Microfluidic Devices for Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 105

A

B (a)

(b)

(c) (d)

(b)

C

(a) (c)

Fig. 4 Microfluidic assays for angiogenesis: A Developed microfluidic system. Left A
photograph of a 2-channel system (top and bottom) with a gel region in between. Right
Fluorescent image showing the sprouting of new vessels into the hydrogel from the endothelial
monolayer seen at the top of the image [ 35 ]—Reproduced by permission of The Royal Society of
Chemistry. B A system in which ECs and fibroblasts are co-seeded in the gel region and form a
microvascular plexus. (a) Schematic representation of the microfluidic system with gel regions
(red) and media channels (cyan). Gel channels are each 400 lm wide and are supported by
hexagonal posts, 100 lm in diameter. (b) Side view of the device showing the relative positions
of the polymerized hydrogels and the media channels (1.5 mm wide). (c) Phase-contrast image
(day 14) of a primitive capillary plexus. Scale bar = 100 lm. (d) Collapsed z-stack of confocal
images showing a 3D projection of the structures [ 89 ]—Reprinted with permission of John Wiley
and Sons. C (a) Schematic of the microfluidic chip shown assembled by connecting a vacuum to
the outer network of channels. (b) Assembly of the system. A liquid gel solution is introduced to
the chamber. Then the biological sample is added. Finally, the flow channel plugs are removed
and the device is assembled. (c) Embryonic kidney stimulated with a gradient of VEGFA, FGF2,
and VEGFC for 48 h showing the asymmetric sprouting of microvessels. [ 88 ]—Reproduced by
permission of The Royal Society of Chemistry

introduced to the side channels after attaching the coverslip, lining the channel
walls including the lateral face of the collagen. Seeded in this way, growth factors
introduced either uniformly or as a gradient were shown to control vascular
sprouting into the gel [ 35 ]. A major advantage of this system was the capability to
image sprout formation in real-time, with sprouts growing approximately in the
imaging plane. This enabled high resolution imaging of vascular sprouts that could
grow several hundred microns in length over just a 24 h period [ 35 ]. In other