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G. Egberts

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Doctoral thesis (2023) - G. Egberts
Burns can make patients’ lives quite miserable. Apart from prominent and thickened, or hypertrophic, scars, the skin may be characterized by contraction. When this contraction is so severe that the patient loses joint mobility, it is called contracture. Then a patient may have difficulties with sports or other daily activities. The consequence can be an enormous psychosocial burden for the patient. Understanding contraction mechanisms is essential to improve and optimize the treatment of contractures. This understanding can arise from clinical (in vivo) and experimental (in vitro) observations but can also be explored using mathematical models (in silico). Mathematical models describe quantitative relations and can explain specific trends and make predictions. Further, in silico models forman alternative for animal experiments. One such mathematical model is the Biomorphoelastic model for post-burn contraction [1]. This model arises from conservation laws expressed in partial differential equations on a continuous (macro) scale. We study this model’s one- and twodimensional counterparts... ...
Journal article (2023) - Ginger Egberts, Fred Vermolen, Paul van Zuijlen
We consider the stability analysis of a two-dimensional model for post-burn 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 formulate stability conditions depending on the decay rate of signaling molecules for both the continuous partial differential equations-based problem and the (semi-)discrete representation. We analyze the difference and convergence between the resulting spatial eigenvalues from the continuous and semi-discrete problems. ...
Journal article (2023) - Ginger Egberts, Fred Vermolen, Paul van Zuijlen
Severe 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. ...
Journal article (2022) - Ginger Egberts, Marianne Schaaphok, Fred Vermolen, Paul van Zuijlen
Burn injuries can decrease the quality of life of a patient tremendously, because of esthetic reasons and because of contractions that result from them. In severe case, skin contraction takes place at such a large extent that joint mobility of a patient is significantly inhibited. In these cases, one refers to a contracture. In order to predict the evolution of post-wounding skin, several mathematical model frameworks have been set up. These frameworks are based on complicated systems of partial differential equations that need finite element-like discretizations for the approximation of the solution. Since these computational frameworks can be expensive in terms of computation time and resources, we study the applicability of neural networks to reproduce the finite element results. Our neural network is able to simulate the evolution of skin in terms of contraction for over one year. The simulations are based on 25 input parameters that are characteristic for the patient and the injury. One of such input parameters is the stiffness of the skin. The neural network results have yielded an average goodness of fit (R2) of 0.9928 (± 0.0013). Further, a tremendous speed-up of 19354X was obtained with the neural network. We illustrate the applicability by an online medical App that takes into account the age of the patient and the length of the burn. ...
Journal article (2022) - Ginger Egberts, Alexis Desmoulière, Fred Vermolen, Paul van Zuijlen
We consider a two-dimensional biomorphoelastic model describing post-burn scar contraction. This model describes skin displacement and the development of the effective Eulerian strain in the tissue. Besides these mechanical components, signaling molecules, fibroblasts, myofibroblasts, and collagen also play a significant role in the model. We perform a sensitivity analysis for the independent parameters of the model and focus on the effects on features of the relative surface area and the total strain energy density. We conclude that the most sensitive parameters are the Poisson’s ratio, the equilibrium collagen concentration, the contraction inhibitor constant, and the myofibroblast apoptosis rate. Next to these insights, we perform a sensitivity analysis where the proliferation rates of fibroblasts and myofibroblasts are not the same. The impact of this model adaptation is significant. ...
Journal article (2021) - Ginger Egberts, Fred Vermolen, Paul van Zuijlen
We consider a one-dimensional morphoelastic model describing post-burn scar contraction. Contraction can lead to a limited range of motion (contracture). Reported prevalence of burn scar contractures are 58.6% at 3–6 weeks and 20.9% at 12 months post-reconstructive surgery after burns. This model describes the displacement of the dermal layer of the skin and the development of the effective Eulerian strain in the tissue. Besides these components, the model also contains components that play a major role in the skin repair after trauma. These components are signaling molecules, fibroblasts, myofibroblasts, and collagen. We perform a sensitivity analysis for many parameters of the model and use the results for a feasibility study. In this study, we test whether the model is suitable for predicting the extent of contraction in different age groups. To this end, we conduct an extensive literature review to find parameter values. From the sensitivity analysis, we conclude that the most sensitive parameters are the equilibrium collagen concentration in the dermal layer, the apoptosis rate of fibroblasts and myofibroblasts, and the secretion rate of signaling molecules. Further, although we can use the model to simulate significant distinct contraction densities in different age groups, our results differ from what is seen in the clinic. This particularly concerns children and elderly patients. In children we see more intense contractures if the burn injury occurs near a joint, because the growth induces extra forces on the tissue. Elderly patients seem to suffer less from contractures, possibly because of excess skin. ...
Journal article (2021) - Ginger Egberts, Fred Vermolen, Paul van Zuijlen
To deal with permanent deformations and residual stresses, we consider a morphoelastic model for the scar formation as the result of wound healing after a skin trauma. Next to the mechanical components such as strain and displacements, the model accounts for biological constituents such as the concentration of signaling molecules, the cellular densities of fibroblasts and myofibroblasts, and the density of collagen. Here we present stability constraints for the one-dimensional counterpart of this morphoelastic model, for both the continuous and (semi-) discrete problem. We show that the truncation error between these eigenvalues associated with the continuous and semi-discrete problem is of order O(h2). Next we perform numerical validation to these constraints and provide a biological interpretation of the (in)stability. For the mechanical part of the model, the results show the components reach equilibria in a (non) monotonic way, depending on the value of the viscosity. The results show that the parameters of the chemical part of the model need to meet the stability constraint, depending on the decay rate of the signaling molecules, to avoid unrealistic results. ...
Conference paper (2021) - Ginger Egberts, Daan Smits, Fred Vermolen, Paul van Zuijlen
We consider a morphoelastic framework that models permanent deformations. The text treats a stability assessment in one dimension and a preservation of symmetry in multiple dimensions. Next, we treat the influence of uncertainty in some of the field variables onto the predicted behaviour of tissue. ...