Photoactivated Antimicrobial Collagen

DESCRIPTION (provided by applicant): The significance of this project is the development of a novel photoactivated collagen dressing with demonstrated bactericidal effects, minimal toxic effects and low susceptibility to mechanisms of microbial resistance in an effort to ultimately expand the armamentarium of antimicrobial agents for the management of wound infections. Approximately 2 million patients develop hospital-acquired (nosocomial) infections with surgical wound infections being the most common. It has been reported that 1 of every 24 (4.1%) patients who have inpatient surgery in the US develops a wound infection. These infections are substantial in terms of their impact on morbidity, mortality and resource use. As many as 100,000 deaths and staggering costs of 3.5B annually are associated with wound infections. In the US wound infections increase costs of hospitalization by more than 3,000/patient. While the conventional treatment of infections includes both focused and broad-spectrum antibiotics there has been a continuing and alarming trend of microbial resistance to these agents. This resistance is believed to occur as a result of chromosomal mutation, inductive expression of a latent chromosomal genes or exchange of genetic material via transformation, bacteriophage transduction, or plasmid conjugation. A preliminary study demonstrated in vitro activity of a light activated, flavin solution against methicillin-resistant Staphylococcus aureus (MRSA). These results suggest that a method could be developed to prevent wound infections and accelerate wound healing using this approach. It is believed that the antimicrobial properties of light-exposed flavin solutions stem from release of oxygen free radicals in combination with the generation of nucleotides that preferentially interrupt the RNA or DNA of pathogens. Development of resistance is unlikely, given the mechanism of action of these compounds. Such a strategy could potentially be effective against a broad spectrum of pathogens including bacteria and viruses. It is proposed to establish feasibility of photoactivated collagen dressings in both in vitro and in vivo studies. The Phase I application describes work to optimize the performance of the collagen dressing. Project tasks include the preparation of collagen dressing, the modification of light sources for optimizing activation parameters and chronic wound models with endpoints including histology and wound cultures. PUBLIC HEALTH RELEVANCE: Millions of surgical and iatrogenic wounds occur on an annual basis. Each requires appropriate management to facilitate healing, reduce the potential for infection and minimize disability and scarring. Wound infection and related complications increase the cost of care by nearly 9000 per occurrence and prolong hospital stays. At the same time, bacterial resistance to antibiotics is increasing at an alarming rate, with community acquired MRSA (Methicillin-resistant Staphylococcus aureus) prevalence approaching 50% in several communities based on wound culture data. This project aims to develop a novel strategy using a combination of visible light and redox-active chromophores to expand the armamentarium of antimicrobial agents for the management of surgical wounds.