Modeling of mass transfer and fluid flow in perfusion bioreactors

Abstract

Tissue engineering is an emerging field with the aim to produce artificial organs and tissues for transplant treatments. Cultivating cells on scaffolds by means of bioreactors is a critical step to forming the organ or tissue substitutes prior to transplantation. Among various bioreactors, the perfusion bioreactor is known for its enhanced convection through the cell-scaffold constructs. The enhanced convection will significantly increase the mass transport and at the same time, will increase the shear stress acting on the cells and scaffolds. To manipulate the scaffold-based cell culture process, knowledge of the mass transport and fluid flow (featured by flow velocity and shear stress) in bioreactors is required. Due to the complicated microstructure and multiphase flow involved in this process, the development of models for capturing the aforementioned knowledge has proven to be a challenging task. In this research, the mass transport and fluid flow in scaffolds cultivated in perfusion bioreactors was studied using numerical methods. In the first stream of this research, a novel mathematical model was developed to represent the nutrient transport and cell growth within three-dimensional scaffolds. Based on the developed model, the effect of such factors as the scaffold porosity, the culture time, and the flow rate were investigated. In the second stream, the flow field within the scaffold was studied with an emphasis on representing the shear stress distribution over the scaffold surface. The commercial computational fluid dynamics software ANSYS-CFX was used to simulate and represent the effect of factors, such as the diameter of the scaffold strand, the horizontal span between two strands, and the flow rate, on the shear stress distribution. Results showed that the nutrient concentration and cell volume fraction are time dependent and sensitive to the porosity and flow rate. The diameters of the strands, the horizontal span and the flow rate affect the magnitude of the shear stress. The knowledge obtained in this study provides new insight into the scaffold-based cell culture process in perfusion bioreactors and allows for potential optimization of the cell culture process by regulating the process parameters as well as the scaffold structure during its fabrication.