Technical Papers and Presentations

In biotechnology and medicine, cells are frequently grown on scaffolds with a three-dimensional channel structure. The oxygen and nutrient supply of the cells is realized by a medium flowing through the channels of the scaffolds. However, it is often difficult to obtain a confluent colonization of the cells in the interior regions of the scaffolds. Therefore, the oxygen supply inside a MG-63 osteoblast-populated complex 3D-scaffold was analyzed at different medium flow rates with COMSOL Multiphysics^®.

A section of a complex scaffold (channel radius: 80-250 µm) was reconstructed in the Model Builder and the boundaries were realized via Periodic Flow conditions. A confluent colonization of the channel walls with MG-63 cells was simulated by a surface layer in the geometry. The local oxygen concentration and shear forces were calculated as a function of the medium flow rate by simulating the balance of oxygen consumption by the cells and oxygen supply by flow and diffusion. The simulation was carried out by a combination of the Laminar Flow and Transport of Diluted Species physics interfaces; oxygen consumption was achieved by a reaction rate with Michaelis-Menten kinetics [1,2].

The simulation results demonstrate that without flow, a critical oxygen depletion occurs in the interior regions of the scaffold. When the medium flow rate is increased, the critically depleted area shifts towards the outflow of the scaffold channels. For the simulated channel geometries, an adequate oxygen supply is only possible at such high flow rates, where pathological shear forces occur. The simulations explain the results of cell culture experiments [3] and indicate that a sufficient oxygen supply inside a confluent populated scaffold cannot be achieved by direct flow, but requires a cross-linked structure with diffusion regions.

References

[1] F. Coletti, S. Macchietto, and N. Elvassore, Mathematical modeling of three-dimensional cell cultures in perfusion bioreactors, Ind. Eng. Chem. Res. (2006) 45:8158.

[2] P. Buchwald, FEM-based oxygen consumption and cell viability models for avascular pancreatic islets, Theor. Biol. Med. Model. (2009) 6:5.

[3] C. Bergemann, P. Elter, R. Lange, V. Weißmann, H. Hansmann, E.-D. Klinkenberg, B. Nebe, Cellular Nutrition in Complex Three-Dimensional Scaffolds: A Comparison between Experiments and Computer Simulations, Int. J. Biomater (2015) 2015:584362.