Distraction osteogenesis is an effective means to stimulate new bone formation through manipulation of the healing callus. The approach shows considerable promise for the treatment of craniofacial disorders in children. Most of our understanding of the biology of distraction comes from animal models using limb bones. These are also largely limited to descriptive histological studies. We propose to establish and characterize a rat model for mandibular distraction and to examine the effects of the magnitude of distraction and age on the regenerate bone.
The aims of this project are as follows: 1) To quantify bone turnover and healing in distraction sites at various times following minimal, moderate and extensive mandibular distraction in both young and adult rats. 2) To assess the roles in healing of the recruitment of cells from stem cell pools, proliferation of osteoprogenitors, and apoptosis of bone cells 3) to quantify the strength of regenerate bone. Studies on the distraction osteogenesis procedure have described three distinct periods: latency distraction and consolidation. Latency is from the time of osteotomy/device placement to initial callus formation (days 0-3 in the rat); distraction is the period of strain application (days 4-9 in the rat); consolidation represents a period of healing when no new strains are applied (days 10-37 in the rat). This project will examine mandibles at five times: the start of distraction (day 3), early in distraction (day 5), late in distraction (day 9), mid consolidation (day 23) and after consolidation (day 37). There will be two ages: young and adult rats. There will also be four distraction groups: extensive (0.5 mm/day), moderate (0.25 mm/day), minimal (0.1 mm/day) and sham (0.0/day). All treated and contralateral hemimandibles will be assessed for healing of the regenerate using bone histomorphometry; bone cell dynamics will be assessed using immunohistochemical methods combined with stereology; the quality of the regenerate dynamics will also be assessed using measures of bone mineral density, bone mineral content and strength in bending. The main deliverables of this project will be 1) a well-characterized animal model for studies of the regenerate in mandibular distraction and 2) sufficient data to design human trials. The animal model will also facilitate future animal studies designed to examine molecular mechanisms in distraction osteogenesis and studies designed to test the feasibility of improving distraction protocols through pharmacological, growth factor, dietary or cellular approaches.
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