Biomedical Engineering Reference
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blood vessels observed in the regenerating skin. The AFS treatment resulted in larger, mature vessels
that strongly stained for SMA and was found to contain RBCs inside the vasculature in the regenerating
skin. However, the authors noted that since the cells in the printed patch remained at the wound surface,
they did not migrate into the underlying tissue, thus indicating that the printed cells did not permanent-
ly integrate with the host tissue. In addition to patches, geometrically defined endothelial cords were
developed and transplanted into mice by Baranski et al. (
Baranski et al., 2013
). Endothelialized cords
were micropatterned using a PDMS mold and then transplanted to mice after the cords were polymer-
ized between fibrin layers, encasing the cords. Indeed, formation of blood vessels, which were large
and poorly organized on day 3 but remodeled into smaller, lumenized capillaries as early as 7 days,
was evident in implanted endothelialized cords (
Figure 8.3
D). Additionally, the authors demonstrated
that the cellular organization of the cords was vital for the vascularization response of the implant due
to the presence of blood and vessels throughout the length of the cords. Anastomosis of neovessels
was verified by perfusion studies and imaging of colabeled capillaries, which indicated the presence of
chimeric composition of host and implanted cells in some vessels. The authors also developed endo-
thelialized cords containing hepatocyte aggregates to demonstrate that the encapsulated cells exhibited
enhanced hepatic function due to enhanced vascular supply as a result of neovessels formation along
the tissue constructs.
8.1.7
ADVANCED TECHNOLOGIES WHICH MAY ASSIST IN VASCULAR TISSUE
FABRICATION
Although much has been accomplished to fabricate 3D constructs with multiscale vasculature, 3D
bioprinting technologies will need to advance to become more rapid, and achieve high throughput and
resolution for translational purposes. Additionally, further techniques may need to be developed to
pattern complex biochemical and biomechanical patterns within scaffolds to better mimic the
in vivo
environment.
To significantly increase the throughput in 3D bioprinting technology, Hansen et al. developed a
method involving microvascular multinozzle print heads for printing of planar and multilayered ar-
chitectures composed of single and multicomponent materials (
Hansen et al., 2013
). The multinozzle
print heads are obtained by patterning a bifurcating network into a clear acrylic substrate using CNC
machining, solvent-welding the patterned substrate to a flat acrylic substrate, resulting in a monolithic
block that contains the embedded microvascular network. The authors were able to fabricate nozzle
heads consisting of six branching generations, where each channel width and depth is 200
m
m. The
authors also demonstrated that their design is scalable for large-area, rapid fabrication of planar and 3D
functional microarchitectures with microscale features. They also validated uniform ink-flow within
the fabricated microvascular print heads to achieve high-fidelity, reproducible printed features. Fur-
ther work for creating rapid vascularized, heterogeneous tissue constructs was also demonstrated by
the same group by developing a custom-designed, large-area 3D bioprinter with four independently
controlled print heads (
Kolesky et al., 2014
). These print heads contain inks consisting of cells and an
aqueous fugitive ink that was removed from the final tissue construct. The authors showed the ability to
print multiple cell types in the fabricated constructs, which are subsequently embedded in a pure Gel-
MA matrix. 1D microchannel arrays were printed with final diameters ranging from 100
m
m to 1 mm.
Engineered construct channels were seeded with endothelial cells, and after 2 days, high viability of
cells as well as assembly into a nearly confluent layer were observed (
Figure 8.2
G).
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