139injury site, increased the neuronal differentiation of NPSCs, and enhanced neurite
outgrowth [ 262 ]. In a separate study, IKVAVA SAPs were demonstrated to inhibit glial
scar formation and promote axon elongation in a murine model of SCI [ 263 ]. SAPs
were administered 24 h after dorsoventral compression, and signifi cant reductions in
astrogliosis were observed in IKVAVA treated groups as compared to non-bioactive
molecule treated groups [ 263 ]. Tysseling et al. observed that IKVAV peptide amphi-
phile (PA) injection promoted plasticity in serotonergic fi bers, axon growth, and
reduced the glial scar in rat contusion and mouse compression models of spinal cord
injury [ 263 , 264 ]. These fi ndings may be due to the extremely high density of the
IKVAV epitope within the scaffold (almost 10^3 greater than laminin) and differences
in IKVAV versus laminin signaling mechanisms, though these suggestions require
continued investigation to fully elucidate [ 262 , 264 ]. Another study investigating
RADA16-I functionalized SAPs found that not only did RADA16-I groups support
attachment and differentiation of NPSCs in vitro and in vivo , but also served to bridge
the injured spinal cord of rats after in vivo transplantation [ 265 ].
7.6.2 Nanofi bers for Neuroregeneration
Nanofi bers are porous networked fi ber structures with individual fi ber diameter of
less than 1 μm that mimic the architecture of the ECM. The high surface area to
volume ratio and extraordinary mechanical strength make nanofi bers excellent
materials for neuroregeneration applications. Compared to traditional biomaterials,
nanofi bers have the advantages of topography and porosity that mimic the naturally
occurring extracellular matrix. Additionally, they exhibit excellent biocompatibility
with low immunogenicity and are endowed with properties that help to bridge the
lesion gap in transection injuries. Therefore, nanofi bers serve as effective delivery
systems for cellular grafts and/or therapeutic drugs. The major processing tech-
niques available to produce nanofi bers are electrospinning [ 266 ], molecular self-
assembly [ 267 ], drawing out [ 268 ], and catalytic synthesis [ 269 ]. Electrospinning
and self-assembling nanofi bers are the most studied techniques for developing scaf-
folds for neural tissue engineering.
One of the major benefi ts of electrospinning is the ability to control fi ber align-ment, which has been shown to signifi cantly impact neurite outgrowth, cellular
proliferation, and cell fate. Parallel-aligned nanofi bers have yielded increased rates
of NPSC differentiation and neurite outgrowth along the direction of fi ber orienta-
tion as compared to randomly orientated fi bers from both MSCs and human embry-
onic stem cell (hESC)-derived NPSCs [ 270 – 272 ]. Similar studies demonstrated
oriented neurite outgrowth and glial migration from dorsal root ganglia explants on
a collagen/poly-ɛ-caprolactone blend and on poly- L -lactate electrospun scaffolds
[ 270 , 273 ]. Topographic alignment also affects cell phenotype. Specifi cally,
Mahairaki et al. observed a signifi cant increase in neuronal differentiation and neu-
rite outgrowth in mouse embryonic stem cells [ 274 ]. In addition to spatial orienta-
tion, other physical properties of nanofi bers, like nanofi ber diameter and patterns,
7 Regenerative Strategies for the Central Nervous System