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Review Article

J Biomech Eng. 2018;140(2):020801-020801-9. doi:10.1115/1.4037790.

The development of bright bisintercalating dyes for deoxyribonucleic acid (DNA) in the 1990s, most notably YOYO-1, revolutionized the field of polymer physics in the ensuing years. These dyes, in conjunction with modern molecular biology techniques, permit the facile observation of polymer dynamics via fluorescence microscopy and thus direct tests of different theories of polymer dynamics. At the same time, they have played a key role in advancing an emerging next-generation method known as genome mapping in nanochannels. The effect of intercalation on the bending energy of DNA as embodied by a change in its statistical segment length (or, alternatively, its persistence length) has been the subject of significant controversy. The precise value of the statistical segment length is critical for the proper interpretation of polymer physics experiments and controls the phenomena underlying the aforementioned genomics technology. In this perspective, we briefly review the model of DNA as a wormlike chain and a trio of methods (light scattering, optical or magnetic tweezers, and atomic force microscopy (AFM)) that have been used to determine the statistical segment length of DNA. We then outline the disagreement in the literature over the role of bisintercalation on the bending energy of DNA, and how a multiscale biomechanical approach could provide an important model for this scientifically and technologically relevant problem.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(2):020802-020802-16. doi:10.1115/1.4038638.

Almost a decade ago, hyperspectral imaging (HSI) was employed by the NASA in satellite imaging applications such as remote sensing technology. This technology has since been extensively used in the exploration of minerals, agricultural purposes, water resources, and urban development needs. Due to recent advancements in optical re-construction and imaging, HSI can now be applied down to micro- and nanometer scales possibly allowing for exquisite control and analysis of single cell to complex biological systems. This short review provides a description of the working principle of the HSI technology and how HSI can be used to assist, substitute, and validate traditional imaging technologies. This is followed by a description of the use of HSI for biological analysis and medical diagnostics with emphasis on single-cell analysis using HSI.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(2):020803-020803-13. doi:10.1115/1.4038704.

Development of a closed circulatory system requires that large arteries adapt to the mechanical demands of high, pulsatile pressure. Elastin and collagen uniquely address these design criteria in the low and high stress regimes, resulting in a nonlinear mechanical response. Elastin is the core component of elastic fibers, which provide the artery wall with energy storage and recoil. The integrity of the elastic fiber network is affected by component insufficiency or disorganization, leading to an array of vascular pathologies and compromised mechanical behavior. In this review, we discuss how elastic fibers are formed and how they adapt in development and disease. We discuss elastic fiber contributions to arterial mechanical behavior and remodeling. We primarily present data from mouse models with elastic fiber deficiencies, but suggest that alternate small animal models may have unique experimental advantages and the potential to provide new insights. Advanced ultrastructural and biomechanical data are constantly being used to update computational models of arterial mechanics. We discuss the progression from early phenomenological models to microstructurally motivated strain energy functions for both collagen and elastic fiber networks. Although many current models individually account for arterial adaptation, complex geometries, and fluid–solid interactions (FSIs), future models will need to include an even greater number of factors and interactions in the complex system. Among these factors, we identify the need to revisit the role of time dependence and axial growth and remodeling in large artery mechanics, especially in cardiovascular diseases that affect the mechanical integrity of the elastic fibers.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(2):020804-020804-16. doi:10.1115/1.4038705.
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Within several weeks of use as coronary artery bypass grafts (CABG), saphenous veins (SV) exhibit significant intimal hyperplasia (IH). IH predisposes vessels to thrombosis and atherosclerosis, the two major modes of vein graft failure. The fact that SV do not develop significant IH in their native venous environment coupled with the rapidity with which they develop IH following grafting into the arterial circulation suggests that factors associated with the isolation and preparation of SV and/or differences between the venous and arterial environments contribute to disease progression. There is strong evidence suggesting that mechanical trauma associated with traditional techniques of SV preparation can significantly damage the vessel and might potentially reduce graft patency though modern surgical techniques reduces these injuries. In contrast, it seems possible that modern surgical technique, specifically endoscopic vein harvest, might introduce other mechanical trauma that could subtly injure the vein and perhaps contribute to the reduced patency observed in veins harvested using endoscopic techniques. Aspects of the arterial mechanical environment influence remodeling of SV grafted into the arterial circulation. Increased pressure likely leads to thickening of the medial wall but its role in IH is less clear. Changes in fluid flow, including increased average wall shear stress, may reduce IH while disturbed flow likely increase IH. Nonmechanical stimuli, such as exposure to arterial levels of oxygen, may also have a significant but not widely recognized role in IH. Several potentially promising approaches to alter the mechanical environment to improve graft patency are including extravascular supports or altered graft geometries are covered.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(2):020805-020805-11. doi:10.1115/1.4037886.

