Annals of Biomedical Engineering

Introduction: Metastatic spinal lesions substantially alter vertebral mechanical properties and increase fracture risk. Computed tomography (CT) based finite element (FE) models can estimate vertebral strength, but their accuracy depends on how CT derived material properties are represented. This study evaluated the effect of two material grouping strategies on simulated strength and stiffness in metastatic vertebrae. Methods: We compared Adaptive Clustering (AC) with Uniform fixed width grouping in 44 vertebrae from 11 donors (8 osteolytic, 12 osteoblastic, 12 mixed, 12 no observed lesion (NOL)). FE models were generated based on CT scans with 2 to 500 material groups and compared for material mapping error and simulated strength and stiffness. Overall and lesion stratified agreement with experimental measurements was assessed in an exploratory analysis. Results: AC showed significantly lower Young's modulus root mean square error than Uniform (p < 0.05). Simulated strength and stiffness stabilised by 50 material groups. At 50 groups, simulated strength showed moderate correlation with experimental strength overall (R2 = 0.57), strongest in NOL vertebrae (R2 = 0.82) and lower in lesion-bearing vertebrae (R2 = 0.4-0.59). Stiffness showed weaker correlation overall (R2 = 0.27), highest in NOL vertebrae (R2 = 0.48) and negligible in mixed lesions (R2 = 0.007). Bland Altman analyses indicated systematic underestimation of experimental fracture load. Discussion: AC improved material-mapping fidelity, whereas increasing material groups beyond 50 had little influence on simulated strength or stiffness. Numerical stabilisation therefore did not imply experimental accuracy. Lesion stratified findings were exploratory and should be interpreted cautiously because of limited subgroup sizes.

Purpose: Quantifying aortic morphology is central to surgical planning for thoracic endovascular aortic repair (TEVAR), yet no consensus exists on how best to represent three-dimensional aortic shape for outcome prediction. Two broad strategies have emerged: statistical shape analysis (SSA), which relies on statistical methods and dimensionality reduction to capture the most significant shape modes, and geometrically-informed approaches that extract descriptors grounded in differential geometry. Here, we directly compare these paradigms on a cohort of 290 CTA scans classified by surgical outcome (non-pathological, successful TEVAR, failed TEVAR). Methods: For the geometrically-informed approach, we use a two-dimensional feature space using normalized fluctuation in integrated Gaussian curvature $\widetilde{\delta K}$ and mean aortic radius $R$. For SSA, we construct a point-cloud shape model with dimensionality reduction using Principal Component Analysis (PCA) and evaluate classification performance as a function of the number of retained principal components. Results: SSA's leading principal components encode variations in global aortic size and are statistically redundant with ($R$, $\widetilde{\delta K}$), yet they lack a one-to-one correspondence with interpretable anatomical quantities. Testing on an unseen, independent dataset reveals that the geometrically-informed approach provided better generalizability than SSA. Using Gaussian process classification with 10-fold cross-validation, we find that the geometrically-informed approach achieves a higher weighted $F_1$ score than SSA achieves with up to 20 principal components. While SSA's full-dataset accuracy rises above 90\% with increasing dimensionality, this gain is driven by overfitting rather than genuine discriminative power. Conclusion: These results demonstrate that geometrically-informed descriptors offer a more interpretable, robust, and clinically translatable framework for aortic disease classification than data-driven statistical shape representations.

