Accepted Manuscripts

Feng Liu, Priyatanu Roy, Qi Shao, Chunlan Jiang, Jeunghwan Choi, Connie Chung, Dushyant Mehra and Dr. John Bischof
J Biomech Eng   doi: 10.1115/1.4039375
Atrial fibrillation affects millions of people in the US. Focal therapy is an attractive treatment for atrial fibrillation that avoids the debilitating effects of drugs for disease control. Perhaps the most widely used focal therapy for atrial fibrillation (AF) is heat-based radiofrequency (heating), although cryotherapy (cryo) is rapidly replacing it due to a reduction in side effects and positive clinical outcomes. A third focal therapy, irreversible electroporation (IRE), is also being considered. This study was designed to help guide treatment thresholds and compare mechanism of action across heating, cryo, and IRE. Testing was undertaken on HL-1 cells, a well-established cardiomyocyte cell line, to assess injury thresholds for each treatment method. Cell viability, as assessed by Hoechst and PI staining, was found to be minimal after exposure to temperatures =-40 °C (cryo), =60 °C (heating), and when field strengths =1500 V/cm (IRE) were used. Viability was then correlated to protein denaturation fraction (PDF) as assessed by Fourier Transform Infrared (FTIR) spectroscopy, and protein loss fraction (PLF) as assessed by Bicinchoninic Acid (BCA) assay after the three treatments. These protein changes were assessed both in the supernatant and the pellet of cell suspensions post treatment. We found that dramatic viability loss (=50%) correlated strongly with =12% protein change (PLF, PDF or a combination of the two) in every focal treatment. These studies help in defining both cellular thresholds and protein-based mechanisms of action that can be used to improve focal therapy application for atrial fibrillation.
TOPICS: Heat, Performance, Proteins, Electroporation, Patient treatment, Heating, Pharmacokinetics, Wounds, Testing, Diseases, Drugs, Fourier transforms, Temperature, Spectroscopy, Fourier transform infrared spectroscopy
Eric Poon, Vikas Thondapu, Umair Hayat, Peter Barlis, Chooi Yap, Po Kuo, Qisen Wang, Jiawei Ma, Shuang Zhu, Stephen Moore and Andrew Ooi
J Biomech Eng   doi: 10.1115/1.4039306
One particular complexity of coronary artery is the natural tapering of the vessel with proximal segments having larger caliber and distal tapering as the vessel get smaller. The natural tapering of a coronary artery often leads to proximal incomplete stent apposition (ISA). ISA alters coronary hemodynamics and creates pathological path to develop complications such as in-stent restenosis, and more worryingly, stent thrombosis. By employing state-of-the-art computer-aided design software, generic stent hoops were virtually deployed in an idealized tapered coronary artery with decreasing malapposition distance. Pulsatile blood flow simulations were carried out using computational fluid dynamics (CFD) on these computer-aided design models. CFD results reveal unprecedented details in both spatial and temporal development of micro-recirculation environments throughout the cardiac cycle. Arterial tapering also introduces secondary micro-recirculation. These primary and secondary micro-recirculations provoke significant fluctuations in arterial wall shear stress (WSS). There has been a direct correlation with changes in WSS and the development of atherosclerosis. Further, the presence of these micro-recirculations influence strongly on the local levels of blood viscosity in the vicinity of the malapposed stent struts. The observation of secondary micro-recirculations and changes in blood rheology is believed to complement the wall (-based) shear stress, perhaps providing additional physical explanations for tissue accumulation near ISA detected from high resolution optical coherence tomography. This work may aid in helping to optimize future stent properties and designs that will translate to innovations that directly impact clinical outcomes.
