Infections of chronic wounds, including diabetic foot ulcers, pressure ulcers, and venous leg ulcers, pose a major challenge to wound management. Biofilms are microscopically identifiable in up to 90% of chronic wounds. For example, diabetes mellitus affects 23.6 million people in the United States and approximately 20-25% of diabetic patients will develop foot ulceration during the course of the disease. Among them, 63.4% of diabetic patients develop infections. The direct annual expenditure toward managing these ulcers is $9 billion to $13 billion in the United Sates alone. Bacteria in biofilms are more likely to cooperate and exchange their genes resulting in much higher antibiotic resistance than planktonic bacteria. The composition and organization of biofilms limits diffusion of molecules, including antibiotics, through the structure and into the biofilm or out to the bulk fluid. Consequently, bacteria in a biofilm are refractory to host response and antibiotic treatment. The poor treatment outcomes result in high healthcare cost, amputations, a decreased quality of life, and an increased mortality. There is an urgent need to develop novel therapies for effective treatment of biofilms in chronic wounds. The primary objective of this proposal is to develop a Janus-type antimicrobial dressing by immobilizing dissolvable microneedle arrays to the surface of three-dimensional (3D) nanofiber foams to effectively treat biofilms and promote diabetic wound healing. This proposed study is framed on important inventions made by both PIs, allowing us to generate a unique platform to treat biofilm in chronic wounds. To prove the concept, we have recently demonstrated that Janus-type antimicrobial dressings are indeed effective against the biofilms of resistant pathogens ex vivo and in vivo. Based on the findings, we hypothesize that the Janus-type dressings, consisting of microneedle arrays and 3D nanofiber foams with incorporation of molecularly engineered peptides, can physically penetrate biofilms and release peptides both inside and outside biofilms to effectively eradicate biofilms in chronic wounds and promote cellular infiltration and wound healing. To test the hypothesis and accomplish the objective, we propose the following specific aims: 1) Establish methods for fabrication and characterization of novel Janus-type dressings; 2) Assess the antibacterial efficacy, biocompatibility and antibiofilm mechanism of engineered peptides and their Janus-type dressings in vitro; and 3) Test the efficacy and immune regulation of optimized Janus-type dressings against biofilms in type 2 diabetic mice wounds and ex vivo human skin wounds. We expect completion of these aims to generate an effective intervention with great commercial potential that could effectively treat biofilms, improve quality of wound care, decrease costs, avoid amputations, and most importantly save lives of patients.
Infections of chronic wounds pose a major challenge to wound management. Biofilm is present in 60-90% of chronic wounds. Failure to prevent or manage such infections has resulted in amputation, sepsis, and even death. This application outlines a strategy to develop a new Janus-type antimicrobial dressing which can deliver molecularly engineered peptides inside and outside biofilms for eradicating biofilms in chronic wounds without surgical debridement and simultaneously enhancing wound healing.