Background: Articulated laparoscopic instruments require a reliable mechanical connection between the handle and shaft to maintain the intended instrument configuration during surgical manipulation. The handle shaft locking interface should resist unintended relative displacement under external loading. However, the appropriateness of a specific slip resistance threshold must be evaluated in relation to the instrument design and intended conditions of use. Objective: To evaluate the mechanical performance associated with an 8 N slip resistance specification for the locked handle shaft interface of an articulated laparoscopic instrument using a controlled bench model. Methods: A bench based mechanical evaluation method was designed using the instrument under test, mechanical fixtures, a calibrated force measurement device, and displacement measurement equipment. After engagement of the handle shaft locking mechanism, external forces were applied to evaluate resistance to relative displacement. Testing included axial loading, loading in relevant transverse directions, and repeated locking unlocking cycles. The primary outcome was the force corresponding to the onset of relative slippage at the locked interface. Secondary outcomes included displacement under load, complete locking failure, and changes in mechanical performance after repeated operation. Acceptance criteria should be established before confirmatory testing. Results: All 30 instruments from three production batches met the 8 N axial requirement (30/30). The axial slip onset force was 12.40 N . Under a sustained load of 8 N for 60 s, mean relative displacement increased from 0.06 mm to 0.10 mm, and mean residual displacement was 0.02 mm. After 1,000 cycles, the axial slip-onset force was 12.00 N . Conclusions: This study provides a bench-testing framework for evaluating an 8 N slip resistance specification for the handle shaft locking interface of an articulated laparoscopic instrument. Whether this specification provides adequate mechanical stability can be determined only by comparing the measured performance with engineering acceptance criteria established in advance on the basis of the instrument's intended use and foreseeable loading conditions.

This study demonstrates the feasibility of using a Teflon-AF-based tube-in-tube saturator for fast and precise adjustment of oxygen concentrations in liquids, extending its relevance to human cell culture applications beyond organ-on-chip systems. The system achieves high, near-saturation oxygen concentrations of the liquid phase, with performance influenced by various parameters such as temperature, volume flow rate, and tube length. We demonstrate that the tube-in-tube saturator exhibits high sensitivity to variations in these parameters at low oxygen concentrations, whereas this sensitivity diminishes as saturation is approached. To elucidate the underlying mass transfer processes, kinetic experiments were combined with computational fluid dynamics simulations. The simulation results are in good agreement with the experimental data, and the developed model enables a reliable prediction of oxygen concentrations in the liquid phase under varying operating conditions. Owing to its design, performance, versatility, and portability, this system introduces a new approach for the precise and rapid control of oxygen concentrations in liquids for microscale and macroscale human cell culture applications, offering seamless integration with natural vascular or artificial perfusion networks.

Maternal thermal strain is associated with adverse pregnancy outcomes, yet fetal temperatures cannot currently be directly measured, limiting quantification of fetal thermal strain. Here, we develop two steady-state models for estimating internal temperatures in a near-term fetus. First, we improve the only previously published human fetal thermoregulation model, deriving a closed-form solution within its simplified uniform-cylinder representation. Second, we introduce a multilayer, anatomically segmented model that resolves tissue-specific temperatures. Both couple the fetal body to central blood pool and amniotic fluid compartments and incorporate a new placenta-umbilical cord heat-exchanger representation. Predictions agree with available intrauterine scalp measurements, with fetal core and head-center temperatures approximately 0.5{degrees}C and 0.8{degrees}C above maternal core, respectively. Physiologically plausible changes in umbilical cord heat-exchanger effectiveness or blood flow increased fetal temperatures by approximately 0.3{degrees}C. These models enable estimation of otherwise inaccessible temperatures, while the multilayer formulation lays a foundation for transient, coupled maternal-fetal thermoregulation modeling.

