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 wall shear stress (WSS) topology. By maintaining identical meshes, boundary conditions, and postprocessing 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 solvers for high-fidelity hemodynamic predictions.

Markerless motion capture (MMC) shows promise for examining human movement across many domains because of its nonintrusive nature and negligible per-subject setup time. However, published MMC systems typically require specific hardware. This validation study compared lower-body joint kinematics from Ergomechanic, a hardware-agnostic pose model-based MMC system, to an established marker-based motion capture (MBMC) system. Static trial data from eighteen people were used to register MMC keypoints within a widely used musculoskeletal model. The registered model was used to calculate joint kinematics for static pose, squatting, and walking trials. A novel perturbation analysis estimated the contributions to differences in MBMC and MMC approaches to measurement disparities. Very good (0.87-1.0) correlations between the systems were calculated for ankle, knee, and hip flexion-extension angles. Good (0.70-0.86) correlations were found for hip external-internal and abduction-adduction. Pelvis and lumbar spine angles had a wider range of correlation results (-0.06 to 0.95), likely due to the few MMC keypoints in these body regions. Relative contributions from the perturbation analysis were (i) 75% from variations in MMC data relative to MBMC; (ii) 8% because MMC keypoints (26) < MBMC markers (67); and (iii) 3% from differences in musculoskeletal model scaling. These results validate Ergomechanic for leg kinematics during standing, walking, and squatting. Further, they suggest system improvements for pelvis and torso kinematics and provide new insights into the sources of known differences between MMC and MBMC measurements.

Pelvic organ prolapse (POP) is a common pelvic floor disorder resulting from weakened supportive muscles and ligaments. Although the demand for surgeries involving surgical meshes is expected to increase, current options remain limited. In 2019, the Food and Drug Administration (FDA) banned polypropylene mesh for transvaginal anterior compartment prolapse due to safety concerns. This study aimed to develop and evaluate computational models of biodegradable implants made of polycaprolactone, designed to replicate the mechanical behavior of the uterosacral ligaments (USLs) and mitigate complications associated with traditional synthetic meshes. The goal was to assess whether such implants could effectively restore pelvic support under varying degrees of USLs damage. Sacrocolpopexy was simulated using two distinct implant geometries: three square and one sinusoidal configuration. These were integrated into a pelvic cavity computational model to evaluate performance during the Valsalva maneuver under conditions of 50% and 90% damage, as well as total rupture of the USLs. The model, established without implants, demonstrated that complete USL rupture led to an approximate 41% increase in vaginal displacement when contrasted with the healthy model. All implants demonstrated a beneficial effect, decreasing vaginal displacement. Some of these implants successfully reversed the damage-induced displacement, nearing the level of a healthy vaginal model. While further clinical and in vivo validation is essential, these findings illustrate a promising direction and contribute to the growing evidence supporting the potential of biodegradable meshes in POP surgery. However, current outcomes are derived from computational models and serve primarily as a biomechanical proof of concept.

Cardiovascular diseases are the leading cause of death. Clinical data used to decide treatment are hard to integrate and interpret, making optimal treatment selection difficult. Personalized models can be used to integrate clinical data into a physics and physiology-constrained framework, but their clinical application faces limitations due to complex calibration and validation. In this study, we present a novel systematic calibration method for a whole-heart, multiscale, electromechanics model using emulators, sensitivity analysis, and history matching. Using cardiac motion derived from ECG-gated computed tomography (CT) and invasive left ventricular (LV) pressure data, we calibrated 25 model parameters to match the LV end-diastolic (ED) and peak pressure, ED and end-systolic (ES) volumes (EDV and ESV), right ventricle EDV, and the left atrium EDV, ESV, and the maximum volume during venous return. After calibration, all features were fit within [0.8, 10.8]% of the mean target value, and fell within 1.4 experimental standard deviations from the target values. We validated the model by comparing CT-derived and simulated atrioventricular plane displacement (AVPD) (8.2 versus 8.1 mm) and the ED and ES configurations against the CT images. The model replicated the measured acute hemodynamic response to biventricular (BIV) pacing (simulated: 222 mmHg/s versus clinical: 213±65 mmHg/s). This study provides a systematic method to integrate clinical data into a whole-heart, multiscale electromechanics framework. The validation shows that the model replicates local heart motion and response to therapy, demonstrating potential in assisting clinical decision-making.

This study was to investigate the effect of enlarged internal carotid artery (ICA) bifurcation angles on hemodynamic stresses and direct flow impingement center (DFIC) in facilitating aneurysm formation at the bifurcation apex. Three-dimensional (3D) angiographic datasets of 53 patients with (n = 23) and without (n = 30) ICA bifurcation aneurysms were retrospectively collected for computational fluid dynamic (CFD) analysis. All hemodynamic parameters were analyzed. The ICA bifurcation angle was significantly (P < 0.0001) greater in patients with than those without ICA bifurcation aneurysms. The hemodynamic stresses on the aneurysmal bifurcation apex after virtual aneurysm removal were all significantly (P < 0.0001) greater than those on the aneurysm dome or on the nonaneurysmal bifurcation apex. In the wall shear stress (WSS) profile, the WSS was minimal at the DFIC center, and two peaks were present in both the aneurysmal and nonaneurysmal bifurcations. The total pressure profile had the maximal value at the DFIC center. Peak 1 WSS value and the peak-peak distance on the aneurysmal bifurcation apex were significantly (P < 0.05) greater than those on the nonaneurysmal bifurcation. Blood flow directly impinged the DFIC on the aneurysmal bifurcation apex after virtual aneurysmal removal, with the DFIC corresponding to the aneurysm neck. In nonaneurysmal bifurcations, blood flow directly impacted the DFIC on the bifurcation apex, and the DFIC enlarged with increase of the bifurcation angle. Enlarged ICA bifurcation angles may increase hemodynamic stresses on the ICA bifurcation to facilitate aneurysm formation, which in turn is to reduce the abnormally enhanced hemodynamic stresses.

