Research Papers

J Biomech Eng. 2018;140(10):101001-101001-9. doi:10.1115/1.4040246.

Mechanical interaction of cell with extracellular environment affects its function. The mechanisms by which mechanical stimuli are sensed and transduced into biochemical responses are still not well understood. Considering this, two finite element (FE) bendo-tensegrity models of a cell in different states are proposed with the aim to characterize cell deformation under different mechanical loading conditions: a suspended cell model elucidating the global response of cell in tensile test simulation and an adherent cell model explicating its local response in atomic force microscopy (AFM) indentation simulation. The force-elongation curve obtained from tensile test simulation lies within the range of experimentally obtained characteristics of smooth muscle cells (SMCs) and illustrates a nonlinear increase in reaction force with cell stretching. The force-indentation curves obtained from indentation simulations lie within the range of experimentally obtained curves of embryonic stem cells (ESCs) and exhibit the influence of indentation site on the overall reaction force of cell. Simulation results have demonstrated that actin filaments (AFs) and microtubules (MTs) play a crucial role in the cell stiffness during stretching, whereas actin cortex (AC) along with actin bundles (ABs) and MTs are essential for the cell rigidity during indentation. The proposed models quantify the mechanical contribution of individual cytoskeletal components to cell mechanics and the deformation of nucleus under different mechanical loading conditions. These results can aid in better understanding of structure-function relationships in living cells.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101002-101002-10. doi:10.1115/1.4039895.

The development of a multi-axial failure criterion for trabecular skull bone has many clinical and biological implications. This failure criterion would allow for modeling of bone under daily loading scenarios that typically are multi-axial in nature. Some yield criteria have been developed to evaluate the failure of trabecular bone, but there is a little consensus among them. To help gain deeper understanding of multi-axial failure response of trabecular skull bone, we developed 30 microstructural finite element models of porous porcine skull bone and subjected them to multi-axial displacement loading simulations that spanned three-dimensional (3D) stress and strain space. High-resolution microcomputed tomography (microCT) scans of porcine trabecular bone were obtained and used to develop the meshes used for finite element simulations. In total, 376 unique multi-axial loading cases were simulated for each of the 30 microstructure models. Then, results from the total of 11,280 simulations (approximately 135,360 central processing unit-hours) were used to develop a mathematical expression, which describes the average three-dimensional yield surface in strain space. Our results indicate that the yield strain of porcine trabecular bone under multi-axial loading is nearly isotropic and despite a spread of yielding points between the 30 different microstructures, no significant relationship between the yield strain and bone volume fraction is observed. The proposed yield equation has simple format and it can be implemented into a macroscopic model for the prediction of failure of whole bones.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101003-101003-10. doi:10.1115/1.4040247.

Kinetics assessment of the human head-arms-trunk (HAT) complex via a multisegment model is a useful tool for objective clinical evaluation of several pathological conditions. Inaccuracies in body segment parameters (BSPs) are a major source of uncertainty in the estimation of the joint moments associated with the multisegment HAT. Given the large intersubject variability, there is currently no comprehensive database for the estimation of BSPs for the HAT. We propose a nonlinear, multistep, optimization-based, noninvasive method for estimating individual-specific BSPs and calculating joint moments in a multisegment HAT model. Eleven nondisabled individuals participated in a trunk-bending experiment and their body motion was recorded using cameras and a force plate. A seven-segment model of the HAT was reconstructed for each participant. An initial guess of the BSPs was obtained by individual-specific scaling of the BSPs calculated from the male visible human (MVH) images. The intersegmental moments were calculated using both bottom-up and top-down inverse dynamics approaches. Our proposed method adjusted the scaled BSPs and center of pressure (COP) offsets to estimate optimal individual-specific BSPs that minimize the difference between the moments obtained by top-down and bottom-up inverse dynamics approaches. Our results indicate that the proposed method reduced the error in the net joint moment estimation (defined as the difference between the net joint moment calculated via bottom-up and top-down approaches) by 79.3% (median among participants). Our proposed method enables an optimized estimation of individual-specific BSPs and, consequently, a less erroneous assessment of the three-dimensional (3D) kinetics of a multisegment HAT model.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101004-101004-8. doi:10.1115/1.4040311.