TOPICS: Hemorheology, stents, Coronary arteries, Computational fluid dynamics, Computer-aided design, Shear stress, Vessels, Atherosclerosis, Thrombosis, Blood flow, Cardiac cycle, Engineering simulation, Performance, Computer software, Hemodynamics, Simulation, Coherence (Optics), Rheology, Fluctuations (Physics), Resolution (Optics), Biological tissues, Blood
Andrea Fotticchia, Emrah Demirci, Cristina Lenardi and Y Liu
J Biomech Eng   doi: 10.1115/1.4039307
There is lack of investigation capturing the complex mechanical interaction of tissue engineered IVD (intervertebral disc) constructs in physiologically-relevant environmental conditions. In this study, mechanical characterisation of anisotropic eletrospinning (ES) substrates made of polycaprolactone (PCL) was carried out in wet and dry conditions and viability of human bone marrow derived mesenchymal stem cells (hMSCs) seeded within double layers of ES PCL was also studied. Cyclic compression of IVD-like constructs composed of an agarose core confined by ES PCL double-layers was implemented using a bioreactor and the cellular response to the mechanical stimulation was evaluated. Tensile tests showed decrease of elastic modulus of ES PCL as the angle of stretching increased and at 60° stretching angle in wet, maximum ultimate tensile strength was observed. Based on the configuration of IVD-like constructs, the calculated circumferential stress experienced by the ES PCL double layers was 40 times of the vertical compressive stress. Confined compression of IVD-like constructs at 5% and 10% displacement dramatically reduced cell viability, particularly at 10%, although cell presence in small and isolated area can still be observed after mechanical conditioning. Hence, material mechanical properties of tissue-engineered scaffolds, composed of fibril structure of polymer with low melting point, are affected by the testing condition. Circumferential stress induced by axial compressive stimulation, conveyed to the ES PCL double-layer wrapped around an agarose core, can affect the viability of cells seeded at the interface, depending on the mechanical configuration and magnitude of the load.
TOPICS: Biological tissues, Compression, Electrospinning, Intervertebral discs, Hoop stress, Agar, Anisotropy, Mechanical properties, Melting point, Tensile strength, Stress, Stem cells, Compressive stress, Displacement, Elastic moduli, Bone, Polymers, Testing, Bioreactors
Inge A.E.W. van Loosdregt, Giulia Weissenberger, Marc P.F.H.L. van Maris, Cees W.J. Oomens, Sandra Loerakker, Oscar Stassen and Carlijn V.C Bouten
J Biomech Eng   doi: 10.1115/1.4039308
Contractile stress generation by adherent cells is largely determined by the interplay of forces within their cytoskeleton. It is known that actin stress fibers, connected to focal adhesions, provide contractile stress generation, while microtubules and intermediate filaments provide cells compressive stiffness. Recent studies have shown the importance of the interplay between stress fibers and the intermediate filament vimentin. Therefore, the effect of the interplay between the stress fibers and vimentin on stress generation was quantified in this study. We hypothesized that the net stress generation comprises the stress fiber contraction combined with the vimentin resistance. We expected an increased net stress in vimentin knockout (VimKO) mouse embryonic fibroblasts (MEFs) compared to their wild-type (VimWT) counterparts, due to the decreased resistance against stress fiber contractility. To test this, the net stress generation by VimKO and VimWT MEFs was determined using the thin film method combined with sample-specific finite element modeling. Additionally, focal adhesion and stress fiber organization were examined via immunofluorescent staining. Net stress generation of VimKO MEFs was three-fold higher compared to VimWT MEFs. No differences in focal adhesion size or stress fiber organization and orientation were found between the two cell types. This suggests that the increased net stress generation in VimKO MEFs was caused by the absence of the resistance that vimentin provides against stress fiber contraction. Taken together, these data suggest that vimentin resists the stress fiber contractility, as hypothesized. Thus indicating the importance of vimentin in regulating cellular stress generation by adherent cells.
TOPICS: Stress, Fibers, Adhesion, Thin films, Finite element analysis, Modeling, Stiffness, Fibroblasts
Eleonora Tubaldi, Michael Paidoussis and Marco Amabili
J Biomech Eng   doi: 10.1115/1.4039284
This study addresses the dynamic response to pulsatile physiological blood flow and pressure of a woven Dacron graft currently used in thoracic aortic surgery. The model of the prosthesis assumes a cylindrical orthotropic shell described by means of nonlinear Novozhilov shell theory. The blood flow is modeled as Newtonian pulsatile flow, and unsteady viscous effects are included. Coupled fluid-structure Lagrange equations for open systems with wave propagation subject to pulsatile flow are applied. Physiological waveforms of blood pressure and velocity are approximated with the first eight harmonics of the corresponding Fourier series. Time responses of the prosthetic wall radial displacement are considered for two physiological conditions: at rest (60 bpm) and at high heart rate (180 bpm). While the response at 60 bpm reproduces the behavior of the pulsatile pressure, higher harmonics frequency contributions are observed at 180 bpm altering the shape of the time response. Frequency-responses show resonance peaks for heart rates between 130 bpm and 200 bpm due to higher harmonics of the pulsatile flow excitation. These resonant peaks correspond to unwanted high-frequency radial oscillations of the vessel wall that can compromise the long term functioning of the prosthesis in case of significant physical activity. Thanks to this study, the dynamic response of Dacron prostheses to pulsatile flow can be understood as well as some possible complications in case of significant physical activity.
