Enhancing orthopedic infection control: carbon scaffold-mediated phage therapy for methicillin-resistant staphylococcus aureus in fracture-related infections

Fracture-related infections are burdensome conditions that affect both a patient's health and financial well-being. Preventing an infection and stabilizing the fracture are critical aspects in a care plan that rely on antibiotics and orthopedic implants, both which need to be improved. Bacteriophage or phage are viruses that specifically kill bacteria and are a promising alternative/companion to antibiotics while enhanced orthopedic implants that are osteoinductive and biodegradable are needed for bone healing. In this work we report the inhibitory effectiveness of three phages Ø K, Ø 0146, and Ø 104023 alone and in combination against a strain of methicillin-resistantStaphylococcus aureus. Single phage and cocktails were mixed with bacteria at multiplicities of infection of 5 and 2.5 and growth was measured using optical density over 48 h. Ø K alone and Ø K + Ø 0146 were able to completely inhibit bacterial growth. We also present and the ability of Ø K to bind to and be released from a biodegradable and biocompatible orthopedic carbon scaffold. The carbon scaffold was soaked in a solution of Ø K, washed, and then incubated in sequential buffer baths while samples were removed at timepoints up to seven days to calculate phage elution. At every timepoint measured including seven days, phages were found to still be eluting from the scaffold. These results indicate that the studied phages are effective bacterial inhibitors and could be used to prevent infections. Furthermore, orthopedic implants such as a carbon scaffold can be coated with phage to provide long-term protection.In vivoinfection experiments on phage loaded scaffold that test bacterial clearance, phage persistence in tissue, resolution of inflammation, and bone regrowth with an active infection are needed to further this work.