Motor proteins play critical roles in the normal function of cells and proper development of organisms. Among motor proteins, failings in the normal function of two types of proteins, kinesin and dynein, have been shown to lead many pathologies, including neurodegenerative diseases and cancers. As such, it is critical to researchers to understand the underlying mechanics and behaviors of these proteins, not only to shed light on how failures may lead to disease, but also to guide research toward novel treatment and nano-engineering solutions. To this end, many experimental techniques have been developed to measure the force and motility capabilities of these proteins. This review will (a) discuss such techniques, specifically microscopy, atomic force microscopy (AFM), optical trapping, and magnetic tweezers, and (b) the resulting nanomechanical properties of motor protein functions such as stalling force, velocity, and dependence on adenosine triphosophate (ATP) concentrations will be comparatively discussed. Additionally, this review will highlight the clinical importance of these proteins. Furthermore, as the understanding of the structure and function of motor proteins improves, novel applications are emerging in the field. Specifically, researchers have begun to modify the structure of existing proteins, thereby engineering novel elements to alter and improve native motor protein function, or even allow the motor proteins to perform entirely new tasks as parts of nanomachines. Kinesin and dynein are vital elements for the proper function of cells. While many exciting experiments have shed light on their function, mechanics, and applications, additional research is needed to completely understand their behavior.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(2):020806-020806-12. doi:10.1115/1.4038710.

Mild blast traumatic brain injury (bTBI) accounts for the majority of brain injury in United States service members and other military personnel worldwide. The mechanisms of primary blast brain injury continue to be disputed with little evidence to support one or a combination of theories. The main hypotheses addressed in this review are blast wave transmission through the skull orifices, direct cranial transmission, skull flexure dynamics, thoracic surge, acceleration, and cavitation. Each possible mechanism is discussed using available literature with the goal of focusing research efforts to address the limitations and challenges that exist in blast injury research. Multiple mechanisms may contribute to the pathology of bTBI and could be dependent on magnitudes and orientation to blast exposure. Further focused biomechanical investigation with cadaver, in vivo, and finite element models would advance our knowledge of bTBI mechanisms. In addition, this understanding could guide future research and contribute to the greater goal of developing relevant injury criteria and mandates to protect our soldiers on the battlefield.

Commentary by Dr. Valentin Fuster

Research Papers

J Biomech Eng. 2018;140(2):021001-021001-17. doi:10.1115/1.4038716.

The mechanics of biological fluids is an important topic in biomechanics, often requiring the use of computational tools to analyze problems with realistic geometries and material properties. This study describes the formulation and implementation of a finite element framework for computational fluid dynamics (CFD) in FEBio, a free software designed to meet the computational needs of the biomechanics and biophysics communities. This formulation models nearly incompressible flow with a compressible isothermal formulation that uses a physically realistic value for the fluid bulk modulus. It employs fluid velocity and dilatation as essential variables: The virtual work integral enforces the balance of linear momentum and the kinematic constraint between fluid velocity and dilatation, while fluid density varies with dilatation as prescribed by the axiom of mass balance. Using this approach, equal-order interpolations may be used for both essential variables over each element, contrary to traditional mixed formulations that must explicitly satisfy the inf-sup condition. The formulation accommodates Newtonian and non-Newtonian viscous responses as well as inviscid fluids. The efficiency of numerical solutions is enhanced using Broyden's quasi-Newton method. The results of finite element simulations were verified using well-documented benchmark problems as well as comparisons with other free and commercial codes. These analyses demonstrated that the novel formulation introduced in FEBio could successfully reproduce the results of other codes. The analogy between this CFD formulation and standard finite element formulations for solid mechanics makes it suitable for future extension to fluid–structure interactions (FSIs).

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(2):021002-021002-12. doi:10.1115/1.4038428.

