Sex-dependent differences in pulmonary vascular mechanics have been reported in both healthy and diseased populations, yet the mechanisms contributing to these differences remain poorly defined. Differences in shear stress responsiveness by the pulmonary endothelial surface may contribute to these differences in mechanics. This study investigated sex differences in shear stress responsiveness by measuring pulmonary pressure-flow relationships in isolated perfused lungs from male and female C57BL/6J mice. Pressure-flow relationships were measured under steady and pulsatile flow conditions before and after treatment with heparinase I to impair shear stress mechanotransduction. Pulmonary vascular resistance (PVR), vascular impedance, wave reflectance (RW), and pulmonary vascular distensibility (a) were quantified from pressure-flow data. Prior to treatment, male and female lungs exhibited comparable pulmonary vascular mechanics. Following heparinase I treatment, female lungs demonstrated significantly greater increases in PVR, 0-Hz impedance (Z0), and RW than male lungs. In contrast, characteristic impedance (ZC) remained unchanged in both sexes post-treatment compared to pre-treatment, indicating preservation of proximal conduit arterial mechanics. Female lungs also exhibited reduced distensibility than males, suggesting reduced pulmonary vascular adaptation to increasing flow. These findings indicate that impaired shear stress mechanotransduction had a greater impact in females than males and predominantly affected distal pulmonary vascular function while preserving proximal arterial properties. Our findings reveal sex differences in pulmonary vascular function with impaired shear stress mechanotransduction. These findings highlight the importance of considering sex as a biological variable in studies of pulmonary vascular biomechanics and vascular adaptation to flow.
The umbilical cord serves as a critical lifeline, connecting the fetus to the pregnant individual. Stillbirth, fetal death at or beyond 20 weeks' gestation, can occur due to developmental anomalies or complications of the umbilical cord. Gestational diabetes (GDM), which affects 8% of pregnancies in the United States, is associated with vascular abnormalities of the placenta and umbilical cord. While cellular and microstructural changes in the umbilical vasculature have been observed in pregnancies complicated by gestational diabetes, it is unknown if these influence the macroscale mechanical properties. Human umbilical arteries and veins from healthy pregnancies (n = 10) and from pregnancies with gestational diabetes requiring insulin for glucose management (n = 5) underwent quantitative histological analysis and circumferential ring testing to characterize the intact tissue and decellularized matrix. Collagen birefringence showed healthy umbilical arteries had a higher ratio of thick to thin collagen fibers than GDM. A two-way ANOVA showed the viscoelastic behavior of the decellularized umbilical arteries was significantly affected by disease (p = 0.01) and pin strain (p = 0.02). GDM decellularized umbilical arteries had a significantly (p = 0.04) lower 1st Piola-Kirchhoff stress than healthy at maximum pin strain. However, these differences did not persist within intact umbilical arteries. Additionally, there were no significant differences in the extracellular matrix content or mechanical properties between healthy and GDM umbilical veins. The results indicate umbilical arteries from pregnancies complicated by GDM have altered mechanical properties of the extracellular matrix, possibly due to decreased collagen fiber size.
Accurately estimating muscle activation remains a major challenge in neuromuscular modeling, particularly when direct measurements are limited by sensor placement, noise, and accessibility constraints. Traditional approaches such as inverse dynamics and static optimization require high-quality kinematic and kinetic data, while surface electromyography (sEMG) signals are often complex, nonlinear, and difficult to interpret directly. This study evaluated whether deep learning models can learn generalizable intermuscular activation relationships using sEMG alone. Measured muscle activations were treated as prediction targets during a standardized forward-reaching task performed by 30 participants. Three architectures, convolutional neural networks (CNN), long short-term memory (LSTM) networks, and hybrid CNN-LSTM models, were compared across different numbers of predicted muscles, training dataset sizes, and leave-one-muscle-out conditions. No single architecture consistently outperformed the others across all target muscles and prediction configurations. CNN-LSTM achieved favorable performance in selected cases, whereas CNN and LSTM produced comparable or better results in others. Compared with a population-mean baseline, the machine learning (ML) models did not consistently produce lower RMSE or higher correlation, suggesting that the standardized reaching task contained shared population-level activation structure captured reasonably well by a simple average profile. Prediction performance depended strongly on target muscle, prediction configuration, and subject-level variability, with the biceps showing consistently lower predictability. Increasing the number of training participants improved performance, but gains plateaued beyond 20 subjects. Overall, these results support the feasibility of sEMG-based deep learning for simultaneous muscle activation prediction, while indicating that its advantage over simpler baselines is configuration-dependent rather than systematic.
