Biomedical Engineering Reference
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can be caused by a magnetic stir bar, a shaft impeller, or a pendulum which is
usually pulled through the fluid by magnetic attraction on a stir plate, causing
continuous mixing in the culture vessel. Throughout the media volume, this
stirring provides a nearly homogenous mixture for oxygen and nutrients,
although the velocity of the fluid varies drastically around the vessel. This results
in variable shear stresses for immobilized constructs, possibly reaching relatively
high shear forces at the surface of a construct. The hydrodynamics of the system
are conditions of turbulent mixing, characterized by eddies at the surface of
constructs, improving nutrient transport into a porous scaffold [12]. However, it
has been shown that this improved transport may not reach into the core of a
construct, leaving diffusion as the main mechanism of transport beyond the outer
edges [39].
2.2.2.
Rotating vessel bioreactor
One of the more popular bioreactor designs involves inducing fluid flow by
rotation of the culture vessel, as with the rotating wall vessel (RWV). The RWV
bioreactor was originally developed by National Aeronautics and Space
Administration (NASA) scientists in order to study the effects of microgravity
upon tissues and cells while on the gravity of earth [40, 41]. They were later used
to promote three-dimensional cell growth without the presence of damaging high
shear forces experienced in spinner flask cultures. The violent forces involved
with other seeding and culture methods such as shaker and spinner flasks do not
always allow adequate attachment interactions between cell and polymer. The
basic design includes one inner, static, gas-permeable cylinder which is
surrounded by a larger, rotating, impermeable cylinder. The cell culture medium
and the culturing constructs are located in the annular region. This design allows
gas exchange through the inner cylinder while the rotating outer cylinder
provides the force needed to generate the mostly laminar fluid flow [42]. This
design allows for the scaffolds near the outer edge to experience a very narrow
range of shear forces, though there is a very low velocity area at the inner
cylinder. The RWV can be a much more consistent method of dynamic cell
culture, as it has been reported that the hydrodynamic culture conditions are
fairly homogenous [43].
Media exchange can also occur through a modified design, the rotating wall
perfused vessel bioreactor (RWPV), which includes both a rotational inner
cylinder and a disk limiting perfusion inlet to the region nearest the outer
cylinder's wall. The rate of fluid perfusion seems to have little effect on the mean
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