Optimization of construct perfusion in radial-flow packed-bed bioreactors for tissue engineering with a 2D stationary fluid dynamic model (original) (raw)
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Processes, 2014
Radial flow perfusion of cell-seeded hollow cylindrical porous scaffolds may overcome the transport limitations of pure diffusion and direct axial perfusion in the realization of bioengineered substitutes of failing or missing tissues. Little has been reported on the optimization criteria of such bioreactors. A steady-state model was developed, combining convective and dispersive transport of dissolved oxygen with Michaelis-Menten cellular consumption kinetics. Dimensional analysis was used to combine more effectively geometric and operational variables in the dimensionless groups determining bioreactor performance. The effectiveness of cell oxygenation was expressed in terms of non-hypoxic fractional construct volume. The model permits the optimization of the geometry of hollow cylindrical constructs, and direction and magnitude of perfusion flow, to ensure cell oxygenation and culture at controlled oxygen concentration profiles. This may help engineer tissues suitable for therapeutic and drug screening purposes.
Three Dimensional Modelling inside a differential laminar Flow Bioreactor filled with porous media
A three-dimensional computational fluid dynamics-(CFD-) model based on a differential pressure laminar flow bioreactor prototype was developed to further examine performance under changing culture conditions. Cell growth inside scaffolds was simulated by decreasing intrinsic permeability values and led to pressure build-up in the upper culture chamber. Pressure release by an integrated bypass system allowed continuation of culture. The specific shape of the bioreactor culture vessel supported a homogenous flow profile and mass flux at the scaffold level at various scaffold permeabilities. Experimental data showed an increase in oxygen concentration measured inside a collagen scaffold seeded with human mesenchymal stem cells when cultured in the perfusion bioreactor after 24 h compared to static culture in a Petri dish (dynamic: 11% O 2 versus static: 3% O 2 ). Computational fluid simulation can support design of bioreactor systems for tissue engineering application.
BioMed Research International, 2015
A three-dimensional computational fluid dynamics-(CFD-) model based on a differential pressure laminar flow bioreactor prototype was developed to further examine performance under changing culture conditions. Cell growth inside scaffolds was simulated by decreasing intrinsic permeability values and led to pressure build-up in the upper culture chamber. Pressure release by an integrated bypass system allowed continuation of culture. The specific shape of the bioreactor culture vessel supported a homogenous flow profile and mass flux at the scaffold level at various scaffold permeabilities. Experimental data showed an increase in oxygen concentration measured inside a collagen scaffold seeded with human mesenchymal stem cells when cultured in the perfusion bioreactor after 24 h compared to static culture in a Petri dish (dynamic: 11% O 2 versus static: 3% O 2 ). Computational fluid simulation can support design of bioreactor systems for tissue engineering application.
Optimization of a perfusion bioreactor for tissue engineering
Biodental Engineering III, 2014
Tissue engineering aims to repair and regenerate damaged tissues by developing biological substitutes mimicking the natural extracellular matrix. It is evident that scaffolds, being a tridimensional matrix, are of extreme importance providing the necessary support for the new tissue. This new tissue is cultivated in vivo or in vitro in a bioreactor in which is placed the scaffold with cells. In order to control the cell culture process inside of a bioreactor it is essential to know the fluid flow inside and around the scaffold in order to know witch parameters must be controlled in order to obtain optimum conditions to cell culture. The wall shear stress must be adequate to the tissue to be cultivated, i.e., bone, muscle, cartilage and it is known that a proper stimulus is necessary to improve the cell proliferation inside the scaffold. This work considers a novel perfusion bioreactor and it is intended to optimize the fluid flow within the chamber and the scaffold by assessing the turbulence kinetic energy, the velocity and the wall shear stress.
Development of a Laminar Flow Bioreactor by Computational Fluid Dynamics
The purpose of this study is to improve the design of a bioreactor for growing bone and other three-dimensional tissues using a computational fluid dynamics (CFD) software to simulate flow through a porous scaffold, and to recommend design changes based on the results. Basic requirements for CFD modeling were that the flow in the reactor should be laminar and any flow stagnation should be avoided in order to support cellular growth within the scaffold. We simulated three different designs with different permeability values of the scaffold and tissue. Model simulation addressed flow patterns in combination with pressure distribution within the bioreactor. Pressure build-up and turbulent flow within the reactor was solved by introduction of an integrated bypass system for pressure release. The use of CFD afforded direct feedback to optimize the bioreactor design.
