Biomedical Engineering Reference
In-Depth Information
ridges (resulting in skin that is extremely sensitive to shear and a hairless “shiny” appearance
that deeply concerns the patient), this work ofers hope for improved skin and hair replacement
therapies.
7.1.3 Vasculature on a Chip
For tissue-engineered organs to function properly, researchers must devise methods to design
or grow capillary networks that will allow for the delivery of blood to the organs. A team led by
Donald Ingber at Children's Hospital in Boston has shown that microvascular endothelial cells
cultured on 10-μm lines of adhesive ibronectin (surrounded by nonadhesive PEG-thiol SAM)
form tubelike structures (
Figure 7.8
). he confocal sectioned image of the cells clearly shows a
hollow lumen inside. he same cells cultured on 30-μm lines, on the other hand, spread as rib-
bons and do not form a hollow lumen.
A large collaborative team led by Joseph Vacanti (MIT), Robert Langer (MIT), and Yadong
Wang (Georgia Tech) were able to produce endothelialized capillary networks within molded
microchannels made of
poly(glycerol sebacate) (PGS)
. PGS is a transparent biodegradable elas-
tomer that replicates following a procedure very similar to that of PDMS, although with lower
resolution (
Figure 7.9
). To produce an enclosed PGS device, the molded PGS side containing
grooves was capped with a half-cured PGS lat cap, and the assembled device was cured over-
night (a similar procedure works for bonding PDMS). To enhance cell adhesion, the devices were
modiied with the pentapeptide Glycine Serine Rarginine Daspartic acid (GRGDS) (although
endothelial cells adhered to PGS too). he capillary networks were endothelialized to conluence
and were perfused up to 4 weeks at physiological low rates without leakage, thus opening the
way for organlike devices that contain their own, predesigned vasculature.
For certain applications, it may be more physiological to directly create the starting matrix in
an ECM protein such as
collagen
. Abraham Stroock's group at Cornell University has produced
microluidic devices that are micromolded in collagen (
Figure 7.10a
), which are then seeded
with human umbilical vein endothelial cells (
HUVECs
). he cells were found to endothelial-
ize the device (
Figure 7.10b
), that is, they completely covered the collagen walls and formed an
impermeable lumen that could be perfused without leakage.
10 µm lines
30 µm lines
Substrate
Substrate
FIGURE 7.8
Microengineered. endothelial. cell. tubules.. (From. Laura. E.. Dike,. Christopher. S.. Chen,.
Milan.Mrksich,.Joe.Tien,.George.M..Whitesides,.and.Donald.E..Ingber,.“Geometric.control.of.switching.
between.growth,.apoptosis,.and.differentiation.during.angiogenesis.using.micropatterned.substrates,”.
In Vitro Cell. Dev. Biol. Anim
.,.35,.441-448,.1999..Reprinted.with.permission.from.Springer..Figure.
contributed.by.George.Whitesides.)
