Microfluidic Devices for Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 106

B

(a)

(b) (c)

A

(d)

Lumen
structure

D

(a) (b) (c) (d)

C

(e) (f) (g) (h) (i)

Fig. 5 Types of invasion into the gel: A 2D capillary morphogenesis in the collagen treated
channel and C 3D sprouting into the gel. B (a)-(d) confocal micrographs showing branched
structures with lumens formed by migration of cells along the bottom of the gel region that
eventually close to form patent lumens across the gel. Scale bar = 250 lm[ 35 ]—Reproduced by
permission of The Royal Society of Chemistry,[ 139 ]—Reprinted with permission of John Wiley
and Sons. D Microvascular endothelial cells sprout to form capillary-like structures. (a)-(i)
Sequence of images demonstrating capillary formation and the initiation of lumen formation
[ 35 ]—Reproduced by permission of The Royal Society of Chemistry

experiments, the cells were seeded either individually in the gel or along the 2D
surface of the coverslip. New capabilities demonstrated in these studies were the
generation of flow either in the media channels or across the gel itself, creating an
interstitial flow. Two types of vascular structures were observed; in one, the
endothelial cells invaded into the gel along the surface of the coverslip, but
eventually folded around to form closed and empty lumens which were demon-
strated to be patent by both confocal microscopy and the flow of microbeads.
An alternative method is to add gel-filling channels to the system that permit the
introduction of gel after bonding the coverslip by plasma treatment [ 90 ]. These
systems were used in multiple investigations. In one, the effect of device coating
was studied [ 91 ]. It had been observed that the endothelial monolayer would often
adhere to and migrate along the walls of the microfluidic device, or that con-
traction of cell-seeded gels would cause gaps to appear between the gel and the
device walls, especially if the gel concentration was low (Fig. 5 A, B) [ 35 ]. Two
methods were found to mitigate this tendency, either to increase the gel stiffness or
to increase the adhesion of the gel to the device surface by an initial coating of