Predictive modelling and simulation in mechano-chemo-biology: a computer multi-approach

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Living tissues are regulated by multi-cellular collectives mediated at cellular level through complex interactions between mechanical and biochemical factors. A further understanding of these mechanisms could provide new insights in the development of therapies and diagnosis techniques, reducing animal experiments. I propose a combined and complementary methodology to advance in the knowledge of how cells interact with each other and with the environment to produce the large-scale organization typical of tissues. I will couple in-silico and in-vitro models for investigating the micro-fabrication of tissues in-vitro using a 3D multicellular environment. By computational cell-based modelling of tissue development, I will use a multiscale and multiphysics approach to investigate various key factors: how environmental conditions (mechanical and biochemical) drive cell behaviour, how individual cell behaviour produces multicellular patterns, how cells respond to the multicellular environment, how cells are able to fabricate new tissues and how cell-matrix interactions affect these processes. In-vitro experiments will be developed to validate numerical models, determine their parameters, improve their hypotheses and help designing new experiments. The in-vitro experiments will be performed in a microfluidic platform capable of controlling biochemical and mechanical conditions in a 3D environment. This research will be applied in three applications, where the role of environment conditions is important and the main biological events are cell migration, cell-matrix and cell-cell interactions: bone regeneration, wound healing and angiogenesis.

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