TOPICS: Prostheses, Pulsatile flow, Nonlinear dynamics, Physiology, Pressure, Shells, Resonance, Dynamic response, Blood flow, Excitation, Fourier series, Frequency response, Oscillations, Vessels, Shapes, Wave propagation, Fluids, Blood, Surgery, Artificial limbs, Displacement
Hosein Naseri and Håkan Johansson
J Biomech Eng   doi: 10.1115/1.4039176
In modelling the mechanical behavior of soft tissues, the proper choice of an experiment for identifying material parameters is not an easy task. In this study, a finite element computational framework is used to virtually simulate and assess commonly used experimental setups; rotational rheometer tests, confined- and unconfined- compression tests, and indentation tests. Variance-based global sensitivity analysis is employed to identify which parameters in different experimental setups govern model prediction, and are thus more likely to be determined through parameter identification processes. Therefore, a priori assessment of experimental setups provides a base for systematic and reliable parameter identification. It is found that in indentation tests and unconfined-compression tests, incompressibility of soft tissues (adipose tissue in this study) plays an important role at high strain rates. That means bulk stiffness constitutes the main part of the mechanism of tissue response, thus these experimental setups may not be appropriate for identifying shear stiffness. Also, identified material parameters through loading-unloading shear tests at a certain rate might not be reliable for other rates, since adipose tissue shows highly strain rate dependent behavior. Frequency sweep tests at a wide-enough frequency range seem to be the best setup to capture the strain rate behavior. Moreover, analyzing the sensitivity of model parameters in the different experimental setups provides further insight about the model itself.
TOPICS: Biological tissues, Mechanical testing, Sensitivity analysis, Stiffness, Soft tissues, Shear (Mechanics), Compression, Rheometers, Finite element analysis, Mechanical behavior, Modeling
Ramesh Marrey, Brian Baillargeon, Maureen Dreher, Jason D Weaver, Srinidhi Nagaraja, Nuno Rebelo and Xiao-Yan Gong
J Biomech Eng   doi: 10.1115/1.4039173
Evaluating risk of fatigue fractures in cardiovascular implants via non-clinical testing is essential to provide an indication of their durability. This is generally accomplished by experimental accelerated durability testing and often complemented with computational simulations to calculate "fatigue safety factors". While many methods exist to calculate fatigue safety factors, none have been validated against experimental data. The current study presents three methods for calculating fatigue safety factors and compares them to experimental fracture outcomes under axial fatigue loading, using cobalt-chromium test specimens designed to represent cardiovascular stents. Fatigue safety factors were generated by calculating mean and alternating stresses using a simple Scalar Method, a Tensor Method which determines principal values based on averages and differences of the stress tensors, and a Modified Tensor Method which accounts for stress rotations. The results indicate that the Tensor Method and the Modified Tensor Method consistently predicted fracture or survival (to 10 million cycles) for specimens subjected to experimental axial fatigue. In contrast, for one axial deformation condition, the Scalar Method incorrectly predicted survival even though fractures were observed in experiments. These results demonstrate limitations of the Scalar Method and potential inaccuracies. A separate computational analysis of torsional fatigue was also completed to illustrate differences between the Tensor Method and the Modified Tensor Method. Because of its ability to account for changes in principal directions across the fatigue cycle, the Modified Tensor Method offers a general computational method that can be applied for improved predictions for fatigue safety regardless of loading conditions.
