In order to develop an efficient and safe direct ventricular assist device, this study analyzed the effects of compression, torsion, and compression-torsion loading modes on the ventricles. A three-dimensional (3D) dynamic biventricular finite element model of a patient with heart failure (HF) was developed, and three different loading modes of direct ventricular assist devices were simulated to evaluate their advantages by comparing the hemodynamic and biomechanical parameters. For the compression and torsion modes, the range of left ventricular ejection fraction (LVEF) increased from a baseline of 36.2% to a maximum of 47.9% and 40.6%. For the compression-torsion mode, applying a 40 deg torsion angle at 2.5 kPa compression mode increased the LVEF from 40.45% to 43.6%. However, applying a 40 deg torsion angle on the 7.5 kPa compression mode, the ejection fraction decreased from 47.7% to 45.9%. Meanwhile, the maximum principal stresses in the compression mode were generally below 80 kPa, whereas the maximum principal stresses in the multiple nodes of torsion and compression-torsion were greater than 150 kPa. The compression assist mode is more effective and safer than the torsion mode. Applying torsion at lower pressure (2.5 kPa + 40 deg) further increased the output, whereas applying torsion at higher pressure (7.5 kPa + 40 deg) decreased the output of the device. These experiments provide a theoretical basis for the design and optimization of direct ventricular assist devices.

Trabecular bone is a lightweight porous tissue with critical load-bearing function that is optimized through load-driven structural remodeling. One critical feature of trabecular bone microstructure at the level of whole trabeculae is the predominance of plate-like and rod-like forms with distinct orientations, material properties, and mechanical roles. Trabecular plates primarily align in the direction of typical loads and dominate structural stiffness under such loads. Thinner, less dense trabecular rods primarily align transverse to typical loads, contribute little to structural stiffness, but preferentially serve as sites for early tissue failure. These distinct roles impart resistance to both overload (plates) and fatigue failure (rods), and topological decomposition algorithms like individual trabecular segmentation (ITS) enable identification of plates and rods and their orientations in 3D images of trabecular bone. However, no existing metric describes the degree of organization between plates and rods, which is critical to their complementary functions. To quantify this feature of trabecular microstructure, we present a novel structural organization index (SOI), which accounts for variability in the orientations of trabecular plates and rods, and their degree of orthogonality relative to each other. In human vertebral trabecular bone, SOI was positively associated with experimentally-measured apparent-level yield strain, as well as the proportion of failed tissue in trabecular rods assessed through finite element analysis. We conclude that SOI produces valuable insights related to trabecular bone damage and yielding and may be particularly useful in cases where homeostatic remodeling is perturbed, such as during pregnancy or spaceflight.

Computational fluid dynamics (CFD) is commonly used to investigate hemodynamics in the cardiovascular system, particularly in regions prone to cardiovascular disease such as the carotid artery bifurcation. Despite its potential, significant variability exists across different computational approaches, highlighting the need for systematic solver comparisons. This study provides a comprehensive evaluation of three open-source finite element method (FEM) solvers--SimVascular, FEBio, and FEniCS Oasis--for simulating blood flow in a subject-specific carotid artery model. We conducted a rigorous comparison using a model derived from 4D phase-contrast magnetic resonance imaging (4D Flow MRI), examining solver performance across multiple mesh resolutions. This analysis focused on key hemodynamic metrics, including velocity fields, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and WSS topology. By maintaining identical meshes, boundary conditions, and post-processing methods, we isolated solver-specific characteristics while focusing on high-resolution mesh refinements. All solvers demonstrated similar capability in representing the 4D-Flow MRI data. Notably, all solvers consistently identified critical hemodynamic regions, such as flow disturbance zones in the carotid sinus. Mesh convergence analysis showed the ability of all solvers to achieve converged predictions at relatively lower mesh resolutions. The computational time was also compared across the three solvers. While demonstrating the capabilities of each solver in predicting physiologically relevant hemodynamic patterns, our study underscores the utility of open-source solver for high-fidelity hemodynamic predictions.

