Pediatric mandibular deficiencies are the second most common developmental craniofacial anomaly. These disorders not only compromise speech, nutrition, and the airway, but also place children at risk for psychosocial maladjustment. Conventional techniques to reconstruct and rehabilitate mandibular deficiencies are fraught with significant problems including; high failure rates; unpredictable outcomes, and long, frequent, and costly hospitalizations. A method of endogenous tissue engineering for the reconstruction and replacement of pediatric mandibular deficiency would help to alleviate a significant psychosocial and biomedical burden. Distraction osteogenesis (DO), the creation of new bone by the gradual separation of two bony fronts, is the ultimate method of tissue engineering because it provides an anatomical and functional replacement of deficient tissue with endogenous tissue generated from local substrate. The newly engineered bone acts as a biomimetic reconstruction by harnessing the body's adaptive response as a mechanism of tissue replacement. Although the clinical parameters of long bone DO have been studied extensively, almost nothing is known about the cellular, molecular or biomechanical mechanisms that regulate DO in the mandible. The central hypothesis to be tested in this proposal is that the creation of newly engineered bone generated by mandibular DO is the result of an adaptive response by bone and the surrounding soft tissue envelope. The investigators further hypothesize that there is a fundamental difference in the mechanism of this adaptive response, characterized by the creation of new bone, and a maladaptive response, characterized by injury and fibrous non-union. To test this hypothesis, the investigators will utilize a novel rodent model to determine the cellular, molecular, and biomechanical mechanisms that distinguish the adaptive from the maladaptive response in mandibular DO. This interdisciplinary proposal is timely and relevant because mandibular DO is rapidly becoming the treatment of choice for reconstructing pediatric mandibular deficiencies. The long term objective of this work is to gain insight into the mechanisms that regulate osteogenesis in general and, mandibular DO in particular, in order to advance the discipline of osseous tissue engineering.
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