Peptide surface modification of methacrylamide chitosan for neural tissue engineering applications

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.