Non-animal models (NAMs) provide an important platform for studying musculoskeletal tissue formation under controlled conditions while reducing reliance on vertebrate animal models. In this study, we advanced a simple, scaffold-free 3D NAM system to guide the self-assembly of murine C3H/10T1/2 mesenchymal stem cells (MSCs) and C2C12 myoblast progenitor cells into neotendon and neomuscle structures. Custom 3D-printed molds and biologically inert agarose were used to form non-adherent wells that promoted high cell density and directed cell?cell adhesion without exogenous extracellular matrix (ECM) or biomaterial scaffolds. TGFβ2 treatment enhanced actin cytoskeleton alignment in neotendons, with initial collagen fibril formation observed by day 7. C2C12 myoblasts exhibited progressive actin alignment, myotube formation and desmin production by day 14. A custom bioreactor was used to apply cyclic tensile loading to the neotendons early in their development. Co-cultures of C3H/10T1/2 MSCs and C2C12 myoblasts formed cohesive structures, with aligned cytoskeletal organization and desmin distribution throughout, suggesting potential interactions at the developing myotendinous junction. This scaffold-free NAM system enables the evaluation of key biochemical and mechanical cues that regulate early musculoskeletal tissue formation in vitro. By recapitulating features of the embryonic environment, this approach refines current in vitro methods and establishes a simple, versatile platform to ultimately reduce the need for vertebrate animal models in developmental studies.

Acute injuries to the spine, including slips and falls and motor vehicle accidents, most commonly occur when the spine is positioned in flexion. Therefore, the purpose of this study was to investigate how spine position influences the morphology of vertebral fractures following rapid intervertebral disc pressurization.

Clinical risk factors for hip fracture can influence both fall-induced loading and underlying femur morphology/strength; however, these effects are generally studied in isolation. We evaluated the potential effects of fall-type, biological sex, and trochanteric soft tissue thickness (TSTT) on femoral neck stresses and fracture risk index during lateral impacts. Thirty-two young adults completed voluntary falls representative of falls in older adults. Peak impact force magnitude, direction, and point of application were extracted and applied to subject-specific beam models generated from dual-energy x-ray absorptiometry (DXA) scans. Falls with loading vectors directed more perpendicular to the femoral shaft were associated with increased compressive stress in the superior-lateral cortex (a demonstrated site of fracture initiation). Despite 44.5% greater impact force among males, no sex-based differences in femoral neck stresses were observed. Low-TSTT participant experienced greater femoral neck stresses than high-TSTT participants despite no differences in impact force magnitude. These findings highlight the importance of considering underlying differences in narrow neck mechanical properties (which vary across sex and TSTT-groups) when assessing tissue-level loading. Consistent with clinical findings, increased TSTT was associated with reduced fracture risk index among females but not males. This study provides novel insights into the mechanistic pathways through which different fall-types, biological sex, and TSTT may modulate hip fracture risk. Coupling of experimental fall simulations with tissue-level models enabled a computationally efficient method to investigate hip fracture risk, which is sensitive to biological variability.

Cervical spine finite element (FE) models often terminate at T1, which may introduce boundary-induced alterations, particularly at the cervicothoracic junction (C7-T1). This is relevant in multilevel anterior cervical discectomy and fusion (ACDF) constructs that terminate at C7, leaving C7-T1 as the inferior adjacent segment. This study analyzes the biomechanical response of a three-level anterior cervical discectomy and fusion (ACDF), which included the lowest cervical vertebra C7, using two FE models: a conventional C2-T1 model and an extended C2-T2 model. Postoperative range of motion (ROM) is evaluated under physiological flexion and extension loads of 2 Nm. A 7% increase in flexion ROM was observed in the C2-T2 ACDF model at C7-T1 when compared with the C2-T1 ACDF model. This change reflected the influence of shifting the inferior boundary to T2. The findings demonstrate that adding T2 preserved global kinematics, but the increase in the adjacent segment mobility (C7-T1) may lead to disc degeneration. The influence of rib and the responses under dynamic loading conditions have to be assessed for the use of caudal multi-level constructs in cervical spine modeling.

