Microfluidic Devices for Quantifying the Role of Soluble Gradients in Early Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 64

in vitro mimic of diseased tissue for the development of novel interventions, such
as engineered growth factors [ 91 ] and gene delivery strategies [ 92 ]. These
mechanistic studies are expected to help elucidate the complex etiology and
possible treatments of vascular disease.
6 Conclusion
Restricted-flow microfluidic devices are ideal for performing quantitative, reduc-
tive, and systematic studies on the role of soluble gradients in sprouting morpho-
genesis. By allowing a diffusion gradient to form across a cell culture chamber that
is shielded from convective flow, these devices create stable concentration profiles
that both avoid shear-activation of endothelial cells and are independent of culture
substrate and dimensionality. In addition, these devices enable gradient-mediated
anisotropic signaling to influence cultured cells over indefinite time periods,
thereby allowing time-lapse observation of cellular behavior over multiple days.
Current use of the devices has focused on (1) the quantitative, reductionist evalu-
ation of VEGF concentration requirements for 2D chemotaxis, (2) the interplay
between 3D matrix microenvironment and VEGF gradient signaling, and (3) the
identification of novel regulators of organ-specific angiogenesis. Future applica-
tions of the device may include optimization of multiple soluble gradients to
enhance their angiogenic potential in regenerative medicine therapies, high-
throughput screening of pro-angiogenic biomaterials for tissue engineering appli-
cations, and mechanistic studies of chronic ischemia and tumor vascularization.
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