Introduction: The femoropopliteal artery undergoes substantial axial compression, bending, torsion, and pinching during limb flexion. When an implanted stent does not accommodate these deformations, repetitive biomechanical mismatch may alter the vascular response to implantation and contribute to restenosis. We tested whether designing a peripheral stent to better accommodate physiologic limb-flexion deformation reduces the subsequent inflammatory and neointimal response. Methods: A nitinol stent was developed using multi-objective computational optimization to maintain arterial apposition while reducing wall stress and luminal pinching during physiologic deformation. Sixteen Yucatan minipigs were studied in independent 3- and 6-month cohorts (n=8 each). Each animal received the optimized stent in one limb and a commercial stent with representative biomechanical behavior contralaterally. CTA quantified in vivo limb-flexion deformation, while CT and histology assessed stenosis, neointimal accumulation, inflammatory-cell burden, SMA-positive tissue, and extracellular-matrix composition. Results: The optimized stent accommodated greater axial shortening than the commercial comparator at both 3 months (11.2{+/-}2.7% vs. 6.6{+/-}2.1%, p=0.003) and 6 months (13.7{+/-}4.4% vs. 6.8{+/-}2.3%, p=0.004). Intimal hyperplasia volume was lower with the optimized stent at 3 months (227.5{+/-}85.2 vs. 350.0{+/-}130.5 mm3, p=0.002) and 6 months (183.6{+/-}46.2 vs. 261.2{+/-}60.6 mm3, p=0.001), with significantly lower maximum, mean, and median stenosis at both timepoints. At 3 months, macrophage and total inflammatory-cell counts were 51% and 45% lower, respectively, with the optimized stent. Histologic tissue area was 28% lower at 3 months and 12% lower at 6 months. SMA-positive tissue fraction was higher with the optimized stent at both timepoints, whereas elastin, glycosaminoglycan, and collagen fractions were similar between devices. Discussion: Improved accommodation of limb-flexion deformation was associated with a smaller inflammatory and neointimal response to stent implantation through 6 months, while overall neointimal matrix composition remained largely unchanged. These findings provide in vivo evidence that biomechanical compatibility with the dynamic lower-limb environment can influence vascular healing and should be considered a mechanistic design criterion for peripheral artery stents.

The temporal resolution of medical imaging sequences used to drive patient-specific computational fluid dynamics (CFD) simulations remains limited, typically providing 10-20 frames per cardiac cycle. Therefore, temporal interpolation to reconstruct left atrial (LA) wall motion and boundary conditions is required, but its impact on hemodynamic predictions has not been systematically characterized. To investigate this, we constructed high-temporal-resolution reference wall-motion data using electromechanical (EM) simulations on five patient-specific atrial geometries with a history of atrial fibrillation. We then generated temporally downsampled datasets to emulate clinical frame rates (5, 10, 20, and 40 frames per cycle) and performed CFD simulations to isolate the effects of temporal undersampling on hemodynamic metrics. The focus was placed on kinetic energy, KE, and residence time, TR, particularly in the left atrial appendage (LAA), where thrombosis is most likely to occur. We employed an immersed boundary method to prescribe the wall motion and computed blood TR through a passive scalar transport equation. Results indicate that while global LA hemodynamic indices were marginally affected by the frame rate (errors < 9%), LAA metrics were more sensitive with errors up to 31% compared to reference values. The results based on 20 and 40 frames per cycle yielded favorable agreement with reference results, while 5-and 10-frame reconstructions showed larger, though not systematically biased, deviations from the reference. Importantly, patient ranking by blood-stasis indices was largely preserved. The analysis suggests that patientspecific LA reconstructions derived from dynamic CT imaging provide a reliable basis for estimating LAA blood-stasis indices. Higher frame rates ([&ge;] 20 per cycle) offer improved quantitative accuracy, while lower temporal resolutions may remain informative for patient stratification purposes, where relative ranking is more relevant than absolute accuracy.

