Biomechanics and Modeling in Mechanobiology最新文献

Synthetic bone graft scaffolds aim to generate new bone tissue and alleviate the limitations of autografts and allografts. To meet that aim, it is essential to have a design approach able to generate scaffold architectures that will promote bone formation. Here, we present a topology-varying design optimization method, the “mixed-topology” approach, that generates new designs from a set of starting structures. This approach was used with objective functions focusing on improving the scaffold’s local mechanical microenvironments to mechanobiologically promote bone formation within the scaffold and constraints to ensure manufacturability and achieve desired macroscale properties. The results demonstrate that this approach can successfully generate scaffold designs with improved microenvironments, taking into account different combinations of relevant stimuli and constraints.

This study challenges the conventional belief that animal cell membranes lack a significant hydrostatic gradient, particularly under anisotonic conditions, as demonstrated in the human hepatoma cell line HepG2. The Boyle van’t Hoff (BvH) relation describes volumetric equilibration to anisotonic conditions for many cells. However, the BvH relation is simple and does not include many cellular components such as the cytoskeleton and actin cortex, mechanosensitive channels, and ion pumps. Here we present alternative models that account for mechanical resistance to volumetric expansion, solute leakage, and active ion pumping. We found the BvH relation works well to describe hypertonic volume equilibration but not hypotonic volume equilibration. After anisotonic exposure and return isotonic conditions cell volumes were smaller than their initial isotonic volume, indicating solutes had leaked out of the cell during swelling. Finally, we observed HepG2 cells undergo regulatory volume decrease at both 20 °C and 4 °C, indicating regulatory volume decrease to be a relatively passive phenomenon and not driven by ion pumps. We determined the turgor-leak model, which accounts for mechanical resistance and solute leakage, best fits the observations found in the suite of experiments performed, while other models were rejected.

Spinal cord stress and strain contribute to degenerative cervical myelopathy (DCM), while cervical kyphosis is known to negatively impact surgical outcomes. In DCM, the relationship between spinal cord biomechanics, sagittal alignment, and cord compression is not well understood. Quantifying this relationship can guide surgical strategies. A previously validated three-dimensional finite element model of the human cervical spine with spinal cord was used. Three models of cervical alignment were created: lordosis (C2–C7 Cobb angle: 20°), straight (0°), and kyphosis (− 9°). C5–C6 spinal stenosis was simulated with ventral disk protrusions, reducing spinal canal diameters to 10 mm, 8 mm, and 6 mm. Spinal cord pre-stress and pre-strain due to alignment and compression were quantified. Cervical flexion and extension were simulated with a pure moment load of 2 Nm. The Von Mises stress and maximum principal strain of the whole spinal cord were calculated during neck motion and the relationship between spinal cord biomechanics, alignment, and compression was analyzed using linear regression analysis. Spinal cord pre-stress and pre-strain were greatest with kyphosis (7.53 kPa, 5.4%). Progressive kyphosis and stenosis were associated with an increase in spinal cord stress (R² = 0.99) and strain (R² = 0.99). Cervical kyphosis was associated with greater spinal cord stress and strain during neck flexion–extension and the magnitude of difference increased with increasing stenosis. Cervical kyphosis increases baseline spinal cord stress and strain. Incorporating sagittal alignment with compression to calculate spinal cord biomechanics is necessary to accurately quantify spinal stress and strain during neck flexion and extension.

Accurate modeling of blood dynamics in the coronary microcirculation is a crucial step toward the clinical application of in silico methods for the diagnosis of coronary artery disease. In this work, we present a new mathematical model of microcirculatory hemodynamics accounting for microvasculature compliance and cardiac contraction; we also present its application to a full simulation of hyperemic coronary blood flow and 3D myocardial perfusion in real clinical cases. Microvasculature hemodynamics is modeled with a compliant multi-compartment Darcy formulation, with the new compliance terms depending on the local intramyocardial pressure generated by cardiac contraction. Nonlinear analytical relationships for vessels distensibility are included based on experimental data, and all the parameters of the model are reformulated based on histologically relevant quantities, allowing a deeper model personalization. Phasic flow patterns of high arterial inflow in diastole and venous outflow in systole are obtained, with flow waveforms morphology and pressure distribution along the microcirculation reproduced in accordance with experimental and in vivo measures. Phasic diameter change for arterioles and capillaries is also obtained with relevant differences depending on the depth location. Coronary blood dynamics exhibits a disturbed flow at the systolic onset, while the obtained 3D perfusion maps reproduce the systolic impediment effect and show relevant regional and transmural heterogeneities in myocardial blood flow (MBF). The proposed model successfully reproduces microvasculature hemodynamics over the whole heartbeat and along the entire intramural vessels. Quantification of phasic flow patterns, diameter changes, regional and transmural heterogeneities in MBF represent key steps ahead in the direction of the predictive simulation of cardiac perfusion.

