(55f) Understanding the Tissue Growth Process Via Fluid Shear and Nutrient Transport Simulation in 3D Porous Scaffolds Used in a Perfusion Bioreactor

A wide variety of scaffold geometries are available for culturing osteoblastic cells in a flow perfusion bioreactor with the aim at bone tissue engineering applications, yet the question remains: what scaffold design and flow conditions are optimal for bone tissue growth? The answer depends on several factors, such as the flow rate under which the tissue is cultured, the amount of fluid shear forces experienced by the cells within the scaffold (resulting in mechanostimulation, or maybe in detachment or bursting of cells) and the efficiency of nutrient/waste transport to/away from the cells (affecting osteoblast differentiation, proliferation, upregulation of angiogenic and osteogenic factors, and mineralized matrix production). Fundamental understanding of factors that lead to favorable cell differentiation can lead to scaffold design procedures that would maximize tissue growth. However, due to the random and complex architecture of the internal porous structure of synthetic scaffolds, any theoretical prediction of tissue growth is impractical. Therefore, the focus of this work is to model local flow-induced shear force and mass transport within typical scaffolds (salt leeched and nonwoven fiber mesh PLLA) via computation. The modeling results are compared against high resolution Micro-Computed Tomography scans of tissue growth as the tissue culturing process advances with time. The juxtaposition of the local tissue growth and computer simulation results is used to obtain insights into the tissue growth process with the ultimate goal of being able to predict where the tissue will grow a priori ? based only on the scaffold geometry. To the best of our knowledge this is the first study of its kind.

The scaffolds are prepared locally via solvent casting and particulate leaching techniques using sodium chloride (NaCl, VWR) as the porogen (non-woven fiber mesh scaffolds are prepared via the melt spinning process). Micro-Computed Tomography (μCT) with 10 μm resolution is used to obtain their structure nondestructively. The μCT images are filtered and reconstructed in three dimensions. Flows of osteogenic media through the scaffolds are modeled via the Lattice Boltzmann Method [1]. Macroscopic mass transfer is modeled using the Lagrangian Scalar Tracking method, which has been found to work well in convective transport cases [2]. High performance computing in conjunction with an in-house MPI parallelized scheme is employed in order to take advantage of the inherent parallelizability of the LBM/LST methodology. Tissue growth is monitored via μCT imaging after a two week growth period. The results are validated against histology and calcium DNA assays.

References

[1] Voronov, R., VanGordon S., Sikavitsas, V.I., and D.V. Papavassiliou, ?Local velocity and stress fields within 3D porous scaffolds used in perfusion bioreactors for bone tissue growth,? submitted to J. of Biomechanics.

[2] Papavassiliou, D.V, "Scalar dispersion from an instantaneous line source at the wall of a turbulent channel for medium and high Prandtl number fluids," Int. J. Heat and Fluid Flow, 23(2), 161-172, 2002.