Inhibition of Orthopaedic Implant Infections by Immunomodulatory Effects of Host Defense Peptides

The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. Public reporting burden for this c ollection of information is esti mated to average 1 hour per res ponse, including the time for reviewing instruc tions, searching existing data sources, gathering and mai ntaini ng the data needed, and completing and reviewing this collecti on of information. Send c omments regarding this burden esti mate or an y other as pect of this c ollection of information, including suggestions for reducing this burden to Department of Defense, Washi ngton H eadquarters Ser vices, Directorate for Information Operations and R eports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. R espondents should be awar e that notwithstandi ng any other provision of law, no pers on s hall be s ubject to any penalty for failing to c ompl y with a coll ection of infor mati on if it does not di splay a currentl y valid OMB c ontrol number. 14. ABSTRACT-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 ort hopaedic 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 …