Mild traumatic brain injuries, or concussions, can result from head acceleration during sports. Wearable sensors like the GForceTrackerTM (GFT) can monitor an athlete's head acceleration during play. The purpose of this study was to evaluate the accuracy of the GFT for use in boys' and girls' lacrosse. The GFT was mounted to either a strap connected to lacrosse goggles (helmetless) or a helmet. The assembly was fit to a Hybrid III (HIII) headform instrumented with sensors and impacted multiple times at different velocities and locations. Measurements of peak linear acceleration and angular velocity were obtained from both systems and compared. It was found that a large percent error between the GFT and headform system existed for linear acceleration (29% for helmetless and 123% for helmet) and angular velocity (48% for helmetless and 17% for helmet). Linear acceleration data transformed to the center of gravity (CG) of the head still produced errors (47% for helmetless and 76% for helmet). This error was substantially reduced when correction equations were applied based on impact location (3–22% for helmetless and 3–12% for helmet impacts at the GFT location and transformed to the CG of the head). Our study has shown that the GFT does not accurately calculate linear acceleration or angular velocity at the CG of the head; however, reasonable error can be achieved by correcting data based on impact location.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101005-101005-13. doi:10.1115/1.4040230.

Understanding of in vivo brain biomechanical behavior is critical in the study of traumatic brain injury (TBI) mechanisms and prevention. Using tagged magnetic resonance imaging, we measured spatiotemporal brain deformations in 34 healthy human volunteers under mild angular accelerations of the head. Two-dimensional (2D) Lagrangian strains were examined throughout the brain in each subject. Strain metrics peaked shortly after contact with a padded stop, corresponding to the inertial response of the brain after head deceleration. Maximum shear strain of at least 3% was experienced at peak deformation by an area fraction (median±standard error) of 23.5±1.8% of cortical gray matter, 15.9±1.4% of white matter, and 4.0±1.5% of deep gray matter. Cortical gray matter strains were greater in the temporal cortex on the side of the initial contact with the padded stop and also in the contralateral temporal, frontal, and parietal cortex. These tissue-level deformations from a population of healthy volunteers provide the first in vivo measurements of full-volume brain deformation in response to known kinematics. Although strains differed in different tissue type and cortical lobes, no significant differences between male and female head accelerations or strain metrics were found. These cumulative results highlight important kinematic features of the brain's mechanical response and can be used to facilitate the evaluation of computational simulations of TBI.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101006-101006-11. doi:10.1115/1.4040020.

The main objective was to analyze the changes in the spatial and temporal step parameters during a dual-task: walking with a forearm crutch to partially unload the body weight of the subject. The secondary objective was to determine the influence of the use of the crutch with the dominant or nondominant hand in the essential gait parameters. Seven healthy subjects performed gait without crutches (GWC) and unilateral assisted gait (UAG) with the crutch carried out by dominant hand (dominant crutch (DC)) and nondominant hand (nondominant crutch (NDC)). Gait was recorded using a Vicon System; the GCH System 2.0 and the GCH Control Software 1.0 controlled the loads. The variables were step length, step period, velocity, step width, and step angle. The Wilcoxon signed-rank test compared GWC and UAG while also analyzing the parameters measured for both legs with DC and NDC in general and in each subject. Wilcoxon test only found significant differences in 1 of the 15 general comparisons between both legs. In the analysis by subject, step length, step period, and velocity showed significant differences between GWC and UAG. These parameters obtained less differences in DC. The effect of a forearm crutch on UAG caused a reduction in step length and velocity, and an increase in step period. However, it did not entail changes in step angle and step width. UAG was more effective when the DC carried the crutch. The unloading of 10% body weight produced an assisted gait which closely matched GWC.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101007-101007-11. doi:10.1115/1.4040457.

