Biology Reference
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delivery systems, wound-healing agents, lung surfactant additives, and tissue
engineering scaffolds for tissue regeneration of skin, bone, and cartilage
( Drury & Mooney, 2003; Gan & Wang, 2007; Janes, Fresneau, Marazuela,
Fabra, & Alonso, 2001; Madihally & Matthew, 1999; Roy, Mao, Huang, &
Leong, 1999; Suh & Matthew, 2000; Ueno et al., 1999; Yuan, Zhang,
Yang,Wang, &Gu, 2004; Zuo et al., 2006 ). Yet, chitosan is a versatilematerial
currently used in clinical wound dressings, primarily for its hemostatic property
( Gustafson, Fulkerson, Bildfell, Aguilera, & Hazzard, 2007 ).
Another important application of chitosan is the development of drug
delivery systems such as nanoparticles, hydrogels, microspheres, films, and
tablets. The abundance of primary amine groups enables chitosan to be
ionically or covalently coupled to various biomolecules because the amine
moieties become predominantly protonated and positively charged below
pH 6.5, whereas they are increasingly deprotonated at pH 6.5 and above.
As a result of its cationic character, chitosan is able to react with polyanion
giving rise to polyelectrolyte complexes ( Acosta, Aranaz, Peniche, & Heras,
2003 ; Peniche, Arguelles-Monal, Peniche, & Acosta, 2003 ).
Moreover, due to its positive charge, chitosan can interact with negative
molecules such as DNA. This property has been used to prepare a nonviral
vector gene delivery system ( Mumper, Wang, Claspell, & Rolland, 1995 ).
Among the different tissue organs, many studies have investigated the use
of chitosan for repair, not only because of its biocompatibility, biodegradabil-
ity, low toxicity, and cost but also because of its excellent potential for
supporting three-dimensional organization of regenerating tissues ( Evans
et al., 1999; Ho et al., 2005; Ma et al., 2003; Madihally & Matthew, 1999;
Novikova, Novikov, & Kellerth, 2003; Vasconcelos & Gay-Escoda, 2000 ).
Here, we review the main chitosan-based bioengineering strategies for
peripheral nerve and spinal cord injury (SCI) repair. This review has been
divided into the following sections: in the first part, we report in vitro studies
on the evaluation of chitosan properties, the second and the third parts cover
in vivo studies for spinal cord and peripheral nerve repairs, respectively.
2. IN VITRO EVIDENCE: CHITOSAN PROPERTIES,
BIOCOMPATIBILITY, AND SURFACE MODIFICATION
2.1. Chitosan physical properties
2.1.1 Mechanical strength
Chitosan matrices have been shown to have low mechanical strength under
physiological conditions ( Itoh et al., 2003; Madihally &Matthew, 1999 ) and
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