Host defense peptides represent a promising new approach to inhibit infection. The anti -infective actions of these peptides are primarily due to their immunomodulatory effects. Since they regulate multiple aspects of the mammalian immune system, host defense peptides are also less likely to induce bacterial resistance than are traditional antibiotics. The local delivery of anti-bacterial agents allows for both high local concentrations to increase efficacy and low systemic levels to reduce toxicity. A promising strategy for the local delivery of anti-bacterial agents is to bind them directly to the surfaces of orthopaedic implants. The progress in the second year of this project has demonstrated: 1. Development of a quantitative and reproducible murine model of orthopaedic implant infection. 2. Preliminary results indicate that the soluble host defense peptide reduces orthopaedic implant infection in the murine model. 3. Preliminary results indicate that the soluble host defense peptides increases osseointegration in mice that were not inoculated with bacteria. The host defense peptides have the potential to substantially reduce infections of fractures sustained on the battlefield and in civilian settings. If the synthetic peptide reduces infections in the studies proposed in this application, more extensive pre-clinical testing would precisely determine its potential benefits and risks and determine whether the peptide is a high priority for human trials.
