Optimization of a Bioreactor for Tissue Engineering Scaffolds

Mamatha Devarapalli and Sundararajan V. Madihally. School of Chemical Engineering, Oklahoma State University, 423 Engineering North, Stillwater, OK 74078

The goal of this study was to understand the flow distrbution in a reactor for growing large tissues (10 cm diameter and 2 mm thick) in vitro. For this purpose a parallel plate reactor would be ideal because of its construct which would give support to the scaffold and continuous flow ensures replenishment of the nutrients. However, rectangular reactors possess inherent problems related to dead spaces at the edges. Hence circular reactors which minimize the dead spaces within the reactor were used. First, fourteen differnt outlet and inlet configurations were assed for fluid distribution. From this, reactor with better fluid distribution was selected. Two aspects were considered for further analysis: (i) to ensure uniform distribution of the nutrients, residence time distribution (RTD) studies were carried out and (ii) to optimize the flow rate at which the nutrients are to be supplied for the cells to grow, oxygen and glucose consumptions were studied at varying flow rates using rate constants from literature. For nutrient consumption four different four differnt cell types were used. The simulations were done using the computational fluid dynamics packages CFX 11 (ANSYS Inc, Canonsburg, PA.) and/or Comsol 3.3 Multiphysics Package with Reaction Engineering Module (COMSOL, Inc., Burlington, MA). Experiments were performed using chitosan porous structures and reactors manufactured to the dimensions of the simulated condition. From the RTD studies it was observed that the RTD function E(t) peak shifted towards left showing that there is an increase in channeling with the porous structure than without the porous structure. The concentration profiles of oxygen and glucose were simulated for different cell types and it was observed that the optimum flow rate for all the cell types simulated were in between the range of 0.1-0.01ml/min and at around 0.001ml/min flow rate, almost all the nutrients were consumed. The pressure drop and shear stress distributions within the reactor were also studied. The reactor systems used here have distinct advantages for regenerating large tissue constructs. Scaffolds for skin, bladder, and cartilage can have very large surface area to volume ratios with very small thickness. Flow dynamics and mass transfer of the nutrients are two important concepts to be studied and understood well while designing a bioreactor for tissue engineering purposes. The computational and experimental techniques being developed show promise to further enhance the fundamental understanding of the processes for tissue regeneration.