Engineering novel models for craniofacial bone regeneration in presence or absence of insulin
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AIM & HYPOTHESIS: We hypothesized that Diabetic ex-vivo bone model can be created by culturing the calvarial bone in BSA media which contains a high glucose level with lack of insulin hormone. Insulin has a direct effect on bone toward bone formation and can be as a local measure to enhance bone healing in critical bone defects and in bone regeneration with the use of bone graft substitutes. Chick embryo model can be used as an effective in-vivo model system to study bone biology. MATERIALS & METHODS: We utilized an ex-vivo diabetic calvarial bone culture system to evaluate the effect of insulin on bone biology under conditions of static versus dynamic, and formation versus resorption in order to interpret cellular and biological impact induced by insulin. In addition, we tested the effect of insulin on healing of critical bone defect with different bone graft material such as demineralized freezed dried bone (DFDBA) using ex-vivo calvarial bone model. Also, we evaluated the efficacy of using chick embryo model as a bone regeneration model system. RESULTS: In our resorption and formation model insulin induced osteoblastic bone formation. In the calvarial defect repair model the defect healed much faster in the presence of insulin with complete closure of the defect at 40 days. EMD showed superior regenerative effect on bone defect compared to other variables used both at 21 and 40 days. Chick embryo model showed that all transplanted calvarial bones were vital and integrated to the embryonic membrane. CONCLUSION: Insulin has a direct positive effect on bone biology by enhancing osteoblast differentiation which indirectly suppresses the osteoclast differentiation and bone resorptive effect of PTH. The results of our studies demonstrated the potential of using an ex-vivo live craniofacial bone organ culture models using critical defects with the capacity to test rapidly and cost effectively bone graft materials for validation, development and discovery. We have developed a novel in-vivo chick embryo organ culture model systems which can be used for variety of mechanistic and biological studies to further understand the behavior of bone, bone repair and bone regeneration.