TOPICS: Fatigue, Safety, Cardiovascular system, stents, Computational methods, Tensors, Fracture (Process), Fracture (Materials), Scalars, Stress, Durability, Cycles, Testing, Risk, Stress tensors, Engineering simulation, Performance, Simulation, Deformation, Cobalt
Shady Elmasry, Shihab Asfour and Francesco Travascio
J Biomech Eng   doi: 10.1115/1.4039174
Percutaneous pedicle screw fixation (PPSF) is a minimally invasive surgery (MIS) employed in the treatment of thoracolumbar burst fractures (TBF). However, hardware failure and loss of angular correction are common limitations caused by the poor support of the anterior column of the spine. Balloon Kyphoplasty (KP) is another MIS successfully used in the treatment of compression fractures by augmenting the injured vertebral body with cement. To overcome its limitations as a stand-alone procedure, it was suggested to augment PPSF with KP when treating TBF. Yet, little is known about the biomechanical alteration occurring to the spine after performing such a procedure. This study aimed at evaluating and comparing the post-operative biomechanical performance of stand-alone PPSF, stand-alone KP, and KP-augmented PPSF procedures. Novel 3D finite element models of the thoracolumbar junction mimicking the fractured spine and the three investigated procedures were developed and tested under physiological loading conditions. Spinal stiffness, stresses at the implanted hardware, and intradiscal pressure at adjacent segments were measured and compared. The results showed no major differences in all the measured parameters when stand-alone PPSF or KP-augmented PPSF procedures were simulated. In addition, it was shown that stand-alone KP may be a suitable approach in the attempt of restoring the stiffness of the intact spine. In conclusion, the results reported in this analysis suggest that, when treating TBF, the augmentation of PPSF with KP does not improve the biomechanical performance of the spine in the immediate post-operative term.
TOPICS: Biomechanics, Fracture (Materials), Finite element analysis, Fracture (Process), Spinal pedicle screws, Hardware, Stiffness, Spinal fractures, Physiology, Stress, Cements (Adhesives), Pressure, Surgery, Compression, Failure, Finite element model, Junctions
Kellie Stoka, Justine Maedeker, L Bennett, Siddharth Bhayani, William Gardner, Jesse Procknow, Austin J Cocciolone, Tezin Walji, Clarissa Craft and Jessica E. Wagenseil
J Biomech Eng   doi: 10.1115/1.4039175
Increased arterial stiffness is associated with atherosclerosis in humans, but there have been limited animal studies investigating the relationship between these factors. We bred elastin wildtype (Eln+/+) and heterozygous (Eln+/-) mice to apolipoprotein E wildtype (Apoe+/+) and knockout (Apoe-/-) mice and fed them normal (ND) or Western diet (WD) for 12 weeks. Eln+/- mice have increased arterial stiffness. Apoe-/- mice develop atherosclerosis on ND that is accelerated by WD. It has been reported that Apoe-/- mice have increased arterial stiffness and that the increased stiffness may play a role in atherosclerotic plaque progression. We found that Eln+/+Apoe-/- arterial stiffness is similar to Eln+/+Apoe+/+ mice at physiologic pressures, suggesting that changes in stiffness do not play a role in atherosclerotic plaque progression in Apoe-/- mice. We found that Eln+/-Apoe-/- mice have increased structural arterial stiffness compared to Eln+/+Apoe-/- mice, but they only have increased amounts of ascending aortic plaque on ND, not WD. The results suggest a change in atherosclerosis progression but not end stage disease in Eln+/-Apoe-/- mice due to increased arterial stiffness. Possible contributing factors include increased blood pressure and changes in circulating levels of interleukin-6 (IL6) and transforming growth factor beta 1 that are also associated with Eln+/- genotype.
TOPICS: Stiffness, Atherosclerosis, Physiology, Pressure, Blood, Diseases
Technical Brief  
Logan Miller, Calvin Kuo, Lyndia C. Wu, Jillian Urban, David Camarillo and Joel D Stitzel
J Biomech Eng   doi: 10.1115/1.4039165
Head impact exposure in popular contact sports is not well understood, especially in the youth population, despite recent advances in impact-sensing technology which has allowed widespread collection of real-time head impact data. Head kinematics have been measured in previous studies using instrumented helmets, skin patches, skull caps, and instrumented mouthpieces. A limitation of instrumented helmets is that they cannot be used in contact sports where the athletes do not wear helmets, such as soccer and women's lacrosse. The accuracy of measuring impact kinematics using some of these methods, however, has been recently questioned. Measurement errors have been observed in the skin patch and skull cap sensors due to relative motion between the sensor and the skull. Previous studies indicate that a custom instrumented mouthpiece is a superior method for collecting accurate head acceleration data. The objective of this study was to evaluate the efficacy of mounting a sensor device inside an acrylic retainer form factor to measure 6-degree-of-freedom (6DOF) head kinematic response. The current study compares 6DOF mouthpiece kinematics at the head center of gravity (CG) to kinematics measured by an anthropomorphic test device (ATD).
