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IN THIS ISSUE

### Research Papers

J Biomech Eng. 2018;141(2):021001-021001-8. doi:10.1115/1.4041743.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021002-021002-9. doi:10.1115/1.4041767.

Human gait is the result of a complex and fascinating cooperation between different joints and segments in the lower extremity. This study aims at investigating the existence of this cooperation or the so-called synergy between the shank motion and the ankle motion. One potential use of this synergy is to develop the high level controllers for active foot prostheses/orthoses. The central point in this paper is to develop a high level controller that is able to continuously map shank kinematics (inputs) to ankle angles and torques (outputs). At the same time, it does not require speed determination, gait percent identification, switching rules, and look-up tables. Furthermore, having those targets in mind, an important part of this study is to determine which input type is required to achieve such targets. This should be fulfilled through using minimum number of inputs. To do this, the Gaussian process (GP) regression has been used to estimate the ankle angles and torques for 11 subjects at three walking speeds (0.5, 1, and 1.5 m/s) based on the shank angular velocity and angle. The results show that it is possible to estimate ankle motion based on the shank motion. It was found that the estimation achieved less quality with only shank angular velocity or angle, whereas the aggregated angular velocity and angle resulted in much higher output estimation quality. In addition, the estimation quality was acceptable for the speeds that there was a training procedure before and when it was tested for the untrained speeds, the estimation quality was not as acceptable as before. The pros and cons of the proposed method are investigated at different scenarios.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021003-021003-10. doi:10.1115/1.4041904.

Embryological transport features a very interesting and complex application of peristaltic fluid dynamics. Electro-osmotic phenomena are also known to arise in embryo transfer location. The fluid dynamic environment in embryological systems is also known to be non-Newtonian and exhibits strong viscoelastic properties. Motivated by these applications, the present article develops a new mathematical model for simulating two-dimensional peristaltic transport of a viscoelastic fluid in a tapered channel under the influence of electro-osmosis induced by asymmetric zeta potentials at the channel walls. The robust Jeffrey viscoelastic model is utilized. The finite Debye layer electro-kinetic approximation is deployed. The moving boundary problem is transformed to a steady boundary problem in the wave frame. The current study carries significant physiological relevance to an ever-increasing desire to study intrauterine fluid flow motion in an artificial uterus. The consequences of this model may introduce a new mechanical factor for embryo transport to a successful implantation site. Hydrodynamic characteristics are shown to be markedly influenced by the electro-osmosis, the channel taper angle, and the phase shift between the channel walls. Furthermore, it is demonstrated that volumetric flow rates and axial flow are both enhanced when the electro-osmotic force aids the axial flow for specific values of zeta potential ratio. Strong trapping of the bolus (representative of the embryo) is identified in the vicinity of the channel central line when the electro-osmosis opposes axial flow. The magnitude of the trapped bolus is observed to be significantly reduced with increasing tapered channel length whereas embryo axial motility is assisted with aligned electro-osmotic force.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021004-021004-12. doi:10.1115/1.4041901.

The ability to maintain living articular cartilage tissue in long-term culture can serve as a valuable analytical research tool, allowing for direct examination of mechanical or chemical perturbations on tissue behavior. A fundamental challenge for this technique is the recreation of the salient environmental conditions of the synovial joint in culture that are required to maintain native cartilage homeostasis. Interestingly, conventional media formulations used in explanted cartilage tissue culture investigations often consist of levels of metabolic mediators that deviate greatly from their concentrations in synovial fluid (SF). Here, we hypothesize that the utilization of a culture medium consisting of near-physiologic levels of several highly influential metabolic mediators (glucose, amino acids, cortisol, insulin, and ascorbic acid) will maintain the homeostasis of cartilage explants as assessed by their mechanical properties and extracellular matrix (ECM) contents. Results demonstrate that the aforementioned mediators have a strong effect on the mechanical and biochemical stability of skeletally immature bovine cartilage explants. Most notably, (1) in the absence of cortisol, explants exhibit extensive swelling and tissue softening and (2) in the presence of supraphysiologic levels of anabolic mediators (glucose, amino acids, insulin), explants exhibit increased matrix accumulation and tissue stiffening. In contrast, the administration of physiologic levels of these mediators (as present in native SF) greatly improves the stability of live cartilage explants over one month of culture. These results may have broad applicability for articular cartilage and other musculoskeletal tissue research, setting the foundation for important culture formulations required for examinations into tissue behavior.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021005-021005-12. doi:10.1115/1.4041575.

