MICRO-AND NANOTECHNOLOGY FOR VASCULAR TISSUE ENGINEERING - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 248

tissue engineering applications (Fig. 11.2c). The Stroock group later demonstrated
the ability to fabricate these gels in the presence of cells and maintain their
viability. 95 Capitalizing on the microfluidic channels and permeability of the
gels, the group demonstrated supreme spatial and temporal control of both large
and small solutes. Additionally, multiple independent networks could be used as
sources or sinks to establish and sustain concentration gradients within the con-
structs. It has been shown that many angiogenic processes are enhanced or even
dependent on the presence of concentration gradients. These seminal studies
established a basis for growth, and recently microfluidic and microfabrication
approaches have been extended into a variety of hydrogel and 3D tissue engineering
constructs. 96-101

11.6.4 Micropatterning

Patterning microchannels into scaffolds has been proposed as an attractive mecha-
nism to drive vascular formation and infiltration deep within a construct. Bryant
et al. created porous poly(hydroxyethylmethacrylate) (polyHEMA) scaffolds with
patterned channels between 200 and 500 m using photo-patterning techniques. 96

In this work, a photomask was used to block UV irradiation of a polymer precursor
solution, which could be washed away from masked regions after irradiation.
However, construct thickness is limited by the relatively shallow penetration of
conventional UV patterning techniques. Other limitations of this approach include
detrimental effects from exposure of cells to UV light and solvents. Another study
from the Ratner laboratory showed the fabrication of a porous poly(HEMA)-co-
(methacrylic acid) scaffold with channels by using sacrificial polycarbonate fibers
embedded within the construct upon initial polymerization. 97 The fibers were
dissolved afterward, leaving parallel channels of the diameter of the fiber, which
allows for precise control of the diameter and spacing of the channels, with uniform
properties throughout the depth of the scaffold. Scaffolds with 60 m m channels
were implanted into rat myocardium for 4 weeks and found to enhance the
neovascular response. By perfusing the rats before sacrifice, the group demon-
strated functional vessels throughout the scaffold that successfully inosculated with
the host. Additionally, SMCs were found surrounding ECs, suggesting mature
vasculature had formed.
The Stroock group sought to transition to materials that could be remodeled by
cells because they are more usable in tissue engineering applications. Collagen gels
were selected because they would allow adhesion, proliferation, and modification by
ECs. The group chose to use dense collagen gels to achieve superior mechanical
properties without altering the structure or function of collagen. Micromolding was
used to create patterned channels within the gels and could be successfully
performed on gel concentrations as low as 0.3%. 98 Again, diffusion of large
macromolecules (dextran 70 kDa) was shown. HUVECs that were seeded onto
the channels showed attachment and the ability to remodel the matrix through either
displacement or degradation. Tube formation was evident within 3 days, and
networks grew over time. Finally, the study demonstrated that HUVECs could

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