IMMOBILIZATION OF ANTIMICROBIAL PEPTIDES

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Each year, 850,000 cases of implant-related infections occur in the United States. Infection of catheters, orthopedic and dental prostheses, vascular grafts and valves, pacemaker leads, breast implants, and cerebrospinal fluid shunts can lead to re-operation, amputation, or death. The infectious organisms are either iatrogenically introduced during implantation or introduced post-surgery through septicemic routes. Administration of antibiotics is often an ineffective treatment; prevention is the most promising approach to decreasing device-associated septicemia. One approach to preventing bacterial colonization is by attaching antimicrobial agents to the device prior to implantation. During the Phase I project, we successfully derivatized, purified, and covalently immobilized antimicrobial peptides to model support matrices and performed preliminary assessments of the retained microbial activities. Proof-of-concept for this project was demonstrated by preparing modified surfaces that resist colonization of infectious organisms, as tested in vitro. In Phase II, we plan to optimize the chemistry and further explore the microbicidal activity of model substrate materials in vitro. In addition, a supplementary method for retardation of bacterial colonization involving a slow release mechanism of peptide will be explored. Bacterial colonization and toxicity testing will be performed on modified materials in vitro; toxicity and efficacy studies will be conducted in vivo.