Fibrous soft tissues are biopolymeric materials that are made of extracellular proteins, such as different types of collagen and proteoglycans, and have a high water content. These tissues have nonlinear, anisotropic, and inelastic mechanical behaviors that are often categorized into viscoelastic behavior, plastic deformation, and damage. While tissue's elastic and viscoelastic mechanical properties have been measured for decades, there is no comprehensive theoretical framework for modeling inelastic behaviors of these tissues that is based on their structure. To model the three major inelastic mechanical behaviors of tissue's fibrous matrix, we formulated a structurally inspired continuum mechanics framework based on the energy of molecular bonds that break and reform in response to external loading (reactive bonds). In this framework, we employed the theory of internal state variables (ISV) and kinetics of molecular bonds. The number fraction of bonds, their reference deformation gradient, and damage parameter were used as state variables that allowed for consistent modeling of all three of the inelastic behaviors of tissue by using the same sets of constitutive relations. Several numerical examples are provided that address practical problems in tissue mechanics, including the difference between plastic deformation and damage. This model can be used to identify relationships between tissue's mechanical response to external loading and its biopolymeric structure.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021006-021006-11. doi:10.1115/1.4041769.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021007-021007-10. doi:10.1115/1.4041966.

Trabeculae carneae account for a significant portion of human ventricular mass, despite being considered embryologic remnants. Recent studies have found trabeculae hypertrophy and fibrosis in hypertrophied left ventricles with various pathological conditions. The objective of this study was to investigate the passive mechanical properties and microstructural characteristics of trabeculae carneae and papillary muscles compared to the myocardium in human hearts. Uniaxial tensile tests were performed on samples of trabeculae carneae and myocardium strips, while biaxial tensile tests were performed on samples of papillary muscles and myocardium sheets. The experimental data were fitted with a Fung-type strain energy function and material coefficients were determined. The secant moduli at given diastolic stress and strain levels were determined and compared among the tissues. Following the mechanical testing, histology examinations were performed to investigate the microstructural characteristics of the tissues. Our results demonstrated that the trabeculae carneae were significantly stiffer (Secant modulus SM2 = 80.06 ± 10.04 KPa) and had higher collagen content (16.10 ± 3.80%) than the myocardium (SM2 = 55.14 ± 20.49 KPa, collagen content = 10.06 ± 4.15%) in the left ventricle. The results of this study improve our understanding of the contribution of trabeculae carneae to left ventricular compliance and will be useful for building accurate computational models of the human heart.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021008-021008-9. doi:10.1115/1.4040250.

Nowadays, both usability and comfort play a key role in the development of medical and wearable products. When designing any device that is in contact with the human body, the mechanical behavior of the embraced soft tissue must be known. The unavoidable displacement of the soft tissue during motion may lead to discomfort and, thus, the removal of the wearable product. This paper presents a new methodology to design and test a wearable device based on the measurement of the dynamic skin strain field. Furthermore, from this field, the anatomical lines with minimum strain (lines of nonextension (LoNEs)) are calculated to design the structural parts of the wearable device. With this new criterion, the resulting product is not only optimized to reduce the friction in skin-device interface, but fully personalized to the patient's morphology and motion. The methodology is applied to the design of an ankle-foot wearable orthosis for subjects with ankle dorsiflexors muscles weakness due to nervous system disorders. The results confirm that the use of LoNEs may benefit the design of products with a high interaction with the skin.

Topics: Design , Skin , Orthotics
Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021009-021009-7. doi:10.1115/1.4042012.

