1,721,033 research outputs found
Numerical Methods to Compute Stresses and Displacements from Cellular Forces: Application to the Contraction of Tissue
No full textWe consider a mathematical model for wound contraction, which is based on solving a momentum balance under the assumptions of isotropy, homogeneity, Hooke's Law, in-finitesimal strain theory and point forces exerted by cells. However, point forces, described by Dirac Delta distributions lead to a singular solution, which in many cases may cause trouble to finite element methods due to a low degree of regularity. Hence, we consider several alternatives to address point forces, that is, whether to treat the region covered by the cells that exert forces as part of the computational domain or as 'holes' in the computational domain. The formalisms develop into the immersed boundary approach and the 'hole approach', respectively. Consistency between these approaches is verified in a theoretical setting, but also confirmed computationally. However, the 'hole approach' is much more expensive and complicated for its need of mesh adaptation in the case of migrating cells while it increases the numerical accuracy, which makes it hard to adapt to the multi-cell model. Therefore, for multiple cells, we consider the polygon that is used to approximate the boundary of cells that exert contractile forces. It is found that a low degree of polygons, in particular triangular or square shaped cell boundaries, already give acceptable results in engineering precision, so that it is suitable for the situation with a large amount of cells in the computational domain.Authors acknowledge the China Scholarship Council (CSC) for financial support to this project
Agent-based modelling and parameter sensitivity analysis with a finite-element method for skin contraction
No full textIn this paper, we extend the model of wound healing by Boon et al. (J Biomech 49(8):1388–1401, 2016). In addition to explaining the model explicitly regarding every component, namely cells, signalling molecules and tissue bundles, we categorized fibroblasts as regular fibroblasts and myofibroblasts. We do so since it is widely documented that myofibroblasts play a significant role during wound healing and skin contraction and that they are the main phenotype of cells that is responsible for the permanent deformations. Furthermore, we carried out some sensitivity tests of the model by modifying certain parameter values, and we observe that the model shows some consistency with several biological phenomena. Using Monte Carlo simulations, we found that there is a significant strong positive correlation between the final wound area and the minimal wound area. The high correlation between the wound area after 4 days and the final/minimal wound area makes it possible for physicians to predict the most probable time evolution of the wound of the patient. However, the collagen density ratio at the time when the wound area reaches its equilibrium and minimum, cannot indicate the degree of wound contractions, whereas at the 4th day post-wounding, when the collagen is accumulating from null, there is a strong negative correlation between the area and the collagen density ratio. Further, under the circumstances that we modelled, the probability that patients will end up with 5% contraction is about 0.627.Numerical Analysi
Point forces in elasticity equation and their alternatives in multi dimensions
Full text linkDeep dermal wounds induce skin contraction as a result of the traction forcing exerted by (myo)fibroblasts on their immediate environment. These (myo)fibroblasts are skin cells that are responsible for the regeneration of collagen that is necessary for the integrity of skin We consider several mathematical issues regarding models that simulate traction forces exerted by (myo)fibroblasts. Since the size of cells (e.g. (myo)fibroblasts) is much smaller than the size of the domain of computation, one often considers point forces, modelled by Dirac Delta distributions on boundary segments of cells to simulate the traction forces exerted by the skin cells. In the current paper, we treat the forces that are directed normal to the cell boundary and toward the cell centre. Since it can be shown that there exists no smooth solution, at least not in H1 for solutions to the governing momentum balance equation, we analyse the convergence and quality of approximation. Furthermore, the expected finite element problems that we get necessitate to scrutinize alternative model formulations, such as the use of smoothed Dirac Delta distributions, or the so-called smoothed particle approach as well as the so-called ‘hole’ approach where cellular forces are modelled through the use of (natural) boundary conditions. In this paper, we investigate and attempt to quantify the conditions for consistency between the various approaches. This has resulted into error analyses in the L2-norm of the numerical solution based on Galerkin principles that entail Lagrangian basis functions. The paper also addresses well-posedness in terms of existence and uniqueness. The current analysis has been performed for the linear steady-state (hence neglecting inertia and damping) momentum equations under the assumption of Hooke's law.Numerical Analysi
On the fundamental solutions-based inversion of Laplace matrices
No full textThe discretisation of the Laplacian results into the well-known Laplace matrix. In the case of a one dimensional problem, an explicit formula for its inverse is derived on the basis of fundamental solutions (Green's functions) for general boundary conditions. For a linear reaction-diffusion equation, approximations of the inverse are given. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Upscaling between an agent-based model (smoothed particle approach) and a continuum-based model for skin contractions