Cardiac fibrosis is a pathological condition linked to various diseases, involving remodeling that impair the cardiac function. Common forms include replacement fibrosis, where damaged myocytes are substituted by collageneous tissue, and interstitial fibrosis, involving matrix expansion between individual myocytes. These occur alongside other remodeling processes, including myocardial stiffening and collagen alignment. However, the mechanical impact of each factor remains poorly understood. In this work, we used a computational model with explicit myocyte and collagen geometry to study the microscale mechanical effects of fibrotic remodeling. Replacement fibrosis was simulated by substituting half of the myocytes with extracellular matrix, while interstitial fibrosis was modeled by increasing transverse spacing. These geometric changes were combined with increased matrix and myocyte stiffness and collagen alignment to assess combined effects during contraction and stretch. Myocyte replacement led to substantially higher stresses during contraction (12.2 kPa vs. 5.0 kPa at baseline) and slightly reduced shortening (17% vs. 20%). Collagen alignment and myocyte stiffening mitigated increased stress levels. Stretch experiments showed that replacement fibrosis decreased fiber-direction stiffness, reducing tissue anisotropy. In contrast, interstitial expansion alone had minimal effect on contraction but, when combined with stiffening, proportionally increased tissue stiffness (doubling load values) during stretch while preserving tissue anisotropy. Our findings suggest that myocyte replacement leads to elevated stress in surviving myocytes, whereas interstitial fibrosis primarily contributes to tissue stiffening. Collagen alignment and myocyte stiffening may serve compensatory roles. Integrating microscale modeling with experimental data may offer deeper insights into the mechanical consequences of fibrotic remodeling.

New Approach Methodologies (NAMs) can reduce reliance on animal testing and enable outcomes assessments in humans that were previously possible only in animal studies. Translating NAMs from animals to clinical use requires consideration of differences between the preclinical and clinical settings. The objective of this study was to translate and assess the performance of virtual mechanical testing of tibial fracture healing from a large animal model to clinical use. We translated a dual-zone material model for soft and hard callus, which we previously validated in sheep, to clinical use. Image-based models, also known as digital twins were generated from CT scans of healing human tibiae at 12 weeks post-op. Scaling adjustments were applied to correct for scanner-specific variability in X-ray attenuation values. The threshold for differentiation between soft and hard callus was inferred from sheep using comparative densiometric analysis. The selected hard/soft callus cutoff value was 998 HU, corresponding to 0.5372 of the expected cortical bone density mode of 1858 HU. The human-scaled dual-zone model reduced virtual torsional rigidity (VTR) by 41% compared to a single-zone material model developed based on cortical bone mechanics. With the dual-zone model, half the cohort achieved torsional rigidities in the range of intact tibiae, which corresponded well with modified radiographic union (mRUST) scores showing that half the patients achieved union (mRUST >=11) at this timepoint. These results demonstrate the potential for translation of a validated preclinical virtual mechanical test to clinical use.

To investigate the effect of enlarged internal carotid artery (ICA) bifurcation angles on hemodynamic stresses and direct flow impingement center (DFIC) to facilitate aneurysm formation at the bifurcation apex.

To better understand the mechanisms of bone stress injuries (BSI) in metatarsals, we developed an algorithm that adapts finite element (FE) models of metatarsals to simulate fatigue displacements through progressive stiffness loss. Twenty-two human metatarsals were imaged using computed tomography (CT) and then cyclically loaded in uniaxial compression until failure. CT images were used to generate specimen-specific FE models and a custom program was developed to iteratively simulate cyclic loading and progressive stiffness loss associated with microdamage accumulation. Probability was incorporated into microdamage accumulation through a Weibull distribution. Simulations were able to accurately represent experimental trends in how metatarsal stiffness and displacement changed throughout the mechanical testing. Simulated displacement at failure was not significantly different from experimentally measured displacement. Simulated fatigue life, displacement, and rate of stiffness loss were significantly affected by 1) the Weibull scatter variable, m, and 2) the critical strain value, describing whether damage occurred before or after yielding. These simulations represent a novel alternative method (NAM) that is significant because it helps us better understand the factors that influence fatigue life and observed mechanical behavior during fatigue testing in whole bones. Advanced adaptive simulations such as the one described here can be leveraged to reduce the reliance on physical testing, generate and test hypotheses regarding damage accumulation in materials, and eventually, be deployed in predictive algorithms with clinical applications.

