Peptide surface modification of methacrylamide chitosan for neural tissue engineering applications

Abstract

Nerve fibres are guided to their targets by the combined actions of chemotactic and haptotactic stimuli; however, translating these stimuli to a scaffold that will promote nerve regeneration is nontrivial. In pursuit of this goal, we synthesized and characterized cell-adhesive, biodegradable chitosan scaffolds. Chitosan amine groups were reacted with methacrylic anhydride resulting in a water soluble methacrylamide chitosan (MC) that was then crosslinked by radical polymerization resulting in a scaffold. Biodegradability by lysozyme and penetrability of the scaffold by rat superior cervical ganglion (SCG) neurons were studied. Maleimide-terminated cell adhesive peptides, mi-GDPGYIGSR and mi-GQASSIKVAV, were coupled to a thiolated form of MC to promote cell adhesion. The MC scaffold was found to be porous, biodegradable, and to allow neurite penetration. Interestingly, all of these properties were found to depend upon the amount of initiator used in crosslinking. Covalent modification of the MC scaffold with cell adhesive peptides significantly improved neuronal adhesion and neurite outgrowth. The MC can be crosslinked to form a novel scaffold, where our results demonstrate its suitability in neural tissue engineering and its potential for other engineered tissues, such as cartilage repair, where chitosan has already demonstrated some utility.

Neural ECM mimetics

“…The manipulation of chitosan and the resulting degree of deacetylation have been reported to influence the adhesion and migration behavior of cells on the surface of the matrix (Chatelet et al, 2001). However, the growth-promoting effects of chitosan scaffolds can be further enhanced via the introduction of functionalized groups or combination with growth factors Cheng et al, 2007;Goraltchouk et al, 2006;Nomura et al, 2008;Yu et al, 2007).…”

DNA gel particles: An overview

“…In many applications, it is important to control their degradation rates, which is usually achieved by incorporating hydrolytically or enzymatically cleavable groups into the polymer structure [16][17][18][19][20][21][22][23]. Biodegradable polymer constructs can also be prepared via reversible physical cross-linking, where the degradation rates depend on the strength of electrostatic, hydrophobic, or hydrogen bonding interactions [24][25][26][27].…”

The Use of Chitosan-Based Scaffolds to Enhance Regeneration in the Nervous System

“…When neurons are plated on a chitosan film characterized by distinct immobilized NGFpatterned areas surrounded by unmodified chitosan, remained as single spread cells in the NGFpatterned region and formed clusters resulting in lower cell survival in the unmodified chitosan areas. Moreover, the immobilized NGF induces axonal sprouting compared with the unmodified chitosan (Yu, Wosnick, & Shoichet, 2008). Finally, a recent study showed that photo-cross-linkable streptavidinmodified methacrylamide chitosan 3D hydrogel, along with the recombinant biotininterferon-g promotes neuronal differentiation of neuronal stem/progenitor cells (NSPCs, Leipzig, Wylie, Kim, & Shoichet, 2011).…”