Successful instrumented fusion of the lumbar spine is a complex surgical challenge, with positive patient outcomes dependent on careful surgical planning. Material selection is of critical importance to a mechanical construct supporting successful spinal fusion. Therefore, the aims of this study were to (a) evaluate the potential clinical use of finite element analysis (FEA) and (b) conduct a retrospective mechanical analysis of different implant materials in patients having undergone spinal fusion using FEA. Our methodology involved segmenting the spine from post-operative computed tomography (CT) image data from patients with previous spinal fusion. FEA models representing post-surgery cases were developed and different biomechanical loading conditions such as compression, flexion, bending and extension whilst testing pedicle screws of different materials were simulated. Patient specific finite element models were created, and biomechanical analysis were completed for all three patients. Polyetheretherketone (PEEK) constructs typically demonstrated lower peak implant stress when compared to titanium constructs for all spinal fusion levels. Furthermore, increasing the spinal fusion level resulted in significant differences in the maximum von Mises stress within both the bone and the instrumentation, whereas the 2-level fusion exhibited comparable stress levels in the bone irrespective of the instrumentation material. This pilot explores the potential of FEA as a clinical tool for assessing device and bone stresses. In our cohort, different materials can influence the stresses in both the instrumentation and the instrumented vertebrae, suggesting FEA can be useful pre- operative tool with regards to instrument selection and post-operatively to assess instrumentation and bone stresses. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/742715v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@55959aorg.highwire.dtl.DTLVardef@d0b9d6org.highwire.dtl.DTLVardef@158c348org.highwire.dtl.DTLVardef@7ce828_HPS_FORMAT_FIGEXP M_FIG C_FIG

This study presents a physiologically detailed biomechanical model of the mouse distal forelimb that incorporates intrinsic musculature, tendon routing, and digit-level skeletal anatomy, features simplified or omitted in existing musculoskeletal models. Using high-resolution anatomical reconstruction and computational modeling, we created a physiological representation of the wrist and digits capable of simulating complex forelimb movements. The model enables simulation of coordinated distal forelimb movement and digit-level muscle behavior during grasping-related tasks. Simulations were performed for multiple tasks, including grasping, grasping with supination, wrist flexion, and digit I flexion, with analysis focused on the grasping task due to its integration of both intrinsic and extrinsic musculature. Model performance was evaluated through comparisons of marker trajectories between torque-driven reference motion and muscle-driven simulations, temporal shuffle control, and comparisons between experimentally recorded electromyography (EMG) activity and model-predicted muscle excitation profiles. The model successfully reproduced coordinated distal forelimb kinematics, demonstrated strong agreement between torque-driven and muscle-driven simulation approaches, and generated physiologically plausible muscle excitation patterns consistent with experimentally observed EMG activity during grasping-related movement. These findings establish the model as a framework for studying fine motor control, neuromuscular coordination, and movement-related impairments in mice while providing a foundation for future investigation of neurological disorders and their underlying biomechanical mechanisms.

Purpose: Fibrotic remodeling of the uterus, associated with aging, disease, and environmental exposures, alters collagen organization and tissue stiffness, yet how these changes influence organ-level mechanical behavior remains poorly understood. Glutaraldehyde (GA)-induced collagen crosslinking was used as a controlled surrogate for fibrotic remodeling to determine whether image-informed inverse finite element analysis (iFEA), combined with inflation testing and micro-computed tomography (microCT), could detect and quantify the resulting changes in uterine constitutive behavior. Methods: Murine uteri (n = 6 untreated, n = 6 GA-crosslinked) underwent volume-controlled balloon inflation with simultaneous microCT imaging to quantify deformation of the inner and outer wall boundaries for iFEA. Specimen-specific Gasser-Ogden-Holzapfel (GOH) finite element models were optimized by adjusting model parameters to reproduce experimentally measured wall contours throughout inflation. Model performance was evaluated using contour root mean square error (RMSE), and parameter identifiability was assessed through sensitivity analyses. Results: GA treatment significantly increased inflation work, linear stiffness, and maximum inflation resistance (p < 0.001). The iFEA framework accurately reproduced experimental deformation (RMSE < 3%) and revealed significant increases in the estimated GOH parameters C10 (9.2-fold), k1 (2.0-fold), and k2 (2.7-fold), consistent with increased effective tissue stiffness and a shift toward earlier collagen fiber recruitment. Sensitivity analyses demonstrated unique, well-defined minima for all parameter combinations. Conclusion: Image-informed iFEA provides a quantitative framework for relating collagen remodeling to organ-level uterine mechanics through specimen-specific constitutive parameter estimation. This approach establishes a foundation for investigating the mechanical consequences of uterine fibrosis and other remodeling processes.

