Role of nutrient supply on cell growth in bioreactor design for tissue engineering of hematopoietic cells.
In the present study, a dynamic mathematical model for the growth of granulocyte progenitor cells in the hematopoietic process is developed based on the principles of diffusion and chemical reaction. This model simulates granulocyte progenitor cell growth and oxygen consumption in a three-dimensional (3-D) perfusion bioreactor. Material balances on cells are coupled to the nutrient balances in 3-D matrices to determine the effects of transport limitations on cell growth. The method of volume averaging is used to formulate the material balances for the cells and the nutrients in the porous matrix containing the cells. All model parameters are obtained from the literature. The maximum cell volume fraction reached when oxygen is depleted in the cell layer at 15 days and is nearly 0.63, corresponding to a cell density of 2.25 x 10(8) cells/mL. The substrate inhibition kinetics for cell growth lead to complex effects with respect to the roles of oxygen concentration and supply by convection and diffusion on cell growth. Variation in the height of the liquid layer above the cell matrix where nutrient supply is introduced affected the relative and absolute amounts of oxygen supply by hydrodynamic flow and by diffusion across a gas permeable FEP membrane. Mass transfer restrictions of the FEP membrane are considerable, and the supply of oxygen by convection is essential to achieve higher levels of cell growth. A maximum growth rate occurs at a specific flow rate. For flow rates higher than this optimal, the high oxygen concentration led to growth inhibition and for lower flow rates growth limitations occur due to insufficient oxygen supply. Because of the nonlinear effects of the autocatalytic substrate inhibition growth kinetics coupled to the convective transport, the rate of growth at this optimal flow rate is higher than that in a corresponding well-mixed reactor where oxygen concentration is set at the maximum indicated by the inhibitory kinetics.
Pathi
Pragyansri
P
Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University and Florida A & M University, Tallahassee, Florida 32310-6046, USA.
Ma
Teng
T
Locke
Bruce R
BR
D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods*; D048429:Cell Size; D003198:Computer Simulation; D018481:Convection; D003470:Culture Media / Q000737:chemistry; D004058:Diffusion; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D007700:Kinetics; D008962:Models, Theoretical; D010101:Oxygen Consumption; D010477:Perfusion; D023822:Tissue Engineering
D003470:Culture Media