MODELING RADIAL-FLOW PACKED BED BIOREACTORS (RPBBS) FOR LONG-BONE TISSUE ENGINEERING: THE ROLE OF EXTERNAL RESISTANCE TO SOLUTE TRANSPORT

Objectives: Modelling flow and solutes transport in bioreactors for tissue engineering is generally approached with pseudo-homogeneous models or with models describing fine details of porous scaffold seeded with adherent cells. The former neglect solute concentration gradients near the cells and do...

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Bibliographic Details
Published in:International journal of artificial organs 2023-07, Vol.46 (7), p.448
Main Authors: Fragomeni, G, De, Napoli L, Morrone, G, Catapano, G
Format: Article
Language:English
Subjects:
Adherent cells
Anoxic conditions
Bioreactors
Cell culture
Cell surface
Column packings
Computer applications
Computers
Concentration gradient
Convection
Dissolved oxygen
Finite element method
Hypoxia
Long bone
Mathematical models
Microenvironments
Monitoring
Oxygen
Packed beds
Radial flow
Scaffolds
Solute transport
Solutes
Tissue engineering
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Summary:Objectives: Modelling flow and solutes transport in bioreactors for tissue engineering is generally approached with pseudo-homogeneous models or with models describing fine details of porous scaffold seeded with adherent cells. The former neglect solute concentration gradients near the cells and do not properly account for hypoxic or anoxic zones, but have not high computational requirements. The latter properly describe transport to cells but require powerful computers and long processing times. Poor predictions of severe culture conditions and long running times, respectively, make both models unfit for real-time monitoring and control of the pericellular culture microenvironment in TE bioreactor. Aim of this study was to propose how a pseudo-homogeneous transport model may be modified to account for solute transport resistance from medium bulk to cell surface in scaffold pores (i.e., external to cells) and become feasible for monitoring and control purposes. Methods: The pseudo-homogenous model was built to describe the steady-state transport of momentum and dissolved oxygen through void spaces and scaffold in an rPBB according to the Navier-Stokes, Brinkman and convection-dispersion-reaction equations, respectively. The scaffold was modelled as a transport equivalent bed of Raschig rings and resistance to oxygen transport was accounted for with available semiempirical correlations for solute transport. Balance equations were solved numerically with the FEM Comsol Multiphysics software for conditions typical of long-bone TE. Results: The model soundly predicted culture under hypoxic or anoxic conditions in scaffold zones where medium stagnates, as in poor bioreactor design, and/or when highly metabolically active cells are cultured at high concentrations, as when tissue matures. High radial perfusion rates could correct the imbalance between oxygen supply and increasing metabolic demand till scaffold maturation without excessive computational power and times. Conclusions: Use of this type of model appears promising for monitoring and controlling the pericellular microenvironment in TE bioreactors
ISSN:0391-3988
1724-6040