Understanding the permeability characteristics of renal tubular epithelial cells is essential for exploring the mechanobiological regulation of solute and fluid transport in kidney physiology. In this study, we investigated the depth-dependent mechanical properties of renal tubular epithelial cells using atomic force microscopy (AFM)-based nanoindentation in combination with finite element analysis (FEA). Two material models-viscoelastic (VE) and poroviscoelastic (PVE)-were applied to fit the force-relaxation response at various indentation depths. The PVE model demonstrated better fitting performance in capturing time- and depth-dependent behavior within the tested indentation range, by incorporating the effects of fluid redistribution within the cytoplasm. Furthermore, we assessed the impact of cytochalasin D on the mechanical response of cells. Drug treatment led to a significant reduction in elastic modulus and an increase in hydraulic permeability, indicating a softening effect and enhanced fluid mobility associated with cytoskeletal disruption. These findings have important implications for renal reabsorption and secretion, where fine regulation of water and solute movement is vital. This work provides new insights into how mechanical cues modulate epithelial barrier function, contributing to a better understanding of renal physiology and potential dysfunction in renal disease.
With patient dissatisfaction rates in total knee arthroplasty currently at 20%, smart knee technology seeks to provide an in vivo method for tracking postoperative joint forces, which could aid in early diagnosis of postoperative complications and provide key data to help improve implant designs and surgical procedures. This study investigates the design, simulation, and experimental evaluation of a piezoelectric force sensing system integrated into a commercially available knee implant that preserves the overall implant geometry. Finite element simulation and parametric analysis are used to identify the transducer arrangement with the lowest error in sensing compartmental joint contact forces. A prototype is then subjected to an axial load profile simulating walking using a joint motion simulator. Total and compartmental contact forces are evaluated, and accuracy of compartmental center of pressure localization is evaluated via ±3 mm and ±6 mm anterior-posterior translations. Results show the ability to track the axial force profile and demonstrate center of pressure deviations of ∼1 mm or better at 3-A and 3-P translations and ∼3-4 mm at 6-A and 6-P translations. Error of the order of ∼15% is observed in the total force measurement at maximum load. Suspected sources of error include plastic deformation of the tibial bearing insert and high stress levels in the piezoelectric transducers that suggest partial depolarization. Overall, our piezoelectric smart knee replacement shows promise for in vivo joint sensing, and this work marks a path for further development for integration into commercial knee replacement components.
For a detailed analysis of complex movements, such as disturbed locomotion, a combination of common approaches is helpful (calculation of 3D kinematics, measurements of myoelectrical activities, and ground reaction forces). The use of internal markers increased the accuracy of motion capturing and allowed the calculation of kinematics in 3D space, even long-axis rotation. Two implantation methods were designed and compared concerning their accuracy. Therefore, a double set of tantalum beads was implanted into the right forelimb of rats (test method versus glued reference). Our results showed that injecting the beads (1) via needle was the fastest method but caused considerable relative movements to the bones, which affected the angular 3D calculation (Ø root-mean-square (RMS) 3.4-31.6 deg), especially in the humerus. However, (2) embedding the internal markers into the muscles close to the periosteum enabled comparable results to the glued reference (Ø RMS 1.3-7.5 deg), while the surgery became easier and faster.
