Accepted Manuscripts

Carrie E. Barnum, Jennifer L. Fey, Stephanie N. Weiss, Guillermo Barila, Amy G. Brown, Brianne K. Connizzo, Snehal S. Shetye, Michal A. Elovitz and Louis J. Soslowsky
J Biomech Eng   doi: 10.1115/1.4036473
The cervix is a unique organ able to dramatically change its shape and function by serving as a physical barrier for the growing fetus and then undergoing dramatic dilation allowing for delivery of a term infant. As a result, the cervix endures changing mechanical forces from the growing fetus. There is an emerging concept that the cervix may change or remodel “early” in many cases of spontaneous preterm birth. However, the mechanical role of the cervix in both normal and preterm birth remains unclear. Therefore, the primary objective of this study was to determine the mechanical and structural response of murine cervical tissue throughout a normal gestational time course. In this study, both tissue structural and material properties were determined via a quasi-static tensile load-to-failure test while simultaneously obtaining dynamic collagen fiber re-alignment via cross-polarization imaging. This study demonstrated that the majority of the mechanical properties evaluated decreased at mid-gestation and not just at term, while collagen fiber re-alignment occurred earlier in the loading curve for cervices at term. This suggests that although structural changes in the cervix occur throughout gestation, the differences in material properties function in combination with collagen fiber re-alignment as mechanical precursors to regulate term gestation. This work lays a foundation for investigating cervical biomechanics and the role of the cervix in preterm birth.
TOPICS: Fibers, Mechanical properties, Biological tissues, Materials properties, Polarization (Waves), Failure, Shapes, Imaging, Polarization (Electricity), Stress, Biomechanics, Polarization (Light)
Zifeng Yang, Hongtao Yu, George P. Huang and Bryan Ludwig
J Biomech Eng   doi: 10.1115/1.4036484
Detailed blood velocity map in vascular system can be obtained by applying the optical flow method (OFM) in processing fluoroscopic digital subtracted catheter angiographic images, however, there are still challenges with the accuracy of this method. In the present study, a divergence compensatory Optical Flow Method (DC-OFM), in which a non-zero divergence of velocity is assumed due to the finite resolution of the image, was explored and applied to the digital subtraction angiography (DSA) images of blood flow. The objective of this study is to examine the applicability and evaluate the accuracy of DC-OFM in assessing the blood flow velocity in vessels. First, an Oseen vortex flow was simulated on the standard particle image to generate an image pair. Then, the DC-OFM was applied on the particle image pair to recover the velocity field for validation. Second, DSA images of intracranial arteries were used to examine the accuracy of the current method. For each set of images, the first image is the in vivo DSA image, and the second image is generated by superimposing a given flow field. The recovered velocity map by DC-OFM agrees well with the exact velocity for both the particle images and the angiographic images. In comparison with the traditional OFM, the present method can provide more accurate velocity estimation. The accuracy of the velocity estimation can also be improved by implementing pre-process techniques including image intensification, Gaussian filtering and “image -shift”.
TOPICS: Flow (Dynamics), Blood, Particulate matter, Blood flow, Resolution (Optics), Filtration, Catheters, Vessels, Vortex flow
Arnold D. Gomez, Huashan Zou, Megan E. Bowen, Xiaoqing Liu, Edward W. Hsu and Stephen H. McKellar
J Biomech Eng   doi: 10.1115/1.4036485
Right ventricular failure (RVF) is a lethal condition in diverse pathologies. Pressure overload is the most common etiology of RVF, but our understanding of the tissue structure remodeling and other biomechanical factors involved in RVF is limited. Some remodeling patterns are interpreted as compensatory mechanisms including myocyte hypertrophy, extracellular fibrosis, and changes in fiber orientation. However, the specific implications of these changes, especially in relation to clinically observable measurements, are difficult to investigate experimentally. In this computational study, we hypothesized that, with other variables constant, fiber orientation alteration provides a quantifiable and distinct compensatory mechanism during RV pressure overload. Numerical models were constructed using a rabbit model of chronic pressure overload RVF based on intraventricular pressure measurements, CINE magnetic resonance imaging (MRI), and diffusion tensor MRI (DT-MRI). Biventricular simulations were conducted under normotensive and hypertensive boundary conditions using variations in RV wall thickness, tissue stiffness, and fiber orientation to investigate their effect on RV pump function. Our results show that a longitudinally aligned myocardial fiber orientation contributed to an increase in RV ejection fraction (RVEF). This effect was more pronounced in response to pressure overload. Likewise, models with longitudinally aligned fiber orientation required a lesser contractility for maintaining a target RVEF against elevated pressures. In addition to increased wall thickness and material stiffness (diastolic compensation), systolic mechanisms in the forms of myocardial fiber realignment and changes in contractility are likely involved in the overall compensatory responses to pressure overload.
