with a pointed needle at the tip. A commercial finite element method (FEM) package, COMSOL Multiphysics 3.4a, has been used to simulate the performance of needle tip choke antenna. The performance of the antenna has been evaluated numerically, taking into account the specific absorption rate, antenna impedance matching and geometry of the obtained thermal lesion, and the temperature distribution plot obtained shows that maximum temperature was attained in this simulation. The antenna is also capable of creating a spherical-shaped ablation zone. The size and shape of the ablation zone can be slightly adjusted by adjusting the choke position in order to maintain spherical ablation zones.     

Impact loading history modulates hip fracture load and location: A finite element simulation study of the proximal femur in female athletes

Sideways falls impose high stress on the thin superolateral cortical bone of the femoral neck, the region regarded as a fracture-prone region of the hip. Exercise training is a natural mode of mechanical loading to make bone more robust. Exercise-induced adaptation of cortical bone along the femoral neck has been previously demonstrated. However, it is unknown whether this adaption modulates hip fracture behavior. The purpose of this study was to investigate the influence of specific exercise loading history on fall-induced hip fracture behavior by estimating fracture load and location with proximal femur finite element (FE) models created from magnetic resonance images (MRI) of 111 women with distinct exercise histories: 91 athletes (aged 24.7 ± 6.1 years, >8 years competitive career) and 20 women as controls (aged 23.7 ± 3.8 years). The athletes were divided into five groups based on typical loading patterns of their sports: high-impact (H-I: 9 triple-jumpers and 10 high jumpers), odd-impact (O-I: 9 soccer and 10 squash players), high-magnitude (H-M: 17 power-lifters), repetitive-impact (R-I: 18 endurance runners), and repetitive non-impact (R-NI: 18 swimmers). Compared to the controls, the H-I, O-I, and R-I groups had significantly higher (11–26%, p < 0.05) fracture loads. Also, the fracture location in the H-I and O-I groups was significantly more proximal (7–10%) compared to the controls. These results suggest that an exercise loading history of high impacts, impacts from unusual directions, or repetitive impacts increases the fracture load and may lower the risk of fall-induced hip fracture.     

Development and validation of a weight-bearing finite element model for total knee replacement

Total knee arthroplasty (TKA) is a successful procedure for osteoarthritis. However, some patients (19%) do have pain after surgery. A finite element model was developed based on boundary conditions of a knee rig. A 3D-model of an anatomical full leg was generated from magnetic resonance image data and a total knee prosthesis was implanted without patella resurfacing. In the finite element model, a restarting procedure was programmed in order to hold the ground reaction force constant with an adapted quadriceps muscle force during a squat from 20° to 105° of flexion. Knee rig experimental data were used to validate the numerical model in the patellofemoral and femorotibial joint. Furthermore, sensitivity analyses of Young’s modulus of the patella cartilage, posterior cruciate ligament (PCL) stiffness, and patella tendon origin were performed. Pearson’s correlations for retropatellar contact area, pressure, patella flexion, and femorotibial ap-movement were near to 1. Lowest root mean square error for retropatellar pressure, patella flexion, and femorotibial ap-movement were found for the baseline model setup with Young’s modulus of 5 MPa for patella cartilage, a downscaled PCL stiffness of 25% compared to the literature given value and an anatomical origin of the patella tendon. The results of the conducted finite element model are comparable with the experimental results. Therefore, the finite element model developed in this study can be used for further clinical investigations and will help to better understand the clinical aspects after TKA with an unresurfaced patella.     

Development of structural and material clavicle response corridors under axial compression and three point bending loading for clavicle finite element model validation

Clavicle injuries were frequently observed in automotive side and frontal crashes. Finite element (FE) models have been developed to understand the injury mechanism, although no clavicle loading response corridors yet exist in the literature to ensure the model response biofidelity. Moreover, the typically developed structural level (e.g., force–deflection) response corridors were shown to be insufficient for verifying the injury prediction capacity of FE model, which usually is based on strain related injury criteria. Therefore, the purpose of this study is to develop both the structural (force vs deflection) and material level (strain vs force) clavicle response corridors for validating FE models for injury risk modeling. 20 Clavicles were loaded to failure under loading conditions representative of side and frontal crashes respectively, half of which in axial compression, and the other half in three point bending. Both structural and material response corridors were developed for each loading condition. FE model that can accurately predict structural response and strain level provides a more useful tool in injury risk modeling and prediction. The corridor development method in this study could also be extended to develop corridors for other components of the human body.     

