This is an original study to quantify and grade defect healing in a large animal cranial bone substitute model. The study of various therapies to heal cranial defects requires an appropriate ?critical? animal model. An experimental animal model should be analogous and recognizable as an appropriate challenge to human physiology. In addition, the defect must fail to heal unless treated with the tissue engineering therapy under study. Sheep as a large animal model was chosen because of its ability to tolerate creation of large skull defects analogous to clinical scenario, and its biology of healing as a high order mammal would be closer human beings. There is no agreement on the critical size limits for cranial defects. Various sizes have been termed "critical" in publications utilizing sheep. These ranged from 20-22mm. This study will investigate whether a 20mm defect is adequate. Bilateral circular cranial defects of 10, 20 and 25mm diameters were created in 12 adult sheep. Based on guided tissue engineering principles, defect protection was utilized to prevent in-growth of fibroblasts and other connective tissue cells from the surroundings. As bone tissue regeneration strategies usually involve osteoconduction element, an animal model that considered the defect protection role of osteoconduction would be more appropriate. Repopulation and regeneration of the defect was maximized as an added challenge Bioresorbable polylactic acid co-polymer mesh (MacroPoreTM) and Titanium mesh (TiMeshTM) was used as defect protection. The cranial defects were harvested at 8 and 16 weeks. The end-point analysis included Faxitron X-ray images, DEXA (Dual Energy X-ray Absorptiometry), and histology. The defects were graded to assess their ability to eventually heal. 10mm defects fully healed at 16 weeks. There was new bone formation spanning the entire defect seen on histology. 25mm defects were spanned by thin fibrous tissue only. There was variability in the healing potential of 20mm defect. Based on presence of bone islands within the defect, half of the 20mm defects demonstrated ability to heal while the other half actually had new bone spanning the defects on histology. Critical size cranial defect in sheep for the study of bone graft substitute has to be larger than 25mm diameter. The model is then utilized to study the use of Pro Osteon and AGF compared with the gold standard of autologous bone graft.

This is an original study to quantify and grade defect healing in a large animal cranial bone substitute model. The study of various therapies to heal cranial defects requires an appropriate ?critical? animal model. An experimental animal model should be analogous and recognizable as an appropriate challenge to human physiology. In addition, the defect must fail to heal unless treated with the tissue engineering therapy under study. Sheep as a large animal model was chosen because of its ability to tolerate creation of large skull defects analogous to clinical scenario, and its biology of healing as a high order mammal would be closer human beings. There is no agreement on the critical size limits for cranial defects. Various sizes have been termed "critical" in publications utilizing sheep. These ranged from 20-22mm. This study will investigate whether a 20mm defect is adequate. Bilateral circular cranial defects of 10, 20 and 25mm diameters were created in 12 adult sheep. Based on guided tissue engineering principles, defect protection was utilized to prevent in-growth of fibroblasts and other connective tissue cells from the surroundings. As bone tissue regeneration strategies usually involve osteoconduction element, an animal model that considered the defect protection role of osteoconduction would be more appropriate. Repopulation and regeneration of the defect was maximized as an added challenge Bioresorbable polylactic acid co-polymer mesh (MacroPoreTM) and Titanium mesh (TiMeshTM) was used as defect protection. The cranial defects were harvested at 8 and 16 weeks. The end-point analysis included Faxitron X-ray images, DEXA (Dual Energy X-ray Absorptiometry), and histology. The defects were graded to assess their ability to eventually heal. 10mm defects fully healed at 16 weeks. There was new bone formation spanning the entire defect seen on histology. 25mm defects were spanned by thin fibrous tissue only. There was variability in the healing potential of 20mm defect. Based on presence of bone islands within the defect, half of the 20mm defects demonstrated ability to heal while the other half actually had new bone spanning the defects on histology. Critical size cranial defect in sheep for the study of bone graft substitute has to be larger than 25mm diameter. The model is then utilized to study the use of Pro Osteon and AGF compared with the gold standard of autologous bone graft.

Includes bibliographical references (leaves 226-273.) Investigates the regulation of the expression of CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA, both in the bone and in the kidney, with the aim to determine whether the regulation of the vitamin D metabolism in the bone is independent from that in the kidney. The effects of age, dietary calcium and vitamin D status on the expression of these genes in both the kidney and the bone, as well as on a number of biochemical factors known to regulate the renal metabolism of 1,25D, such as PTH, calcium and 1,25D itself, were examined. CYP27B1 mRNA expression was also studied in histological sections of rat femoral bone.

Includes bibliographical references. Electronic publication; Full text available in PDF format; abstract in HTML format. Investigates the regulation of the expression of CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA, both in the bone and in the kidney, with the aim to determine whether the regulation of the vitamin D metabolism in the bone is independent from that in the kidney. The effects of age, dietary calcium and vitamin D status on the expression of these genes in both the kidney and the bone, as well as on a number of biochemical factors known to regulate the renal metabolism of 1,25D, such as PTH, calcium and 1,25D itself, were examined. CYP27B1 mRNA expression was also studied in histological sections of rat femoral bone. Electronic reproduction.[Australia] :Australian Digital Theses Program,2001.