Controlling the Degradation of Covalently Cross-linked Carboxymethyl Chitosan Utilizing Bimodal Molecular Weight Distribution

Degradability is often a critical property of materials utilized in tissue engineering. Although chitosan, a naturally derived polysaccharide, is an attractive material due to its biocompatibility and ability to form scaffolds, its slow and uncontrollable rate of degradation can be an undesirable feature. In this study, we characterize chitosan derivatives formed using a combination of carboxymethylation and a bimodal molecular weight distribution. Specifically, chitosan is carboxymethylated to a theoretical extent of ~30% as described in our previous work, in which carboxyl groups possessing negative charges are created at a physiological pH. Carboxymethyl chitosan is used to form films and constructs by varying the ratio of high to low molecular weight (MW) while maintaining the mechanical properties of the polymer. The rate of degradation is found to be dependent upon both the carboxymethylation and the ratio of high to low MW polymer, as determined by dry weight loss in lysozyme solution in PBS. Subsequently, biocompatibility is examined to determine the effects of these modifications upon Neuro-2a cells cultured on these films. Neuro-2a cells adher and proliferate on the modified films at a comparable rate to those cultured on unmodified films. This data indicates that these chitosan derivatives exhibit tunable degradation rates and result in a promising material system for neural tissue engineering.