Aortic dissection is a life-threatening disease that consists in the development of a tear in the wall of the aorta. The initial tear propagates as a discontinuity leading to separation within the aortic wall, which can result in the creation of a so-called false lumen. A fatal threat occurs if the rupture extends through the whole thickness of the aortic wall, as blood may then leak. It is generally accepted that the dissection, which can sometime extend along the entire length of the aorta, propagates via a delamination mechanism. The aim of the present paper is to provide experimentally validated parameters of a mathematical model for the description of the wall’s cohesion. A model of the peeling experiment was built in Abaqus. The delamination interface was described by a piecewise linear traction-separation law. The bulk behavior of the aorta was assumed to be nonlinearly elastic, anisotropic, and incompressible. Our simulations resulted in estimates of the material parameters for the traction-separation law of the human descending thoracic aorta, which were obtained by minimizing the differences between the FEM predictions and the delamination force given by the regression of the peeling experiments. The results show that the stress at damage initiation, T_c, should be understood as an age-dependent quantity, and under the assumptions of our model this dependence can be expressed by linear regression as Tc =  − 13.03·10⁻⁴·Age + 0.2485 if the crack front advances in the axial direction, and Tc =  − 7.58·10⁻⁴·Age + 0.1897 if the crack front advances in the direction of the aortic circumference (T_c [MPa], Age [years]). Other model parameters were the stiffness K and the separation at failure, δ_f–δ_c (K = 0.5 MPa/mm, δ_f–δ_c = 0.1 mm). The material parameters provided by our study can be used in numerical simulations of the biomechanics of dissection propagation through the aorta especially when age-associated phenomena are studied.

A human laryngeal model, incorporating all the cartilages and the intrinsic muscles, was reconstructed based on MRI data. The vocal fold was represented as a multilayer structure with detailed inner components. The activation levels of the thyroarytenoid (TA) and cricothyroid (CT) muscles were systematically varied from zero to full activation allowing for the analysis of their interaction and influence on vocal fold dynamics and glottal flow. The finite element method was employed to calculate the vocal fold dynamics, while the one-dimensional Bernoulli equation was utilized to calculate the glottal flow. The analysis was focused on the muscle influence on the fundamental frequency (f_o). We found that while CT and TA  activation increased the f_o in most of the conditions, TA activation resulted in a frequency drop when it was moderately activated. We show that this frequency drop was associated with the sudden increase of the vertical motion when the vibration transited from involving the whole tissue to mainly in the cover layer. The transition of the vibration pattern was caused by the increased body-cover stiffness ratio that resulted from TA activation.

The mechanism behind hemodialysis arteriovenous fistula (AVF) failure remains poorly understood, despite previous efforts to correlate altered hemodynamics with vascular remodeling. We have recently demonstrated that transitional flow induces high-frequency vibrations in the AVF wall, albeit with a simplified model. This study addresses the key limitations of our original fluid–structure interaction (FSI) approach, aiming to evaluate the vibration response using a more realistic model. A 3D AVF geometry was generated from contrast-free MRI and high-fidelity FSI simulations were performed. Patient-specific inflow and pressure were incorporated, and a three-term Mooney–Rivlin model was fitted using experimental data. The viscoelastic effect of perivascular tissue was modeled with Robin boundary conditions. Prescribing pulsatile inflow and pressure resulted in a substantial increase in vein displacement ((+400)%) and strain ((+317)%), with a higher maximum spectral frequency becoming visible above -42 dB (from 200 to 500 Hz). Transitioning from Saint Venant–Kirchhoff to Mooney–Rivlin model led to displacement amplitudes exceeding 10 micrometers and had a substantial impact on strain ((+116)%). Robin boundary conditions significantly damped high-frequency displacement ((-60)%). Incorporating venous tissue properties increased vibrations by 91%, extending up to 700 Hz, with a maximum strain of 0.158. Notably, our results show localized, high levels of vibration at the inner curvature of the vein, a site known for experiencing pronounced remodeling. Our findings, consistent with experimental and clinical reports of bruits and thrills, underscore the significance of incorporating physiologically plausible modeling approaches to investigate the role of wall vibrations in AVF remodeling and failure.

