| dc.description.abstract | Perfusion bioreactor systems have been developed to improve mass transport throughout three-dimensional tissue-engineered scaffolds cultured in vitro. In addition to enhancing the exchange of nutrients depletion and product accumulation, these systems simultaneously deliver flow-mediated shear stresses to cells seeded within the constructs. In this work, a computational model explaining, as well as predicting, cell proliferation and random walk within the porous scaffold, nutrients consumption and product accumulation, is developed. It incorporates a modified Contois cell-growth model that includes the effects of nutrient saturation, competitive product inhibition to describe the scaffold–cell system. To assess the extent to which mass transfer can be influenced theoretically, extreme cases were distinguished in which the culture medium was assumed fully sufficient in static culture. A comparison between predictions and experimental evidence found in the literature shows that cell-scaffold constructs that rely solely on diffusion for supply of nutrients will inevitably produce proliferation-dominated regions near the outer edge of the scaffold. When the cells are cultured in a scaffold subjected to a perfused velocity field, they penetrate to a greater extent into the scaffold core and give uniform spatial distribution. The amount of cells in the perfusion culture is more than in static culture, and increases with the velocity of perfusion, and it will tend to a constant as the perfusion is intensified. Relating the simulation results to perfusion experiments, an average surface shear stress of 0.06 mPa (6e-4 dyne/cm^2) was found at a flow rate of 0.0024 cm^3/s, and which is similar with other studies. We find the properties of random walks will influence the growth of cells, and it may let cell distribute uniformly when the random walk velocity increases. A parametric analysis is performed and the result is compared qualitatively with previous findings in the literature. Additional cases, where cell nonuniform-seeding and the change of tube diameter can be influential for a perfusion bioreactor system, are also studied. | en_US |