Since the development of running specific prosthetics (RSP) in the 1980?s, lower extremity amputees have been able to engage in more modes of physical activity including running competitively and recreationally. Researchers have been led to investigate different mechanical properties like stiffness and hysteresis using machine testing. However, machine testing is limited by loading and deformation rates that are well below those recorded during running. The purpose of this investigation is to examine the mechanical properties of RSPs in situ. Three-dimensional motion capture and force platforms were used to record deformation and external loading while two participants ran at their 1-mile pace using their prescribed prosthetic device. Linear and non-linear prosthetic stiffness and hysteresis were calculated for each trial across loading and restoration phases using the vector magnitudes of 3-dimesional force and deformation measured via markers affixed to the prosthetic. Linear stiffness during the loading phase was relatively similar across participants (~26kN/m), despite differences in prosthetic type, body mass, and running speeds. However, linear stiffness was reduced by 5-10% during the restoration phase. Overall, both prosthetic's force-deformation relationships were nonlinear, exhibiting variable stiffness throughout each phase, a crossover point ("pinched hysteresis curve"), and smooth transitions between loading restoration phases. Machine tested stiffness values from the literature were approximately 5kN/m lower compared to in situ stiffness values. These findings illustrate the importance of understanding the in-situ properties for RSPs and for each user.

Increasing forward propulsion is a common goal of gait rehabilitation after stroke, but not all individuals demonstrate improved function after rehabilitation. Haptic, or vibrotactile, feedback has been used to promote improvements in spatiotemporal gait biomechanics in unimpaired and clinical populations, but there is limited research on the use of haptic feedback to promote increased forward propulsion in either unimpaired individuals or individuals with chronic stroke. The purpose of this study was to determine if haptic feedback could be used to increase ankle plantarflexion and, by extension, forward propulsion in unimpaired individuals. Thirty-two unimpaired individuals completed two overground walking trials while wearing five inertial measurement units to calculate real-time joint angles and deliver haptic feedback. In the baseline trial, subjects were instructed to walk normally and no feedback was delivered. In the feedback trial, haptic feedback was given when the subject's plantarflexion angle exceeded 10% more than the peak plantarflexion angle from the baseline trial. Peak ankle plantarflexion and anterior ground reaction force were compared between trials using a paired t-test (α = 0.05) and increased statistically significantly between trials (both p < 0.001). Individuals were able to interpret haptic feedback and change their gait accordingly, resulting in substantial increases in plantarflexion and propulsion. These results suggest that haptic feedback on plantarflexion angle may be a simple and effective way to increase forward propulsion in a post-stroke population, although future research is needed to confirm these results in individuals with chronic stroke.

Capstone design focused on medical/assistive devices provides a golden opportunity to educate young biomedical engineers in business and entrepreneurship. What constitutes a healthy balance of engineering and business subject matter, however, remains unclear. The present manuscript describes the history of the senior capstone design course sequence in Biomedical Engineering at the author?s institution, for which he was lead instructor. The focus is on the business content, which was first increased to encourage an entrepreneurial mind-set among students, then later decreased, based on student feedback, instructor assessment, and related grant proposal reviews, which suggested that engineering aspects of the design process were being compromised. Business and engineering topics included in the current course sequence are described to help course designers strike a healthy balance that provides students with the skills to be successful as design engineers with healthy business acumen.

