New mathematical models for perfusion bioreactors in tissue engineering

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The goal of tissue engineers is to grow functional tissues and organs in the laboratory to replace those which have become defective through age, trauma, and disease, and which can be used in drug screening applications. To achieve this goal, tissue engineers aim to control accurately the biomechanical and biochemical environment of the growing tissue construct, in order to engineer tissues with the desired properties. A common approach is to place a porous biomaterial scaffold, seeded with cells, in a flow perfusion bioreactor. Perfusion bioreactors offer the potential for enhanced mass transfer to the construct (overcoming diffusion limitations encountered in static culture environments). Furthermore, such bioreactors are increasingly being used to provide mechanical loads to mechanosensitive tissues which accelerates tissue formation in vitro, thus minimising production time. When determining the optimum stimulatory environment required to generate in vitro a tissue construct that remains functional for significant periods of time, tissue engineers typically adopt a reductionist experimental approach in which attention is focused on a component part of the system. However, the system is more than the sum of its parts, and the challenge lies in determining how all the components interact. Mathematical modelling has a central role to play in elucidating the mechanisms underlying the complex fluid-tissue interactions in such perfusion systems.The proposed research will formulate and solve novel mathematical models to provide fundamental insights into the role of the fluid flow in ensuring adequate substrate delivery to the biologically active porous medium, and optimising the stress field felt by the mechanosensitive tissue. This is a challenging mathematical problem as the biological system is highly complex involving numerous mechanical and chemical interactions between mixed cell populations in spatially and temporally evolving domains. A feature of the research will be continual dialogue with internationally-leading experimental researchers; this will facilitate the calibration, verification and refinement of the theoretical models, and enable theoretical predictions to be experimentally tested.