Modeling nutrient consumptions in large flow-through bioreactors for tissue engineering.

Flow-through bioreactors are utilized in tissue regeneration to ensure complete nutrient distribution and apply defined hydrodynamic stresses. The fundamental concepts in designing these bioreactors for regenerating large high aspect ratio tissues (large surface area relative to the thickness of the matrix such as skin, bladder, and cartilage) are not well defined. Further, tissue regeneration is a dynamic process where the porous characteristics change due to proliferation of cells, de novo deposition of matrix components, and degradation of the porous architecture. These changes affect the transport characteristics and there is an imminent need to understand the influence of these factors. Using computational fluid dynamic tools, changes in the pressure drop, shear stress distribution and nutrient consumption patterns during tissue regeneration were assessed in rectangular and circular reactors described by Lawrence et al. [Biotechnol Bioeng 2009;102(3):935-947]. Further, six new designs with different inlet and outlet shapes were analyzed. The fluid flow was defined by the Brinkman equation on the porous regions using the pore characteristics of 85 microm and 120 pores/mm(2). The minimum flow requirements to satisfy nutrient (oxygen and glucose) requirements for three different cell types (SMCs, chondrocytes, and hepatocytes) was evaluated using convective diffusion equation. For consumption reaction, the Michaelis-Menten rate law was used, with constants (k(m) and v(m) values) extracted from literature. Simulations were performed by varying the flow rate as well as the cell number. One of the circular reactors with semicircular inlet and outlet shape decreased (i) non-uniformity in hydrodynamic stress within the porous structure and (ii) non-uniform nutrient distribution. All cell types showed increased consumption of oxygen than glucose. Hepatocytes needed a very high flow rate relative to other cell types. Increase in cell number suggested a need for increasing the flow in circular reactors.