Project 458903

More than six million bone fractures occur in North America each year, and fracture-related infection (FRI) remains a serious risk, engendering long-term health complications. Up to 30% of skeletal trauma patients are afflicted with FRI, which can result in repeat surgeries, loss-of-function, and even amputation. An FRI must be eliminated both swiftly and completely for proper bone regeneration and patient recovery. Historically, FRI management has consisted of a combination of wound cleaning and antibiotic regimens; however, antibiotic therapy is a short-term solution as antimicrobial-resistant pathogens are projected to surpass cancer as the leading cause of death by 2050. Bacteriophages - natural, bacteria-targeting viruses which seek out and eliminate infection - offer a promising alternative FRI treatment strategy and have been demonstrated as safe in human clinical trials. To explore the potential of bacteriophage therapy to treat FRI, a preclinical model must first be established. We propose to develop an FRI-bacteriophage model in mice, the first of its kind, which will examine the potential of bacteriophage therapy to eliminate FRI and improve skeletal stem cell (SSC)-mediated tissue regeneration. Developing a reliable FRI-bacteriophage model is a critical step towards demonstrating the utility of bacteriophage therapy as an alternative to antibiotics in treating FRI, and will be essential to reach clinical applications. Ultimately, development of this model will improve outcomes for skeletal trauma patients as we strive to prevent loss of limb, decrease recovery time, and improve patient quality-of-life.