Acute ischemic stroke (AIS) remains a driver of mortality and long-term impairment, with clinical outcomes depending strongly on the final lodging site of emboli within the cerebrovasculature. However, the physical mechanisms governing embolus migration and partitioning remain incompletely understood. Further, due to the paucity of experimental data in realistic anatomical models under pulsatile flow conditions, computational modeling of embolus migration in AIS remains largely unvalidated. The study objective is to acquire experimental benchmark data of embolus migration in an in vitro anatomical model comprising the aorta and the cerebrovasculature. Experiments are performed under pulsatile flow to quantify the migration of 480 rigid nylon spheres (1.58-4.76 mm) and 160 deformable blood emboli (2.53-3.95 mm). Emboli are injected into both Newtonian and non-Newtonian blood analogs to evaluate the influence of size, deformability, and fluid rheology. Results demonstrate an inverse relationship between embolus size and the propensity to migrate into the cerebrovasculature. Furthermore, when comparing emboli of similar dimensions, deformable blood clots exhibited consistently higher migration rates to the supra-aortic branches. While rheology slightly influences the migration of rigid spheres, it has a negligible effect on the partitioning of blood emboli. These findings suggest that embolus deformability plays a more dominant role than rheology in dictating whether realistic blood emboli migrate to the cerebral circulation. Consequently, to predict embolus trajectories and lodging sites in AIS, future in silico studies should incorporate fluid-structure interaction modeling to account for realistic clot deformability.
Aging musculoskeletal tissues have a progressively declining ability to maintain homeostasis, increasing the risk of tendinopathy and tendon rupture. In young rats (3 months old), in vivo mechanical overload induced adaptive changes at 8 weeks, where load-bearing ability increased, which transitioned to degenerative changes at 16-weeks, where mechanical properties declined. It is unknown how maturation will influence the timeline of tendon outcomes to overload. The primary objective of this study was to evaluate mechanical and structural responses to overload in "middle-aged" (12-month-old) rats, representing an age when human tendon injuries become more prevalent, using a synergist ablation (SynAb) model. 12-month-old rats demonstrated adaptive changes in structural properties after 8-weeks of overload and no alterations in material properties, similar to prior findings in 3-month-old rats. Contrary to our findings in young animals, middle-age animals did not exhibit mechanical degeneration but rather they returned to control levels. MRI and μCT revealed no overload-dependent differences in tissue-scale structure, tendon cellularity, and collagen organization at either timepoint. A secondary objective was to evaluate natural age-related changes in untreated tendons. Twelve-month-old tendons, compared to 3-month-old tendons, exhibited greater load bearing-capacity, reduced extensibility, increased linear modulus, more heterotopic ossification, and a shift toward rounder nuclear morphology. These findings indicate that maturation still induces an initial adaptive response but does not lead to degeneration at later timepoints, differing from younger rats.
Clavicle fractures are among the most common orthopedic injuries and frequently require plate fixation to restore anatomical alignment and mechanical stability. The biomechanical performance of fixation constructs is strongly influenced by the contact interactions between the plate, bone, and screws. This study investigated the effect of four contact formulations (bonded, no-separation, frictionless, and frictional) on the structural stiffness, stress distribution, and interfragmentary strain of clavicle fixation plates using finite element analysis. A three-dimensional clavicle model reconstructed from computed tomography data was subjected to 200 N inferior bending, 200 N axial compression, and 4 Nm torsional loading. The bonded model exhibited the highest structural stiffness under all loading conditions (+66% bending, +60% compression, and +38% torsion), but also generated high stress concentrations, reaching 620.3 MPa under bending. The frictional and frictionless models produced lower stiffness values (+64% bending, +16% compression, and +28% torsion), while the no-separation model demonstrated intermediate stiffness. Peak plate stress varied considerably among contact formulations, with the no-separation model producing the highest value under bending (655.3 MPa). Interfragmentary strain was lowest in the bonded model (<2%), whereas frictional and frictionless models generated higher strain levels (2-10%), corresponding to mechanical conditions associated with secondary healing. The no-separation model exhibited intermediate strain values. These findings demonstrate that contact conditions strongly influence the biomechanical behavior of clavicle fixation constructs. Incorporating physiologically realistic contact models may improve finite element predictions and support the optimization of fixation strategies and implant design.