Most injury risk functions (IRFs) for dynamic axial loading of the leg have been targeted toward automotive applications such as predicting injury caused by intrusion into the occupant compartment from frontal collisions. Recent focus on leg injuries in the military has led to questions about the applicability of these IRFs shorter duration, higher amplitude loading associated with underbody blast (UBB). To investigate these questions, data were collected from seven separate test series that subjected post-mortem human legs to axial impact. A force and impulse-based Weibull survival model was developed from these studies to estimate fracture risk. Specimen age was included as a covariate to reduce variance and improve survival model fit. The injury criterion estimated 50% risk of injury for a leg exposed to 13 N s of impulse at peak force and 8.07 kN of force for force durations less than and greater than half the natural period of the leg, respectively. A supplemental statistical analysis estimated that the proposed IRF improves injury prediction accuracy by more than 9% compared to the predictions from automobile-based risk functions developed for automotive intrusion. The proposed leg IRF not only improves injury prediction for higher rate conditions but also provides a single injury prediction tool for an expanded range of load durations ranging from 5 to 90 ms, which spans both automotive and military loading environments.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021010-021010-8. doi:10.1115/1.4042013.

Severely calcified plaque is of great concern when planning and implementing a stenting intervention. In this work, computational models were developed to investigate the influence of calcium characteristics on stenting outcomes. The commonly used clinical measurements of calcium (i.e., the arc angle, maximum thickness, length, and volume) were varied to estimate stenting outcomes in terms of lumen gain, stent underexpansion, strut malapposition, and stress or strain distributions of the stenotic lesion. Results have shown that stenting outcomes were most sensitive to the arc angle of the calcium. A thick calcium with a large arc angle resulted in poor stenting outcomes, such as severe stent underexpansion, D-shaped lumen, increased strut malapposition, and large stresses or strains in the plaque. This was attributed to the circumferential stretch of the tissue. Specifically, the noncalcium component was stretched significantly more than the calcium. The circumferential stretch ratios of calcium and noncalcium component were approximately 1.44 and 2.35, respectively, regardless of calcium characteristics. In addition, the peak stress or strain within the artery and noncalcium component of the plaque occurred at the area adjacent to calcium edges (i.e., the interface between the calcium and the noncalcium component) coincident with the location of peak malapposition. It is worth noting that calcium played a protective role for the artery underneath, which was at the expense of the overstretch and stress concentrations in the other portion of the artery. These detailed mechanistic quantifications could be used to provide a fundamental understanding of the impact of calcium quantifications on stent expansions, as well as to exploit their potential for a better preclinical strategy.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021011-021011-11. doi:10.1115/1.4042014.

Although the underlying mechanisms of pelvic organ prolapse (POP) remain unknown, disruption of elastic fiber metabolism within the vaginal wall extracellular matrix (ECM) has been highly implicated. It has been hypothesized that elastic fiber fragmentation correlates to decreased structural integrity and increased risk of prolapse; however, the mechanisms by which elastic fiber damage may contribute to prolapse are poorly understood. Furthermore, the role of elastic fibers in normal vaginal wall mechanics has not been fully ascertained. Therefore, the objective of this study is to investigate the contribution of elastic fibers to murine vaginal wall mechanics. Vaginal tissue from C57BL/6 female mice was mechanically tested using biaxial extension–inflation protocols before and after intraluminal exposure to elastase. Elastase digestion induced marked changes in the vaginal geometry, and biaxial mechanical properties, suggesting that elastic fibers may play an important role in vaginal wall mechanical function. Additionally, a constitutive model that considered two diagonal families of collagen fibers with a slight preference toward the circumferential direction described the data reasonably well before and after digestion. The present findings may be important to determine the underlying structural and mechanical mechanisms of POP, and aid in the development of growth and remodeling models for improved assessment and prediction of changes in structure–function relationships with prolapse development.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021012-021012-8. doi:10.1115/1.4042043.

