Application of Chitosan-Based Biomaterials in Tissue Engineering - Chitosan Based Hydrogels: Functions and Applications - page 445

by increasing the attachment, differentiation, and growth of the nerve cells. The improved
nerve cell affinity for the chitosan-poly(l-lysine) composite materials had been attributed
to the increased hydrophilicity by the abundant hydroxyl group and the positive surface
charge of chitosan [183]. The inner surface of artificial nerve conduits is expected to serve
for regenerating nerves. However, recent research found that the nerve tissue regenerates
not directly attached to the conduits surface but rather in a fibrin matrix scaffold inside the
conduits. While laminin (an 800 kDa glycoprotein from the basement membrane) can aid
nerve growth, synthetic laminin peptides were preferred in studies intended to facilitate
nerve regeneration in vivo with the aid of chitosan conduits covalently coated with the said
peptides. Laminin associating with the inner surface of the conduits may be favorable for
the attachment and migration of Schwann cells and growth cones [184]. Itoh and cowork-
ers [185] coupled laminin on the inner surface of chitosan conduits to support nerve regen-
eration on the inner surface of chitosan conduits. In particular, glial cell line-derived nerve
growth factor and laminin were blended with chitosan to fabricate factor + lami-
nin + chitosan guides, which can enhance both functional and sensory recovery [186].
The main drawback of using poly(l-lysine), fibronectin, and laminin is their high cost.
Therefore, nerve guides are currently being fabricated by adding certain proteins that
support nerve repair and regeneration, and by optimizing the biological properties of a
nerve guide. The addition of collagen to the chitosan network has an effect on the quality
of nerve repair compared with using the chitosan material alone. The chitosan-collagen
nerve conduits have a smooth inner and outer surface texture. The chitosan-collagen
conduits scaffold exhibits better physical and chemical properties at the quantity ratio of
chitosan to collagen of 3:1 [187]. Chitosan-collagen composites provide a better environ-
ment to support the survival, migration, proliferation, and differentiation of neural stem
cells and their differentiating cells. And the differentiating percentage from neural stem
cells into neurons was significantly increased compared with pure chitosan [188]. Compared
with pure chitosan, collagen-chitosan conduits improved the axonal maturation measured
by a significant increase in axon diameter and axon area [189]. Moreover, the chitosan-
collagen conduits enhanced motor and sensory nerve recovery [190]. Wei et al. [191] evalu-
ated a chitosan-collagen film as a nerve wrap conduit to repair completely resected sciatic
nerve. Histological analysis revealed nerve regeneration at 8 weeks post surgery using the
10 mm conduits. Ciardelli and Chiono [192] found that chitosan-gelatin can also promote
nerve regeneration.
Collapse of an unfilled circular conduit is a major block to nerve regeneration in tubuli-
zation. Chitosan conduits can be molded into various configurations, which make them
effective in enhancing nerve regeneration. Itoh et al. [193] prepared circular and triangular
chitosan tubes via melting molding for nerve regeneration ( cf. Figure 9.35) . After implant-
ing in a nerve defect of rat, some of the circular tubes somewhat narrowed with time, and
nerve regeneration occurred toward one side. However, the volume for regenerating nerves
in a triangular tube was rather preserved, and the nerve tissue equally distributed in the
tube. This may be ascribed to its (a) superior mechanical property, (b) preservation of the
space for nerve regeneration, and (c) contact phase enlargement between the tube surface
and penetrating cells from the nerve ends.
However, the application of chitosan-based conduits prepared using melting molding
is subject to certain restrictions owing to the low porosity and low permeability, which
hinders the inflow of nutrients through the conduit walls. Porous and fiber chitosan-based
conduits can overcome these disadvantages. Gander and coworkers [182] prepared porous
chitosan-alginate conduits ( cf. Figure 9.36). These have a good permeability for solutes and
adequate mechanical strength. Recently, bilayered fiber chitosan conduits comprising an