The effect of microwave radiation on the stability and formation of gramicidin-A channels in lipid bilayer membranes.

The effects of microwaves on the single-channel kinetics of gramicidin-A channels in lipid bilayer membranes were examined. Attempts were made to separate thermal and athermal effects by accurate measurements of temperature at the site of the membrane and by relating the measured parameters to their previously characterized temperature dependence. It was found that microwave radiation does not affect single-channel conductance or channel life time to a degree that is significantly different from that expected of a purely thermal effect. On the other hand, the rate of channel formation is decreased during exposure, which is opposite to that expected of a purely thermal effect. The mechanism of this effect is discussed in terms of the dimerization process of channel formation.     

Effect of screw position on load transfer in lumbar pedicle screws: a non-idealized finite element analysis

Angled screw insertion has been advocated to enhance fixation strength during posterior spine fixation. Stresses on a pedicle screw and surrounding vertebral bone with different screw angles were studied by finite element analysis during simulated multidirectional loading. Correlations between screw-specific vertebral geometric parameters and stresses were studied. Angulations in both the sagittal and axial planes affected stresses on the cortical and cancellous bones and the screw. Pedicle screws pointing laterally (vs. straight or medially) in the axial plane during superior screw angulation may be advantageous in terms of reducing the risk of both screw loosening and screw breakage.     

Effect of round curvature of anterior implant-supported zirconia frameworks: finite element analysis and in vitro study using digital image correlation

Two groups of 4-unit zirconia frameworks were produced by CAD/CAM to simulate the restoration of an anterior edentulous gap supported by 2 implant-abutment assemblies. Group 1 comprised straight configuration frameworks and group 2 consisted of arched frameworks. Specimens were made with the same connector cross-section area and were cemented and submitted to static loads. Displacements were captured with two high-speed photographic cameras and analysed with video correlation system. Frameworks and the implant-abutment assembly were scanned and converted to 3DCAD objects by reverse engineering process. A specimen of each group was veneered and the corresponding 3D geometry was similarly obtained after scanning. Numerical models were created from the CAD objects and the FE analysis was performed on the zirconia frameworks and on the FPDs bi-layered with porcelain (veneered frameworks). Displacements were higher for the curved frameworks group, under any load. The predicted displacements correlated well with the experimental values of the two framework groups, but on the straight framework the experimental vertical displacements were superior to those predicted by the FEA. The results showed that the round curvature of zirconia anterior implant-supported FPDs plays a significant role on the deformation/stress of FPDs that cannot be neglected neither in testing nor in simulation and should be considered in the clinical setting.     

Effects of eight different ligament property datasets on biomechanics of a lumbar L4-L5 finite element model

Ligaments assist trunk muscles in balancing external moments and providing spinal stability. In absence of the personalized material properties for ligaments, finite element (FE) models use dispersed data from the literature. This study aims to investigate the relative effects of eight different ligament property datasets on FE model responses. Eight L4-L5 models distinct only in ligament properties were constructed and loaded under moment (15 N m) alone or combined with a compressive follower load (FL). Range of motions (RoM) of the disc-alone model matched well in vitro data. Ligament properties significantly affected only sagittal RoMs (∼3.0–7.1° in flexion and ∼3.8–5.8° in extension at 10 N m). Sequential removal of ligaments shifted sagittal RoMs in and out of the corresponding in vitro ranges. When moment was combined with FL, center of rotation matched in vivo data for all models (3.8 ± 0.9 mm and 4.3 ± 1.8 mm posterior to the disc center in flexion and extension, respectively). Under 15 N m sagittal moments, ligament strains were often smaller or within the in vitro range in flexion whereas some posterior ligament forces approached their failure forces in some models. Ligament forces varied substantially within the models and affected the moment-sharing and internal forces on the disc and facet joints. Intradiscal pressure (IDP) had the greatest variation between models in extension. None of the datasets yielded results in agreement with all reported measurements. Results emphasized the important role of ligaments especially under larger moments and the need for their accurate representation in search for valid spinal models.     

