Biomedical Engineering Reference
In-Depth Information
astrocytes, and oligodendrocytes with clear neuritis while also exhibiting comparable biocompatibility
and expression of neural markers with cells cultured on poly-L-ornithine, one of the most popular
substrates for neural stem cells.
14.2.3
ELECTROSPUN POLYMERIC NANOFIBROUS NEURAL SCAFFOLD
In order to repair a complex neural network, guided neurite outgrowth is required toward the synaptic
targets with spatially distributed cell populations placed into a specific pattern (
Xie et al., 2009a
).
Aligned nanofibrous scaffolds can provide patterned cues to achieve this goal. Over the past decade,
the development of innovative nanofibrous scaffolds has greatly enhanced the involvement of polymers
in neural regeneration. Among various nanofibrous scaffold fabrication techniques, electrospinning has
been widely investigated for neural tissue regeneration due to its versatility in implementing a variety
of synthetic and natural polymeric biomaterials for the creation of highly aligned fibrous scaffolds.
These scaffolds have shown promising results due to their structural similarity to fibrous proteins found
in native ECM thus facilitating the outgrowth of neurites (
Dahlin et al., 2011; Ma et al., 2005
).
Electrospinning can be easily tailored by altering polymeric solutions and processing parameters
to fabricate scaffolds with varying mechanical and biological properties, as well as fiber and gross
scaffold morphology (
Sill and von Recum, 2008
;
Theron et al., 2004; Vasita and Katti, 2006
). More
than 100 types of natural and synthetic polymers have been employed in electrospinning for vari-
ous tissue engineering applications (
Burger et al., 2006
). Biodegradable polyesters, including poly-
caprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and poly(lactic acid) (PLA) are the most
popular synthetic polymers currently used for neural tissue engineering applications (
Table 14.1
).
These polymers can be easily tailored for specific mechanical properties and topography by altering
the fiber diameter which can range from nano- to microscale for improved cell response (
Keun Kwon
et al., 2005; Kumbar et al., 2008
). Studies have demonstrated the effects of fiber diameter on neu-
ral stem cell proliferation and differentiation. Christopherson et al. investigated hippocampus-derived
adult neural stem cell response to laminin-coated electrospun polyethersulfone meshes with various
fiber diameters (283 ± 45 nm, 749 ± 153 nm and 1452 ± 312 nm) (
Christopherson et al., 2009
). They
found cells exhibited a trend of improved proliferation and spreading, and reduced aggregation with
deceasing fiber diameter. In addition to fiber diameter, another topographical cue, fiber orientation, has
been shown to play a critical role in neural regeneration. Oriented fibers can serve to guide neurite ex-
tension to target injured tissues or organs. Xie et al. examined the neurite outgrowth of primary dorsal
root ganglia on electrospun PCL nanofibers with varied fiber orientation, structure, and surface proper-
ties (
Xie et al., 2009a
). They found neurites illustrated radial distribution when cultured on randomly
oriented nanofibers. A parallel array of aligned nanofibers, by contrast, guided neurite extension along
the direction of the nanofiber. Interestingly, when cultured at the border between aligned and random
nanofibers, the same dorsal root ganglia exhibited neurite outgrowth in response to the underlying
aligned and randomly oriented nanofibers, respectively (
Figures 14.7
A-B
). In order to achieve further
improved cytocompatibility, synthetic polymers can be co-electrospun with natural polymers such as
chitosan, fibrin, and collagen or integrated with self-assembling nanobiomaterials that mimic natural
ECM chemistry. In a study by Gelain et al., a novel neural guidance channel was fabricated by com-
bining electrospun nanofibers and self-assembling peptides (
Figures 14.7
C-E
) (
Gelain et al., 2011
).
Self-assembling peptide RADA16-I-BMHP1 (Ac-RADARADARADARADAGGPFSSTKT- CONH
2
)
was assembled into PLGA/PCL blended electrospun microchannels followed by implantation within
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