Eukaryotic cell rheology has important consequences for vital processes such as adhesion, migration, and differentiation. Experiments indicate that cell cytoplasm can exhibit both elastic and viscous characteristics in different regimes, while the transport of fluid (cytosol) through the cross-linked filamentous scaffold (cytoskeleton) is reminiscent of mass transfer by diffusion through a porous medium. To gain insights into this complex rheological behaviour, we construct a computational model for the cell cytoplasm as a poroviscoelastic material formulated on the principles of nonlinear continuum mechanics, where we model the cytoplasm as a porous viscoelastic scaffold with an embedded viscous fluid flowing between the pores to model the cytosol. Baseline simulations (neglecting the viscosity of the cytosol) indicate that the system exhibits seven different regimes across the parameter space spanned by the viscoelastic relaxation timescale of the cytoskeleton and the poroelastic diffusion timescale; these regimes agree qualitatively with experimental measurements. Furthermore, the theoretical model also allows us to elucidate the additional role of pore fluid viscosity, which enters the system as a distinct viscous timescale. We show that increasing this viscous timescale hinders the passage of the pore fluid (reducing the poroelastic diffusion) and makes the cytoplasm rheology increasingly incompressible, shifting the phase boundaries between the regimes.

Cellular contractility, migration, and extracellular matrix (ECM) mechanics are critical for a wide range of biological processes including embryonic development, wound healing, tissue morphogenesis, and regeneration. Even though the distinct response of cells near the tissue periphery has been previously observed in cell-laden microtissues, including faster kinetics and more prominent cell-ECM interactions, there are currently no models that can fully combine coupled surface and bulk mechanics and kinetics to recapitulate the morphogenic response of these constructs. Mailand et al. (Biophys J 117(5):975–986, 2019) had shown the importance of active elastocapillarity in cell-laden microtissues, but modeling the distinct mechanosensitive migration of cells on the periphery and the interior of highly deforming tissues has not been possible thus far, especially in the presence of active elastocapillary effects. This paper presents a framework for understanding the interplay between cellular contractility, migration, and ECM mechanics in dynamically morphing soft tissues accounting for distinct cellular responses in the bulk and the surface of tissues. The major novelty of this approach is that it enables modeling the distinct migratory and contractile response of cells residing on the tissue surface and the bulk, where concurrently the morphing soft tissues undergo large deformations driven by cell contractility. Additionally, the simulation results capture the changes in shape and cell concentration for wounded and intact microtissues, enabling the interpretation of experimental data. The numerical procedure that accounts for mechanosensitive stress generation, large deformations, diffusive migration in the bulk and a distinct mechanism for diffusive migration on deforming surfaces is inspired from recent work on bulk and surface poroelasticity of hydrogels involving elastocapillary effects, but in this work, a two-field weak form is proposed and is able to alleviate numerical instabilities that were observed in the original method that utilized a three-field mixed finite element formulation.

Brain injuries resulting from mechanical trauma represent an ongoing global public health issue. Several in vitro and in vivo models for traumatic brain injury (TBI) continue to be developed for delineating the various complex pathophysiological processes involved in its onset and progression. Developing an in vitro TBI model that is based on cortical spheroids is especially of great interest currently because they can replicate key aspects of in vivo brain tissue, including its electrophysiology, physicochemical microenvironment, and extracellular matrix composition. Being able to mechanically deform the spheroids are a key requirement in any effective in vitro TBI model. The spheroids’ shape and size, however, make mechanically loading them, especially in a high-throughput, sterile, and reproducible manner, quite challenging. To address this challenge, we present an idea for a spheroid-based, in vitro TBI model in which the spheroids are mechanically loaded by being spun by a centrifuge. (An experimental demonstration of this new idea will be published shortly elsewhere.) An issue that can limit its utility and scope is that imaging techniques used in 2D and 3D in vitro TBI models cannot be readily applied in it to determine spheroid strains. In order to address this issue, we developed a continuum mechanics-based theory to estimate the spheroids’ strains when they are being spun at a constant angular velocity. The mechanics theory, while applicable here to a special case of the centrifuge-based TBI model, is also of general value since it can help with the further exploration and development of TBI models.