TOPICS: Kinematics, Sensors, Skin, Sports, Center of mass, Errors, Wear
Katrina Knight, Pamela Moalli and Steven D. Abramowitch
J Biomech Eng   doi: 10.1115/1.4039058
Pelvic organ prolapse meshes are exposed to predominately tensile loading conditions in vivo that can lead to pore collapse by 70-90%, decreasing overall porosity, and providing a plausible mechanism for the contraction/shrinkage of mesh observed following implantation. To prevent pore collapse, we proposed to design synthetic meshes with a macrostructure that results in auxetic behavior, the pores expand laterally, instead of contracting when loaded. Such behavior can be achieved with a range of auxetic structures/geometries. This study utilized finite element analysis to assess the behavior of mesh models with 8 auxetic pore geometries subjected to uniaxial loading to evaluate their potential to allow for pore expansion while simultaneously providing resistance to tensile loading. Overall, substituting auxetic geometries for standard pore geometries yielded more pore expansion, but often at the expense of increased model elongation, with 2 of the 8 auxetics not able to maintain pore expansion at higher levels of tension. Meshes with stable pore geometries that remain open with loading will afford the ingrowth of host tissue into the pores and improved integration of the mesh. Given the demonstrated ability of auxetic geometries to allow for pore size maintenance (and pore expansion), auxetically designed meshes have the potential to significantly impact surgical outcomes and decrease the likelihood of major mesh related complications.
TOPICS: Design, Computer simulation, Collapse, Porosity, Tension, Shrinkage (Materials), Biological tissues, Finite element analysis, Performance, Surgery, Elongation, Maintenance
Bora Sul, Zachary Oppito, Shehan Jayasekera, Brian Vanger, Amy Zeller, Michael Morris, Kai Ruppert, Talissa Altes, Vineet Rakesh, Steven Day, Risa J. Robinson, Jaques Reifman and Anders Wallqvist
J Biomech Eng   doi: 10.1115/1.4038896
Computational models are useful for understanding respiratory physiology. Crucial to such models are the boundary conditions specifying the flow conditions at truncated airway branches (terminal flow rates). However, most studies make assumptions about these values, which are difficult to obtain in vivo. We developed a computational fluid dynamics (CFD) model of airflows for steady expiration to investigate how terminal flows affect airflow patterns in respiratory airways. First, we measured in vitro airflow patterns in a physical airway model, using particle image velocimetry. The measured and computed airflow patterns agreed well, validating our CFD model. Next, we used the lobar flow fractions from a healthy or chronic obstructive pulmonary disease (COPD) subject as constraints to derive different terminal flow rates (i.e., three healthy, one COPD), and computed the corresponding airflow patterns in the same geometry. To assess airflow sensitivity to the boundary conditions, we used the correlation coefficient of the shape similarity (R) and the root mean square of the velocity magnitude difference (Drms) between two velocity contours. Airflow patterns in the central airways were similar across healthy conditions (minimum R, 0.80) despite variations in terminal flow rates, but markedly different for COPD (minimum R, 0.26; maximum Drms, 10 times that of healthy cases). In contrast, those in the upper airway were similar for all cases. Our findings quantify how variability in terminal and lobar flows contribute to airflow patterns in respiratory airways. They highlight the importance of using lobar flow fractions to examine physiologically relevant airflow characteristics.