Paravalvular leak (PVL) is a relatively frequent complication after transcatheter aortic valve replacement (TAVR) with increased mortality. Currently, there is no effective method to pre-operatively predict and prevent PVL. In this study, we developed a computational model to predict the severity of PVL after TAVR. Nonlinear finite element (FE) method was used to simulate a self-expandable CoreValve deployment into a patient-specific aortic root, specified with human material properties of aortic tissues. Subsequently, computational fluid dynamics (CFD) simulations were performed using the post-TAVR geometries from the FE simulation, and a parametric investigation of the impact of the transcatheter aortic valve (TAV) skirt shape, TAV orientation, and deployment height on PVL was conducted. The predicted PVL was in good agreement with the echocardiography data. Due to the scallop shape of CoreValve skirt, the difference of PVL due to TAV orientation can be as large as 40%. Although the stent thickness is small compared to the aortic annulus size, we found that inappropriate modeling of it can lead to an underestimation of PVL up to 10 ml/beat. Moreover, the deployment height could significantly alter the extent and the distribution of regurgitant jets, which results in a change of leaking volume up to 70%. Further investigation in a large cohort of patients is warranted to verify the accuracy of our model. This study demonstrated that a rigorously developed patient-specific computational model can provide useful insights into underlying mechanisms causing PVL and potentially assist in pre-operative planning for TAVR to minimize PVL.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101008-101008-8. doi:10.1115/1.4040338.

Calcific aortic valve disease (CAVD) is a progressive disease in which minerals accumulate in the tissue of the aortic valve cusps, stiffening them and preventing valve opening and closing. The process of valve calcification was found to be similar to that of bone formation including cell differentiation to osteoblast-like cells. Studies have shown the contribution of high strains to calcification initiation and growth process acceleration. In this paper, a new strain-based calcification growth model is proposed. The model aims to explain the unique shape of the calcification and other disease characteristics. The calcification process was divided into two stages: Calcification initiation and calcification growth. The initiation locations were based on previously published findings and a reverse calcification technique (RCT), which uses computed tomography (CT) scans of patients to reveal the calcification initiation point. The calcification growth process was simulated by a finite element model of one aortic valve cusp loaded with cyclic loading. Similar to Wolff's law, describing bone response to stress, our model uses strains to drive calcification formation. The simulation grows calcification from its initiation point to its full typical stenotic shape. Study results showed that the model was able to reproduce the typical calcification growth pattern and shape, suggesting that strain is the main driving force behind calcification progression. The simulation also sheds light on other disease characteristics, such as calcification growth acceleration as the disease progresses, as well as sensitivity to hypertension.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101009-101009-8. doi:10.1115/1.4040458.

A wide range of materials have been used for the development of intervertebral cages. Poly(propylene fumarate) (PPF) has been shown to be an excellent biomaterial with characteristics similar to trabecular bone. Hydroxyapatite (HA) has been shown to enhance biocompatibility and mechanical properties of PPF. The purpose of this study was to characterize the effect of PPF augmented with HA (PPF:HA) and evaluate the feasibility of this material for the development of cervical cages. PPF was synthesized and combined with HA at PPF:HA wt:wt ratios of 100:0, 80:20, 70:30, and 60:40. Molds were fabricated for testing PPF:HA bulk materials in compression, bending, tension, and hardness according to ASTM standards, and also for cage preparation. The cages were fabricated with and without holes and with porosity created by salt leaching. The samples as well as the cages were mechanically tested using a materials testing frame. All elastic moduli as well as the hardness increased significantly by adding HA to PPF (p < 0.0001). The 20 wt % HA increased the moduli significantly compared to pure PPF (p < 0.0001). Compressive stiffness of all cages also increased with the addition of HA. HA increased the failure load of the porous cages significantly (p = 0.0018) compared with nonporous cages. PPF:HA wt:wt ratio of 80:20 proved to be significantly stiffer and stronger than pure PPF. The current results suggest that this polymeric composite can be a suitable candidate material for intervertebral body cages.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101010-101010-8. doi:10.1115/1.4040312.

