Biomechanics and Modeling in Mechanobiology最新文献

Studying tumor immune microenvironment (TIME) is pivotal to understand the mechanism and predict the outcome of cancer immunotherapy. Systems biology mathematical models can consider and control various factors of TIME and therefore explore the anti-tumor immune response meticulously. However, the role of tumor vasculature in the recruitment of T cells and the mechanism of T cell migration through TIME have not been studied comprehensively. In this work, we developed a hybrid discrete-continuum multi-scale model to study TIME. The mathematical model includes angiogenesis and T cell recruitment via tumor vasculature. Moreover, solid tumor growth, vascular growth and remodeling, interstitial fluid flow, hemodynamics, and blood rheology are all considered in the model. In addition, different aspects of T cells, including their migration, proliferation, subtype conversion, and interaction with tumor cells are thoroughly included. The model reproduces spatiotemporal distribution of tumor infiltrating T cells that mimics histopathological patterns. Furthermore, TIME model robustly recapitulates different phases of tumor immunoediting. We also examined a number of biomarkers to predict the outcome of immune checkpoint blockade (ICB) treatment. The results demonstrated that although tumor mutational burden (TMB) may predict non-responders to ICB, a combination of different biomarkers is essential to predict the majority of the responders. Based on our results, the ICB response rate varies significantly from 28 to 89% depending on the values of different parameters, even in the cases with high TMB.

Recent years have seen the development of multiple in silico lung models, notably with the aim of improving patient care for pulmonary diseases. These models vary in complexity and typically only consider the implementation of pleural pressure, a depression that keeps the lungs inflated. Gravity, often considered negligible compared to pleural pressure, has been largely overlooked, also due to the complexity of formulating physiological boundary conditions to counterbalance it. However, gravity is known to affect pulmonary functions, such as ventilation. In this study, we incorporated gravity into a recent lung poromechanical model. To do so, in addition to the gravitational body force, we proposed novel boundary conditions consisting in a heterogeneous pleural pressure field constrained to counterbalance gravity to reach global equilibrium of applied forces. We assessed the impact of gravity on the global and local behavior of the model, including the pressure–volume response and porosity field. Our findings reveal that gravity, despite being small, influences lung response. Specifically, the inclusion of gravity in our model led to the emergence of heterogeneities in deformation and stress distribution, compatible with in vivo imaging data. This could provide valuable insights for predicting the progression of certain pulmonary diseases by correlating areas subjected to higher deformation and stresses with disease evolution patterns.

Dense communities of bacteria, also known as biofilms, are ubiquitous in all of our everyday life. They are not only always surrounding us, but are also active inside our bodies, for example in the oral cavity. While some biofilms are beneficial or even necessary for human life, others can be harmful. Therefore, it is highly important to gain an in-depth understanding of biofilms which can be achieved by in vitro or in vivo experiments. Since these experiments are often time-consuming or expensive, in silico models have proven themselves to be a viable tool in assisting the description and analysis of these complicated processes. Current biofilm growth simulations are using mainly two approaches for describing the underlying models. The volumetric approach splits the deformation tensor into a growth and an elastic part. In this approach, the mass never changes, unless some additional constraints are enforced. The density-based approach, on the other hand, uses an evolution equation to update the growing tissue by adding mass. Here, the density stays constant, and no pressure is exerted. The in silico model presented in this work combines the two approaches. Thus, it is possible to capture stresses inside of the biofilm while adding mass. Since this approach is directly derived from Hamilton’s principle, it fulfills the first and second law of thermodynamics automatically, which other models need to be checked for separately. In this work, we show the derivation of the model as well as some selected numerical experiments. The numerical experiments show a good phenomenological agreement with what is to be expected from a growing biofilm. The numerical behavior is stable, and we are thus capable of solving complicated boundary value problems. In addition, the model is very reactive to different input parameters, thereby different behavior of various biofilms can be captured without modifying the model.

Lymph Nodes (LNs) are crucial to the immune and lymphatic systems, filtering harmful substances and regulating lymph transport. LNs consist of a lymphoid compartment (LC) that forms a porous bulk region, and a subcapsular sinus (SCS), which is a free-fluid region. Mathematical and mechanical challenges arise in understanding lymph flow dynamics. The highly vascularized lymph node connects the lymphatic and blood systems, emphasizing its essential role in maintaining the fluid balance in the body. In this work, we describe a mathematical model in a steady setting to describe the lymph transport in a lymph node. We couple the fluid flow in the SCS governed by an incompressible Stokes equation with the fluid flow in LC, described by a model obtained by means of asymptotic homogenisation technique, taking into account the multiscale nature of the node and the fluid exchange with the blood vessels inside it. We solve this model using numerical simulations and we analyze the lymph transport inside the node to elucidate its regulatory mechanisms and significance. Our results highlight the crucial role of the microstructure of the lymph node in regularising its fluid balance. These results can pave the way to a better understanding of the mechanisms underlying the lymph node’s multiscale functionalities which can be significantly affected by specific physiological and pathological conditions, such as those characterising malignant tissues.

The purpose of this study was to assess whether growth and remodeling (G&R) theory could explain staphyloma formation from a local scleral weakening—as could occur from age-related elastin degradation, myopia progression, or other factors. A finite element model of a healthy eye was reconstructed, including the lamina cribrosa, the peripapillary sclera, and the peripheral sclera. The homogenized constrained mixture model was employed to simulate the adaptation of the sclera to alterations in its biomechanical environment over a duration of 13.7 years. G&R processes were triggered by reducing the shear stiffness of the ground matrix in the peripapillary sclera and lamina cribrosa by 85%. Three distinct G&R scenarios were investigated: (1) low mass turnover rate in combination with transmural volumetric growth; (2) high mass turnover rate in combination with transmural volumetric growth; and (3) high mass turnover rate in combination with mass density growth. In scenario 1, we observed a significant outpouching of the posterior pole, closely resembling the shape of a Type-III staphyloma. Additionally, we found a notable change in scleral curvature and a thinning of the peripapillary sclera by 84%. In contrast, scenario 2 and 3 exhibited less drastic deformations, with stable posterior staphylomas after approximately 7 years. Our proposed framework suggests that local scleral weakening is sufficient to trigger staphyloma formation under a normal level of intraocular pressure. Our model also reproduced characteristics of Type-III staphylomas. With patient-specific scleral geometries (as could be obtained with wide-field optical coherence tomography), our framework could be clinically translated to help us identify those at risks of developing posterior staphylomas.

Lung alveoli are modeled as spherical caps, lined internally by a thin surfactant-laden liquid film, and the periodic wall shear stress exerted along the epithelium during small-amplitude radial oscillations of their wall is computed. A novel set of boundary conditions, applied at the rim, reveals the dominant role of Marangoni stresses. These stresses develop along the air/liquid interface due to spatial gradients of interfacial surfactant concentration and are transported to the wall by the action of viscosity. The effect of a variety of geometric and functional characteristics, including rim interstitial thickness, alveolar opening angle and liquid film thickness and viscosity, is interrogated, and the results are discussed in relation to the onset and evolution of acute and chronic lung diseases, such as asthmatic attacks, pulmonary emphysema and pulmonary fibrosis.