Optimisation of perfusion bioreactor for bone tissue growth

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Bone tissue engineering is an emerging therapy for treating patients undergoing orthopaedic trauma or disease. The core of the method is the growth of bone tissue on a initial artificial porous scaffold which mimics real bone. The growth is achieved by flowing stem cells through the scaffold until it is replaced by bone tissue which closely resembles the patients own bone. However, much optimisation is needed before this therapy can be implemented. One of the important factors is the number of cells that are placed on scaffold at the start of the several week culture period necessary to create the tissue engineered construct. The correct number and location of starting cells placed onto a scaffold is critical in determining the functionality of the resulting construct. This project aims to optimise cell-seeding methods on the scaffolds, by developing an experimentally validated computer model. The validation, and subsequent investigation, will import real experimental geometries into the flow model; these will be achieved using digital data captured by micro tomography and other methods. The modelling component is a vital element of the proposed project; it overcomes (i) the problem of the inaccessibility of experimental data in complex flow geometries and (ii) the high cost of exploring the potential parameter space experimentally. Expertise from both Keele University (in tissue engineering and bioreactor design) and Sheffield Hallam University (in flow modelling techniques) will be utilised synergistically in order to address the project aims in this joint proposal. Cell type, attachment proteins, scaffold geometry/chemistry, media perfusion rates and mixing techniques will all be analysed in order to investigate the optimal method of cell seeding for bone tissue engineering. The optimised flow model, which will also make timely use of the most recent mathematical modelling information available (eg King, 2005), will then be practically tested in a sterile laboratory environment. Biochemical assessment will be undertaken to determine the efficacy of the predicted, optimised methodology. Utilising modelling techniques in this way, it is possible to significantly reduce time and costs that would otherwise be spent in the laboratory optimising these essential parameters for tissue engineering.