The goal of this proposal is to develop nitric oxide releasing dendrimers to inhibit biofilm based periodontopathogens and associated periodontal disease. The rationale for pursuing this work is based on nitric oxide's broad spectrum antimicrobial activity, rapid diffusion through biofilms, short half-life (thus imparting local acton) and physiological role in the immune response to pathogens. The use of a macromolecular NO release scaffold enables us to maximize bactericidal activity while minimizing the cytotoxic impact on healthy oral cells and tissue. We will study the influence of dendrimer size/molecular weight, charge, exterior functionality, and NO release properties on pathogenic plaque bacteria killing. We will systematically study both dendrimer and nitric oxide penetration into in vitro models of oral plaque biofilms as a function of biofilm composition, maturity and mass. An established murine model for periodontal infection will be employed to evaluate how dendrimer composition and nitric oxide release influence inflammation, host immune response, and biofilm eradication.
The goal of this proposal is to study the efficacy of exogenous nitric oxide derived from dendrimers to prevent and treat periodontal disease. Our hypothesis is that localized nitric oxide delivery to periodontal pockets will significantly reduce microbial burden and eradicate dental plaque biofilms that cause periodontal disease. In addition to evaluating anti-biofilm utility and cytotoxicity, we will study the associated physiological response to dendrimers and nitric oxide in an established murine model of infection that mimics the subgingival biofilms characteristic of periodontal disease.
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|Suchyta, Dakota J; Soto, Robert J; Schoenfisch, Mark H (2017) Selective monophosphorylation of chitosan via phosphorus oxychloride. Polym Chem 8:2552-2558|
|Backlund, Christopher J; Worley, Brittany V; Schoenfisch, Mark H (2016) Anti-biofilm action of nitric oxide-releasing alkyl-modified poly(amidoamine) dendrimers against Streptococcus mutans. Acta Biomater 29:198-205|
|Backlund, C J; Worley, B V; Sergesketter, A R et al. (2015) Kinetic-dependent Killing of Oral Pathogens with Nitric Oxide. J Dent Res 94:1092-8|