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Moreover, chitosan carrier loaded with neurotrophin 3 (NT-3) pro-
vided an ideal environment for adhesion, proliferation, and differentiation
of NSCs ( Yang, Duan, Mo, Qiao, & Li, 2010 ).
NSCs seeded in fibrin scaffolds within a chitosan channel, containing
PLGA microspheres releasing dibutyryl cyclic-AMP, differentiate in vitro
to b -III-tubulin positive neurons providing further confirmation of chitosan
scaffold biocompatibility ( Kim, Zahir, Tator, & Shoichet, 2011 ).
Yet, scaffolds made of chitin, chitosan, and gelatin with pore geometry of
inverted colloidal crystals have been successfully used to guide the differen-
tiation of iPS cells into neurons ( Kuo & Lin, 2013 ).
Finally, hADSCs have been successfully transdifferentiated from mesen-
chymal into the neural lineage onto a chitosan-coated surface ( Hsueh,
Chiang, Wu, & Lin, 2012 ). hADSCs are a subset of multipotent mesenchy-
mal stem cells with less ethical conflict and minimal invasive surgical proce-
dure to obtain cells and can thus be tentatively proposed as agents for
promoting nerve regeneration in patients.
NEPs are NSCs with multipotentiality for neuronal and glial differentia-
tion. NEPs have been reported to adhere and grow on chitosan fibers. More-
over, they could differentiate into neurons and glia ( Fang et al., 2010 ). This
study demonstrated that chitosan fibers have good biocompatibility
with NEPs.
2.3. Chitosan surface modification
Improving nerve cell affinity for chitosan is a key issue for improving its
effectiveness for neural regeneration ( Dhiman, Ray, & Panda, 2004;
Haipeng et al., 2000; Zhu, Gao, He, Liu, & Shen, 2003; Zielinski &
Aebischer, 1994 ). Combining chitosan with poly- L -lysine, laminin, laminin
peptide, or collagen may increase cell adhesion, growth, and viability.
Blending chitosan with poly- L -lysine improved PC12 cell affinity in
comparison with chitosan and chitosan-collagen films as demonstrated
by increasing attachment, growth, and differentiation into nerve cells.
The increased cell affinity might be due to both the increased surface charge
and hydrophilicity of composite materials ( Mingyu et al., 2004 ).
Another study also reported that poly- L -lysine-, collagen-, or albumin-
blended chitosan exhibit better nerve cell affinity, neurite outgrowth, and
proliferation of PC12 and fetal mouse celebral cortex cells than original
chitosan ( Cheng, Cao, et al., 2003 ).
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