Physical and numerical design of a fluidised bed bioreactor for stem cell expansion

Bone substitutes with enhanced biological activity are required for the replacement, repair and regeneration of skeletal tissue. This project aims to design a bioreactor for stem cell expansion on novel hydroxyapatite bone substitute materials designed for accelerated osseointegration of implants. Mathematical modelling has been used alongside physical and biological experiments to define the bioreactor environment.
Initial experiments have been carried out using the osteogenic cell line MG63 seeded on both porous particles^1,2 and disks of HA/TCP (hydroxyapatite/tricalcium phosphate). A purpose built flow chamber has been developed to study the shear stress required to detach cells from the HA/TCP surfaces. The CFD package FLUENT has been used to model the fluid dynamics in a fluidised bed bioreactor to investigate the distributor design, aspect ratio and flowrates of the system. Experiments have been carried out to investigate the fluidisation behaviour of the HA/TCP particles.
Particles (2-4 mm diameter) in a bioreactor (0.02 m diameter, 0.12 m height) were shown to have a minimum fluidisation velocity of 0.04 m s^-1 with an overall pressure drop of 3500 kPa m^-1, and a ‘complete’ fluidisation velocity of 0.05 m s^-1 with an overall pressure drop of 2800 kPa m^-1. MG63s under static conditions have been shown to expand upon the HA/TCP particles.

References: Hsu, Y. et al. Key Eng. Mat. 284-286, 305-308 (2005). 2. Hsu, Y. et al. Materials Sci.: Mat. in Med. 18, 1931-1937 (2007)