Difficulties encountered in tissue engineering invited the use of perfusion bioreactors to deliver essential nutrients to cells within tissue-engineered constructs. Despite the increased nutrient transport achieved, solute perfusion caused harmful mechanical stresses to the cells. Interestingly, some bioreactors are employed to mechanically stimulate cells, improving their biological functions. However, stresses associated with perfusion bioreactors are counterproductive. Currently, to address this issue, perfusion rate is lowered to minimise mechanical implications to the cells. Consequently, nutrient delivery is sacrificed. Therefore, this project aims to balance the nutritional advantage offered by perfusion, and its associate cell-death. By doing so, essential nutrients may be perfused to all regions of tissue-engineered constructs, at flow rates whose mechanical implications are harmless, or even encouraging to cells. To alleviate the costly and iterative experiments necessary to achieve these aims, the use of computational modelling will be central to the project, and incidentally, forms the training objective of the proposal. However, key findings will be corroborated with laboratory experiments. Combining techniques associated with cell biology, material science, and mechanical engineering. The specific objectives of the proposed study are to: Model the fluid flow-induced deformation of cells within tissue-engineered constructs. Using fluorescent staining, corroborate relationship between fluid flow and cellular deformation. Design a system to mechanically deform cells without fluid flow. Investigate the influence of cellular deformation, with and without fluid flow to their viability and biological activities. Extrapolate the individual contributions of fluid flow and mechanical deformation. Determine theoretically, and experimentally, useful ranges of fluid flow and mechanical deformation, conducive to developing functional neo-tissues in vitro.
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