Scope A: Tissue Repair and Regeneration Following Orthopedic and Craniofacial Trauma

Background The explosion-induced majority of trauma sustained by armed service members results in loss of tissue and contamination with a variety of materials, biological and nonbiological. Repair of large defects can be challenging under aseptic conditions, but even low levels of microbial contamination initiate a chronic inflammatory response that undermines surrounding tissues. Objective/Hypothesis This project will develop materials to treat traumatcially induced orthopedic and craniofacial injuries that occur in microbially contaminated environments. More specifically, a moldable bone graft substitute providing localized, sequential release of antimicrobial and osteogenic agents will enable timely and complete healing of large, infected bone defects. The hypothesis to be tested is that the proposed multifunctional material will provide superior healing compared to simply grafting with bone substitute, even in the prescence of systemically administered antibiotics. Specific Aims The technical objectives of this project are to: 1) develop and characterize a moldable filler for grafting infected bone defects, and 2) measure the biological activity of the bone filler in vivo in an infected segmental defect model. Study Design The first phase of experiments will systematically examine parameters contributing to a bone fill material that is moldable, biodegradable, and provides controlled release of antimocrobial and osteogenic molecules. These studies will involve extensive in vitro investigations. The second proof-of-principle phase will determine bilogical performance of materials meeting specific chriteria in an animal model of infected bone defects. Relevance Orthopedic and craniofacial wounds resulting from explosions remain a significant concern for military personnel. Such blast injuries not only involve significant damage to both hard and soft tissues, but they also frequently contaminate the wounds with clothing, soil and "environmental debris" leading to positive cultures. Multifunctional materials that target both antimicrobial and osteogenic activities may enhance regenration of large, contaminated bone defects.