Amputations, pain, death, and the high cost of healthcare resources are just some of the negative consequences of battling orthopaedic-related infections after trauma. Recent military conflicts have produced an alarming incidence of infection in extremity wounds, particularly those caused by multidrug-resistant bacteria. Many of these bacterial strains adhere to tissue and implanted medical devices within the wound to form biofilms, which are attached communities of bacteria that form a coating layer of complex sugars. Biofilms are resistant to antibiotic therapy and the patient's own immune system. Multiple bacterial strains are often found within biofilms, which further complicates the treatment of these infections since efficacy of individual antibiotics is strain-dependent. Warriors with open traumatic extremity wounds are at particularly high risk for biofilm-based bacterial infections, due to factors such as the complexity of injury, presence of necrotic tissue, and materials used in internal fracture stabilization. Not only do these problematic infections threaten the health of the wounded Warrior, but they may also spread within hospitals, both at home and abroad, to become prominent resistant infections. In this project, a custom-sizable, dual antibiotic-loaded, chitosan sponge will be developed for adjunctive treatment at the time of initial surgical procedures, such as removing dead and injured tissues, washing wounds, and setting fractures. Local delivery of a clinician-selected combination of antibiotics from the degradable chitosan sponge to the site of the injury will prevent bacterial infection and alleviate the current dependence on high doses of systemic (delivery through blood vessels) antibiotics and reduce the negative side effects associated with systemic delivery.

Drug release characteristics will be tailored through modifications of chitosan sponge composition and manufacturing methods. Efficacy of antibiotic-loaded sponges in killing bacteria will be measured, as well as compatibility with injured tissue. This project will also implement preclinical models contaminated with two types of bacteria that commonly cause infections in these complex injuries. These studies will evaluate the efficacy of chitosan sponges loaded with two different antibiotics, each with directed action against common infection-causing microorganisms, to prevent and treat problematic infections in large, complex extremity wounds. These studies are expected to result in a novel therapy to prevent and treat traumatic orthopaedic wound infection, thereby reducing the impact of extremity injuries on military healthcare resources and enhancing extremity treatment for both military and civilian trauma patients. This advanced technology, based on materials that have already been approved for human use, may be available for clinical use within 3-5 years.