Microfluidic Devices for Quantifying the Role of Soluble Gradients in Early Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 45

Microfluidic Devices for Quantifying
the Role of Soluble Gradients in Early
Angiogenesis

Patrick Benitez and Sarah Heilshorn

Abstract Early angiogenesis, as defined by endothelial polarization and directional
sprouting, is regulated by gradients of soluble factors in addition to a multitude of
other anisotropic cues including interstitial flow, insoluble gradients, and topography
of the extracellular matrix (ECM). Adding to this complexity, other microenviron-
mental inputs, such as matrix density and rigidity, are known to modulate the extent
to which vascular endothelial cells react to these anisotropic cues. Given this
complexity, novel platforms are needed to decouple and systematically assess
signals regulating early angiogenesis. To this end, we discuss a microfluidic device
that achieves stable, matrix-independent soluble gradients via passive diffusion,
which shields the culture chamber from shear-induced anisotropy. These devices
enable direct time-lapse imaging of single cell and collective cell phenomena within
both two-dimensional (2D) and three-dimensional (3D) cultures. These experi-
mental platforms have been used to quantify the growth factor concentration
requirements that induce endothelial cell chemotaxis, to identify previously
unknown regulators of brain angiogenesis, to screen biomaterials for their angio-
genic potential, and to investigate the navigational ability of nascent sprouts.

P. Benitez
Department of Bioengineering, Stanford University, 476 Lomita Mall,
McCullough Room 246, Stanford, CA 94305-4045, USA
S. Heilshorn (

)
Department of Materials Science and Engineering, Stanford University, 476 Lomita Mall,
McCullough Room 246, Stanford, CA 94305-4045, USA
e-mail: [e-mail]

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