NANOTECHNOLOGY AND 3D BIOPRINTING FOR NEURAL TISSUE REGENERATION - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 313

14.3 3D BIOPRINTING FOR NEURAL TISSUE REGENERATION
3D bioprinting is achieving great popularity in tissue engineering as a means of fabricating customized
3D cellular tissue constructs. The outstanding advantage of 3D bioprinting techniques is their capacity
to directly produce complex tissue scaffolds with precise spatial distribution and biomimetic architec-
ture. These techniques can be classified into two categories: scaffold printing and cell or cell-containing
material printing.
14.3.1 3D BIOPRINTING NEURAL SCAFFOLDS
Photolithography and ink-jet bioprinting are two popular 3D bioprinting techniques for the manufacture
of neural scaffolds. Shepherd et al. fabricated 3D poly(2-hydroxyethyl methacrylate) (pHEMA) neural
scaffolds via photolithography ( Shepherd et al., 2011 ). In the study, a photopolymerizable hydrogel ink
composed of branched pHEMA chains, HEMA monomer, comonomer, photoinitiator, and water was
prepared. The ink was deposited and cross-linked under UV radiation to form a 3D interpenetrating
hydrogel network for primary rat hippocampal neuron growth. Results showed scaffold architecture
can be controlled precisely and the structure influenced both cell distribution and aligned extension of
neurons. In addition, Melissinaki et al. explored a photocurable biodegradable PLA-based resin and
fabricated scaffolds via a direct laser writing method ( Melissinaki et al., 2011 ). They conjugated pho-
tocurable methacrylate groups to PLA resin and cross-linked using a femtosecond Ti:sapphire laser.
Resultant porous scaffolds displayed a maximum resolution of 800 nm and enabled guided neuronal
growth. In our lab, we have developed a novel 3D printed nanonerve scaffold through the integration
of conductive graphene nanobiomaterials with 3D stereolithography ( Figure 14.9 ). Our results have
shown that the construct with graphene nanoplatelets has very good cytocompatibility properties. In ad-
dition, the graphene nanoplatelets can greatly improve the conductivity of the scaffold, which make the
conductive scaffold promising for neural regeneration. Ink-jet printing is another convenient tech-
nique to create patterned polymeric structures for the promotion of desired cellular behavior. This
technique can readily deposit cell adhesive biomaterials in a precise pattern to guide neural cell growth.
A study by Sanjana et al. revealed ink-jet-printed collagen/poly-D-lysine (PDL) on a poly(ethylene)
glycol surface can support rat hippocampal neurons and glial growth in defined patterns when com-
pared to collagen/PDL absent regions (Sanjana and Fuller, 2004). With the advancement of molecular
biology and development of novel cell-favorable factors, biomimetic nanomaterials could be printed
on a traditional scaffolds' surface to obtain more cell-favorable features. Moreover, 3D bioprinting has
also provided a means for the incorporation of electrically conductive materials within neural scaf-
folds. Weng et al. ink-jet-printed PPy/collagen scaffolds and incorporated electrical stimulation into the
system ( Weng et al., 2012 ). In this study, PPy and collagen were microstructured on polyarylate film
by ink-jet printing for electrical stimulation of a spatially controlled system. The PPy/collagen track
was illustrated to guide PC-12 adherence and growth, while electrical stimulation showed the ability to
promote neurite outgrowth and orientation ( Figure 14.10 ).
14.3.2 3D BIOPRINTING CELLS FOR NEURAL APPLICATIONS
In addition to the aforementioned 3D scaffold printing technologies, there is also great interest in 3D
bioprinting neural cells and other native cells in precise spatial distribution for neural applications.
Figure 14.11 shows several important 3D cell bioprinting systems, including laser-based writing,