(638b) Design of a Radial Bioreactor for Tissue Regeneration

Tissue Engineering deals with regenerating tissues and organs to replace or support the function of defective body parts.Fabrication of tissues in the laboratory environment requires engineering of scaffolds, the three dimensional synthetic frame structures which serve as a mimic of extracellular matrix for cell adhesion, migration and proliferation.  Bioreactors of different configurations and flow systems have been utilized for regenerating tissues in seeded technique. However, quality of regenerated tissues is poor, attributed to incomplete understanding of fluid flow characteristics.

In this study, fluid flow characteristics in radial flow bioreactors were investigated.  First, simulations were performed using Computational Fluid Dynamics (CFD) technique to understand the effect of i) inlet/outlet diameters ii) diameter of the porous structure, thickness of the porous structure, and iv) flow rate on i) nutrient distribution, ii) pressure drop and iii) shear stress developed in the system.  In addition, baffle design was also considered to improve nutrient distribution.  Michaels-Mentens equation was used to describe the nutrient (oxygen and glucose)consumption for the smooth muscle cell, using literature data. As a starting point, minimum volumetric flow rate was calculated using previously established relationship [1].Fluid flow through the porous structure was described using Brinkman Equation, with the characteristics of chitosan-gelatin scaffolds formed using freeze drying.  No slip at the walls and outlet pressure of 1 atm were the boundary conditions.

The study was performed using COMSOL 4.1Multiphysics software with reaction engineering module for different i) inlet diameters(3, 6 and 9 mm)and outlet diameters(10, 20 and 30 mm), ii) scaffold diameter (20, 50, 100 mm), iii) volumetric flow rates(0.001, 0.01, 0.1 and 1 mL/min) and iv) scaffold thickness(2,4 and 6mm).To validate the simulation results, one of the bioreactor configurations was built in-house and experiments were conducted using porous chitosan-gelatin scaffolds.  Measured pressure drop and residence time distribution characteristics validated the simulated results.  Based on these findings, important factors to consider are discussed.

References

[1] Devarapalli M, Lawrence BJ, Madihally SV.  Modeling Nutrient Consumptions in Large Flow-Through Bioreactors for Tissue Engineering.Biotechnology/ Bioengineering. 103(5):1003-1015, 2009.