论文和技术资料

In many medical and biotechnological applications, cells are grown in dynamic cell cultures. Usually, the cells are cultivated on a scaffold with a complex channel structure through which the nutrient fluid flows and into which the cells can grow. However, a known problem is that the cells grow well in the outer regions of the scaffolds, but the inner regions are hardly colonized. This is attributed, among other things, to an undersupply of oxygen in the inner regions of the scaffold [1]. In this COMSOL Multiphysics® study, the local oxygen concentration in scaffolds with different channel structures was calculated and the geometry of the channels was optimized for a sufficient supply to the cells.

The channel structure inside the scaffolds was simplified in a 2D-model and the local oxygen concentration was calculated by a combination of the "Laminar Flow" and the "Transport of Diluted Species" physics interfaces. The walls of the channels were assumed to be populated with a dense monolayer of cells. The cell-populated areas were realized as a narrow layer with a thickness of 15 µm on the channel walls and the oxygen consumption in these regions was modeled using a reaction rate with Michaelis-Menten kinetics [2,3]. The reservoir regions above and below the scaffold were assumed to be large and far away from the cells and consequently, the oxygen concentration was maintained constant there by the boundary conditions. For the flow of the nutrient medium, the lower boundary was set as an inlet and the upper boundary as an outlet. The velocity field from the CFD simulation was transferred to diffusion study. All model parameters were adopted from a previous study [1]. The influence of different flow rates (0 - 250 µl/min), different nesting depths(1 - 3 levels), different channel widths (50 - 500 µm) and different channel lengths (50 - 5000 µm) was investigated.

The simulation results show for all simulated channel structures that there was a critical undersupply of oxygen inside the scaffold without flow. Low flow rates only shifted the undersupplied region, because flow and diffusion counteracted each other in the supply of oxygen. For structures with low nesting depth, sufficient oxygen supply could only be achieved for high flow rates at which the resulting shear forces were pathologically high. Only a combination of wide channels with a high flow rate and smaller, more branched channels resulted in regions in the scaffold that had sufficient oxygen supply at low shear forces.

Our study demonstrates that the cell behavior in dynamic cell cultures can basically be understood within the framework of the presented model and provides information on how channel structures can be optimized for better cell colonization.