Identification and treatment of pregnancies at risk for preterm birth is a central challenge in obstetric research. Many of the known causes of preterm birth originate from mechanical failure in reproductive tissues. To better understand the biomechanical environment of the gravid uterus and its potential contribution to preterm birth, this computational study presents a parametric method for modeling maternal reproductive anatomy during the early second trimester. A finite element modeling approach was built using existing sonographic measurements from early second-trimester maternal anatomy and material properties from published mechanical tests. We applied the same physiologically relevant intrauterine pressure to all models and quantified the resulting tissue stretch. The sensitivity of the stretch in the proximal cervix was explored by varying material properties and sonographic maternal anatomy dimensions. Cervical material properties, particularly the fiber stiffness modulus and ground substance Young's modulus, were found to have the greatest effect on proximal cervix stretch compared to other material properties and sonographic dimensions. Among the sonographic dimension measurements, those defining the region surrounding the proximal cervix had the greatest effect on proximal cervix stretch, including the curvature of the posterior uterine wall and the thickness of the lower uterine segment. The computational modeling approach presented here enables future patient-specific studies of gravid reproductive tissues to elucidate differences between individuals who do and do not deliver preterm. Additionally, this study is foundational for building digital twins to support future virtual clinical studies on diagnostic and therapeutic device design to prevent preterm birth.
Traumatic brain injury (TBI), resulting from blunt or blast impact to the head, affects approximately 1.6 million Americans per year. Brain biomechanics and injury models play a fundamental role in the TBI community as they can be used to evaluate protective equipment, refine safety standards, and improve individual treatment plans. To maximize clinical relevance, these models require accurate and precise mechanical input parameters relevant to expected injuries. Magnetic resonance elastography (MRE) offers a noninvasive method to quantify the viscoelastic properties of soft tissues by phase-encoding mechanical waves as they propagate through a tissue. While MRE has advanced our understanding of brain tissue mechanics, characterizing nonlinear behavior under large deformations remains a critical challenge for improving TBI models. Here, we coupled ex vivo MRE with incremental compression to characterize brain tissue mechanics beyond the linear elastic and linear viscoelastic regimes, which are more relevant for injury. Using a custom-made MR-compatible compression device, controlled axial pre-strain was applied to fresh brain tissue-agar phantoms. On average, the tissue storage modulus increased by 73.6% when approximately 6.4% of strain was applied. The resulting experimental data, namely storage modulus and applied pre-strain, were successfully fit to a phenomenological equation to output material parameters, including a nonlinearity metric. These findings provide novel, strain-dependent mechanical data for brain tissue that extend beyond small-strain assumptions. The results will improve computational models of TBI by supplying mechanical input parameters for predicting brain response under injury-relevant loading conditions.
The occurrence of blunt abdominal injuries resulting from thoracic high-rate non-penetrating impacts (NPBIs) are often missed and associated with increased mortality and morbidity. Diagnosis of penetrating gunshot wounds successfully predicts injury locations using bullet trajectory, but no similar correlation has been applied for blunt impacts. Historically, thoracic NPBIs have been studied on ovine subjects and have reported thoracic only and thoracoabdominal injuries for impacts at the same location. The purpose of this study is to investigate if the finite element ovine thorax model (FE-OTM) can indicate changes in multi-compartment injury risk based on impact angle and determine a method for measuring this change. Twelve thoracic NPBIs were run over six impact angles (0 — 25°). Tissue directly under the impactor and along the path of impact, was analyzed for changes in composition and strain. Tissue composition analysis identified abdominal, lung, and liver as key tissue types. Cumulative volume analysis was used to determine a combine strain – volume metric for regions of interest. Within each region, Spearman's rank correlation was used to determine the strength of the relationship between this metric and impact angle. The key tissues experienced very strong correlations with impact angles and directionalities that corresponded to their change in volume. In conclusion, the FE-OTM can be used to indicate changes to multi-compartment injury risk based on impact angle. A 1st principal strain-volume based metric in the key tissue types is recommended.