The reduction of excessive, nonphysiologic shear stresses leading to blood trauma can be the key to overcome many of the associated complications in blood recirculating devices. In that regard, computational fluid dynamics (CFD) are gaining in importance for the hydraulic and hemocompatibility assessment. Still, direct hemolysis assessments with CFD remain inaccurate and limited to qualitative comparisons rather than quantitative predictions. An underestimated quantity for improved blood damage prediction accuracy is the influence of near-wall mesh resolution on shear stress quantification in regions of complex flows. This study investigated the necessary mesh refinement to quantify shear stress for two selected, meshing sensitive hotspots within a rotary centrifugal blood pump (the blade leading edge and tip clearance gap). The shear stress in these regions is elevated due to presence of stagnation points and the flow around a sharp edge. The nondimensional mesh characteristic number y+, which is known in the context of turbulence modeling, underestimated the maximum wall shear stress by 60% on average with the recommended value of 1, but was found to be exact below 0.1. To evaluate the meshing related error on the numerical hemolysis prediction, three-dimensional simulations of a generic centrifugal pump were performed with mesh sizes from 3 × 106 to 30 × 106 elements. The respective hemolysis was calculated using an Eulerian scalar transport model. Mesh insensitivity was found below a maximum y+ of 0.2 necessitating 18 × 106 mesh elements. A meshing related error of up to 25% was found for the coarser meshes. Further investigations need to address: (1) the transferability to other geometries and (2) potential adaptions on blood damage estimation models to allow better quantitative predictions.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;141(2):021013-021013-10. doi:10.1115/1.4042173.

Transmural advective transport of solute and fluid was investigated in mouse carotid arteries with either a genetic knockout of fibulin-5 (Fbln5−/−) or treatment with elastase to determine the influence of a disrupted elastic fiber matrix on wall transport properties. Fibulin-5 is an important director of elastic fiber assembly. Arteries from Fbln5−/− mice have a loose, noncontinuous elastic fiber network and were hypothesized to have reduced resistance to advective transport. Experiments were carried out ex vivo at physiological pressure and axial stretch. Hydraulic conductance ($LP$) was measured to be 4.99 × 10−6±8.94 × 10−7, 3.18−5±1.13 × 10−5 (p < 0.01), and 3.57 × 10−5 ±1.77 × 10−5 (p < 0.01) mm·s−1·mmHg−1 for wild-type, Fbln5−/−, and elastase-treated carotids, respectively. Solute fluxes of 4, 70, and 150 kDa fluorescein isothiocyanate (FITC)-dextran were statistically increased in Fbln5−/− compared to wild-type by a factor of 4, 22, and 3, respectively. Similarly, elastase-treated carotids demonstrated a 27- and 13-fold increase in net solute flux of 70 and 150 kDa FITC-dextran, respectively, compared to untreated carotids, and 4 kDa FITC-dextran was unchanged between these groups. Solute uptake of 4 and 70 kDa FITC-dextran within Fbln5−/− carotids was decreased compared to wild-type for all investigated time points. These changes in transport properties of elastic fiber compromised arteries have important implications for the kinetics of biomolecules and pharmaceuticals in arterial tissue following elastic fiber degradation due to aging or vascular disease.

Commentary by Dr. Valentin Fuster

### Technical Brief

J Biomech Eng. 2018;141(2):024501-024501-6. doi:10.1115/1.4041902.

Lower leg injuries commonly occur in frontal automobile collisions, and are associated with high disability rates. Accurate methods to predict these injuries must be developed to facilitate the testing and improvement of vehicle safety systems. Anthropomorphic test devices (ATDs) are often used to assess injury risk by mimicking the behavior of the human body in a crash while recording data from sensors at discrete locations, which are then compared to established safety limits developed by cadaveric testing. Due to the difference in compliance of cadaveric and ATD legs, the force dissipating characteristics of footwear, and the lack of direct measurement of injury risk to the foot and ankle, a novel instrumented insole was developed that could be applied equally to all specimens both during injury limit generation and during safety evaluation tests. An array of piezoresistive sensors were calibrated over a range of speeds using a pneumatic impacting apparatus, and then applied to the insole of a boot. The boot was subsequently tested and compared to loads measured using ankle and toe load cells in an ATD, and found to have an average error of 10%. The sensors also provided useful information regarding the force distribution across the sole of the foot during an impact, which may be used to develop regional injury criteria. This work has furthered the understanding of lower leg injury prediction and developed a tool that may be useful in developing accurate injury criteria in the future for the foot and lower leg.

Commentary by Dr. Valentin Fuster