3D PRINTING AND PATTERNING VASCULATURE IN ENGINEERED TISSUES - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 167

oxygen can be delivered ( Yannas et al., 1982 ). However, precise spatial control of scaffold architecture
is not easily achieved with these methodologies ( Harley et al., 2010 ).
Soft lithography, a suite of techniques adapted from the microprocessor industry, offered spatial
control of scaffold architecture through photopatterning with photolithography. With these technologies
of patterning and then replica molding patterns into silicone substrates, detailed studies could be con-
ducted at the cell-material interface ( Whitesides et al., 2001; Kane et al., 1999 ). Early soft lithography
and photolithography work involved fabricating substrates with grooves and microbeds surfaces, and
chemical modifications to the substrate surface, to study cell adhesion, migration, and proliferation
( Truskett and Watts, 2006 ). These approaches generally resulted in planar scaffolds to elucidate
topological effects on cell behavior.
To control the cellular microenvironment in a more 3D fashion, Vozzi et al. developed macroporous
scaffolds out of poly(dimethylsiloxane) (PDMS) templates which were cast into poly(L-lactic-co-glycolic
acid) (PLGA) multilayer scaffolds ( Figure 8.1 ) ( Vozzi et al., 2003 ). Fabrication of macroporous
scaffolds containing living cells was investigated by Liu et al. by combining tissue engineering with
photolithographic methods ( Liu and Bhatia, 2002 ). An apparatus was designed in which the prepolymer
solution was injected into a chamber, with specified height controlled by spacer thickness, and then a
mask was placed on top of the chamber and exposed to UV light ( Figure 8.1 ). Multilayered hydrogel
FIGURE 8.1
Patterned macroporous scaffolds can be fabricated by various methods. (A) Top: Micromachined masters can
be replica-molded into multilayered microfluidic devices. Bottom: Single-layered and multilayered 3D PLGA
scaffolds. Scale bars = 200 m m; figure adapted from Vozzi et al . (2003) . (B) Top: Methodology for additive
photopatterning with physical photomasks to fabricate cell-laden hydrogels with macroscale features. Bottom:
Fluorescent images of photopatterned cell-laden hydrogels with various macroscale patterns. Scale bar = 500 m m;
figure adapted from Liu Tsang et al . (2007) . (C) Top: Dynamic photomasking with a computer-controlled digital
mirror projection stereolithography system can be used to engineer multilayered structures in a highly automated
fashion. Bottom: Cell infiltration of a 3D hexagonal printed scaffold over the course of 4 days. Scale bar = 100 m m;
figure adapted from Gauvin et al. (2012) .