Development and validation of a finite element model to simulate the opening of a medial opening wedge high tibial osteotomy

Medial opening wedge high tibial osteotomy (MOWHTO) is a surgical procedure intended to alter the coronal and sagittal plane alignment of the lower limb to primarily relieve the symptoms of osteoarthritis in the medial compartment of the knee. The purpose of this work was to develop and validate a finite element model to simulate the opening of a high tibial osteotomy and determine whether a pilot hole at the cortical hinge reduces the risk of lateral cortical fracture. Fifteen models were reconstructed from CT images of eight cadaveric specimens. The validated models indicated that the addition of the pilot hole increased the stresses and likelihood of a type-I and type-II fractures during the opening of a medial open wedge high tibial osteotomy compared to the no-hole condition.     

The effect of implant design of linked total elbow arthroplasty on stability and stress: a finite element analysis

Several linked total elbow arthroplasty designs exist, which function similar to a loose hinge joint. Constraint behaviour is an important design consideration, as it affects joint stability, or how much secondary [e.g. varus–valgus (VV)] motion is permitted. Implant durability is also a concern, as bearing failures have been reported. This finite element analysis investigates the constraint characteristics and ultra high molecular weight polyethylene bearing stresses of three linked elbow design concepts [cylindrical (CY), hourglass (HG) and concave cylinder (CC)]. The bearing of the CY design was subjected to elevated Von Mises stresses (2.1–5.4 times higher than the HG and CC designs) due to edge loading. The HG design maintained low stresses, but was unable to provide consistent VV stability. The CC design also maintained low stresses while providing consistent VV stability. These results suggest that CC designs may provide better stability characteristics and durability in vivo, compared to the other two designs.     

Effects of lumbo-pelvic rhythm on trunk muscle forces and disc loads during forward flexion: A combined musculoskeletal and finite element simulation study

Previous in-vivo studies suggest that the ratio of total lumbar rotation over pelvic rotation (lumbo-pelvic rhythm) during trunk sagittal movement is essential to evaluate spinal loads and discriminate between low back pain and asymptomatic population. Similarly, there is also evidence that the lumbo-pelvic rhythm is key for evaluation of realistic muscle and joint reaction forces and moments predicted by various computational musculoskeletal models. This study investigated the effects of three lumbo-pelvic rhythms defined based on in-vivo measurements on the spinal response during moderate forward flexion (60°) using a combined approach of musculoskeletal modeling of the upper body and finite element model of the lumbosacral spine. The muscle forces and joint loads predicted by the musculoskeletal model, together with the gravitational forces, were applied to the finite element model to compute the disc force and moment, intradiscal pressure, annular fibers strain, and load-sharing. The results revealed that a rhythm with high pelvic rotation and low lumbar flexion involves more global muscles and increases the role of the disc in resisting spinal loads, while its counterpart, with low pelvic rotation, recruits more local muscles and engages the ligaments to lower the disc loads. On the other hand, a normal rhythm that has balanced pelvic and lumbar rotations yields almost equal disc and ligament load-sharing and results in more balanced synergy between global and local muscles. The lumbo-pelvic rhythm has less effect on the intradiscal pressure and annular fibers strain. This work demonstrated that the spinal response during forward flexion is highly dependent on the lumbo-pelvic rhythm. It is therefore, essential to adapt this parameter instead of using the default values in musculoskeletal models for accurate prediction of muscle forces and joint reaction forces and moments. The findings provided by this work are expected to improve knowledge of spinal response during forward flexion, and are clinically relevant towards low back pain treatment and disc injury prevention.