Full text linkSkin contraction is an important biophysical process that takes place during and after recovery of deep tissue injury. This process is mainly caused by fibroblasts (skin cells) and myofibroblasts (differentiated fibroblasts which exert larger pulling forces and produce larger amounts of collagen) that both exert pulling forces on the surrounding extracellular matrix (ECM). Modelling is done in multiple scales: agent-based modelling on the microscale and continuum-based modelling on the macroscale. In this manuscript we present some results from our study of the connection between these scales. For the one-dimensional case, we managed to rigorously establish the link between the two modelling approaches for both closed-form solutions and finite-element approximations. For the multi-dimensional case, we computationally evidence the connection between the agent-based and continuum-based modelling approaches.Numerical Analysi
Biomorphoelasticity alone: limitations in modeling post-burn contraction and hypertrophy without finite strains
No full textWe present a continuum hypothesis-based two-dimensional biomorphoelastic model describing post-burn scar hypertrophy and contraction. The model is based on morphoelasticity for permanent deformations and combined with a chemical-biological model that incorporates cellular densities, collagen density, and the concentration of chemoattractants. We perform a sensitivity analysis for the independent parameters of the model and focus on the effects on the features of the post-burn dermal thickness given a low myofibroblast apoptosis rate. We conclude that the most sensitive parameters are the equilibrium collagen concentration, the signaling molecule secretion rate and the cell force constant, and link these results to stability constraints. Next, we observe a relationship between the simulated contraction and hypertrophy and show the effects for significant variations in the myofibroblast apoptosis rate (high/low). Our ultimate goal is to optimize post-burn treatments, by developing models that predict with a high degree of certainty. We consider the presented model and sensitivity analysis to be a step toward their construction.The authors are grateful for the fnancial support
from the Dutch Burns Foundation under projects 17.105 and 22.10
A formalism for modelling traction forces and cell shape evolution during cell migration in various biomedical processes
No full textThe phenomenological model for cell shape deformation and cell migration Chen (BMM 17:1429–1450, 2018), Vermolen and Gefen (BMM 12:301–323, 2012), is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity theory. The resulting partial differential differential equations are solved by the use of the finite element method. The paper treats various biological scenarios that entail cell migration and cell shape evolution. The experimental observations in Mak et al. (LC 13:340–348, 2013), where transmigration of cancer cells through narrow apertures is studied, are reproduced using a Monte Carlo framework.</p
High-speed predictions of post-burn contraction using a neural network trained on 2D-finite element simulations
No full textSevere burn injuries often lead to skin contraction, leading to stresses in and around the damaged skin region. If this contraction leads to impaired joint mobility, one speaks of contracture. To optimize treatment, a mathematical model, that is based on finite element methods, is developed. Since the finite element-based simulation of skin contraction can be expensive from a computational point of view, we use machine learning to replace these simulations such that we have a cheap alternative. The current study deals with a feed-forward neural network that we trained with 2D finite element simulations based on morphoelasticity. We focus on the evolution of the scar shape, wound area, and total strain energy, a measure of discomfort, over time. The results show average goodness of fit (R2) of 0.9979 and a tremendous speedup of 1815000X. Further, we illustrate the applicability of the neural network in an online medical app that takes the patient's age into account.Numerical Analysi
Comparison between a phenomenological approach and a morphoelasticity approach regarding the displacement of extracellular matrix
Full text linkPlastic (permanent) deformations were earlier, modeled by a phenomenological model in Peng and Vermolen (Biomech Model Mechanobiol 19(6):2525–2551, 2020). In this manusctipt, we consider a more physics-based formulation that is based on morphoelasticity. We firstly introduce the morphoelasticity approach and investigate the impact of various input variables on the output parameters by sensitivity analysis. A comparison of both model formulations shows that both models give similar computational results. Furthermore, we carry out Monte Carlo simulations of the skin contraction model containing the morphoelasticity approach. Most statistical correlations from the two models are similar, however, the impact of the collagen density on the severeness of contraction is larger for the morphoelasticity model than for the phenomenological model.Numerical Analysi
Analysis of linearized elasticity models with point sources in weighted Sobolev spaces: applications in tissue contraction
No full textIn order to model the contractive forces exerted by fibroblast cells in dermal tissue, we propose and analyze two modeling approaches under the assumption of linearized elasticity. The first approach introduces a collection of point forces on the boundary of the fibroblast whereas the second approach employs an isotropic stress point source in its center. We analyze the resulting partial differential equations in terms of weighted Sobolev spaces and identify the singular behavior of the respective solutions. Two finite element method approaches are proposed, one based on a direct application and another in which the singularity is subtracted and a correction field is computed. Finally, we confirm the validity of the modeling approach, demonstrate convergence of the numerical methods, and verify the analysis through the use of numerical experiments
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