S-Nitrosothiol-Modified Chitosan Oligosaccharides with Self-Triggered NO Release for Wound Healing (2013)

Undergraduates: Anand Shah, Yuan Lu

Faculty Advisor: Mark Schoenfisch
Department: Business Administration

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Chitosan oligosaccharides were functionalized by either 2-iminothiolane hydrochloride or 3-acetamido-4,4-dimethylthietan-2-one to produce primary or tertiary thiol-modified chitosan oligosaccharides, respectively. The free thiols on the chitosan oligosaccharides were then nitrosated to yield S-nitrosothiol NO donors. The primary and tertiary S-nitrosothiol-modified chitosan oligosaccharide (CSO-SNO) have a total NO storage of 300 ¿ 14 and 350 ¿ 25 nmol/mg, respectively. NO release was initiated by light radiation and heat. Photo initiated NO release yielded similar total NO release of ~76 nmol/mg for both chitosan, while thermal initiated release resulted in the tertiary CSO-SNO having double the total release of the primary CSO-SNO. In both instances, the primary CSO-SNO proved to be more stable as indicated by a slower release profile. The wound healing application of CSO-SNO was evaluated through a study of mouse fibroblast proliferation and migration in vitro. The effects of the NO releasing chitosan oligosaccharides were dependent on scaffold concentration and NO-release kinetics. The CSO-SNOs exhibited an enhanced effect in stimulating cell migration and proliferation compared to the controls. The primary CSO-SNO had an optimal effect at 500 ¿g/mL for both proliferation and migration, as compared to 750 and 500 ¿g/mL, respectively, for the tertiary CSO-SNO.