Repetitive low-intensity blast (LIB) exposure has been identified as a probable cause of mild blast-induced traumatic brain injury (mbTBI) and a chronic injury risk to U.S. military personnel. However, the human brains biomechanical response to this loading regime remains poorly characterized. Using blast-exposure-validated 3D models of human anatomy, we simulated the intracranial tissue response to blast pressure typically experienced by Warfighters during weapons training. Two scenarios were evaluated, a single-dose exposure and a repetitive-dose exposure, to study intracranial pressure (ICP), shear strains, and spectral content. Ansys LS-DYNA was used to generate planar blast waves with peak overpressures of 4-90 kPa and positive phase durations of 2.2-10 ms. Single exposures produced ICP ranging from 4.7-112.7 kPa, dependent on dose and positive phase duration. Under repetitive LIB exposure, peak ICP increased by 8-26% relative to single exposures, with an increase of high-frequency components (>2 kHz). These results demonstrate that LIB can produce measurable intracranial responses that are amplified through repetition, producing pronounced spectral content and elevated pressures despite low strain levels. This study underscores the need to further investigate cumulative dose effects and the value of computational approaches to clarify hypothesized mbTBI mechanisms in operationally relevant conditions.

Background: Spinal cord injury (SCI) is frequently associated with orthostatic hypotension, defined by a sustained decrease in blood pressure upon assuming an upright posture due to impaired autonomic regulation. Cardiovascular spinal cord epidural stimulation (CV-scES) can regulate systolic blood pressure (SBP) in people with SCI, but stimulation paradigms are highly individualized. To make this treatment available to more patients, we developed an algorithm to tailor individualized CV-scES paradigms that closely mimic researcher-developed paradigms. Methods: We performed an offline analysis using datasets collected from eight individuals with SCI with epidural stimulators implanted over the lumbosacral spinal segments. During data collection, researchers modulated stimulation parameters with the goal of maintaining SBP between 110-120 mmHg. Each two-hour dataset included synchronized SBP and stimulation recordings. We ran optimization analyses offline to determine temporal requirements before modifying stimulation amplitude to mitigate out-of-range SBP. Results: The algorithm parameters that best matched researcher-selected stimulation changed relatively quickly during the first 12 min (one every ~40 sec), and more slowly thereafter (one every ~79 sec). Overall, algorithmic stimulation closely tracked researcher-controlled stimulation, with a mean correlation coefficient of 0.94. To evaluate online performance, we tested the algorithm in real time with a single participant. We found that a faster approach was needed to respond to changes in SBP caused by rapid, unpredictable events, such as postural changes. We implemented a sigmoid-based paradigm that determined the time to wait before changing stimulation as a function of the current SBP, with worse SBP values requiring faster responses. The new paradigm outperformed the original algorithm and researcher-controlled stimulation across measures of SBP stability, though recovery from a postural tilt maneuver remained slower than with researcher control. Conclusions: Our results indicate that algorithmic stimulation may minimize assistance required from researchers and participants, making CV-scES more feasible for clinical translation.

Healing of the gastrointestinal (GI) tract following surgical interventions is governed by coupled mechanobiological processes and may lead to severe complications such as perforation or stricture formation. A first comprehensive mechanobiological modeling framework of GI healing is herein proposed. The framework addresses two clinically relevant applications of bioprinting: endoscopic treatment of GI tissue defects and bioprinting-assisted surgical anastomosis. Tissue remodeling is based upon a hyperelastic material model with fiber dispersion coupling the spatiotemporal reaction diffusion dynamics of fibroblasts and cytokines with collagen deposition, reorientation, and plastic deformation. An active stress formulation drives fibroblasts and myofibroblast contraction while a multiplicative decomposition approach is adopted for collagen remodeling as a permanent change. The governing equations are discretised in time with an implicit Euler scheme, finite element in space and solved by a staggered algorithm implemented in the open-source platform FEniCS. Numerical simulations show that the initial collagen fibers content and orientation strongly influence fibroblast infiltration and scar contracture formation. The study quantifies the advantage of having a collagen bioprinted architecture aligned with tissue fibers, to reduce structural remodeling distortion. The model also predicts a strong correlation between collagen deposition and luminal burst pressure during the recovery of mechanical integrity in GI anastomosis.

