Background: Blood clot formation is one of the first events in bone regeneration and osseointegration. The blood clot adheres to dental implants with hydrophilic surfaces more favorably than to those with hydrophobic surfaces. This appears to result in better bone healing and bone fill of defects around dental implants. Objective: To assess the impact of blood clot stabilization at modSLA titanium implants on bone formation in chronic-type defects in a dog model. Material & methods: Ten modSLA implants were installed in 5 dogs after creation of saddle-type buccal-lingual bony defects. In 5 implants (test sites), the blood clot was removed by sterile saline irrigation, while the clot was left undisturbed on the other 5 implants (control sites). After 8 weeks of healing, the animals were sacrificed and sections were prepared for histomorphometric analysis. The following measurements were performed: The residual defect length (DL), the buccal and lingual most coronal level of bone in contact with the implant (CBI-b and CPI-l), the new bone height (NBH), the percentage of bone to implant contact (BIC), the area of new bone fill (BF), the difference in buccal and lingual dimensions of CBI (D-CBI), and percentage of linear bone fill (PLF). Results: the mean values of DL were similar in both groups (3.4 mm). All parameters assessed were consistently more favorable in control sites: CBI-b: 1.3 vs. 1.5, CBI-l: 1.3 vs. 0.8, D-CBI: -0.2 vs -0.5, NBH: 1.9 mm vs. 2.1 mm, PLF: 57.1% vs. 64.5% and BF: 4.4 mm? vs. 6.0 mm?. However, these differences were not statistically significant. Conclusion: In the light of consistently more favorable parameters assessed for the healing of saddle-shaped bony defects around implants, it is assumed that a stabilized blood clot contributed to early bone regeneration and osseointegration. Undisturbed blood clot formation may, indeed, be a prerequisite for optimal treatment outcomes. However, owing to the small sample size in the present study, these tendencies ought to be explored in further studies. / published_or_final_version / Dental Surgery / Master / Master of Dental Surgery

Thesis (M.S.)--University of Hawaii at Manoa, 2007. / Includes bibliographical references (leaves 92-95). / ix, 95 leaves, bound ill. (some col.) 29 cm

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 109-154) Also available in print.

Thesis (doctoral)--Göteborg Universitet, 1993. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (Ph. D.)--Drexel University, 2004. / Includes abstract and vita. Includes bibliographical references (leaves 180-189).

Thesis (doctoral)--Göteborg Universitet, 1993. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (Ph. D.)--Rutgers University, 2007. / "Graduate Program in Biomedical Engineering." Includes bibliographical references (p. 154-175).

Abstract Angiogenesis is essential for the replacement of cartilage by bone during skeletal growth and regeneration. Vascular endothelial growth factor-A (VEGF-A) is a key regulator of angiogenesis whereas endostatin, a potent inhibitor of endothelial cell proliferation and migration, is a natural antagonist of VEGF-A. The regulatory roles of these peptides in angiogenesis, bone formation and bone cells were investigated in this study. In the present work we studied the effects of VEGF-A, delivered with an adenoviral vector, on the recovery of bone drilling defects in rat femur. Our data confirm the important role of VEGF in bone healing and that adenoviral VEGF gene transfer may modify bone defect healing in a rodent model. We studied the effects of VEGF-A and endostatin on bone resorption activity. It was found that VEGF-A is a potent stimulator of bone resorption and osteoclast differentiation in vitro and endostatin can antagonize this stimulatory effect when acting directly on bone cells. This suggests that endostatin is indeed a regulator of bone resorption, but not a critical one. In the present study we induced ectopic bone formation in the hamstring muscles of adult mice. The effects of VEGF-A and endostatin in the ectopic bone formation assay were evaluated by the simultaneous delivery of both peptides with recombinant adenoviral vectors. It was found that endostatin retards the cartilage phase in endochondral ossification that subsequently reduces bone formation. We conclude that bone growth and healing, which share features with ectopic bone formation, may be regulated by endostatin. To confirm in vivo effects on bone formation we further investigated the effects of endostatin and VEGF-A on mouse pre-osteoblastic cells in vitro. Finally the effects of endostatin on bone were studied in transgenic mouse lines overexpressing endostatin, and mice lacking collagen XVIII.

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy