Dispersion-enhanced solute transport in a cell-seeded hollow fibre membrane bioreactor

Pearson, Natalie C.; Shipley, Rebecca J.; Waters, Sarah L.; Oliver, James M.

doi:10.1007/s10665-015-9819-5

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…For cases where cell proliferation is important, this may be incorporated following existing approaches in the literature (e.g. [9][10][11]). To demonstrate how we may characterize different types of reaction between the solute and the cells, we present two common reaction mechanisms.…”

Section: Solute Reaction With the Cellsmentioning

confidence: 99%

“…For example, models of fluid flow and solute transport have been employed to optimize chamber design [5], design a gradient generator for drug toxicity testing [6], predict concentration gradients [7] and maximize mass transfer while controlling shear stress levels [8]. Other studies have adopted multiphase approaches to investigate the effect of flow on tissue growth [9] and elucidate the relationship between shear stress and cell yield and distribution within hollow-fibre bioreactors [10]. A comprehensive review of continuum modelling approaches in artificial scaffolds and bioreactors more generally, covering cell population dynamics, the cell's mechanical environment and cell-environment interactions, within a multiphase framework, may be found in [11].…”

Section: Introductionmentioning

confidence: 99%

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Mathematical modelling of fluid flow and solute transport to define operating parameters forin vitroperfusion cell culture systems

et al. 2020

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In recent years, there has been a move away from the use of static in vitro two-dimensional cell culture models for testing the chemical safety and efficacy of drugs. Such models are increasingly being replaced by more physiologically relevant cell culture systems featuring dynamic flow and/or three-dimensional structures of cells. While it is acknowledged that such systems provide a more realistic environment within which to test drugs, progress is being hindered by a lack of understanding of the physical and chemical environment that the cells are exposed to. Mathematical and computational modelling may be exploited in this regard to unravel the dependency of the cell response on spatio-temporal differences in chemical and mechanical cues, thereby assisting with the understanding and design of these systems. In this paper, we present a mathematical modelling framework that characterizes the fluid flow and solute transport in perfusion bioreactors featuring an inlet and an outlet. To demonstrate the utility of our model, we simulated the fluid dynamics and solute concentration profiles for a variety of different flow rates, inlet solute concentrations and cell types within a specific commercial bioreactor chamber. Our subsequent analysis has elucidated the basic relationship between inlet flow rate and cell surface flow speed, shear stress and solute concentrations, allowing us to derive simple but useful relationships that enable prediction of the behaviour of the system under a variety of experimental conditions, prior to experimentation. We describe how the model may used by experimentalists to define operating parameters for their particular perfusion cell culture systems and highlight some operating conditions that should be avoided. Finally, we critically comment on the limitations of mathematical and computational modelling in this field, and the challenges associated with the adoption of such methods.

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Section: Solute Reaction With the Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mathematical modelling of fluid flow and solute transport to define operating parameters forin vitroperfusion cell culture systems

et al. 2020

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“…We model the dynamics in the central region of the bioreactor only, excluding the ECS ports, which allows us to make analytical progress whilst still capturing key features of the system. The effect of these excluded regions will be captured via upstream and downstream boundary conditions on our reduced domain and is investigated in more detail in Pearson et al (2014b). We also exploit the symmetry of this region and model the dynamics in the upper half of the domain only.…”

Section: Model Descriptionmentioning

confidence: 99%

A multiphase model for chemically- and mechanically- induced cell differentiation in a hollow fibre membrane bioreactor: minimising growth factor consumption

Pearson

Oliver

Shipley

et al. 2015

Biomech Model Mechanobiol

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We present a simplified two-dimensional model of fluid flow, solute transport, and cell distribution in a hollow fibre membrane bioreactor. We consider two cell populations, one undifferentiated and one differentiated, with differentiation stimulated either by growth factor alone, or by both growth factor and fluid shear stress. Two experimental configurations are considered, a 3-layer model in which the cells are seeded in a scaffold throughout the extracapillary space (ECS), and a 4-layer model in which the cell-scaffold construct occupies a layer surrounding the outside of the hollow fibre, only partially filling the ECS. Above this is a region of free-flowing fluid, referred to as the upper fluid layer. Following previous models by the authors (Pearson et al. in Math Med Biol, 2013, Biomech Model Mechanbiol 1-16, 2014a, we employ porous mixture theory to model the dynamics of, and interactions between, the cells, scaffold, and fluid in the cell-scaffold construct. We use this model to determine operating conditions (experiment end time, growth factor inlet concentration, and inlet fluid fluxes) which result in a required percentage of differentiated cells, as well as maximising the differentiated cell yield and minimising the consumption of expensive growth factor.

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Mathematical modeling of elastodynamics and cell growth inside a deformable scaffold fitted to the periphery of a bioreactor

Kumar

Sekhar

2021

Math Methods in App Sciences

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A mathematical model is developed for fluid flow, nutrient transport, and cell growth inside a bioreactor with a scaffold at the periphery and lumen at the centerline. The scaffold material is assumed to be deformable. In order to deal with the deformation of the solid phase and fluid phase inside the scaffold, biphasic mixture theory equations are adopted, which are derived from the theory of mixtures. The flow inside the lumen is governed by Stokes equation.Advection-diffusion-reaction equation is used for the mass balance of the nutrient within the scaffold region. Cell growth depends on the nutrient concentration and is expressed by the Contois equation that accounts for contact inhibition. We use lubrication approximation to reduce the system of hydrodynamic and nutrient transport equations. This leads to a coupled system of partial differential equations (PDEs) with time-dependent variables. Laplace transformation is used to deal with time-dependent terms, and Durbin's algorithm is used to retrieve the time dependency. We investigate the outreach of nutrients inside the scaffold region, which regulates the growth of cells at a particular time.Based on the available experimental data, we consider relevant reaction kinematics of the cells and observe the corresponding nutrient distribution inside the bioreactor. The factors that affect the nutrient concentration are lumen radius, porosity, and permeability of the scaffold, Thiele modulus, pressure gradient, and so forth. The total mass transfer rate is computed to understand the nutrient distribution across various regions of the bioreactor.

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Dispersion-enhanced solute transport in a cell-seeded hollow fibre membrane bioreactor

Cited by 6 publications

References 23 publications

Mathematical modelling of fluid flow and solute transport to define operating parameters forin vitroperfusion cell culture systems

Mathematical modelling of fluid flow and solute transport to define operating parameters forin vitroperfusion cell culture systems

A multiphase model for chemically- and mechanically- induced cell differentiation in a hollow fibre membrane bioreactor: minimising growth factor consumption

Mathematical modeling of elastodynamics and cell growth inside a deformable scaffold fitted to the periphery of a bioreactor

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