On the rheology of red blood cell suspensions with different amounts of dextran: separating the effect of aggregation and increase in viscosity of the suspending phase

Flormann, Daniel; Schirra, Katharina; Podgorski, Thomas; Wagner, Christian

doi:10.1007/s00397-015-0882-7

Cited by 20 publications

(22 citation statements)

References 21 publications

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“…Recently, the rheology of concentrated suspensions of cells, similar to concentrations found in therapeutic formulations for cell therapy, has been investigated (Maisonneuve, Roux, Thorn, & Cooper-White, 2013;Maisonneuve, Roux, Thorn, & Cooper-White, 2015;Shi et al, 1993). In addition, the effects of particle dynamics have been shown to have a large effect on the rheology of blood (Fedosov et al, 2014;Flormann, Schirra, Podgorski, & Wagner, 2016;Windberger, Pöschl, Peters, Huber, & van den Hoven, 2017). The effect of hematocrit, analogous to cell density in cultures, and serum on the rheological characterization of blood has been investigated (Chien, Usami, Dellenback, & Gregersen, 1970;Chien, Usami, Taylor, Lundberg, & Gregersen, 1966).…”

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“…The effect of hematocrit, analogous to cell density in cultures, and serum on the rheological characterization of blood has been investigated (Chien, Usami, Dellenback, & Gregersen, 1970;Chien, Usami, Taylor, Lundberg, & Gregersen, 1966). In addition, the effects of particle dynamics have been shown to have a large effect on the rheology of blood (Fedosov et al, 2014;Flormann, Schirra, Podgorski, & Wagner, 2016;Windberger, Pöschl, Peters, Huber, & van den Hoven, 2017). As a fluid comprising densely concentrated cells, blood behaves in a similar manner to concentrated cell suspensions, but the behavior of dilute cell suspensions commonly found in bioreactors cannot be predicted this way, as dilute regimes of particulate suspensions behave differently than concentrated suspensions (Mueller et al, 1995).…”

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Non‐Newtonian rheology in suspension cell cultures significantly impacts bioreactor shear stress quantification

Wyma

Martin-Alarcon

Walsh

et al. 2018

Biotech & Bioengineering

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The fields of regenerative medicine and tissue engineering require large-scale manufacturing of stem cells for both therapy and recombinant protein production, which is often achieved by culturing cells in stirred suspension bioreactors. The rheology of cell suspensions cultured in stirred suspension bioreactors is critical to cell growth and protein production, as elevated exposure to shear stress has been linked to changes in growth kinetics and genetic expression for many common cell types. Currently, little is understood on the rheology of cell suspensions cultured in stirred suspension bioreactors. In this study, we present the impact of three common cell culture parameters, serum content, cell presence, and culture age, on the rheology of a model cell line cultured in stirred suspension bioreactors. The results reveal that cultures containing cells, serum, or combinations thereof are highly shear thinning, whereas conditioned and unconditioned culture medium without serum are both Newtonian. Non-Newtonian viscosity was modeled using a Sisko model, which provided insight on structural mechanisms driving the rheological behavior of these cell suspensions. A comparison of shear stress estimated by using Newtonian and Sisko relationships demonstrated that assuming Newtonian viscosity underpredicts both mean and maximum shear stress in stirred suspension bioreactors. Non-Newtonian viscosity models reported maximum shear stresses exceeding those required to induce changes in genetic expression in common cell types, whereas Newtonian models did not. These findings indicate that traditional shear stress quantification of cell or serum suspensions is inadequate and that shear stress quantification methods based on non-Newtonian viscosity must be developed to accurately quantify shear stress.