Extrusion-based bioprinting enables the development of tissue-like constructs; however, the impact of printing-associated shear stress on cell viability and function remains a critical consideration. To address this, we developed a comprehensive workflow combining rheological characterization, computational fluid dynamics (CFD) modelling, and experimental validation to predict and assess shear stress effects during bioprinting. The rheological properties of gelatin methacryloyl (GelMA) at 5 % (w/v, 20 {degrees}C) and 10 % (30 {degrees}C) concentrations were modelled, comparing various non-Newtonian regression models. CFD simulations were validated using micro-particle image velocimetry, showing agreement between predicted and measured velocities. The impact of bioprinting-associated shear stress on cell viability was assessed using a co-culture of human umbilical vein endothelial cells and breast epithelial cells. Immediate post-printing analysis revealed increased apoptosis in GelMA 5 % (w/v, 20 {degrees}C), although 10 % (w/v) GelMA demonstrated higher shear stress levels compared to 5 % GelMA. After 1 day of culture in crosslinked hydrogels, apoptosis increased in extrusion pressure, demonstrating the impact of low levels of acute shear stress. This workflow provides a robust methodology for predicting acute shear stress impacts during bioprinting, laying the foundation for future optimization studies.

Human engineered cardiac tissues (ECTs) provide an in vitro model for studying human cardiac physiology and drug responses, but their performance remains limited by culture systems that do not fully reproduce the heart's electrical and mechanical environment. Electrical stimulation (ES) and mechanical stimulation (MS) have each been used to improve ECT function. Their combination, referred to as electromechanical stimulation (ES+MS), can provide further benefits. However, ES+MS depends not only on the presence of both cues but also on how they are coordinated in time. Here, we developed an incubator-compatible biophysical platform that delivers ES and MS independently or in combination, with programmable control over timing, amplitude, frequency, duration, and waveform. Calibration and dynamic characterization demonstrated tissue-relevant strain delivery, rapid and repeatable motion, and minimal attenuation and timing lag at the designated frequency of 1.5 Hz. We then compared four 6 h conditioning regimens: unstimulated control, ES alone, unsynchronized ES+MS, and synchronized ES+MS. We hypothesized that the synchronized ES+MS group, in which electrical excitation was aligned with peak externally applied strain, would produce the greatest increase in contractile force. Consistent with this hypothesis, synchronized ES+MS increased normalized twitch force by approximately 44% on average, whereas the other groups showed no comparable improvement. Twitch-timing metrics did not exhibit coordinated enhancement after 6 h, suggesting that the force increase reflects an adaptive biomechanical response rather than broad tissue maturation. These findings identify ES-MS timing as an important design parameter for ECT conditioning.

