CELL-GROWTH AND DIFFERENTIATION ON FEEDER LAYERS IS PREDICTED TO BE INFLUENCED BY BIOREACTOR GEOMETRY

Tissue function is comprised of a complex interplay between biological and physicochemical rate processes. The design of bioreactors for tis sue engineering must account for these processes simultaneously in ord er to obtain a bioreactor that provides a uniform environment for tiss ue growth and development. In the present study we consider the effect s of fluid flow and mass transfer on the growth of a tissue in a paral lel-plate bioreactor configuration. The parenchymal cells grow on a pr eformed stromal (feeder) layer that secretes a growth factor that stim ulates parenchymal stem cell replication and differentiation. The biol ogical dynamics are described by a unilineage model that describes the replication and differentiation of the tissue stem cell. The physicoc hemical rates are described by the Navier-Stokes and convective-diffus ion equations. The model equations are solved by a finite element meth od. Two dimensionless groups govern ern the behavior of the solution. One is the Graetz number (Gz) that describes the relative rates of con vection and diffusion, and the other a new dimensionless ratio (design ated by P) that describes the interplay of the growth factor productio n, diffusion, and stimulation. Four geometries (slab, gondola, diamond , and radial shapes) for the parallel-plate bioreactor are analyzed. T he uniformity of cell growth is measured by a two-dimensional coeffici ent of variance. The concentration distribution of the stroma-derived growth factor was computed first based on fluid flow and bioreactor ge ometry. Then the concomitant cell density distribution was obtained by integrating the calculated growth factor concentration with the paren chymal cell growth and unilineage differentiation process. The spatiot emporal cell growth patterns in four different bioreactor configuratio ns were investigated under a variety of combinations of Gz (10(-1), 10 (0), and 10(1)) and P(10(-2), 10(-1), 10(0), 10(1), and 10(2)). The re sults indicate high cell density and uniformity can be achieved for pa rameter values of P = 0.01,...,0.1 and Gz = 0.1,...,1.0. Among the fou r geometries investigated the radial-flow-type bioreactor provides the most uniform environment in which parenchymal cells can grow and diff erentiate ex vivo due to the absence of walls that are parallel to the flow paths creating slow flowing regions. (C) 1996 John Wiley & Sons, Inc.