This project will address the hypothesis that poor healing of many chronic wounds is due to the formation of infectious microbial biofilms. Biofilms are known to form preferentially on dead or damaged tissue and contribute to persistence because microorganisms in biofilms evade killing by antibiotics and by the host defenses. A corollary of the hypothesis is that therapies that effectively target microbial biofilms will improve healing of these wounds. The goal of this project is to develop knowledge and techniques needed to evaluate the potential utility of anti-biofilm therapies in the context of wound healing. This will be accomplished by characterizing the presence, speciation, structure, arid oxygen availability in wound biofilms (Aim #1), developing a suite of in vitro and in vivo models of chronic wound biofilm infection that simulate diverse aspects of biofilms in wounds (Aim #2), and applying these models to evaluate the efficacy and safety of several potential anti-biofilm technologies (Aim #3). The models include polymicrobial biofilms grown in laboratory systems, a keratinocyte scratch model interfaced with bacterial biofilm, a rafted organ culture model and mouse models of chronic wound infection. Success in this project depends on merging expertise from biofilm science and technology with expertise in wound healing and therefore requires a multidisciplinary team of biofilm microbiologists and engineers, dermatologists, cell biologists, and clinical collaborators. He project is innovative and high-risk in three important respects. This project involves investing in the biofilm concept by bringing in investigators who are outside the wound healing community. The marriage of microbial biofilm to tissue culture and animal wound models is innovative. And finally, some of the proposed anti-biofilm strategies are clearly high-risk. Wounds that fail to heal, such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers are a major source of morbidity, mortality, and health care expenditure. Therapies that target biofilms may provide a significant improvement in the treatment of chronic wounds. Furthermore, the results of this research may impact the treatment of other biofilm-related diseases, such as osteomyelitis, endocarditis, prostatitis, otitis media, and sinusitis. ? ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
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Application #
Study Section
Special Emphasis Panel (ZGM1-PPBC-9 (WH))
Program Officer
Ikeda, Richard A
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Montana State University - Bozeman
Engineering (All Types)
Schools of Engineering
United States
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James, Garth A; Ge Zhao, Alice; Usui, Marcia et al. (2016) Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds. Wound Repair Regen 24:373-83
Zhao, Ge; Usui, Marcia L; Underwood, Robert A et al. (2012) Time course study of delayed wound healing in a biofilm-challenged diabetic mouse model. Wound Repair Regen 20:342-52
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Tavakkol, Zarry; Samuelson, Derrick; deLancey Pulcini, Elinor et al. (2010) Resident bacterial flora in the skin of C57BL/6 mice housed under SPF conditions. J Am Assoc Lab Anim Sci 49:588-91
Rickard, A H; Colacino, K R; Manton, K M et al. (2010) Production of cell-cell signalling molecules by bacteria isolated from human chronic wounds. J Appl Microbiol 108:1509-22

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