Accurately generating joint motion trajectories for infant crawling is crucial for developing effective control strategies for exoskeletons. However, the limited availability of infant crawling data, owing to the high costs of data collection and privacy concerns, presents a challenge to the performance of such models and controllers. This study introduces a novel spatiotemporal dual-discriminator generative adversarial network (SDGAN) to generate synthetic kinematic data for infant crawling. The generator produces 3D joint coordinate sequences (101 time steps × 36 dimensions for 12 joints) by learning both the spatial joint relationships (via a spatial discriminator) and the temporal dynamics (via a temporal discriminator). To evaluate the model's effectiveness, the SDGAN was compared with existing benchmark models-the TimeGAN, DAT-GAN, and MTS-GAN. Additionally, we assessed the impact of varying synthetic-to-real data mixing ratios (0:1, 1:2, 1:1, 3:2, 2:1, 5:2, and 3:1) on the accuracy of joint angle predictions using a long short-term memory (LSTM) network. The results suggest that the SDGAN is a promising approach for addressing the challenge of limited infant crawling data and improving joint angle prediction accuracy in rehabilitation applications.

The uterine cervix is a soft biological tissue with critical biomechanical functions in pregnancy. It is a mechanical barrier that supports the growing fetus. As pregnancy progresses, the cervix becomes more compliant and eventually opens in late pregnancy to facilitate childbirth. This dual function is facilitated by extensive remodeling of the cervical extracellular matrix (ECM), giving rise to its complex time-dependent material properties. Premature cervical remodeling is known to result in preterm birth, defined as birth before 37 weeks of gestation. While previous work has studied cervical remodeling by various biomechanical methods, it remains unclear how the cervix's intrinsic or flow-independent viscoelastic behavior is influenced by cervical remodeling. In this study, an anisotropic reactive viscoelastic material model was formulated and investigated under tensile deformation to understand material behavior in cervical remodeling. To calibrate the model, experimental force relaxation data was used from uniaxial tension tests on Rhesus macaque cervical specimens from four gestational time points. Results show that cervical tissue equilibrium and instantaneous elastic moduli significantly decreased from the non-pregnant to late pregnancy. Also, cervical tissue in the late third trimester relaxed faster to equilibrium than the other gestational groups, particularly at prescribed tensile strains greater than 30\%. This fast relaxation to equilibrium helps the cervix dissipate tensile hoop stresses induced by the fetus during labor, preventing its rupture. This work provides insights into time-dependent cervical remodeling features, crucial for developing diagnostic methods and treatments for preterm birth.

Axial interfragmentary motion is known to stimulate fracture healing. A mechanically compliant fracture fixation plate incorporating flexures is proposed to provide controlled axial micromotion to long bone fractures. To explore the concept's feasibility, computational modeling of general diaphyseal and distal femur fractures treated with both rigid and compliant plates is conducted. In Part I of this study, a diaphyseal fracture finite element model for novel compliant plates is validated against experimental data with good agreement. In Part II, a parametric analysis is conducted using the validated model to characterize the performance of many compliant plate designs with varying geometry and materials. Under axial loading, all compliant plate configurations provided greater magnitude (1.03mm vs. 0.22mm) and symmetry (270-390%) of axial interfragmentary motion than rigid plates. Steel compliant plates with thicker flexures (0.3-0.6mm) may provide the best performance given their enhanced motion and comparable bending/torsional rigidity. In Part III, compliant plates are adapted for use in treating distal femur fractures. Results demonstrate that compared to a rigid plate, a compliant distal femur plate with increased thickness can effectively modulate interfragmentary motion - that is, increase the insufficient near cortex motion under low loads (from 0.14mm to 0.23mm) and reduce the excessive far cortex motion under large loads (from 7.96mm to 2.54mm). Flexure-based locking plates represent a promising new approach to treating diaphyseal and/or distal femur fractures. Additional research is needed to investigate vivo performance.

The annulus fibrosus(AF) is subjected to complex, multiaxial loading in the spine. Developing accurate constitutive models to predict the AF mechanical response to load is critical to understanding load induced degeneration and pain. Prior work has performed uniaxial tension, uniaxial compression, and biaxial tensile experiments, but no multiaxial compressive-tensile experiments have ever been performed on the AF. Additionally, based on prior comparisons between uniaxial and biaxial optimization of current constitutive models, current coefficients may be unable to accurately explain AF mechanics. To address these limitations, this study established a novel multiaxial compressive and tensile experiment and evaluated whether existing constitutive models can accurately predict multiaxial compressive and tensile mechanics. Porcine AF samples were preconditioned, then tested in uniaxial tension or biaxial compressive-tensile loading. Constitutive models included a fiber matrix model and a fiber matrix interaction model. These models consisted of a Holmes Mow matrix component, an exponential fiber component, and a shear term to capture interlamellar "scissoring". Compression reduced stiffness in the tensile direction and decreased the fiber angle. Coefficients fit to tensile-only data were unable to accurately explain biaxial loading, whereas biaxial coefficients improved model fits. These biaxial optimizations further improved when the fiber angle was manually adjusted to 17.0° to account for compressive loading induced fiber reorientation. These findings underscore the importance of incorporating fiber reorientation and interlamellar interactions to ensure model accuracy. This framework and dataset enable more predictive constitutive models of AF mechanics for spine biomechanics and translational disc repair applications.