TOPICS: Fibers, Pressure, Magnetic resonance imaging, Stiffness, Wall thickness, Biological tissues, Engineering simulation, Pumps, Diffusion (Physics), Pressure measurement, Computer simulation, Simulation, Biomechanics, Tensors, Boundary-value problems, Failure
Chelsey L. Dunham, Ryan M. Castile, Aaron M. Chamberlain, Leesa M. Galatz and Spencer P. Lake
J Biomech Eng   doi: 10.1115/1.4036472
The elbow joint is highly susceptible to joint contracture, and treating elbow contracture is a challenging clinical problem. Previously, we established an animal model to study elbow contracture that exhibited features similar to the human condition including persistent decreased range of motion (ROM) in flexion-extension and increased capsule thickness/adhesions. The objective of this study was to mechanically quantify pronation-supination in different injury models to determine if significant differences compared to control or contralateral persist long-term in our animal elbow contracture model. After surgically inducing soft tissue damage in the elbow, Injury I (anterior capsulotomy) and Injury II (anterior capsulotomy with lateral collateral ligament transection), limbs were immobilized for six weeks (IM). Animals were evaluated after the IM period or following an additional six-weeks of free mobilization (FM). Total ROM for pronation-supination was significantly decreased compared to the uninjured contralateral limb for both IM and FM, although not different from control limbs. Specifically, for both IM and FM, total ROM for Injury I and Injury II were significantly decreased by ~20% compared to contralateral. Correlations of measurements from flexion-extension and pronation-supination divulged that FM did not affect these motions in the same way, demonstrating that joint motions need to be studied/treated separately. Overall, injured limbs exhibited persistent motion loss in pronation-supination when comparing side-to-side differences, similar to human post-traumatic joint contracture. Future work will use this animal model to study how elbow periarticular soft tissues contribute to contracture.
TOPICS: Surgery, Wounds, Soft tissues, Damage
Aref Samadi-Dooki, George Z. Voyiadjis and Rhett W. Stout
J Biomech Eng   doi: 10.1115/1.4036486
Indentation experiments offer a robust, fast, and repeatable testing method for evaluating the mechanical properties of solid state materials in a wide stiffness range. With the advantage of requiring a minimal sample preparation and multiple tests on a small piece of specimen, this method has recently become a popular technique for measuring the elastic properties of the biological materials, especially the brain tissue whose ultra-soft nature makes its mechanical characterization very challenging. Nevertheless, some limitations are associated with the indentation of the brain tissue, such as improper surface detection, negative initial contact force due to tip-tissue moisture interaction, partial contact between the tip and the sample, etc. In this study, an indirect indentation scheme is proposed to overcomethe aforementioned difficulties. In this way, the indentation force is transferred from a sharp tip to the surface of the tissue slices via a rigid cover glass. To demonstrate the accuracy of this method, the linear viscoelastic properties of the white and gray matters of the bovine brain samples are measured by imposing small cyclic loadings at different frequencies. The rate, regional, directional, and postmortem time dependence of the viscoelastic moduli are investigated and compared with the previous results from cyclic shear and monotonic experiments on the brain tissue. While findings of this research present a comprehensive set of information for the viscoelastic properties of the brain, the central goal of this research is to introduce a novel experimentation technique with noticeable advantages for biomechanical characterization of the soft tissue.
