A novel electric current-based treatment system for chronic wound biofilm infections

PROJECT SUMMARY. Chronic, non-healing wounds are currently affecting more than 6 million Americans. They have significant impact on patients’ mobility and quality of life, and can lead to a high incidence of amputation and mortality rate. Biofilm infection is a critical factor that leads to chronic wound formation. Biofilm bacteria are very difficult to kill compared to planktonic bacteria due to their reduced growth and metabolic rates, the presence of persister cells, inducible resistance mechanisms in response to antibiotic challenges, and the mutational resistance development. Current clinical standard of care for chronic wound biofilm infections uses repeated debridement with prolonged systemic or topical administration of antimicrobial agents. This treatment has limited efficacy and imposes a significant burden on both patients and healthcare providers. The development of more effective delivery technologies for antimicrobial agents and physical biofilm treatment methods is a very active research area. However, current technologies reported in the literature offer limited improvement in anti-biofilm efficacy, may cause potential damage to host tissues, or require a long-term application to be effective. There is a critical need for more efficacious and safer biofilm treatment technologies that does not require long-duration and frequent treatment applications to facilitate a timely closure of chronic wounds. Our long-term goal is to apply engineering innovations and technological advances to providing better healthcare to chronic wound patients. Our overall objective in this proposal is to develop a novel, electric current-based system to provide a complete treatment strategy for multispecies chronic wound biofilm infections from the initial reduction of bacterial bioburden to the long-term maintenance of wound sterility during the entire course of wound healing. Our system will perform two functions to achieve this goal: 1) electrical debridement of biofilm by high- intensity electric current application; and 2) rapid delivery of high-concentration antibiotics and antimicrobial nanoparticles by high-intensity iontophoresis. The electrical debridement and antibiotics will achieve a rapid initial reduction of biofilm bacterial count to below the clinical threshold for wound infection (105 CFU/g). The antimicrobial nanoparticles will then maintain a low bacterial bioburden, prevent biofilm reformation and new infections throughout the wound healing process. Our proposed system will be based on a novel hydrogel ionic circuit technology developed in our lab to allow safe application of high-intensity current to wound tissues to significantly enhance electrical debridement efficacy and iontophoretic delivery efficiency for antibiotics and antimicrobial nanoparticles. If successful, our biofilm treatment system will have direct positive impact on all patients suffering from chronic wounds by significantly reducing the wound healing duration, the amputation rate and mortality rate associated with chronic wounds.