NANOTECHNOLOGY AND 3D BIOPRINTING FOR NEURAL TISSUE REGENERATION - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 302

ily influenced by environmental alterations, such as pH, temperature, ionic strength, presence of spe-
cific solutes, and mechanical and electrical stimulation ( Xu and Kopeˇek, 2007 ). These alterations
trigger multiple noncovalent interactions, including hydrogen bonding, electrostatic association, and
van der Waals forces which drive the formation of self-assembling structures ( Stephanopoulos et
al., 2013 ). Natural tissue ECM is composed of various nanostructured components that can spontane-
ously self-assemble. Therefore, the use of biomimetic self-assembling nanobiomaterials holds high
potential in stimulating cell functions and new tissue formation ( Zhang and Webster, 2009; Hauser and
Zhang, 2010 ). In the following, we will discuss several self-assembling peptides used for neural tissue
engineering. In addition, other self-assembling nanomaterials such as self-assembly bacteriophage and
emerging self-assembling nanotubes will be introduced as well.
Peptide amphiphiles are one of the most popular biological molecules for the fabrication of
self-assembling nanobiomaterials. Peptides containing both a hydrophilic and hydrophobic moiety have
been shown to readily self-assemble into nanofibers wherein the hydrophilic component forms the outer
layer and the hydrophobic component is directed toward the core ( Yang et al., 2009 ). They are much
more tractable and scalable when compared to complex biomolecules such as proteins. Particularly,
b -sheet-forming peptides exhibit the unique capability of assembling into one-dimensional nanostruc-
tures via the formation of intermolecular hydrogen bonding ( Lock et al., 2013 ). These one-dimensional
nanostructures could be used as building blocks to construct complex 3D networks. In addition, these
peptide amphiphiles can be readily modified for enhanced biocompatibility and biodegradability
through selecting specific amino acid sequences or controlling over their self-assembling structures
( Maude et al., 2013; Cui et al., 2010 ).
Self-assembling peptide nanofibrous scaffolds (SAPNS) have been used to regenerate PNS and
CNS (brain and spinal cord) both in vitro and in vivo . Zhan et al. reported a novel nanofibrous con-
duit comprised of a blood vessel and filled with RADA16-I (Ac-RADARADARADARADA-CONH 2 )
SAPNS to repair a 10 mm transection in a rat sciatic nerve ( Zhan et al., 2013 ) ( Figure 14.2 ). Com-
pared to a blood vessel only control, the SAPNS-incorporated graft enabled peripheral axons to bridge
the 10 mm gap as well as significantly enhance motor neuron protection, axonal regeneration, and
remylination. The functional recovery illustrates the great potential of SAPNS-based conduits for the
regeneration of peripheral nerve defects. In another work, Liang et al. successfully accelerated brain
tissue regeneration via a novel SAPNS assembled by RADA4 (arginine-alanine-aspartic acid-alanine)
peptide placed upon a cortical gray matter lesion ( Liang et al., 2011 ). Combined with noninvasive man-
ganese-enhanced magnetic resonance imaging, the chronic optic tract lesion displayed regeneration
of axons leading to near-complete repair and return to function. In addition, Ellis-Behnke et al. used
RADA16-I SAPNS to create a permissive environment for brain injury regeneration ( Ellis-Behnke
et al., 2006 ). Their experiments showed peptide scaffolds have the capacity to direct axons to reconnect
to target tissues and return the function of vision using a severed optic tract model in hamsters. Guo
et al. investigated the capacity of RADA16-I SAPNS to repair spinal cord injuries ( Guo et al., 2007 ).
In their study, neural progenitor cells and Schwann cells were isolated from rats and implanted into
the transected dorsal column of the spinal cord after culturing with SAPNS. Results showed host cells
migrated well in SAPNS, blood vessels grew, and the spinal cord lesion was further bridged.
In addition to preassembled SAPNS scaffolds, peptides could be directly injected into injured sites
and self-assembled in vivo . This specific feature makes them an appealing material for the treatment of
SCIs. Once liquid self-assembling peptides are injected into the lesions, they will fill the void, regard-
less of the shape and size, and assemble into a hydrogel. The direct contact between peptides and ECM