TOPICS: Viscoelasticity, Biological tissues, Brain, Stiffness, Soft tissues, Experimental methods, Testing, Elasticity, Glass, Biomechanics, Shear (Mechanics), Mechanical properties
Jeffrey B. Barker, Duane S. Cronin and Roger W. Nightingale
J Biomech Eng   doi: 10.1115/1.4036464
Advanced computational human body models enabling enhanced occupant safety require verification and validation at different levels or scales. Specifically, the motion segments, which are the building blocks of a detailed neck model, must be validated with representative experimental data to have confidence in segment and, ultimately, full neck model response. In this study, we demonstrate the importance of objective validation for quasi-static and dynamic loading. Finite element segment models at all levels in the lower human cervical spine were developed from scans of a 26 year old male subject. Material properties were derived from in vitro experimental testing data. The segment models were simulated in quasi-static loading in flexion, extension, lateral bending and axial rotation, and at dynamic rates in flexion and extension. Single-valued experimental data did not provide adequate information to assess the model biofidelity, while application of traditional corridor methods highlighted that data sets with higher variability could lead to an incorrect conclusion of improved model biofidelity. Data sets with multiple moment-rotation measurements enabled the use of cross-correlation for an objective evaluation of the model with respect to the data. Such an objective validation method is beneficial for assessing the biofidelity of computational models, with the limitation of distinguishing the magnitude but not the orientation of differences. It is recommended that cross-correlation be used to compare motion segment models to individual tests, where these results can be averaged for all test cases and spinal levels to provide an assessment of model biofidelity.
TOPICS: Kinematics, Dynamic testing (Materials), Cervical spine, Rotation, Safety, Blocks (Building materials), Materials properties, Finite element analysis, Testing
Kerianne E. Steucke, Zaw Win, Taylor R. Stemler, Emily E. Walsh, Jennifer L. Hall and Patrick W. Alford
J Biomech Eng   doi: 10.1115/1.4036454
Cardiovascular disease can alter the mechanical environment of the vascular system, leading to mechano-adaptive growth and remodeling. Predictive models of arterial mechano-adaptation could improve patient treatments and outcomes in cardiovascular disease. Vessel-scale mechano-adaptation includes remodeling of both the cells and extracellular matrix. Here, we aimed to experimentally measure and characterize a phenomenological mechano-adaptation law for vascular smooth muscle cells (VSMCs) within an artery. To do this, we developed a highly controlled and reproducible system for applying a chronic step-change in strain to individual VSMCs with in vivo like architecture, and tracked the temporal cellular stress evolution. We found that a simple linear growth law was able to capture the dynamic stress evolution of VSMCs in response to this mechanical perturbation. These results provide an initial framework for development of clinically relevant models of vascular remodeling that include VSMC adaptation.
TOPICS: Muscle, Stress, Cardiovascular system, Diseases, Performance, Patient treatment, Vessels
Zaw Win, Justin M Buksa, Kerianne E Steucke, G.W. Gant Luxton, Victor H Barocas and Patrick W Alford
J Biomech Eng   doi: 10.1115/1.4036440
The stress in a cell due to extracellular mechanical stimulus is determined by its mechanical properties, and the structural organization of many adherent cells suggests that their properties are anisotropic. This anisotropy may significantly influence the cells' mechanotransductive response to complex loads, and has important implications for development of accurate models of tissue biomechanics. Standard methods for measuring cellular mechanics report linear moduli that cannot capture large-deformation anisotropic properties, which in a continuum mechanics framework are best described by a strain energy density function (SED). In tissues, the SED is most robustly measured using biaxial testing. Here, we describe a cellular micro-biaxial stretching (CµBS) method that modifies this tissue-scale approach to measure the anisotropic elastic behavior of individual vascular smooth muscle cells (VSMCs) with native-like cytoarchitecture. Using CµBS, we reveal that VSMCs are highly anisotropic under large deformations. We then characterize a Holzapfel-Gasser-Ogden type SED for individual VSMCs and find that architecture-dependent properties of the cells can be robustly described using a formulation solely based on the organization of their actin cytoskeleton. These results suggest that cellular anisotropy should be considered when developing biomechanical models, and could play an important role in cellular mechano-adaptation.
