The proposed SBIR Phase I research effort will provide foundational data for the development and commercialization of a novel wound dressing for prevention and treatment of infected skin wounds. The design of the dressing will make use of a commonly used polyurethane foam base material, and incorporation of advanced peptides with potent anti-biofilm activity against a panel of wound pathogens. The lead peptides selected for this effort are synthetic variants of the host defense peptides (HDPs) and have been shown to eradicate pre-existing biofilms of clinically relevant Gram positive and Gram negative bacteria, including the ESKAPE pathogens. Furthermore, these peptides possess immunomodulatory properties through suppression of pro-inflammatory cytokines induced by bacterial infection and recruitment of phagocytic cells. While most of the HDPs and their synthetic variants are being investigated for their potent microbicidal properties, we believe that harnessing their versatile immunomodulatory activity in the form of a wound dressing is of particular significance. Incorporation of these peptides within a wound dressing enables a multifaceted approach to treatment of wounds where a single dressing can provide 1) protection against microbial infection, 2) management of pre-existing infections, and 3) augmentation of the natural wound healing process. iFyber has identified a significant niche in the wound care market that the current proposed technology can address; that is, a product that can effectively manage wound infections, and also enhance the natural process of wound healing. To achieve this goal, iFyber has established a collaboration with Dr. Robert E. W. Hancock, a leader in the field of antimicrobial peptide research and is eliciting support from our ongoing collaborator, Prof. Stephen Davis from the University of Miami, a leader in the wound healing field. Altogether, coupled with iFyber?s commercialization experiences, we believe we have as strong team to support the advancement of the proposed technology. Completion of the proposed Phase I efforts will provide a series of candidate peptide-based wound dressings that will provide a basis for the Phase II efforts towards development of the dressing. Phase I studies are designed to provide insight into dressing efficacy with respect to management of microbial colonization and wound infection, and the effects the dressing application has on the wound healing process. The studies will provide crucial data regarding dressing optimization which will be further advanced in Phase II towards a peptide-based wound care product with emphasis on the regulatory pathway and establishing design inputs under design control. Within this Phase I effort we will develop a series of peptide-based prototype dressings using polyurethane foam as a base dressing. The polyurethane foam will also be plasma modified to enhance non-covalent binding of the peptides to the foam and increase the loading of the active components. The loading and release profiles of the peptides from the dressings will be evaluated and correlated with antimicrobial efficacy against a panel of microbial pathogens. The prototype dressings will also be evaluated for their anti-biofilm efficacy in an ex vivo anti-biofilm porcine skin model, against single species and polymicrobial biofilms, and in a human skin equivalent (HSE) models. The HSE models will also be used to provide additional information regarding immunomodulatory properties of the prototype dressings. Finally, based on the information from previous tasks, 2-3 prototype dressings will be selected for evaluation of efficacy in biofilm eradication using an in vivo porcine wound model. Collectively, these preliminary data will serve as a guide for the design of the Phase II efforts and advancement of the technology.
Wound infection is one of the most important factors impeding wound healing, in particular due to formation of microbial colonies called biofilms. The inherent tolerance of biofilms to classical anti-infectious treatments, including systemic and topical antibiotics and general topical biocides, significantly impairs the wound healing process and prolongs the patient recovery time. The goal of the current SBIR Phase I research effort is to develop prototype dressings that will assist the wound healing process on two fronts: (1) inhibiting and managing microbial colonization and (2) promoting the natural wound healing process. This dual approach was designed to enhance treatment efficacy and thus facilitate quicker patient recovery and improve outcomes.