TOPICS: Air flow, Computational fluid dynamics, Lung, Flow (Dynamics), Boundary-value problems, Diseases, Geometry, Particulate matter, Shapes, Physiology
Tammy L. Haut Donahue
J Biomech Eng   doi: 10.1115/1.4038748
TOPICS: Anterior cruciate ligament
Ajay Bhandari, Ankit Bansal, Anup Singh and Niraj Sinha
J Biomech Eng   doi: 10.1115/1.4038746
Systemic administration of drugs in tumors is a challenging task due to unorganized microvasculature and non-uniform extravasation. There is an imperative need to understand the transport behaviour of drugs when administered intravenously. In this study, a transport model is developed to understand the therapeutic efficacy of a free drug and liposome encapsulated drugs (LED), in heterogeneous vasculature of human brain tumors. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data is employed to model the heterogeneity in tumor vasculature that is directly mapped onto the computational fluid dynamics (CFD) model. Results indicate that heterogeneous vasculature leads to preferential accumulation of drugs at the tumor position. Higher drug accumulation was found at location of higher interstitial volume, thereby facilitating more tumor cell killing at those areas. Liposome released drug (LRD) remains inside the tumor for longer time as compared to free drug, which together with higher concentration enhances therapeutic efficacy. The interstitial as well as intracellular concentration of LRD is found to be 2 to 20 fold higher as compared to free drug, which are in line with experimental data reported in literature. Close agreement between the predicted and experimental data demonstrates the potential of the developed model in modeling the transport of LED and free drugs in heterogeneous vasculature of human tumors.
TOPICS: Magnetic resonance imaging, Brain, Tumors, Anticancer drugs, Drugs, Computational fluid dynamics, Modeling, Resonance, Imaging
Swithin Razu and Trent M. Guess
J Biomech Eng   doi: 10.1115/1.4038507
This study leveraged data from the "Sixth Grand Challenge Competition to Predict in Vivo Knee Loads" to create a full-body musculoskeletal model that incorporates subject specific geometries of the right leg in order to concurrently predict knee contact forces, ligament forces, muscle forces, and ground contact forces. The objectives of this paper are twofold: First, to describe an electromyography (EMG)-driven modeling methodology to predict knee contact forces, and second to validate model predictions by evaluating the model predictions against known values for a patient with an instrumented total knee replacement (TKR) for three distinctly different gait styles (normal, smooth, and bouncy gait). A novel EMG-driven feedforward with feedback trim motor control strategy was used to concurrently estimate muscle forces and knee contact forces from standard motion capture data collected on the individual subject. The predicted medial, lateral, and total tibiofemoral forces represented the overall measured magnitude and temporal patterns with good root mean squared errors (RMSEs) and Pearson's correlation (?2). The model accuracy was high: medial, lateral, and total tibiofemoral contact force RMSEs = 0.15, 0.14, 0.21 body weight (BW), and (0.92< ?2<0.96) for normal gait; RMSEs = 0.18 BW, 0.21 BW, 0.29 BW, and (0.81< ?2<0.93) for smooth gait; and RMSEs = 0.21 BW, 0.22 BW, 0.33 BW, and (0.86< ?2<0.95) for bouncy gait, respectively.
TOPICS: Dynamics (Mechanics), Simulation, Electromyography, Knee, Muscle, Musculoskeletal system, Knee joint prostheses, Weight (Mass), Errors, Feedback, Feedforward control, Stress, Motor controls, Modeling
Peshala / P Thibotuwawa Gamage, Fardin Khalili, MD / Khurshidul Azad and Hansen / A. Mansy
J Biomech Eng   doi: 10.1115/1.4038431
Inspiratory flow in a multi-generation pig lung airways was numerically studied at a steady inlet flow rate of 3.2×10-4 m3/s corresponding to a Reynolds number of 1150 in the trachea. The model was validated by comparing velocity distributions with previous measurements and simulations in simplified airway geometries. Simulation results provided detailed maps of the axial and secondary flow patterns at different cross sections of the airway tree. The vortex core regions in the airways were visualized using absolute helicity values and suggested the presence of secondary flow vortices where two counter rotating vortices were observed at the main bifurcation and in many other bifurcations. Both laminar and turbulent flow were considered. Results showed that axial and secondary flows were comparable in the laminar and turbulent cases. Turbulent kinetic energy vanished in the more distal airways, which indicates that the flow in these airways approaches laminar flow conditions. The simulation results suggested viscous pressure drop values comparable to earlier studies. The monopodial asymmetric nature of airway branching in pigs resulted in airflow patterns that are different from the less asymmetric human airways. The major daughters of the pig airways tended to have high airflow ratios, which may lead to different particle distribution and sound generation patterns. These differences need to be taken into consideration when interpreting the results of animal studies involving pigs before generalizing these results to humans.