The human pancreas secretes digestive fluid that flows through an extensive ductal network before emptying into the duodenum. However, little is known about how hydrodynamic forces influence pancreatic function and development. We hypothesized that pancreatic cells respond to physiological levels of fluid shear stress. In this study, we developed a microfluidic system featuring reversible sealing between the device layer and the cell culture substrate, enabling (1) conventional open-well cell culture prior to fluid shear stress application and (2) selective patterning of proteins and cells for migration studies. Channel dimensions were chosen to support 24-hour perfusion using standard syringe pumps. Using this platform, we investigated effects of physiological shear stress levels representing basal and activated pancreatic function (2, 8 and 33 mPa) on human iPSC-derived pancreatic progenitor cells. Pancreatic progenitor cells exhibit graded sensitivity to shear stress at the transcriptomic level. Specifically, shear stress upregulated expression of cell cycle-related gene sets; endocrine-associated genes including NEUROG3; and Notch receptor ligands (DLL1, DLL3) in a magnitude-dependent manner. The exposure to unidirectional fluid flow also resulted in a reduction in YAP1 protein content, decreased WWTR1 gene expression, and downregulation of YAP/TAZ target genes. Furthermore, barrier-based migration assays under shear stress revealed that cell patches expanded their boundaries both along and against the flow, with greater distance in the direction of flow. Our system and findings may help lay the foundation for understanding biophysical regulation of developmental processes in a physiologically important, yet hard-to-access, epithelial model system.

Tissue expansion is an established technique for the reconstruction of skin defects, but the cost of conventional silicone expanders may limit its application in contexts with lower resource availability. This study evaluated, in an experimental model, whether a container for storing saline solution could act as a low-cost alternative device for tissue expansion. An experimental, prospective, controlled and randomized study was carried out with 10 Wistar rats, distributed in two groups: conventional silicone expander and saline storage container. Both underwent the same surgical and expansion protocol. Abdominal circumference gain, final expanded skin length, histological and histomorphometric aspects of the skin, including collagen types I and III, as well as exploratory cost analysis, were analyzed. The conventional expander produced a greater gain in abdominal circumference, but the final length of the expanded skin was similar between the groups. Microscopic evaluation showed preservation of the cutaneous architecture, intact epidermis, cellularized dermis, and collagen deposition in both groups. There was no significant difference in the proportion of type I or type III collagen. The saline solution container had a substantially lower cost per centimeter of expanded skin than the conventional expander. These findings suggest that the saline container can produce experimental skin expansion with final length and collagen composition similar to the conventional method, at a lower cost, although additional studies are needed before clinical application.

Predicting wear in artificial joints requires integrating joint dynamics, contact mechanics and progressive surface evolution, yet these processes are often treated separately. In total hip arthroplasty (THA), finite-element approaches remain the reference standard, but they are computationally demanding and usually rely on boundary conditions from independent musculoskeletal (MSK) models, hindering consistent coupling and feedback between wear progression and movement dynamics. As a single-subject proof of concept, we present a computational framework that embeds wear estimation within forward MSK simulations through OpenSim-MATLAB integration. Contact variables are computed using an elastic-foundation formulation, and wear is updated through the Archard law, enabling cyclic prediction of contact mechanics and surface evolution within a single workflow at practical computational cost. The framework was evaluated in one subject with right THA during five activities of daily living and numerically benchmarked against finite-element simulations. A long-term walking analysis of 4 million cycles was also performed to assess geometry updating. Across tasks, peak contact pressures remained within 7% of finite-element predictions. Linear wear depth and volumetric loss showed maximum deviations of 16% and 13%, respectively. Accounting for progressive geometry changes yielded a maximum wear depth about 31% lower than linear extrapolation. These preliminary results support the framework's computational feasibility and numerical consistency for the tested case; nevertheless, multi-subject evaluation is required before broader predictive or clinical use.