TOPICS: Density, Anisotropy, Spectral energy distribution, Biological tissues, Deformation, Stress, Biomechanics, Elasticity, Mechanical properties, Continuum mechanics, Cellular mechanics, Testing, Muscle
Alan W. Eberhardt, Shea Tillman, Brandon Kirkland and Brandon Sherrod
J Biomech Eng   doi: 10.1115/1.4036441
There exists a need for educational processes in which students gain experience with design and commercialization of medical devices. This manuscript describes the implementation of, and assessment results from, the first year offering of a “project course” sequence in a Master of Engineering (MEng) in Design and Commercialization at our institution. The three-semester course sequence focused on developing and applying hands-on skills that contribute to product development to address medical device needs found within our university hospital and local community. The first semester integrated computer aided drawing (CAD) as preparation for manufacturing of device-related components (hand machining, CNC, 3D printing and plastics molding), followed by an introduction to microcontrollers and printed circuit boards for associated electronics and control systems. In the second semester, the students applied these skills on a unified project, working together to construct and test multiple weighing scales for wheelchair users. In the final semester, the students applied Industrial Design concepts to four distinct device designs, including user and context reassessment, human factors (functional and aesthetic) design refinement, and advanced visualization for commercialization. Assessment results are described, along with lessons learned and plans for enhancement of the course sequence.
TOPICS: Medical devices, Innovation, Students, Design, Human factors, Visualization, Product development, Machining, Industrial design, Control systems, Manufacturing, Computer-aided engineering, Plastics molding, Computer-aided design, Electronics, Wheelchairs, Printed circuit boards, Computer numerical control machine tools, Additive manufacturing
Stephanie M. George and Zachary J. Domire
J Biomech Eng   doi: 10.1115/1.4036315
As the reliance on computational models to inform experiments and evaluate medical devices grows, the demand for students with modeling experience will grow. In this paper, we report on the three year experience of a National Science Foundation funded Research Experiences for Undergraduates (REU) based on the theme simulations, imaging, and modeling in biomechanics. While directly applicable to REU sites, our findings also apply to those creating other types of summer undergraduate research programs. The objective of the paper is to examine if a theme of simulations, imaging, and modeling will improve students' understanding of the important topic of modeling, provide an overall positive research experience, and provide an interdisciplinary experience. The structure of the program and evaluation plan are described. We report on the results from 25 students over three summers from 2014-2016. Overall, students reported significant gains in knowledge of modeling, the research process, and graduate school based on self-reported mastery levels and open-ended qualitative responses. This theme provides students with a skill set that is adaptable to other applications illustrating the interdisciplinary nature of modeling in biomechanics. Another advantage is that students may also be able to continue working on their project following the summer experience through network connections. In conclusion, we have described the successful implementation of the theme simulation, imaging, and modeling for an REU site and the overall positive response of the student participants.
TOPICS: Modeling, Imaging, Simulation, Biomechanics, Undergraduate research, Students, Undergraduate students, Medical devices
Christopher E. Korenczuk, Lauren E. Votava, Rohit Y. Dhume, Shannen B. Kizilski, George E. Brown, Rahul Narain and Victor H. Barocas
J Biomech Eng   doi: 10.1115/1.4036316
The von Mises (VM) stress is a common stress measure for finite-element models of tissue mechanics. The VM failure criterion, however, is inherently isotropic, and therefore may yield incorrect results for anisotropic tissues, and the relevance of the VM stress to anisotropic materials is not clear. We explored the application of a well-studied anisotropic failure criterion, the Tsai-Hill (TH) theory, to the mechanically anisotropic porcine aorta. Uniaxial dogbones were cut at different angles and stretched to failure. The tissue was anisotropic, with the circumferential failure stress nearly twice the axial (2.67 ± 0.67 MPa compared to 1.46 ± 0.59 MPa). The VM failure criterion did not capture the anisotropic tissue response, but the TH criterion fit the data well (R2 = 0.986). Shear lap samples were also tested to study the efficacy of each criterion in predicting tissue failure. 2D failure propagation simulations showed that the VM failure criterion did not capture the failure type, location, or propagation direction nearly as well as the TH criterion. Over the range of loading conditions and tissue geometries studied, we found that problematic results that arise when applying the VM failure criterion to an anisotropic tissue. In contrast, the TH failure criterion, though simplistic and clearly unable to capture all aspects of tissue failure, performed much better. Ultimately, isotropic failure criteria are not appropriate for anisotropic tissues, and the use of the VM stress as a metric of mechanical state should be reconsidered when dealing with anisotropic tissues.