With the introduction of high-speed cutting tools, clinicians have recognized the potential for thermal damage to the material being cut. Here, we developed a mathematical model of heat transfer caused by drilling bones of different densities and validated it with respect to experimentally measured temperatures in bone. We then coupled these computational results with a biological assessment of cell death following osteotomy site preparation. Parameters under clinical control, e.g., drill diameter, rotational speed, and irrigation, along with patient-specific variables such as bone density were evaluated in order to understand their contributions to thermal damage. Predictions from our models provide insights into temperatures and thresholds that cause osteocyte death and that can ultimately compromise stability of an implant.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101011-101011-9. doi:10.1115/1.4040252.

Current implant materials and designs used in spinal fusion show high rates of subsidence. There is currently a need for a method to predict the mechanical properties of the endplate using clinically available tools. The purpose of this study was to develop a predictive model of the mechanical properties of the vertebral endplate at a scale relevant to the evaluation of current medical implant designs and materials. Twenty vertebrae (10 L1 and 10 L2) from 10 cadavers were studied using dual-energy X-ray absorptiometry to define bone status (normal, osteopenic, or osteoporotic) and computed tomography (CT) to study endplate thickness (μm), density (mg/mm3), and mineral density of underlying trabecular bone (mg/mm3) at discrete sites. Apparent Oliver–Pharr modulus, stiffness, maximum tolerable pressure (MTP), and Brinell hardness were measured at each site using a 3 mm spherical indenter. Predictive models were built for each measured property using various measures obtained from CT and demographic data. Stiffness showed a strong correlation between the predictive model and experimental values (r = 0.85), a polynomial model for Brinell hardness had a stronger predictive ability compared to the linear model (r = 0.82), and the modulus model showed weak predictive ability (r = 0.44), likely due the low indentation depth and the inability to image the endplate at that depth (≈0.15 mm). Osteoporosis and osteopenia were found to be the largest confounders of the measured properties, decreasing them by approximately 50%. It was confirmed that vertebral endplate mechanical properties could be predicted using CT and demographic indices.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101012-101012-7. doi:10.1115/1.4040452.

Recent work utilizing ultrasound imaging demonstrated that individuals with low back pain (LBP) have increased thickness and decreased mobility of the thoracolumbar fascia (TLF), an indication that the TLF may play a role in LBP. This study used a porcine injury model (microsurgically induced local injury)—shown to produce similar results to those observed in humans with LBP—to test the hypothesis that TLF mechanical properties may also be altered in patients with LBP. Perimuscular TLF tissue was harvested from the noninjured side of vertebral level L3-4 in pigs randomized into either control (n = 5) or injured (n = 5) groups. All samples were tested with a displacement-controlled biaxial testing system using the following protocol: cyclic loading/unloading and stress relaxation tests at 25%, 35%, and then 45% of their resting length. Tissue anisotropy was also explored by comparing responses to loading in longitudinal and transverse orientations. Tissues from injured pigs were found to have greater stretch–stretch ratio moduli (measure of tissue stiffness), less energy dissipation, and less stress decay compared to tissues from control pigs. Responses across these variables also depended on loading orientation. Clinical significance: these findings suggest that a focal TLF injury can produce impairments in tissue mechanical properties away from the injured area itself. This could contribute to some of the functional abnormalities observed in human LBP.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101013-101013-13. doi:10.1115/1.4040400.

