Novel Janus-type Antimicrobial Dressings for the Treatment of Biofilms in Chronic Wounds - 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.
