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### Guest Editorial

J Biomech Eng. 2017;139(7):070301-070301-2. doi:10.1115/1.4036697.
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Commentary by Dr. Valentin Fuster

### Research Papers

J Biomech Eng. 2017;139(7):071001-071001-7. doi:10.1115/1.4036604.

Demand of biomedical engineers continues to rise to meet the needs of healthcare industry. Current training of bioengineers follows the traditional and dominant model of theory-focused curricula. However, the unmet needs of the healthcare industry warrant newer skill sets in these engineers. Translational training strategies such as solving real world problems through active, adaptive, and experiential learning hold promise. In this paper, we report our findings of adding a real-world 4-week problem-based learning unit into a biomechanics capstone course for engineering students. Surveys assessed student perceptions of the activity and learning experience. While students, across three cohorts, felt challenged to solve a real-world problem identified during the simulation lab visit, they felt more confident in utilizing knowledge learned in the biomechanics course and self-directed research. Instructor evaluations indicated that the active and experiential learning approach fostered their technical knowledge and life-long learning skills while exposing them to the components of adaptive learning and innovation.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071002-071002-6. 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 3-yr experience of a National Science Foundation (NSF) 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 the evaluation plan are described. We report on the results from 25 students over three summers from 2014 to 2016. Overall, students reported significant gains in the knowledge of modeling, 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.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071003-071003-7. 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 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, computer numeric control (CNC), three-dimensional (3D) printing, and plastics molding), followed by an introduction to microcontrollers (MCUs) and printed circuit boards (PCBs) 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. The assessment results are described, along with lessons learned and plans for enhancement of the course sequence.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071004-071004-4. doi:10.1115/1.4036793.

The creative process is fun, complex, and sometimes frustrating, but it is critical to the future of our nation and progress in science, technology, engineering, mathematics (STEM), as well as other fields. Thus, we set out to see if implementing methods of active learning typical to the theater department could impact the creativity of senior capstone design students in the bioengineering (BE) department. Senior bioengineering capstone design students were allowed to self-select into groups. Prior to the beginning of coursework, all students completed a validated survey measuring engineering design self-efficacy. The control and experimental groups both received standard instruction, but in addition the experimental group received 1 h per week of creativity training developed by a theater professor. Following the semester, the students again completed the self-efficacy survey. The surveys were examined to identify differences in the initial and final self-efficacy in the experimental and control groups over the course of the semester. An analysis of variance was used to compare the experimental and control groups with p < 0.05 considered significant. Students in the experimental group reported more than a twofold (4.8 (C) versus 10.9 (E)) increase of confidence. Additionally, students in the experimental group were more motivated and less anxious when engaging in engineering design following the semester of creativity instruction. The results of this pilot study indicate that there is a significant potential to improve engineering students' creative self-efficacy through the implementation of a “curriculum of creativity” which is developed using theater methods.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071005-071005-9. 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.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071006-071006-10. 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 microbiaxial stretching (CμBS) method that modifies this tissue-scale approach to measure the anisotropic elastic behavior of individual vascular smooth muscle cells (VSMCs) with nativelike 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.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071007-071007-8. 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.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071008-071008-10. 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. Two-dimensional 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.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071009-071009-9. 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 the FCL's optically obtained 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 intersample heterogeneity were found in cervical FCLs than in lumbar specimens. In the cervical FCLs, heterogeneity was manifested in the form of curvy patterns formed by collections of collagen fibers 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. Finally, an affine estimation for the change of correlation length under loading was performed which gave predictions very similar to the actual values. These findings provide structural insights for multiscale mechanical analyses of the FCLs from various spinal regions and also suggest methods for quantitative characterization of complex tissue patterns.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071010-071010-9. doi:10.1115/1.4036686.

