Engineering cell/matrix and cell/cell interactions to control the flow behavior of high volume fraction cell suspensions

Maisonneuve, Benoit (2014). Engineering cell/matrix and cell/cell interactions to control the flow behavior of high volume fraction cell suspensions PhD Thesis, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland. doi:10.14264/uql.2014.130

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Author Maisonneuve, Benoit
Thesis Title Engineering cell/matrix and cell/cell interactions to control the flow behavior of high volume fraction cell suspensions
School, Centre or Institute Australian Institute for Bioengineering and Nanotechnology
Institution The University of Queensland
DOI 10.14264/uql.2014.130
Publication date 2014
Thesis type PhD Thesis
Supervisor Justin Cooper-White
Denis Roux
Total pages 200
Language eng
Subjects 090301 Biomaterials
060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
Formatted abstract
With the rapidly growing interest in the development of bioprocess systems to culture and expand mesenchymal stromal cells (MSCs) for cell therapy and regenerative medicine applications, greater understanding of the structure-function-property characteristics of mesenchymal cell suspensions is required.

In this thesis, the results of a detailed experimental study into the flow behaviour of concentrated suspensions of living mesenchymal cells over a wide range of cell concentrations and in the presence of two macromolecules (hyaluronic acid and polyethylene glycol) often used in cellular therapy applications are presented. The change in the shear viscosity as a function of shear stress and shear rate for cell volume fractions varying from 20 to 60% are firstly presented, showing that these suspensions exhibit highly complex but reproducible rheological footprints, including yield stress, shear thinning and shear-induced fracture behaviours.

The rheological properties of the suspension with the addition of hyaluronic acid (HA), a biomolecule with adhesion sequences for receptors on these types of cells, was then investigated. With the addition of HA, the rheology of these cell suspensions is significantly modified at all volume fractions. Using FACS and confocal imaging, we show that the observed effect of HA addition is due to it significantly modulating the formation of cellular aggregates in these suspensions, and thus the resultant volume spanning network. This understanding permits the rheology of concentrated mesenchymal cell suspensions to be tailored to suit particular processing scenarios.

The third part of this project focused on the addition of polyethylene glycol, a molecule which is not naturally present in tissues but commonly utilised in hydrogels as injectable delivery vehicles for cells to sites of tissue damage. Using three different kinds of PEG, the influence of the charge of the molecules is investigated. The results show the charge is also a crucial parameter to tailor the flow behaviour of cell suspension when biomacromolecules are added, influencing the formation and the compactness of the cellular aggregates.

Considering the aggregates as fractal structures, and by taking into account the changes in volume fractions with shear, a master curve for the range of conditions investigated was successfully achieved through the use of an analytical model. Critically, this model also permitted the estimation of the average adhesion force between cells, across a population of millions of cells. The outcomes of this study not only provide new insight into the complexity of the flow behaviours of concentrated, dynamically adhesive mesenchymal cell suspensions, and their sensitivity to associative biomolecule and synthetic molecule addition, but also a novel, rapid method by which to estimate adhesion forces between cells.
Keyword Rheology
Concentrated suspension
Mesenchymal cells
Cell adhesion force
Hyaluronic acid
Polyethylene glycol

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Created: Thu, 29 May 2014, 19:23:49 EST by Mr Benoit Maisonneuve on behalf of University of Queensland Graduate School