Purpose: Atrial fibrosis is associated with thromboembolic risk in atrial fibrillation, but how fibrosis-related contractile impairment alters blood transport in the left atrium (LA) and left atrial appendage (LAA) remains unclear. Prior multi-physics simulations coupled electromechanical (EM) and computational fluid dynamics (CFD) models to show that fibrosis impairs LA function and flow, but were limited to booster-only contraction and could not separate the effects of fibrosis burden from its spatial distribution. Here we examined how fibrosis burden and spatial pattern independently relate to long-term LA and LAA hemodynamics in full-cycle, multi-beat simulations on a common LA anatomy. Methods: Three fibrosis patterns derived from late gadolinium enhancement MRI were considered: one from the patient providing the common anatomy and two from additional patients, with the latter mapped onto the common anatomy via universal atrial coordinates. All three patterns were applied globally at matched burdens of 15.6% and 31.2%, yielding six global-fibrosis cases and a non-fibrotic reference. Two patterns were also confined to the LAA at three local burdens (10%, 25%, and 50%), yielding six LAA-fibrosis cases. A 3D EM model for the LA anatomy was coupled to a 0D circulatory model, so that the simulations resolved the reservoir, conduit, and booster phases. Full-cycle EM-derived wall motion drove subsequent multi-beat CFD simulations. Region-specific emptying fraction (EF), non-dimensional kinetic energy (KE), and the 90th percentile of blood residence time (TR) were evaluated for the LA and LAA. Results: Left ventricular stroke volume remained nearly constant across cases, while increasing global fibrosis burden progressively reduced LA and LAA EF (LA: 36% to 30-31%; LAA: 44% to 28-38%) and monotonically increased LA TR across all patterns. Non-dimensional LA KE showed an approximately quadratic association with LA EF across patterns, whereas LAA KE was more scattered but still increased with LAA EF. In contrast, the relationship between the 90th percentile of LAA TR and LAA EF showed pattern-specific, non-monotonic trends. Conclusions: Fibrosis burden and spatial distribution jointly shape LA and LAA hemodynamics, but through different mechanisms. LAA EF is a robust functional descriptor of chamber-averaged kinetic energy regardless of fibrosis pattern, whereas LAA blood stasis depends additionally on the spatial distribution of fibrosis beyond what bulk emptying fraction predicts. These findings support incorporating imaging-derived fibrosis pattern, and not only burden, alongside functional metrics when assessing thrombogenic risk in the LAA.

Vector flow mapping (VFM) reconstructs left-ventricular (LV) blood velocity from color-Doppler echocardiography by combining the measured beamwise component with physical and regularizing constraints. Analysis of the discrete VFM formulation shows that the inverse problem is intrinsically ill posed: the occurrence of singular modes can be predicted from the geometry of the segmented blood-pool domain, the imposed boundary conditions, and the degree of smoothing. These modes can propagate uncertainty along entire transverse bands of the reconstructed velocity field, yet conventional VFM neither quantifies this uncertainty nor allows for correcting the blood-pool segmentation. We introduce Bayesian VFM (B--VFM), a hierarchical framework that jointly infers radial and transverse velocities, a probabilistic blood-pool mask, their spatially resolved uncertainties, and hyperparameters weighting Doppler and segmentation fidelity, mass conservation, boundary conditions, and smoothness. The discretized posterior admits a closed-form gradient and exact Hessian, enabling computationally efficient, gradient-based MAP estimation, sampling, and direct analysis of ill-posed modes. Posterior inference combines Gibbs sampling of conjugate Gamma-distributed hyperparameters with conditional maximum-a-posteriori estimation and a Laplace approximation for the high-dimensional velocity and mask fields. To accommodate systematic departures from planar mass conservation, B-VFM can learn the covariance of the planar divergence residual from an ensemble of flows and incorporate it as a structured model-discrepancy prior. Independent chains converged reproducibly, while covariance priors learned from flow ensembles illustrated how model discrepancies can be incorporated into the inference. B--VFM was evaluated using Lamb-Chaplygin dipoles under ideal conditions and with Doppler corruption, Doppler voids, and segmentation defects, and using the Hicks-Moffatt family of spherical vortices to assess violations of planar mass conservation. The method produced smooth reconstructions, localized uncertainty near unreliable measurements and regions of model inconsistency, and used flow information to correct segmentation errors. Within the tested vortex family, the data-informed planar divergence prior reduced velocity bias and mask distortion. B--VFM thus provides an uncertainty-aware reconstruction method and a flexible foundation for future VFM formulations incorporating additional priors, observations, and physical models. Future work will evaluate the method using clinical data and more complex three-dimensional benchmark flows.