Despite major advances made in modeling vascular tissue biomechanics, the predictive power of constitutive models is still limited by uncertainty of the input data. Specifically, key measurements, like the geometry of the stress-free (SF) state, involve a definite, sometimes non-negligible, degree of uncertainty. Here, we introduce a new approach for sensitivity analysis of vascular hyperelastic constitutive models to uncertainty in SF measurements. We have considered two vascular hyperelastic models: the phenomenological Fung model and the structure-motivated Holzapfel–Gasser–Ogden (HGO) model. Our results indicate up to 160% errors in the identified constitutive parameters for a 5% measurement uncertainty in the SF data. Relative margins of errors of up to 30% in the luminal pressure, 36% in the axial force, and over 200% in the stress predictions were recorded for 10% uncertainties. These findings are relevant to the large body of studies involving experimentally based modeling and analysis of vascular tissues. The impact of uncertainties on calibrated constitutive parameters is significant in context of studies that use constitutive parameters to draw conclusions about the underlying microstructure of vascular tissues, their growth and remodeling processes, and aging and disease states. The propagation of uncertainties into the predictions of biophysical parameters, e.g., force, luminal pressure, and wall stresses, is of practical importance in the design and execution of clinical devices and interventions. Furthermore, insights provided by the present findings may lead to more robust parameters identification techniques, and serve as selection criteria in the trade-off between model complexity and sensitivity.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(10):101014-101014-12. doi:10.1115/1.4040249.

The implant stability and biomechanical response of periprosthetic bone in acetabulum around total hip joint replacement (THR) devices depend on a host of parameters, including design of articulating materials, gait cycle and subject parameters. In this study, the impact of shell design (conventional, finned, spiked, and combined design) and liner material on the biomechanical response of periprosthetic bone has been analyzed using finite element (FE) method. Two different liner materials: high density polyethylene–20% hydroxyapatite–20% alumina (HDPE–20%HA–20%Al2O3) and highly cross-linked ultrahigh molecular weight polyethylene (HC-UHMWPE) were used. The subject parameters included bone condition and bodyweight. Physiologically relevant load cases of a gait cycle were considered. The deviation of mechanical condition of the periprosthetic bone due to implantation was least for the finned shell design. No significant deviation was observed at the bone region adjacent to the spikes and the fins. This study recommends the use of the finned design, particularly for weaker bone conditions. For stronger bones, the combined design may also be recommended for higher stability. The use of HC-UHMWPE liner was found to be better for convensional shell design. However, similar biomechanical response was captured in our FE analysis for both the liner materials in case of other shell designs. Overall, the study establishes the biomechanical response of periprosthetic bone in the acetabular with preclinically tested liner materials together with new shell design for different subject conditions.

Commentary by Dr. Valentin Fuster

Technical Brief

J Biomech Eng. 2018;140(10):104501-104501-6. doi:10.1115/1.4040248.

Osteoarthritis sufferers commonly have first metatarsophalangeal joint (MTPJ) problems in which articular surfaces are changed permanently due to fatigue. Therefore, medical devices for early diagnosis would increase the opportunity for prevention of disease progression. In previous studies on stiffness of the first MTPJ many details, although functionally of great importance, have not been fully considered including: design and size of the device, tribology consideration, and errors from device. Therefore, the motivation of our research was to enhance the device design by reducing the size of the device, and device design was enhanced by minimizing measurement errors through development of a new ergonomic left and right foot instrument located medial to the first MTPJ (instead of beneath the foot). The first MTPJ stiffness (N mm/kg radian) measurement was taken on 28 subjects with two replicates per subject by the same tester. The first MTPJ stiffness ranged from 3.49 to 14.42 N mm/kg radian with the mean (SD) value of 8.28 (3.15) N mm/kg radian for the left feet and 3.91 to 11.90 N mm/kg radian with the mean (SD) value of 7.65 (2.07) N mm/kg radian for the right feet. Reliability evaluation was measured using intraclass correlation coefficient and described an excellent reliability between two tests.

Commentary by Dr. Valentin Fuster

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