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confidence: 99%

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confidence: 99%

Non‐Newtonian rheology in suspension cell cultures significantly impacts bioreactor shear stress quantification

Wyma

Martin-Alarcon

Walsh

et al. 2018

Biotech & Bioengineering

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“…Dextran has been previously reported to interact with the RBC membrane at larger concentration of dextran (>10 mg mL -1 ). [24][25][26] The homogeneous color and intensity of the liposomes, however, indicate that the molecules are homogenously distributed within the liposomes (within the resolution limit of the microscope).…”

Section: Liposome Characterization and Encapsulation Of Moleculesmentioning

confidence: 99%

Hybrid Erythrocyte Liposomes: Functionalized Red Blood Cell Membranes for Molecule Encapsulation

et al. 2020

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The modification of erythrocyte membrane properties provides a new tool towards improved drug delivery and biomedical applications. The fabrication of hybrid erythrocyte liposomes is presented by doping red blood cell membranes with synthetic lipid molecules of different classes (PC, PS, PG) and different degrees of saturation (14:0, 16:0–18:1). The respective solubility limits are determined, and material properties of the hybrid liposomes are studied by a combination of X‐ray diffraction, epi‐fluorescent microscopy, dynamic light scattering (DLS), Zeta potential, UV‐vis spectroscopy, and Molecular Dynamics (MD) simulations. Membrane thickness and lipid orientation can be tuned through the addition of phosphatidylcholine lipids. The hybrid membranes can be fluorescently labelled by incorporating Texas‐red DHPE, and their charge modified by incorporating phosphatidylserine and phosphatidylglycerol. By using fluorescein labeled dextran as an example, it is demonstrated that small molecules can be encapsulated into these hybrid liposomes.

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“…Another evident to the rheological behavior of blood flow due to extensional stresses was found by Down et al [37] and Sousa et al, [38] while the latter has exhibited nonlinear viscoelastic behavior, such as the viscous component dominated over the elastic component. Some applications of blood rheological elastic part can be found in Campo-Deaño et al [39] Particularly, the tremendous effect of the nonlinear viscosity on the RBC non-Newtonian fluid behavior was demonstrated by Flormann et al [40] Advanced analytic and experimental models of blood and other rheological fluids have been proposed recently by [41][42][43]. However, those models are not fully completed and limited by geometry (flat plate [41] ) or being semi-empirical without a complete analytical model.…”

Section: Introductionmentioning

confidence: 99%

A parametric investigation of blood flow in a wedge with non‐uniform viscosity and wall friction

Nagler

2019

Z Angew Math Mech

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The radial planar wedge pattern flow with friction and normalized non-uniform viscosity function will be discussed here. Solving this problem will be done using the flow theory equations for Newtonian and Non-Newtonian cases with non-uniform viscosity assumption. General differential equation that connects between the normalized velocity profile and the normalized viscosity has been derived analytically from the flow equations. It was found that for specific wedge semi angle, the radial assumption is no longer valid for the flow velocity. Moreover, it was found that for inlet/outlet conditions the normalized mean hydrostatic pressure for Newtonian fluid is dependent on the geometry, the normalized velocity and the viscosity functions. In addition, it was found that inertia phenomenon can be neglected for small wedge semi angle. A comparison between the axial and the hydrostatic pressure distributions for inlet/outlet conditions was performed for Newtonian and non-Newtonian flows. Finally, it was found that the axial pressure distribution profile was converged to the hydrostatic profile for critical wedge semi angle. K E Y W O R D Sblood flow, hydrostatic pressure difference, non-linear viscosity, non-Newtonian fluid, viscosity, wedge

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On the rheology of red blood cell suspensions with different amounts of dextran: separating the effect of aggregation and increase in viscosity of the suspending phase

Abstract: International audienc

Cited by 20 publications

References 21 publications

Non‐Newtonian rheology in suspension cell cultures significantly impacts bioreactor shear stress quantification

Non‐Newtonian rheology in suspension cell cultures significantly impacts bioreactor shear stress quantification

Hybrid Erythrocyte Liposomes: Functionalized Red Blood Cell Membranes for Molecule Encapsulation

A parametric investigation of blood flow in a wedge with non‐uniform viscosity and wall friction

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