The foot's role in movement varies dramatically across stance, absorbing shock upon heel strike, storing strain energy during midstance, and generating power during push-off. However, how coordination patterns of multi-segment foot kinematics fluctuate with changes in walking speeds remains unknown. The purpose of this study was to quantify three-dimensional foot joint rigidity and multi-segment coordination and variability at two walking speeds. We hypothesized that faster walking speeds would elicit decreased rigidity and more tightly regulated coordination. Sixteen adults (6 males, 10 females; age: 26.9±5.2 years) completed two-minute barefoot walking trials on an instrumented treadmill at two speeds (1.0 m/s,1.4 m/s). We utilized a multi-segment foot model to define the ankle, arch, and toe joints to assess multi-segment foot rigidity (i.e. range of motion), and segmental coordination and variability between the rearfoot, midfoot, and forefoot across early, middle, and late stance phases. Supporting our hypothesis, faster walking reduced joint rigidity and resulted in more tightly regulated coordination, characterized by more synchronized (i.e., greater in-phase or lesser anti-phase) movement and decreased variability across most planes. As a notable departure, only the midfoot-forefoot showed greater anti-phase movement during late stance, indicating less tightly regulated coordination, which may allow for greater extension at faster walking to facilitate mechanical energy return. These findings provide a foundation for understanding changes in foot and ankle due to age and/or injury, surgical intervention, or disease.
Aortic valve disease is a common valvular heart disorder that often progresses to heart failure. Aortic valve replacement with artificial heart valves is the standard treatment, making valve performance critical to patient outcomes and driving growing interest in optimized polymeric heart valves. Although prosthetic valve replacement is widely used, current artificial valves still face durability-hemodynamics tradeoffs. In this study, we sought to explore a computational design framework for improving the flow area, leakage, and stress distribution of a polyurethane-based synthetic polymer heart valve by simultaneously optimizing leaflet thickness and height through a data-driven workflow. A three-dimensional fluid-structure interaction model of a tri-leaflet valve made from siloxane-modified polyurethane was constructed and meshed. Twelve design points and three verification points covering the clinical design space were analyzed for effective orifice area (EOA), regurgitant fraction (RF), and peak von Mises stress. Response-surface surrogate models were fitted and interrogated using a multi-objective genetic algorithm. The leading Pareto solution was subsequently resimulated for half a cardiac cycle to evaluate its predicted performance. The surrogate prediction error was quantified as the absolute difference between surrogate and simulation results, and the ability to identify designs meeting ISO 5840-3 limits (EOA ≥ 125 mm2, RF ≤ 20%) was assessed. The optimized geometry (thickness 0.197 mm; height 15.49 mm) increased EOA from 140.5 mm2 to 164.5 mm2, reduced RF from 3.10% to 2.88%, and lowered peak stress from 1.88 MPa to 1.59 MPa. Surrogate predictions differed from the underlying simulation results by ≤5.3 mm2 for EOA, 0.59 percentage-point for RF, and 0.081 MPa for stress. Coupled optimization of leaflet thickness and height improved simulated hemodynamic and mechanical performance while satisfying ISO 5840-3 requirements. The presented workflow-combining fluid-structure interaction simulation, response-surface modeling, and multi-objective optimization-illustrates a computational methodology for exploring polymeric heart valve design spaces. Because the computational model has not yet been validated against independent experimental measurements, the reported performance improvements should be interpreted as preliminary computational findings pending future validation and comprehensive verification, validation, and uncertainty quantification (VVUQ).
