TRANSPORT MODEL OF RADIAL-FLOW PACKED-BED BIOREACTORS SIMULATING NATURAL BONE VASCULAR AND INTERSTITIAL FLUID NUTRIENTS DELIVERY

Aim: Radial flow perfusion of osteogenic cells seeded in 3D annular porous scaffolds in radial flow packed-bed bioreactors (rPBB) may resemble the pattern of natural nutrients delivery in large engineered bone constructs. So far, little attention has been paid to optimize rPBB design to minimize transport resistance and ensure physiologic nutrients delivery to cells in constructs. In this work, a transport model of rPBBs is proposed aimed to optimize rPBB geometry and operation and simulate the nutrients delivery pattern to cells enabled by bone vascular and interstitial fluids in natural bone. Methods: A pseudo-homogeneous model was used to describe steady-state transport of momentum and dissolved solutes across rPBB compartments according to Navier-Stokes and Brinkman equations and convection-dispersion-reaction equation, respectively. The effect of external transport resistance from bulk fluid to cell surface was accounted for. Solute concentration profiles were predicted with a FEM code for varying values of dimensionless groups determining rPBB behavior. Results: The model permitted to adjust rPBB geometry and minimize flow maldistribution. Transport resistance significantly hindered nutrients delivery to cells. Similar to natural bone in exercise, high radial perfusion velocities could balance transport resistance as cell metabolic requirements increase and yielded smooth radial and axial solutes concentration profiles in the construct. Conclusions: Model results may help optimize rPBB design and allow for physiological nutrients delivery in large bone constructs.