Chronic wounds are a significant public-health problem, imposing a high cost on society and presenting patients with significant quality of life limitations. A large proportion of patients with chronic wounds, such as diabetic foot ulcers, and venous leg ulcers, are unresponsive to conventional treatment, such as moist dressings. The complications and cost associated with unresponsive ulcers has prompted extensive research, and promising breakthroughs toward improved chronic wound care. Technologies like antimicrobial silver, topical growth factors and ultrasound have all contributed to the current state of care. The use of topical negative pressure (TNP) dressings has grown in popularity and is now a mainstream treatment for both surgical wounds and chronic wounds. The therapeutic mechanism for improved healing brought on by TNP dressings is thought to be rooted in several properties. Increased blood flow, reduced edema, and the physical removal of enzymes from the wound bed are all thought to contribute to healing. Despite these putative accelerators of healing, the presence of bacteria and subsequent formation of biofilm within the wound during the application of negative pressure remains a common inhibitor of wound healing. Therefore, chemical or mechanical debridement, removing necrotic tissue and biofilm itself, represents an essential first step toward returning the wounded tissue to a normal state of healing. Instead of any one species of bacteria, most chronic wound biofilms are comprised of multiple species. Any treatment intended to accelerate healing by clearing or killing these infections must therefore have broad antimicrobial activity against the most commonly reported species in the chronic wound clinical literature: Staphylococcus aureus and Pseudomonas aeruginosa. We propose here, the development of a peptide-based delivery system that links antibiotics to the polyurethane sponge used to apply topical negative pressure to wounds. Based on the porous structure of the sponges, and their implantation into the debrided wound site, these materials provide an excellent surface from which to deliver bactericidal doses of antibiotics, thereby providing continued protection against recurrent biofilm. We have identified tobramycin (strongly active against Pseudomonas aeruginosa and Gram positive bacteria) as the clinically preferred agent for this application. Coupling the powerful technology of topical negative pressure with improved biofilm prevention using local antibiotics could provide a unique combination tailored specifically toward the clinical situation found in soft tissue wounds.
The research program proposed here is designed to initiate the development of a local antimicrobial delivery system for the treatment and prevention of biofilm in acute and chronic wounds in combination with topical negative pressure wound dressings. The impact of the proposed product concept on patients, physicians and the state of care would promote enhanced quality of life and potentially a reduction in extended medical care precipitated by complicated wounds.
