Microfluidic Devices for Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 95

Current applications for microfluidic devices span multiple disciplines, with
applications in biotechnology and biochemical processing [ 27 ]; clinical and forensic
analysis [ 28 ]; combinatorial chemistry [ 29 ]; systems biology [ 30 ]; tissue
engineering [ 31 ], cell-based biosensors [ 32 ]; diagnostics and personalized medicine
[ 33 ]; and embryo production [ 34 ]. The biology community has greatly benefited
from these advances, and progress in microfabrication technologies has paved the
way for new approaches to manipulate and observe cells in microenvironments that
more closely mimic in vivo conditions. Microfluidic-based cell culture systems
provide new capabilities for continuous monitoring of dynamic processes, such as
angiogenesis, at high spatial and temporal resolution in a controlled microenvi-
ronment [ 35 ].
2 The Biology of Angiogenesis and Endothelial Cell
Chemotaxis
2.1 Angiogenesis in Development
Although the processes by which microvascular networks form are described in
detail in other chapters, a brief background is useful as motivation for in vitro
studies in microfluidics to follow. The embryonic vasculature is formed by two
distinct processes, vasculogenesis—the de novo vessel formation from endothelial
progenitors, angioblasts—and angiogenesis—the expansion of a pre-existing
vascular network which occurs during the later stages of development. Interest-
ingly, these two processes of vascularization occur in distinct embryonic regions
which are defined by the three germ layers: ectoderm, mesoderm and endoderm.
Vasculogenesis, which gives rise to the primitive vascular plexus, occurs in tissue
of a splanchnopleural origin (includes endoderm and splanchnopleural mesoderm),
while angiogenesis predominantly occurs in tissues of a somatopleural origin
(ectoderm and somatopleural mesoderm) [ 36 ]. Here, in keeping with most of the
existing microfluidic literature, we mainly focus on angiogenesis.
2.2 The Pathways of Angiogenic Sprouting and Network
Formation
Angiogenesis is a complex, multi-step process involving a series of well delineated
steps. Once endothelial cells have acquired an angiogenic phenotype, the fol-
lowing processes occur: (a) protease production increases facilitating degradation
of basement membrane; (b) directional cues initiate migration towards the
angiogenic stimulus; (c) proliferation; (d) tube formation; and (e) maturation. The
regulatory chemical signals produced at the onset of and during angiogenesis