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Abstract(s)
A angiogénese é o processo pelo qual os novos capilares são formados a partir da vasculatura pré-existente e é um evento fulcral na cicatrização de feridas e no crescimento de tumores. Compreender os mecanismos pelos quais a angiogénese é regulada é fundamental para desenvolver novas terapias para tumores ou feridas crónicas. Os biomateriais são candidatos a ser utilizados em futuras terapias que envolvam tanto inibição como indução da angiogénese. Contudo, estudar in vivo os efeitos dos biomateriais na angiogénese é financeiramente dispendioso e existem várias variáveis que são difíceis de controlar. O desenvolvimento de modelos in silico surge como uma opção para testar hipóteses num ambiente completamente manipulável que proporciona resultados comparáveis com estudos experimentais. Neste trabalho um método numérico 2D que simula a angiogénese é proposto. O modelo computacional considera que as células endoteliais migram de acordo com uma equação de reação-difusão que governa o fator de crescimento endotelial vascular (VEGF) e utiliza um método sem malha para resolver as equações que o governam. Um ensaio de angiogénese in vivo foi utilizado para obter redes capilares comparáveis às obtidas pelo modelo. Os efeitos na angiogénese da difusão constante e variável de VEGF por parte de um biomaterial foram estudados. Verificou-se a migração de células endoteliais na direção da maior concentração de VEGF e a obtenção de redes capilares realistas. A uma difusão constante, quão maior a concentração de VEGF no biomaterial mais rápido as células endoteliais começavam a migrar na sua direção e a penetrá-lo. A uma difusão variável, a penetração do biomaterial por parte dos capilares ocorreu em concentrações mais elevadas de VEGF em comparação com resultados obtidos para uma concentração constante. O modelo apresentou bons resultados de acordo com a literatura e foi validado com sucesso recorrendo ao ensaio in vivo. Contudo, os resultados referentes às simulações com o biomaterial ainda requerem validação experimental.
Angiogenesis is the process by which new capillaries are formed from pre-existent vasculature and it is a crucial event in wound healing and tumorous growth. Understanding the mechanisms by which angiogenesis is regulated is pivotal to develop new cancer and wound healing therapies. Biomaterials are strong candidates for future therapies involving the inhibition or induction of angiogenesis. Nevertheless, the in vivo study of the biomaterial’s effects in the angiogenic process are financially expensive and present many variables that are hard to control. The development of in silico models arises as an option to test hypothesis in a completely manipulative environment that presents results comparable with experimental studies. In this work, a 2D numerical method that simulates sprouting angiogenesis is proposed. The model considers that endothelial cells migrate according to a diffusionreaction equation that governs the Vascular Endothelial Growth Factor (VEGF) and makes use of a meshless method to solve its governing equations. The chick chorioallantoic membrane (CAM) assay was used to obtain capillary networks that will be compared to the in silico obtained networks. The angiogenic effects of constant and variable VEGF diffusion by a biomaterial were studied. Endothelial cell migration towards the highest VEGF concentration was verified and realistic capillary networks were obtained. At a constant VEGF diffusion, the higher the VEGF concentration in the biomaterial the earlier the endothelial cells started to migrate towards it and penetrating it. To a variable diffusion rate, the biomaterial penetration occurred at higher VEGF concentrations when compared to the results obtained for a constant VEGF diffusion rate. The developed model presented good results in accordance with the literature. The modelled angiogenesis in response to a wound was validated using the CAM. However, the biomaterial simulations still require experimental validation.
Angiogenesis is the process by which new capillaries are formed from pre-existent vasculature and it is a crucial event in wound healing and tumorous growth. Understanding the mechanisms by which angiogenesis is regulated is pivotal to develop new cancer and wound healing therapies. Biomaterials are strong candidates for future therapies involving the inhibition or induction of angiogenesis. Nevertheless, the in vivo study of the biomaterial’s effects in the angiogenic process are financially expensive and present many variables that are hard to control. The development of in silico models arises as an option to test hypothesis in a completely manipulative environment that presents results comparable with experimental studies. In this work, a 2D numerical method that simulates sprouting angiogenesis is proposed. The model considers that endothelial cells migrate according to a diffusionreaction equation that governs the Vascular Endothelial Growth Factor (VEGF) and makes use of a meshless method to solve its governing equations. The chick chorioallantoic membrane (CAM) assay was used to obtain capillary networks that will be compared to the in silico obtained networks. The angiogenic effects of constant and variable VEGF diffusion by a biomaterial were studied. Endothelial cell migration towards the highest VEGF concentration was verified and realistic capillary networks were obtained. At a constant VEGF diffusion, the higher the VEGF concentration in the biomaterial the earlier the endothelial cells started to migrate towards it and penetrating it. To a variable diffusion rate, the biomaterial penetration occurred at higher VEGF concentrations when compared to the results obtained for a constant VEGF diffusion rate. The developed model presented good results in accordance with the literature. The modelled angiogenesis in response to a wound was validated using the CAM. However, the biomaterial simulations still require experimental validation.
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Keywords
Angiogénese Modelos computacionais Modelo discreto RPIM Angiogénese em feridas Biomateriais Ensaio in vivo Angiogenesis Computational modelling Discrete model Wound healing angiogenesis Biomaterials CAM assay