Optimisation of perfusion bioreactor for bone tissue growth

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.

Bone tissue engineering is an emerging therapy for treating patients undergoing orthopaedic trauma or disease. However, much optimisation is needed before this therapy can be implemented. One of the important factors in bone tissue engineering is the configuration of placing the cells on a scaffold at the start of the several week culture period which is necessary to create the tissue-engineered construct. Determining the optimal number and location of the starting cells placed onto a scaffold is critical to the functionality of the resulting construct. This project aims to optimise cell-seeding methods on porous 3D constructs, using a lattice Boltzmann (LB) mathematical modelling technique employing the real experimental geometries which will be digitally captured using micro computed tomography (CT) and other methods. Cell type, attachment proteins, scaffold geometry/chemistry, media perfusion rates and mixing techniques will all be analysed in order to determine the optimal regime of cell perfusion seeding for bone tissue engineering. 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. Validation of the optimised theoretical model will be performed experimentally using microCT imaging of both fluid flow and cell seeding amongst other techniques.