The Use of Chitosan-Based Scaffolds to Enhance Regeneration in the Nervous System - International Review of Neurobiology - page 9

Finally, the use of cross-linking agents such as hexamethylene
diisocyanate (HDI), epichlorohydrin (ECH), and glutaraldehyde (GA)
may also result in significant decrease in degradation rate compared with
noncross-linked chitosan ( Cao et al., 2005 ).
2.2. Chitosan biocompatibility
Biocompatibility properties of chitin and chitosan depend on the sample
characteristics such as natural source, preparation method, Mw, and DD.
In particular, residual proteins, in chitin and chitosan, derived from produc-
tion methods could cause allergic reactions such as hypersensitivity. Bio-
compatibility is an important issue in the choice of a biomaterial for
peripheral nerve regeneration or SCI repair.
In vitro studies have shown that chitosan exerts biomimetic in the periph-
eral nervous system, allowing neuronal adhesion, differentiation, and
growth ( Cheng, Cao, et al., 2003; Yang et al., 2004 ). Different blends of
chitosan and gelatin cross-linked with genipin allow cell adhesion and pro-
liferation of NIH3T3 mouse fibroblasts and S5Y5 neuroblastoma cells.
Cross-linked samples were found to be biocompatible in particular blends
containing 8% gelatin supporting very well neuroblastoma cell adhesion
and proliferation ( Chiono et al., 2008 ). Among different blends of chitosan
with polyacrylamide, ethyl acrylate, and hydroxyethyl acrylate, chitosan,
poly(methyl acrylate), and 50% (w/w) blends of ethyl acrylate and hydroxy-
ethyl acrylate were the most suitable polymers to promote in vitro cell adhe-
sion and differentiation of neural explants from the medial ganglionic
eminence and the cortical ventricular zone of embryonic rat brains ( Soria
et al., 2006 ).
Polymeric biomaterial composite of chitin, chitosan, and gelatin, with a
pore geometry of inverted colloidal crystals, induced pluripotent stem (iPS)
cell adhesion and proliferation and has the potential to guide and accelerate
differentiation of iPS cells toward a neuron phenotype ( Kuo & Lin, 2013 ).
It has been also shown that rat pheochromocytoma cell line (PC12),
grown on chitosan-gelatin-fibronectin-composed films, differentiates more
rapidly and extends longer neurite than on pure chitosan films ( Cheng,
Deng, et al., 2003 ).
Another study reported that the blending of chitosan with poly-
caprolactone (PCL) increased cell viability and redistribution of actin cyto-
skeletal fibers of mouse embryonic fibroblasts cultured in vitro ( Sarasam &
Madihally, 2005 ).