Heart failure is the leading cause of death in patients with Duchenne muscular dystrophy (DMD), but the mechanisms underlying the associated dilated cardiomyopathy (DCM) are not fully understood. To address this gap, we generated engineered heart tissues (EHTs) using CRISPR-edited human induced pluripotent stem cell-derived cardiomyocytes that lack dystrophin. These dystrophic EHTs reproduced aspects of systolic and diastolic dysfunction seen in DMD-related DCM as they showed impaired contractile function and slower kinetics. Increased beat rate variability was also observed in dystrophic EHTs. Accompanying these facets of the DMD pathology were attenuated Ca2+ transients and delayed kinetics. Lastly, histological analysis of EHTs revealed that dystrophin-null cardiomyocytes had reduced size and shorter sarcomere lengths when compared to isogenic controls. Together, these findings demonstrate that EHTs provide a physiologically relevant human model of DMD-associated DCM and may serve as a valuable platform for mechanistic studies and therapeutic testing.

The aorta, the largest artery in the body, exhibits anisotropy and heterogeneity along its length. Over the past several decades, researchers have characterized the positional differences in various geometric and mechanical properties such as wall thickness, diameter, extracellular matrix composition, mechanical properties, opening angle, and axial stretch. These regional adaptations arise in response to various biochemical and mechanobiological stimuli helping the vessel maintain efficient and resilient blood flow. Early studies, often limited to canine models and uniaxial testing, laid the groundwork for recognizing how composition and mechanics vary with location. Subsequent efforts broadened into comprehensive investigations that included parameters such as wall thickness, diameter, opening angle, and axial stretch, employing diverse animal models and, more recently, human samples. Technological advances in experimental and computational methods have deepened our understanding of these spatial variations, underscoring the aorta?s critical role in overall cardiovascular function and its vulnerability to conditions like aneurysms and atherosclerosis. This review seeks to consolidate and interpret these diverse studies on region-specific geometry and mechanics of the aorta, examining how spatial variations arise and how they support normal circulatory function. Further, we argue that any model of aortic growth and remodeling in disease should be able to predict the observed property variation with position in healthy individuals.

Providing a well-fitting prosthetic foot can improve a user's mobility and satisfaction with their lower-limb prosthesis, but achieving high performance with a prosthetic foot for people with an above-knee amputation can be challenging. Prosthetic feet are generally designed for the needs of below-knee amputees, and these devices do not account for the unique gait patterns common to above-knee amputees, such as a lack of early-stance knee flexion, which can limit potential user outcomes. Hip Trajectory Error (HTE) is a novel framework for designing prosthetic feet that enables near able-bodied hip motion and accounts for this gait deviation. In this study, the performance of HTE feet was compared to users' daily-use prosthetic feet and to predictively designed prosthetic feet for below-knee amputees that have shown close replication of able-bodied biomechanics. The performance of each prosthetic foot was characterized by the deviation of kinetics and kinematics from able-bodied data. The study also evaluated how each prosthetic foot interacted with passive knee mechanisms by investigating the center of pressure and ground reaction force orientation throughout the stance phase. HTE feet demonstrated significantly better performance than the below-knee-specific alternative and the same performance as daily-use prosthetic feet that were chosen and tuned specifically to the user after minimal acclimation time. This work validates and quantifies the benefits of using the HTE framework for designing high-performance prosthetic feet specific to the needs of above-knee amputees.