Modeling of the Flow within Scaffolds in Perfusion Bioreactors
Tissue engineering aims to produce artificial organs and tissues for transplant treatments, in which cultivating cells on scaffolds in bioreactors is of critical importance. To control the cultivating process, the knowledge of the fluid flow inside and around a scaffold in the bioreactor is essential. However, due to the complicated microstructure of a scaffold, it is difficult, or even impossible, to gain such knowledge experimentally. In contrast, numerical methods employing computational fluid dynamics (CFD) have proven promising to alleviate the problem. In this research the fluid flow in perfusion bioreactors is studied with numerical methods. The emphasis is on investigating the effect of the controllable parameters in both the scaffold fabrication (i.e., the diameter of scaffold strand and the distance between two strands) and cell culture process (i.e., the flow rate) on the distribution of shear stress within the scaffold in a perfusion bioreactor. The knowledge obtained in this study will allow for improved control strategies in scaffold fabrication and cell culturing experiments.
In-silico characterization of the flow inside a novel bioreactor for cell and tissue culture
2007
This numerical study considers the steady, axisymmetric flow inside a novel open-top rotating-base bioreactor. The flow is simulated over a Reynolds number range that corresponds to steady axisymmetric flow. The swirling flow consists of two distinct recirculation zones, namely a primary dominant region, and a secondary recirculation bubble that is formed close to the axis of rotation. Of particular interest to tissue engineering is the stress distribution inside the bioreactor. The stress is quantified by the coordinate-independent principal stress terms, namely, the positive tensile, intermediate, and negative compressive components. The analysis indicates that there are three main regions of high strain within the bioreactor: at the rotating bottom lid; on the side walls; and at the surface close to the breakdown bubble. Finally, the local flow environment of a suspended scaffold is determined.
Mathematical modelling of fibre-enhanced perfusion inside a tissue-engineering bioreactor
Journal of Theoretical Biology, 2009
We develop a simple mathematical model for forced flow of culture medium through a porous scaffold in a tissue-engineering bioreactor. Porous-walled hollow fibres penetrate the scaffold and act as additional sources of culture medium. The model, based on Darcy's law, is used to examine the nutrient and shear-stress distributions throughout the scaffold. We consider several configurations of fibres and inlet and outlet pipes. Compared with a numerical solution of the full Navier-Stokes equations within the complex scaffold geometry, the modelling approach is cheap, and does not require knowledge of the detailed microstructure of the particular scaffold being used. The potential of this approach is demonstrated through quantification of the effect the additional flow from the fibres has on the nutrient and shear-stress distribution.
Perfusion Bioreactor Fluid Flow Optimization
Procedia Technology, 2014
Tissue engineering aims to repair and regenerate damaged tissues by developing biological substitutes mimicking the natural extracellular matrix. It is evident that scaffolds, being a tri-dimensional matrix, are of extreme importance providing the necessary support for the new tissue. This new tissue is cultivated in vivo or in vitro in a bioreactor in which is placed the scaffold with cells. In order to control the cell culture process inside of a bioreactor it is essential to know the fluid flow inside and around the scaffold in order to know witch parameters must be controlled in order to obtain optimum conditions to cell culture. The wall shear stress must be adequate to the tissue to be cultivated, i.e., bone, muscle, cartilage and it is known that a proper stimulus is necessary to improve the cell proliferation inside the scaffold. This study considers a novel multifunctional bioreactor with a perfusion system module and it is intended to optimize the fluid flow within the chamber and the scaffold by assessing the turbulence kinetic energy and the velocity.
3-D computational modeling of media flow through scaffolds in a perfusion bioreactor
2005
Media perfusion bioreactor systems have been developed to improve mass transport throughout three-dimensional (3-D) tissue-engineered constructs cultured in vitro. In addition to enhancing the exchange of nutrients and wastes, these systems simultaneously deliver flow-mediated shear stresses to cells seeded within the constructs. Local shear stresses are a function of media flow rate and dynamic viscosity, bioreactor configuration, and porous scaffold microarchitecture.