(430v) Modelling of Cell Transport and Adhesion inside Porous Media

The first step of tissue engineering is creating a porous scaffold on which the desired tissue can be grown. The design of this scaffold is paramount to the successful development of a tissue as its structure and composition will affect all aspects of the tissue growth, from initial cell seeding and cell dispersion through to cell proliferation, migration and nutrient supply.

The internal pore morphology of a tissue engineering scaffold depends greatly on the scaffold fabrication method used, i.e. Temperature Induced Phase Separation (TIPS), particle template, particle sintering etc. These different techniques are commonplace in tissue engineering and all produce varied internal pore structures, however little work has been carried out comparing how different scaffold structures, produced from different fabrication techniques, can affect cell seeding. Along with the fabrication method used many other aspects such as porosity and pore size affect the internal structure of the scaffold and so can have also have a large effect on cell seeding.

It is the aim of this work to develop and validate a model which simulates cell seeding into porous media. The porous media generated in the model have a pore morphology that represents those commonly used in tissue engineering, and investigates the effects of different variables, such as the cell/pore size ratio and cell agglomeration, among others, on the distribution of cells within the medium. This modelling of specific geometries, based on fabrication methods, will enable investigation into comparing different scaffold fabrication methods with the growth of different cell cultures with a view to optimising scaffold design.

A fluid velocity field is then calculated through the porous medium using a volume of fluid technique and the Stokes' equations of fluid flow for low Reynolds numbers. The program has been validated via comparison of the pressure difference from simulations of flow through a cylindrical geometry and the pressure difference calculated using the well-known Poiseuille formula.

Once the fluid flow profile has been calculated for the porous medium our model generates spheres, representing cells, at the beginning of the z axis. These spheres follow the fluid streamlines through the scaffold until either the sphere adheres to a pore surface (representing cell deposition) or is passed through the control volume.

The model is validated using x-ray micro-tomography ? a technique allowing non-invasive three-dimensional visualisation of porous and multi-phase media. A sample of porous medium is first x-rayed before beads are seeded via the use of a custom-designed flow chamber. X-rays of the initial 'empty' medium have been taken and incorporated into the cell seeding program so experimental results from the x-ray of the seeded medium can be compared to simulation results. This allows matching of cell positions in the experimental scaffold with that of the models simulations.

The cell seeding model should allow for investigation into optimising cell seeding via suggesting scaffold properties and fluid regimes that encourage cell dispersion through the scaffold and avoid large cell agglomerations and blockages. The effect of heterogeneous flow and cell agglomeration whilst in transport will also be investigated. After cell seeding has been simulated the model will allow further investigation into nutrient supply, cell proliferation and cell culture development throughout the scaffold.