NANOTECHNOLOGY AND 3D BIOPRINTING FOR NEURAL TISSUE REGENERATION - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 300

on the action potential produced at the synapse. Electrical conductivity of scaffolds can thereby
promote neurite outgrowth and nerve regeneration; (iv) suitable mechanical properties, the scaf-
folds must not increase tension in the lesion site or collapse during regular movement; and (v)
porous interconnectivity, a porous structure which mimics the extracellular matrix (ECM) of native
tissue allowing for good spatial distribution of cells and exchange of nutrients and waste ( Cunha
et al., 2011 ; Subramanian et al., 2009 ). Additionally, it is encouraged to incorporate morphological
and chemical features for improved axonal guidance of the tissue in an effort to bridge discontinu-
ous injuries and facilitate nerve regeneration. Figure 14.1 illustrates the key features that an ideal
neural scaffold should have and several typical tissue-engineered neural scaffolds for CNS and PNS
nerve regeneration.
In order to achieve maximum axonal regeneration and functional recovery in the CNS, it is also
necessary to inhibit scar tissue formation after injury, prevent discontinuity during phagocytosis
of dying cells, and guarantee adult neuron viability for initial axonal extension ( Ellis-Behnke
et al., 2006 ). Researchers have begun to utilize nanotechnology (such as nanomaterials and 3D
nanofabrication techniques) to address these obstacles and improve cell proliferation, migration,
and differentiation in various biomimetic scaffolds ( Kim et al., 2014; Malarkey et al., 2009;
Matson and Stupp, 2011; Saito et al., 2009; Wei et al., 2013; Zhang et al., 2005; Ellis-Behnke
et al., 2006 ). In particular, biologically inspired nanomaterials exhibiting similar dimensions with
tissue ECM can facilitate neural cell growth and guided neural tissue regeneration ( Zhang and
Webster, 2009 ). For instance, carbon-based nanomaterials are extensively investigated in neural
regeneration due to their outstanding electrical conductivity, excellent mechanical strength, and
modifiable surface chemistry ( Hu et al., 2004 ). In addition, nanotechnology in tissue engineering
readily involves the fabrication of 3D nanostructured scaffolds for improved tissue regeneration
( Saracino et al., 2013 ). Currently, two of the widely used nanofabrication techniques typically
include self-assembling and electrospinning ( Cunha et al., 2011 ). The bottom-up self-assembly
process commonly refers to the spontaneous formation of a scaffold from specific nanoscale am-
phipathic molecules while electrospinning utilizes biocompatible polymeric materials to fabricate
nanofibrous scaffolds. All of these nanostructured scaffolds have illustrated promising results in
bridging injured gaps and recovering nerve function ( Cao et al., 2009; Iwasaki et al., 2014; Panseri
et al., 2008; Xie et al., 2010 ).
Although conventional 3D nano/microscaffold fabrication approaches have yielded favorable ef-
fects in repairing nerve injures, intrinsic limitations exist with regards to adequate control of scaffold
outer shape and internal architecture. To circumvent this problem, 3D bioprinting has garnered greater
attention in the production of 3D scaffolds with exact spatial distribution and microstructural cues
( Schmidt and Leach, 2003 ). It allows for the printing of viable cells, bioactive factors, and biomateri-
als individually or in tandem, layer-by-layer, resulting in complex tissue substitutes with controlled
shape and structure based on predesigned models ( Ozbolat and Yu, 2013 ). Furthermore, the capacity
of 3D bioprinting to manufacture patient-specific scaffolds renders it superior to other traditional 3D
tissue manufacturing techniques with rapidly growing interest in the neural tissue engineering field.
This chapter provides an overview of the cutting-edge 3D bioprinting and nanotechnology strate-
gies for nerve regeneration. We will focus on (i) recent development of novel nanomaterials, in-
cluding self-assembling nanomaterials, carbon-based nanomaterials, and conventional biomaterials
for nanoneural scaffold design; and (ii) 3D bioprinting techniques for the fabrication of customized
neural scaffolds.