TOPICS: Anisotropy, Biological tissues, Failure, Stress, Simulation, Shear (Mechanics), Finite element model, Aorta, Engineering simulation
Jeffrey M Mattson and Yanhang Zhang
J Biomech Eng   doi: 10.1115/1.4036261
Elastin and collagen fibers are the major load-bearing extracellular matrix (ECM) constituents of the vascular wall. Arteries function differently than veins in the circulatory system, however as a result from several treatment options veins are subjected to sudden elevated arterial pressure. It is thus important to recognize the fundamental structure and function differences between a vein and an artery. Our research compared the relationship between biaxial mechanical function and ECM structure of porcine thoracic aorta and inferior vena cava. Our study suggests that aorta contains slightly more elastin than collagen due to the cyclical extensibility, but vena cava contains almost four times more collagen than elastin to maintain integrity. Furthermore, multiphoton imaging of vena cava showed longitudinally oriented elastin and circumferentially oriented collagen that is recruited at supraphysiologic stress, but low levels of strain. However in aorta, elastin is distributed uniformly and the primarily circumferentially oriented collagen is recruited at higher levels of strain than vena cava. These structural observations support the functional finding that vena cava is highly anisotropic with the longitude being more compliant and the circumference stiffening substantially at low levels of strain. Overall, our research demonstrates that fiber distributions and recruitment should be considered in addition to relative collagen and elastin contents. Also, the importance of accounting for the structural and functional differences between arteries and veins should be taken into account when considering disease treatment options.
TOPICS: Aorta, Fibers, Stress, Anisotropy, Bearings, Cardiovascular system, Diseases, Imaging, Accounting, Pressure
Joshua D. Roth, Stephen M. Howell and Maury L. Hull
J Biomech Eng   doi: 10.1115/1.4036147
Previous reports of tibial force sensors have neither characterized nor corrected errors in the computed contact location between the femoral and tibial components in total knee arthroplasty (TKA) that are theoretically caused by the curved articular surface of the tibial component. The objectives were to experimentally characterize there errors and to develop and validate an error correction algorithm. The errors were characterized by calculating the difference between the errors in the computed contact location when forces were applied normal to the tibial articular surface and those when forces were applied normal to the tibial baseplate. The algorithm generated error correction functions to minimize these errors and was validated by determining how much the error correction functions reduced the errors in the computed contact location caused by the curved articular surface. The curved articular surfaces primarily caused bias which ranged from 1.0 to 2.7 mm in regions of high curvature. The error correction functions reduced the bias in these regions to negligible levels ranging from 0.0 to 0.6 mm (p < 0.001). Bias in the computed contact locations caused by the curved articular surface of the tibial insert needs to be accounted for because it may inflate the computed internal-external rotation and anterior-posterior translation of femur on the tibia leading to false identifications of clinically undesirable contact kinematics (e.g. external rotation and anterior translation). Our novel error correction algorithm is an effective method to account for this bias to more accurately compute contact kinematics.
TOPICS: Errors, Knee, Arthroplasty, Algorithms, Kinematics, Rotation, Force sensors
Ehsan Ban, Sijia Zhang, Vahhab Zarei, Victor H. Barocas, Beth A. Winkelstein and Catalin R. Picu
J Biomech Eng   doi: 10.1115/1.4036019
The spinal facet capsular ligament (FCL) is primarily comprised of heterogeneous arrangements of collagen fibers. This complex fibrous structure and its evolution under loading play a critical role in determining the mechanical behavior of the FCL. A lack of analytical tools to characterize the spatial anisotropy and heterogeneity of the FCL's microstructure has limited the current understanding of its structure-function relationships. Here, the collagen organization was characterized using spatial correlation analysis of its optically-obtain fiber orientation field. FCLs from the cervical and lumbar spinal regions were characterized in terms of their structure, as was the reorganization of collagen in stretched cervical FCLs. Higher degrees of intra- and inter-sample heterogeneity were found in cervical FCLs than in lumbar specimens. In the cervical FCLs, heterogeneity was manifested in the form of wavy patterns formed by collections of collagen fiber or fiber bundles. Tensile stretch, a common injury mechanism for the cervical FCL, significantly increased the spatial correlation length in the stretch direction, indicating an elongation of the observed structural features. Lastly, an affine estimation for the change of correlation lengths under loading was performed and gave predictions very similar to the actual values. These findings provide structural insights for multiscale mechanical analysis of the FCLs from various spinal regions and also suggest methods for quantitative characterization of complex tissue patterns.
TOPICS: Deformation, Fibers, Anisotropy, Biological tissues, Mechanical behavior, Elongation, Fault current limiters, Injury mechanisms
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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