Abstract
Abstract : The majority of explosion-induced trauma sustained by armed service members results in loss of tissue and contamination with a variety of materials, biological and nonbiological. This project is developing materials to treat bacterially infected osseous injuries, such as those that occur in the long bones, head, and face. More specifically, a moldable bone graft substitute providing localized, controlled, sequential release of antimicrobial and osteogenic agents is being formulated to enable timely and complete healing of large, infected bone defects. Following development and testing of the tunable bone filler system in earlier phases of the project, ongoing efforts are directed at systematically examining the potential for these proactive biomaterials to enhance tissue repair in a rodent model of an infected segmental long bone defect. A dose-dependent increase in bone formation was observed in response to loading of simvastatin in the core of the bone filler system. As expected, a greater amount of mineralized tissue was observed at a longer follow-up time. The effect of localized delivery of antibiotic in enhancing the effect of simvastatin-loaded cores was confirmed. Results thus far have shown that localized delivery of antibiotic outperformed systemic administration through the first month of observation. With the infection at least partially inhibited by sustained release of antibiotics from the implant, simvastatin subsequently released from the core can enhance bone formation.