The Use of Chitosan-Based Scaffolds to Enhance Regeneration in the Nervous System - International Review of Neurobiology - page 6

to be unable to maintain a predefined shape for transplantation, which has
initially limited their use as nerve guidance conduits (NGC; Freier,
Montenegro, Koh, & Shoichet, 2005; Itoh, Suzuki, et al., 2003; Itoh
et al., 2003; Yamaguchi, Itoh, Suzuki, Osaka, & Tanaka, 2003 ).
To improve chitosan mechanical properties, Ao et al. (2006) used a novel
mold and thermally induced phase-separation technique with a unidirec-
tional temperature gradient to produce chitosan conduits containing longi-
tudinally aligned microfibers. This preparation method may allow the
incorporation of therapeutic agents into the matrix for sustained release,
as no toxic substances have been used ( Ao et al., 2006 ). In vitro characteri-
zation using Neuro-2a-cells verified that the mold-based multimicrotubule
chitosan conduit had suitable mechanical strength, microtubule diameter
distribution, porosity, swelling, biodegradability, and nerve cell affinity,
for applications in nerve tissue engineering ( Ao et al., 2006 ).
A novel method to create porous tubular chitosan scaffolds with desirable
mechanical proprieties and controllable inner structure has been developed
by Wang et al. (2006) . Inner matrix, with multiple axially oriented
macrochannels and radially interconnected micropores, was produced using
acupuncture needles as mandrel during the molding process ( Wang et al.,
2006 ). In vitro characterization demonstrated that the scaffolds possessed suit-
able mechanical (porosity, swelling, and biodegradability) and biological
(differentiated Neuro-2a cells grew along the oriented macrochannels)
properties for applications in nerve tissue engineering ( Wang et al.,
2006 ). However, these scaffolds have a lowmechanical strength under phys-
iological conditions, thus limiting their applicability. In order to increase
mechanical strength, chitosan conduits have been reinforced with additives
( Yang et al., 2004 ) or cross-linked with chemical substances such as form-
aldehyde ( Wang et al., 2005 ).
Recently, a mold-casting/lyophilization method was used to fabricate
porous chitosan nerve conduits; however, these conduits still have a low
mechanical strength under physiological conditions. The porous structure
of the chitosan conduit was reinforced by introducing braided chitosan
fibers, leading to an increase in tensile strength ( Wang et al., 2007 ). These
conduits were permeable to molecules ranging in molecular size from 180 to
66,200 Da ( Wang et al., 2007 ). Moreover, in vitro direct contact cytotoxicity
test, using Neuro-2a cells, showed that the conduits were not cytotoxic
( Wang et al., 2007 ).
While chitosan has low mechanical strength under physiological con-
ditions ( Madihally & Matthew, 1999; Yamaguchi et al., 2003; Yang