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IN THIS ISSUE

### Research Papers

J Biomech Eng. 2018;140(8):081001-081001-15. doi:10.1115/1.4040044.

Right ventricular (RV) failure, which occurs in the setting of pressure overload, is characterized by abnormalities in mechanical and energetic function. The effects of these cell- and tissue-level changes on organ-level RV function are unknown. The primary aim of this study was to investigate the effects of myofiber mechanics and mitochondrial energetics on organ-level RV function in the context of pressure overload using a multiscale model of the cardiovascular system. The model integrates the mitochondria-generated metabolite concentrations that drive intracellular actin-myosin cross-bridging and extracellular myocardial tissue mechanics in a biventricular heart model coupled with simple lumped parameter circulations. Three types of pressure overload were simulated and compared to experimental results. The computational model was able to capture a wide range of cardiovascular physiology and pathophysiology from mild RV dysfunction to RV failure. Our results confirm that, in response to pressure overload alone, the RV is able to maintain cardiac output (CO) and predict that alterations in either RV active myofiber mechanics or RV metabolite concentrations are necessary to decrease CO.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(8):081002-081002-8. doi:10.1115/1.4040023.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(8):081003-081003-5. doi:10.1115/1.4040120.

Long procedure times and collateral damage remain challenges in high-intensity focused ultrasound (HIFU) medical procedures. Magnetic nanoparticles (mNPs) and gold nanoparticles (gNPs) have the potential to reduce the acoustic intensity and/or exposure time required in these procedures. In this research, we investigated relative advantages of using gNPs and mNPs during HIFU thermal-ablation procedures. Tissue-mimicking phantoms containing embedded thermocouples (TCs) and physiologically acceptable concentrations (0.0625% and 0.125%) of gNPs were sonicated at acoustic powers of 5.2 W, 9.2 W, and 14.5 W, for 30 s. It was observed that when the concentration of gNPs was doubled from 0.0625% to 0.125%, the temperature rise increased by 80% for a power of 5.2 W. For a fixed concentration (0.0625%), the energy absorption was 1.7 times greater for mNPs than gNPs for a power of 5.2 W. Also, for the power of 14.5 W, the sonication time required to generate a lesion volume of 50 mm3 decreased by 1.4 times using mNPs, compared with gNPs, at a concentration of 0.0625%. We conclude that mNPs are more likely than gNPs to produce a thermal enhancement in HIFU ablation procedures.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(8):081004-081004-10. doi:10.1115/1.4039947.

While the anisotropic behavior of the complex composite myocardial tissue has been well characterized in recent years, the compressibility of the tissue has not been rigorously investigated to date. In the first part of this study, we present experimental evidence that passive-excised porcine myocardium exhibits volume change. Under tensile loading of a cylindrical specimen, a volume change of $4.1±1.95%$ is observed at a peak stretch of 1.3. Confined compression experiments also demonstrate significant volume change in the tissue (loading applied up to a volumetric strain of 10%). In order to simulate the multiaxial passive behavior of the myocardium, a nonlinear volumetric hyperelastic component is combined with the well-established Holzapfel–Ogden anisotropic hyperelastic component for myocardium fibers. This framework is shown to describe the experimentally observed behavior of porcine and human tissues under shear and biaxial loading conditions. In the second part of the study, a representative volumetric element (RVE) of myocardium tissue is constructed to parse the contribution of the tissue vasculature to observed volume change under confined compression loading. Simulations of the myocardium microstructure suggest that the vasculature cannot fully account for the experimentally measured volume change. Additionally, the RVE is subjected to six modes of shear loading to investigate the influence of microscale fiber alignment and dispersion on tissue-scale mechanical behavior.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(8):081005-081005-9. doi:10.1115/1.4039949.