TOPICS: Flow (Dynamics), Modeling, Lung, Vortices, Turbulence, Air flow, Bifurcation, Simulation results, Trachea, Pressure drop, Laminar flow, Reynolds number, Simulation, Cross section (Physics), Engineering simulation, Kinetic energy, Particulate matter
Ivan A. Kuznetsov and Andrey Kuznetsov
J Biomech Eng   doi: 10.1115/1.4038201
The goal of this paper is to use mathematical modeling to investigate the fate of dense core vesicles (DCVs) captured in en passant boutons located in nerve terminals. One possibility is that all DCVs captured in boutons are destroyed, another possibility is that captured DCVs can escape and reenter the pool of transiting DCVs that move through the boutons, and a third possibility is that some DCVs are destroyed in boutons, while some reenter the transiting pool. We developed a model by applying the conservation of DCVs in various compartments composing the terminal, to predict different scenarios that emerge from the above assumptions about the fate of DCVs captured in boutons. The simulations demonstrate that, if no DCV destruction in boutons is assumed and all captured DCVs reenter the transiting pool, the DCV fluxes evolve to a uniform circulation in a type Ib terminal at steady-state and the DCV flux remains constant from bouton to bouton. Because at steady-state the amount of captured DCVs is equal to the amount of DCVs that reenter the transiting pool, no decay of DCV fluxes occurs. In a type III terminal at steady-state, the anterograde DCV fluxes decay from bouton to bouton, while retrograde fluxes increase. This is explained by a larger capture efficiency of anterogradely moving DCVs than of retrogradely moving DCVs in type III boutons, while the captured DCVs that reenter the transiting pool are assumed to be equally split between anterogradely and retrogradely moving components.
TOPICS: Modeling, Flux (Metallurgy), Steady state, Simulation, Engineering simulation
James W. Reinhardt and Keith Gooch
J Biomech Eng   doi: 10.1115/1.4037947
We developed an agent-based model that incorporates repetitively applied traction force within a discrete fiber network to understand how microstructural properties of the network influence mechanical properties and traction force-induced remodeling. An important difference between our model and similar finite-element models is that by implementing more biologically-realistic dynamic traction, we can explore a greater range of matrix remodeling. Here, we validated our model by reproducing qualitative trends observed in three sets of experimental data reported by others: tensile and shear testing of cell-free collagen gels, collagen remodeling around a single isolated cell, and collagen remodeling between pairs of cells. In response to tensile and shear strain, simulated acellular networks exhibited biphasic stress-strain curves indicative of strain-stiffening. Our data support the notion that strain-stiffening might occur as individual fibrils successively align along the axis of strain and become engaged in tension. In simulations with a single, contractile cell, peak collagen displacement occurred closest to the cell and decreased with increasing distance. In simulations with two cells, compaction of collagen between cells appeared inversely related to the initial distance between cells. Further analysis revealed strain energy was relatively uniform around the outer surface of cells separated by 250 microns, but became increasingly non-uniform as the distance between cells decreased. This pattern was partly attributable to the pattern of collagen compaction. These findings are of interest because fibril alignment, density, and strain energy may each contribute to contact guidance during tissue morphogenesis.
TOPICS: Fibers, Network models, Traction, Simulation, Compacting, Shear (Mechanics), Engineering simulation, Testing, Displacement, Finite element model, Stress-strain curves, Mechanical properties, Biological tissues, Density, Tension
Technical Brief  
Nachiket M. kharalkar, Steven C. Bauserman and Jonathan W. Valvano
J Biomech Eng   doi: 10.1115/1.4026559
Effect of formalin fixation on thermal conductivity of the biological tissues is presented. A self-heated thermistor probe was used to measure the tissue thermal conductivity. The thermal conductivity of muscle and fatty tissue samples was measured before the formalin fixation and then 27 hours after formalin fixation. The results indicate that the formalin fixation does not cause a significant change in the tissue thermal conductivity of muscle and fatty tissues. In the clinical setting, tissues removed surgically are often fixed in formalin for subsequent pathological analysis. These results suggest that, in terms of thermal properties, it is equally appropriate to perform in vitro studies in either fresh tissue or formalin-fixed tissue.
TOPICS: Thermal conductivity, Biological tissues, Muscle, Probes, Surgery, Thermal properties

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