Grant: Operating Grant

Distraction osteogenesis (DO) is a surgical technique used to treat limb length discrepancies, deformities and bone loss secondary to trauma, infection and tumours. DO involves performing an osteotomy and gradually distracting the two bone segments with an external fixator, which generates new bone within the distracted gap. One of the problems associated with DO is the long period of time the fixator has to be kept on until the bone has consolidated, which may cause numerous social and medical problems for the patient. Different methods have been studied to accelerate the consolidation phase, including the use of Bone morphogenetic proteins (BMPs). However, the use of large doses of exogenous BMPs is costly and may trigger the onset of unknown side effects. Thus, the first aim of this study is to evaluate the in vivo efficacy of a BMP nanoparticle delivery system (a system we have developed and tested in vitro and in vivo) during DO to provide a sustained release of low doses of BMPs over a prolong period of time. The second aim is to investigate if the bioavailability and efficiency of endogenous BMPs can be increased by reducing the expression of BMP antagonists using targeted gene silencing at the distracted site. Results from this study will help decrease the time required for the fixator to be kept on and improve the functional outcome of patients undergoing DO.