Mechanical cues including stretch, compression, and shear stress play a critical role in regulating the behavior of many cell types, particularly those that experience substantial mechanical stress within tissues. Devices that impart mechanical stimulation to cells in vitro have been instrumental in helping to develop a better understanding of how cells respond to mechanical forces. However, these devices often have constraints, such as cost and limited functional capabilities, that restrict their use in research or educational environments. Here, we describe a low-cost method to fabricate a uniaxial cell stretcher that would enable widespread use and facilitate engineering design and mechanobiology education for undergraduate students. The device is capable of producing consistent and reliable strain profiles through the use of a servomotor, gear, and gear rack system. The servomotor can be programmed to output various waveforms at specific frequencies and stretch amplitudes by controlling the degree of rotation, speed, and acceleration of the servogear. In addition, the stretchable membranes are easy to fabricate and can be customized, allowing for greater flexibility in culture well size. We used the custom-built stretching device to uniaxially strain macrophages and cardiomyocytes, and found that both cell types displayed functional and cell shape changes that were consistent with the previous studies using commercially available systems. Overall, this uniaxial cell stretcher provides a more cost-effective alternative to study the effects of mechanical stretch on cells, and can therefore, be widely used in research and educational environments to broaden the study and pedagogy of cell mechanobiology.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(8):081008-081008-5. doi:10.1115/1.4040293.

Equipping engineering students for career success requires more than technical proficiency; mindset and contextual interpretation also matter. Entrepreneurial mindset learning (EML) is one framework that faculty can use to systematically enrich course projects to encourage development of these important career skills. We present the thought process behind enriching two biomechanics class projects to foster both the entrepreneurial mindset and the technical proficiency in undergraduate engineering students. One project required students to analyze a court case surrounding vertebral fracture in an elderly woman diagnosed one year after a fall in an elevator. In addition to technical analysis, students had to make a recommendation about the likelihood that the injury occurred due to the fall, and contextualize the results within economic and societal terms—how much should the plaintiff sue for and how could such injuries be prevented through design and regulation? The second project asked students to evaluate cervine cancellous bone as a suitable laboratory model for biomechanics research. In addition to technical analysis, students considered the value of cervine vertebrae as a laboratory model within the context of societal and economic benefits of ex vivo animal models, including the relevant policy and regulatory issues. In both projects, implemented at different institutions with similar student demographics, students performed well and enjoyed the “real-world” nature of the projects, despite their frustrations with the open-ended nature of the questions posed. These and other similar projects can be further enhanced to foster the entrepreneurial mindset in undergraduate engineering students without undue burden on the instructor.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(8):081009-081009-8. doi:10.1115/1.4040359.

This study reports our experience of developing a series of biomedical engineering (BME) courses having active and experiential learning components in an interdisciplinary learning environment. In the first course, BME465: biomechanics, students were immersed in a simulation laboratory setting involving mannequins that are currently used for teaching in the School of Nursing. Each team identified possible technological challenges directly related to the biomechanics of the mannequin and presented an improvement overcoming the challenge. This approach of exposing engineering students to a problem in a clinical learning environment enhanced the adaptive and experiential learning capabilities of the course. In the following semester, through BME448: medical devices, engineering students were partnered with nursing students and exposed to simulation scenarios and real-world clinical settings. They were required to identify three unmet needs in the real-world clinical settings and propose a viable engineering solution. This approach helped BME students to understand and employ real-world applications of engineering principles in problem solving while being exposed to an interdisciplinary collaborative environment. A final step was for engineering students to execute their proposed solution from either BME465 or BME448 courses by undertaking it as their capstone senior design project (ENGR401-402). Overall, the inclusion of clinical immersions in interdisciplinary teams in a series of courses not only allowed the integration of active and experiential learning in continuity but also offered engineers more practice of their profession, adaptive expertise, and an understanding of roles and expertise of other professionals involved in enhancement of healthcare and patient safety.

Commentary by Dr. Valentin Fuster

### Technical Brief

J Biomech Eng. 2018;140(8):084501-084501-10. doi:10.1115/1.4039998.

Glaucoma is the leading cause of irreversible blindness and involves the death of retinal ganglion cells (RGCs). Although biomechanics likely contributes to axonal injury within the optic nerve head (ONH), leading to RGC death, the pathways by which this occurs are not well understood. While rat models of glaucoma are well-suited for mechanistic studies, the anatomy of the rat ONH is different from the human, and the resulting differences in biomechanics have not been characterized. The aim of this study is to describe a methodology for building individual-specific finite element (FE) models of rat ONHs. This method was used to build three rat ONH FE models and compute the biomechanical environment within these ONHs. Initial results show that rat ONH strains are larger and more asymmetric than those seen in human ONH modeling studies. This method provides a framework for building additional models of normotensive and glaucomatous rat ONHs. Comparing model strain patterns with patterns of cellular response seen in studies using rat glaucoma models will help us to learn more about the link between biomechanics and glaucomatous cell death, which in turn may drive the development of novel therapies for glaucoma.

Commentary by Dr. Valentin Fuster