Biomedical Engineering Reference
In-Depth Information
Fig. 1 Schematic of three
physiological processes that
can be modeled using
microfluidic devices. When
exposed to a soluble gradient
for a period of days or weeks,
vascular endothelial cells
polarize, angiogenic sprouts
pathfind, and pericytes home.
Spatiotemporally consistent,
quantitatively predictable
gradients within 3D culture
matrices are required to
reproducibly recapitulate
these processes in vitro
1 Motivation: Understanding Vascular Development
In the cellular microenvironment, a soluble gradient is a vector quantity whose
direction and magnitude reflect the greatest spatial rate of change in a soluble
factor's concentration. Vascular endothelial cells respond to three aspects of the
concentration field: the gradient direction, the gradient steepness, and the mag-
nitude of concentration. These multiple inputs play an essential role in regulating
angiogenesis, enabling the development of functional microvasculature by polar-
izing endothelial cells [
1
], guiding sprouts [
2
], and recruiting perivascular cells [
3
]
(Fig.
1
). Strategies to engineer blood vessels, including controlled delivery of
soluble factors [
4
] and use of micro-patterned [
5
] and multivariate biomaterials
[
6
], demand a quantitative, multifactorial understanding of signaling by soluble
gradients.
Microfluidic devices that support specified, substrate-independent, and stable
soluble gradients meet this critical need. First, the user's ability to specify a given
concentration profile enables quantitative screening of chemotactic factors and
decoupling of concentration magnitude from gradient steepness, parameters that
can elicit distinct cell behaviors (Fig.
2
)[
7
,
8
]. Second, the gradient's substrate
independence allows for reductive studies on the role of matrix properties in
chemotaxis. The extracellular matrix affects cellular morphology [
9
], proliferation
[
10
], migration [
11
], and specialization [
12
], impacting a cell's capacity to
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