Despite substantial advances in the availability of bone graft substitute materials in recent years, large bone defects and chronic bone defects represent a large and as yet unsolved clinical challenge. Bone defects are of particular relevance to the recovery and function of injured warriors. Between 2001 and 2005, extremity injuries were responsible for 64% of soldiers treated in Operation Iraqi Freedom and Operation Enduring Freedom who were unable to return to duty. These injuries are so difficult to treat, in part, because the large animal models used to test new therapies are not rigorous enough. Although many of the strategies used most commonly to treat non-healing fractures can repair 100% of bone fractures up to 5 cm, these same strategies fail to repair up to 50% of fractures of the same size in humans. The reason is simple: Traumatic injuries to extremities, in both military and civilian patient populations, are rarely as 'simple' as the animal models used to test therapeutic strategies.Several of the key collaborators in this proposal have been part of a team that is working to develop a better animal model in which to develop and test improved therapies for treatment of bone defects. This model is referred to as the Chronic Caprine Tibial Defect (CCTD). This model has already been very successful in evaluating new and existing bone grafting strategies.In this proposal we propose to expand the use of the CCTD model. To accomplish this goal, two collaborative teams have been united. Team 1, led by Drs. Muschler (Cleveland Clinic) and Pluhar (University of Minnesota), has collaborated to develop the CCTD model. Team 2, led by Drs. Forsberg (Naval Medical Research Center), Davis (Naval Medical Research Center), and Muschler, has collaborated to develop methods to predict the outcome of tissue formation based on clinical factors and the biological conditions in a given patient. The united team also includes Dr. D'Alleyrand, a military surgeon stationed at Walter Reed National Military Medical Center with extensive experience treating severe bone injuries, who is advancing in his career as a musculoskeletal scientist. He will be working in a 'Nested Career Development Program,' expanding his skills and experience in musculoskeletal research.The broad objective of our team is to accelerate the rate at which important questions related to surgical methods, spacer design, and intra-operative decision-making can be translated into clinical practice to improve the care of wounded warriors and civilians. Temporary 'spacers' are frequently used in the treatment of bone defects to preserve a space for bone formation during the early period after an injury.This two-year project involves two directs tests of new therapy strategies: (1) a surgical technique involving the choice of exactly which layer of tissue is best as a bed for effective bone regeneration, and (2) a method for using a spacer that adds texture and surface area to a site of new bone formation, which may improve outcomes.The project also involves collection of detailed information about the quality of the tissue in the graft bed in each animal. These data will be analyzed statistically to define rules that surgeons may be able to apply in the future to predict the likelihood of future success and to know when conditions for success are less favorable and may demand a change in the treatment plan for that specific patient.An important aspect of this project is that its outcome can be immediately used to improve clinical care. Surgical techniques are immediately translatable. The methods or devices to make spacers with a defined texture could be rapidly approved and deployed. Methods to measure the quality of tissues can be shared. Therefore, findings in Aims 1, 2, and 3 could be rapidly implemented in clinical practice.This work will accelerate the rate at which new therapies can be brought to the care of service members and civilians whose lives are disrupted by complex segmental bone defects. 'Raising the bar' using the CCTD model will provide better early assessment of new treatments and decrease the risk that new therapies will fail when they are first used to treat patients. This has the potential to benefit the treatment of the more than 1,000 injured warfighters and 77,000 civilians each year.
|Effective start/end date||30/09/13 → 29/09/15|
- Congressionally Directed Medical Research Programs: $98,602.00