Connective tissue mechanics is highly nonlinear, exhibits a strong Poisson's effect, and is associated with significant collagen fiber re-arrangement. Although the general features of the stress–strain behavior have been discussed extensively, the Poisson's effect received less attention. In general, the relationship between the microscopic fiber network mechanics and the macroscopic experimental observations remains poorly defined. The objective of the present work is to provide additional insight into this relationship. To this end, results from models of random collagen networks are compared with experimental data on reconstructed collagen gels, mouse skin dermis, and the human amnion. Attention is devoted to the mechanism leading to the large Poisson's effect observed in experiments. The results indicate that the incremental Poisson's contraction is directly related to preferential collagen orientation. The experimentally observed downturn of the incremental Poisson's ratio at larger strains is associated with the confining effect of fibers transverse to the loading direction and contributing little to load bearing. The rate of collagen orientation increases at small strains, reaches a maximum, and decreases at larger strains. The peak in this curve is associated with the transition of the network deformation from bending dominated, at small strains, to axially dominated, at larger strains. The effect of fiber tortuosity on network mechanics is also discussed, and a comparison of biaxial and uniaxial loading responses is performed.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(2):021003-021003-10. doi:10.1115/1.4038758.

Dynamic hydrostatic pressure (HP) loading can modulate nucleus pulposus (NP) cell metabolism, extracellular matrix (ECM) composition, and induce transformation of notochordal NP cells into mature phenotype. However, the effects of varying cell density and dynamic HP magnitude on NP phenotype and metabolism are unknown. This study examined the effects of physiological magnitudes of HP loading applied to bovine NP cells encapsulated within three-dimensional (3D) alginate beads. Study 1: seeding density (1 M/mL versus 4 M/mL) was evaluated in unloaded and loaded (0.1 MPa, 0.1 Hz) conditions. Study 2: loading magnitude (0, 0.1, and 0.6 MPa) applied at 0.1 Hz to 1 M/mL for 7 days was evaluated. Study 1: 4 M/mL cell density had significantly lower adenosine triphosphate (ATP), glycosaminoglycan (GAG) and collagen content, and increased lactate dehydrogenase (LDH). HP loading significantly increased ATP levels, and expression of aggrecan, collagen I, keratin-19, and N-cadherin in HP loaded versus unloaded groups. Study 2: aggrecan expression increased in a dose dependent manner with HP magnitude, whereas N-cadherin and keratin-19 expression were greatest in low HP loading compared to unloaded. Overall, the findings of the current study indicate that cell seeding density within a 3D construct is a critical variable influencing the mechanobiological response of NP cells to HP loading. NP mechanobiology and phenotypic expression was also found to be dependent on the magnitude of HP loading. These findings suggest that HP loading and culture conditions of NP cells may require complex optimization for engineering an NP replacement tissue.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(2):021004-021004-11. doi:10.1115/1.4038609.

Vertebral fractures are common in the elderly, but efforts to reduce their incidence have been hampered by incomplete understanding of the failure processes that are involved. This study's goal was to elucidate failure processes in the lumbar vertebra and to assess the accuracy of quantitative computed tomography (QCT)-based finite element (FE) simulations of these processes. Following QCT scanning, spine segments (n = 27) consisting of L1 with adjacent intervertebral disks and neighboring endplates of T12 and L2 were compressed axially in a stepwise manner. A microcomputed tomography scan was performed at each loading step. The resulting time-lapse series of images was analyzed using digital volume correlation (DVC) to quantify deformations throughout the vertebral body. While some diversity among vertebrae was observed on how these deformations progressed, common features were large strains that developed progressively in the superior third and, concomitantly, in the midtransverse plane, in a manner that was associated with spatial variations in microstructural parameters such as connectivity density. Results of FE simulations corresponded qualitatively to the measured failure patterns when boundary conditions were derived from DVC displacements at the endplate. However, quantitative correspondence was often poor, particularly when boundary conditions were simplified to uniform compressive loading. These findings suggest that variations in trabecular microstructure are one cause of the differences in failure patterns among vertebrae and that both the lack of incorporation of these variations into QCT-based FE models and the oversimplification of boundary conditions limit the accuracy of these models in simulating vertebral failure.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(2):021005-021005-4. doi:10.1115/1.4038789.

In July 2018, Ireland will host the World Congress of Biomechanics in Dublin. This Congress is held once every 4 yr and is the premier meeting worldwide in its field, with over 3000 people expected to visit Dublin in July. The awarding of the 2018 Congress to Ireland is a reflection of the strength of biomechanics and bioengineering research in this country. To mark this event, herein we describe the development of biomechanics and bioengineering research in Ireland over the past 40 yr, which has grown in parallel with the medical device industry as well as the expansion of Government investment in science, innovation, and a knowledge-based economy. The growth of this activity has resulted in Ireland becoming established as a global hub in the field.

Commentary by Dr. Valentin Fuster

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