Injury to the growth plate is associated with growth disturbances, most notably premature cessation of growth. The goal of this study was to identify spatial changes in the structure and composition of the growth plate in response to injury to provide a foundation for developing therapies that minimize the consequences for skeletal development. We used contrast-enhanced microcomputed tomography (CECT) and histological analyses of a murine model of growth plate injury to quantify changes in the cartilaginous and osseous tissue of the growth plate. To distinguish between local and global changes, the growth plate was divided into regions of interest near to and far from the injury site. We noted increased thickness and CECT attenuation (a measure correlated with glycosaminoglycan (GAG) content) near the injury, and increased tissue mineral density (TMD) of bone bridges within the injury site, compared to outside the injury site and contralateral growth plates. Furthermore, we noted disruption of the normal zonal organization of the physis. The height of the hypertrophic zone was increased at the injury site, and the relative height of the proliferative zone was decreased across the entire injured growth plate. These results indicate that growth plate injury leads to localized disruption of cellular activity and of endochondral ossification. These local changes in tissue structure and composition may contribute to the observed retardation in femur growth. In particular, the changes in proliferative and hypertrophic zone heights seen following injury may impact growth and could be targeted when developing therapies for growth plate injury.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071011-071011-7. 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 6 weeks (immobilization (IM)). Animals were evaluated after the IM period or following an additional 6 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 was 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.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071012-071012-9. doi:10.1115/1.4036603.

The Pacinian corpuscle (PC) is a cutaneous mechanoreceptor that senses low-amplitude, high-frequency vibrations. The PC contains a nerve fiber surrounded by alternating layers of solid lamellae and interlamellar fluid, and this structure is hypothesized to contribute to the PC's role as a band-pass filter for vibrations. In this study, we sought to evaluate the relationship between the PC's material and geometric parameters and its response to vibration. We used a spherical finite element mechanical model based on shell theory and lubrication theory to model the PC's outer core. Specifically, we analyzed the effect of the following structural properties on the PC's frequency sensitivity: lamellar modulus (E), lamellar thickness (h), fluid viscosity (μ), PC outer radius (Ro), and number of lamellae (N). The frequency of peak strain amplification (henceforth “peak frequency”) and frequency range over which strain amplification occurred (henceforth “bandwidth”) increased with lamellar modulus or lamellar thickness and decreased with an increase in fluid viscosity or radius. All five structural parameters were combined into expressions for the relationship between the parameters and peak frequency, $ωpeak=1.605×10−6N3.475(Eh/μRo)$, or bandwidth, $B=1.747×10−6N3.951(Eh/μRo)$. Although further work is needed to understand how mechanical variability contributes to functional variability in PCs and how factors such as PC eccentricity also affect PC behavior, this study provides two simple expressions that can be used to predict the impact of structural or material changes with aging or disease on the frequency response of the PC.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2017;139(7):071013-071013-8. doi:10.1115/1.4036602.

Proteoglycans (PGs) are broadly distributed within many soft tissues and, among other roles, often contribute to mechanical properties. Although PGs, consisting of a core protein and glycosaminoglycan (GAG) sidechains, were once hypothesized to regulate stress/strain transfer between collagen fibrils and help support load in tendon, several studies have reported no changes to tensile mechanics after GAG depletion. Since GAGs are known to help sustain nontensile loading in other tissues, we hypothesized that GAGs might help support shear loading in human supraspinatus tendon (SST), a commonly injured tendon which functions in a complex multiaxial loading environment. Therefore, the objective of this study was to determine whether GAGs contribute to the response of SST to shear, specifically in terms of multiscale mechanical properties and mechanisms of microscale matrix deformation. Results showed that chondroitinase ABC (ChABC) treatment digested GAGs in SST while not disrupting collagen fibers. Peak and equilibrium shear stresses decreased only slightly after ChABC treatment and were not significantly different from pretreatment values. Reduced stress ratios were computed and shown to be slightly greater after ChABC treatment compared to phosphate-buffered saline (PBS) incubation without enzyme, suggesting that these relatively small changes in stress values were not due strictly to tissue swelling. Microscale deformations were also not different after ChABC treatment. This study demonstrates that GAGs possibly play a minor role in contributing to the mechanical behavior of SST in shear, but are not a key tissue constituent to regulate shear mechanics.

Commentary by Dr. Valentin Fuster