IMMOBILIZATION OF ANTIMICROBIAL PEPTIDES

PROSTHETIC DEVICES ARE ROUTINELY IMPLANTED IN PATIENTS; HOWEVER, AN ESTIMATED 850,000 CASES OF IMPLANTATION INFECTIONS OCCUR IN THE UNITED STATES EACH YEAR. THE INFECTIOUS ORGANISMS ARE MOST LIKELY TO BE INTRODUCED AT THETIME OF SURGERY. CURRENTLY, INFECTIONS RESULTING FROM IMPLANTATION ARE TREATED AS THEY OCCUR; HOWEVER, PREVENTION IS THE MOST PROMISING APPROACH TO DECREASING DEVICE-ASSOCIATED SEPTICEMIA. ONE LIKELY METHOD OF IMPEDINGTHE ATTACHMENT AND SUBSEQUENT GROWTH OF PATHOGENS IS TO COATIMPLANTABLE MATERIALS WITH ANTIMICROBIALS. IN THIS PHASE I EFFORT, IT IS PLANNED TO COVALENTLY COUPLE WIDE-SPECTRUM ANTIMICROBIALS (MAGAININS) TO MODEL INERT SURFACES. THE MAGAININS ARE WELL-STUDIED PEPTIDES THAT ACT BY LYSING PATHOGENS AT THE CELL WALL AND CAN THEREFORE BE ACTIVE EVEN WHEN IMMOBILIZED; I.E., THEY DO NOT NEED TO BE INTERNALIZED. THE ANTICIPATED RESULTS FROM THIS PHASE I PROJECT WILL DEMONSTRATE THE FEASIBILITY OF COVALENTLY COUPLING MAGAININS TO PRODUCE ANTIMICROBIAL SURFACES. DURING PHASE II, IT IS PLANNED TO OPTIMIZE COUPLING CHEMISTRIES AND TO EXPAND THE TESTING OF THIS TECHNOLOGY TO OTHER MODEL SUPPORT MATRICES AND IMPLANTABLE DEVICES.