Blunt traumatic aortic rupture (BTAR) is a life-threatening injury that can occur in high-impact events such as motor vehicle collisions, falls, and sports-related trauma involving the thorax. Despite improvements in vehicle safety features and regulations by using anthropometric test devices, BTAR remains associated with substantial clinical severity and high mortality, and its underlying rupture mechanisms are still poorly understood. We developed a novel proof of concept for a human-thorax surrogate for in vitro crash testing comprising a pulsatile heart pump, anatomically shaped silicone aorta, 3D-printed rib cage, and ballistic gel damping layer to investigate the fluid mechanics response to thoracic impact. The cardiovascular mock circulatory loop system of this surrogate was validated by obtaining physiological pressure waveforms with 120/80 mmHg of pressure and an average flowrate of 5.18 L/min. Subsequently, impacts were delivered to the sternum using a standardized pendulum system commonly employed in crash test dummy calibration. Impact severity was modulated by varying the pendulum's release height, corresponding to different kinetic energy levels. Instantaneous aortic pressure waveforms were recorded before, during, and after impact. The results demonstrate that thoracic impacts induce sharp, transient alterations in aortic pressure magnitude, with greater severity observed at higher energy levels, reaching a peak of aortic pressure of 287.01 mmHg. This experimental approach provides reproducible and physiologically relevant conditions for studying BTAR and offers valuable insights into the mechanisms underlying aortic rupture, which may guide the design of improved prevention and protection strategies.
While fascicular elastic fibers have been shown to significantly affect mechanical properties of tendon in stress relaxation and ramp to failure testing, the contribution of elastin to fatigue properties has only recently been investigated. This study expanded upon recent fatigue-to-failure data in wild-type and limb-specific elastin knockdown mice (Prx1Cre+;Elnfl/fl) by halting tests at 50% of cyclic fatigue (based on normalized strain) instead of completing tests to full tissue failure. Following 50% fatigue loading, Achilles (AT) and tibialis anterior (TB) tendons were subjected to subsequent stress relaxation and ramp to failure testing, enabling comparison to prior properties of nondamaged tendons to determine the effects of subfailure fatigue. Indeed, multiple properties (e.g., ultimate stress and linear modulus) were decreased following fatigue loading, especially in elastin-deficient tendons, and genotype-dependent differences in stress relaxation properties were observed. Quantitative metrics of damage (i.e., collagen denaturation and fiber kinking) were not different between wild-type and elastin knockdown tendons as observed previously following fatigue-induced failure, suggesting that tendon damage develops later in the fatigue lifecycle. In addition, results suggest that elastin mediates collagen fiber alignment more in ATs than TBs, providing evidence that the different effects of elastin on tendon mechanics rely on microstructural mechanisms that vary by tendon type. Clinically, results of this study suggest that individuals with deficient or depleted elastin may experience impaired recovery following repetitive tendon loading, which could have downstream effects on subsequent damage accumulation and tissue remodeling that should be investigated further in future studies.
Temporal coordination of muscle activation is a key determinant of mechanical control in functional movements such as lifting, gait, and sit-to-stand transitions. Although electromyography (EMG) research has traditionally emphasized amplitude-based measures, temporal features-including activation onset, offset, sequencing, and burst duration-provide essential insight into neuromechanical strategies governing joint moment generation, load regulation, and movement stability. This narrative review synthesizes evidence from peer-reviewed studies published between 1990 and 2025 to examine temporal muscle activation patterns across representative functional tasks. Across tasks, a consistent neuromechanical principle emerges: proximal muscle activation precedes distal force generation, supporting trunk stabilization, efficient momentum transfer, and redistribution of joint moments. During lifting, anticipatory trunk activation modulates spinal loading, whereas altered timing and increased cocontraction are associated with inefficient load sharing in low back pain. In gait, aging and pathology are characterized by prolonged distal activation and impaired push-off mechanics. Sit-to-stand transitions show a characteristic sequence initiated by tibialis anterior and trunk musculature, followed by synchronized extensor bursts at seat-off; deviations increase joint loading and reduce mechanical efficiency. These findings highlight temporal EMG patterns as biomechanically meaningful control variables for functional movement assessment.