Nonanimal 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 three-dimensional (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 nonadherent wells that promoted high cell density and directed cell-cell adhesion without exogenous extracellular matrix (ECM) or biomaterial scaffolds. Transforming growth factor (TGF)β2 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.

Myocardial Infarction (MI) occurs when blood flow is blocked to a portion of the left ventricle and leads to necrosis and scar formation. Many therapies are under development to improve infarct healing, and three-dimensional engineered heart tissues (EHTs) offer an in vitro drug screening option to help reduce, refine, and potentially replace animal testing. Unfortunately, existing EHTs oversimplify cardiac mechanics and neglect the spatial variations of the infarcted ventricle in vivo, wherein the passive infarct zone is cyclically stretched under tension as the remote zone cyclically contracts with every heartbeat. We present an in vitro three-dimensional tissue culture platform focused on mimicking the heterogeneous mechanical environment of postinfarct myocardium. Herein, EHTs were subjected to a cryo-wound injury to induce localized cell death in a central portion of beating tissues composed of neonatal rat cardiomyocytes and fibroblasts. After injury, the remote zone continued to contract (i.e., negative strains) while the wounded zone was cyclically stretched (i.e., positive tensile strains) with intermediate strains in the border zone. We also observed increased tissue stiffnesses in the wounded zone and border zone following injury, while the remote zone did not show the same stiffening. Collectively, this work establishes a novel in vitro platform for characterizing myocardial mechanics after injury with both spatial and temporal resolution, contributing to a deeper understanding of MI and offering insights for potential therapeutic approaches.

Surfactant replacement therapy (SRT) is a widely used treatment for neonatal respiratory distress syndrome (NRDS), a condition caused by surfactant deficiency that leads to alveolar collapse and impaired gas exchange. While SRT has significantly improved clinical outcomes for neonates, challenges remain in achieving uniform and effective surfactant delivery throughout the lung. This review provides an overview of the pulmonary surfactant, lung development, and the underlying causes of NRDS to establish the physiological context of SRT. We then examine key advancements in experimental and computational modeling approaches that have been used to study surfactant transport and optimize delivery techniques. Computational models have provided insight into fundamental aspects of transport of surfactant as liquid boli or aerosols and the influence of airway geometry on surfactant spreading on airway walls and distribution in the airway tree. Benchtop models, including 3D multigeneration airway models and planar microfluidic devices, have enabled experimental control and visualization of surfactant spreading in airways. And studies using animal models have enabled testing different dosing strategies and delivery methods with full lung models, albeit interspecies differences in the lung anatomy make direct translation to humans difficult. Together, research using these models has highlighted the importance of optimizing delivery parameters such as dose volume, instillation flow rate, aerosol particle size, and lung orientation to improve therapeutic outcomes. The integration of these multidisciplinary approaches is critical to advance next-generation SRT strategies that are more efficient, less invasive, and better suited to the unique physiology of preterm infants.

We examine the limits of push-off, and we explore when alternate joint actuation might replace it. Using a powered simple walking model (point mass with rigid massless legs), the optimal analytical push-off was derived based on walking speed and step elevation changes. It was observed that higher speeds increased the available push-off to attain greater step-up, e.g., a walker at 1.4 m/s could manage a step-up amplitude of Δh = 0.106 m with a push-off only. Step-up amplitude also required a minimum walking speed for the required push-off. When poststep transition energy compensation was necessary, delayed push-off exerted along the trailing leg led to some wasted work. Walking over smooth surfaces, the delayed push-off cost was up to 7.5 times higher than the optimal push-off, whereas hip-driven compensation was lower at 3.2 times the optimal work. A similar pattern was also observed for step-ups. Our simulation results match young adult walking when terrain view was unrestricted. We utilized available empirical data to quantify the incremental energetic cost of disrupted push-off. It showed that the frequency and poststep transition compensation costs were comparable. As step length further decreased, the cost of poststep transition compensation rose more rapidly, possibly defining a lower limit for step length. The poststep transition compensation rose by 0.18 W/kg/%ΔHz in young adults and 0.2 W/kg/%ΔHz in older adults. Additionally, visual constraints amplified the cost by 0.05 W/kg/%ΔHz.

The design and optimization of ventricular assist devices (VADs) are critical for improving their hydraulic performance and clinical outcomes. This study employs computational modeling, feature importance analysis, and response surface optimization to enhance the performance of a VAD rotor. A three-dimensional, steady-state, incompressible flow model was used to simulate blood flow, with blood modeled as a Newtonian fluid. Predictive model for pressure rise (PR), torque (TO), and hydraulic efficiency (EF) was developed and rigorously evaluated, achieving R2 scores of 0.99, 0.99, and 0.95, respectively, indicating high predictive accuracy. Feature importance analysis revealed that rotational speed is the most influential parameter for pressure rise and torque, while inlet blade angle and clearance gap are critical for hydraulic efficiency. Response surface analysis provided insights into the interactions between key design parameters, guiding the optimization process. The optimized design achieved a pressure rise of 36,900 Pa (a 237.2% improvement over the baseline), a torque of 0.005 N·m (a 37.5% decrease), and a hydraulic efficiency of 36.4% (a 29.5% improvement). These results demonstrate the effectiveness of the optimization approach in balancing competing performance objectives. The findings have significant implications for the development of next-generation VADs, offering improved hemodynamic support and energy efficiency, which could enhance patient outcomes and device durability. Future work will focus on experimental validation and further optimization to address limitations and enhance clinical applicability.