Biomedical Engineering Reference
In-Depth Information
24.3.4
Fluid Dynamics and Mass Transfer
In the majority of current tissue engineering applications, diffu-
sion governs the primary means of mass transport, bringing gases,
nutrients, proteins, cells, and waste products into and/or out of
the constructs.
113
While this might be su
cient for survival, func-
tional parameters can be improved in some applications by incor-
porating some forms of fluid flow. Consider the limitation of large,
cellular spheroids with diameter more than 1 mm, which are gener-
ally organized into viable cells on the rim that surround a hypoxic,
necrotic center.
114
The presence of fluid flow in the form of shear
stress, as well as interstitial flow within tissue engineering con-
structs, is important in two ways. Firstly, the flow-induced stresses
itself, at physiological values, promotes good cellular organization
and function, as previously described, and secondly, fluid flow facil-
itates mass transfer of oxygen and soluble nutrients and removal
of waste products. Scaffold porosity determines the magnitude of
shear stresses experienced by cells. Porosity along with surface
charges also factor into the mass transport properties of a scaffold.
Besides steric hindrance, it is important to consider the interac-
tion between the scaffold and charged nutrients, as repulsive forces
could prevent nutrients to access cells, while attractive forces could
sequester a large pool of nutrients to the scaffold itself.
113
One way
topreciselycontrolmicroscaleflowprofilesistoutilizemicrofluidic
systems where fluid is applied through small 1-100
μ
m channels to
2D or3D cellular constructs cultured within the system.
57
Endothelial cells plated in a monolayer within a macrofluidic
device and subject to laminar shear stress produce angiogenic
sprouts within collagen I gels whose invasion distance was pro-
portional to the magnitude of shear stress.
115
Interstitial flow
causes hepatocytes to aggregate and form a functional mass
116
and
induces interconnected tube formation of endothelial cells cultured
in natural and synthetic gels.
111
In terms of mass transfer prop-
erties, a perfusion culture of hepatocytes has been shown to dra-
matically improve functional activity, such as albumin secretion
and urea genesis rates, as well as morphological stability, includ-
ing tight junctions, glycogen storage, and bile canaliculi.
117
Vari-
ous methods can be used to overcome mass-transfer limitations
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