Designing a Bioreactor for Regenerating High Aspect Ratio Tissues

Abstract

Many tissues have a high aspect ratio (large surface area relative to the thickness of the matrix) and contain multiple cell types. Effect of flow-through configuration within these systems has not been studied. In these scale-up systems, non-ideal fluid distribution conditions could arise from two possible factors: channeling, and dead zones.This study utilized a circular parallel plate reactor that allows large tissue scaffolds. The objective of this study was to understand the flow distribution in a reactor for growing large tissues (10 cm diameter and 2 mm thick) in vitro and to evaluate the nutrient distribution with consumption for three different cell types (namely hepatocytes, smooth muscle cells and chondrocytes). Simulations were performed using CFD packages CFX 11 for flow distribution without porous structure and Comsol Multiphysics 3.4 for flow distribution with nutrient consumption in the porous structure. The flow distribution simulations were validated by doing residence time distribution experiments. 1. The inlet and outlet locations affect the fluid distribution. 2. Presence of porous structure increased the non ideal flow patterns in the system. 3. Location of inlet and outlet over the porous region resulted in high shear stresses. 4. High shear stress regions were eliminated and better nutrient distribution was observed when the inlet and outlet were moved away from the porous region 5. Nutrients flow rate requirements for the cells to grow varied for different cell types