Hyperbaric oxygen results in increased vascular endothelial growth factor (VEGF) protein expression in rabbit calvarial critical-sized defects Tommy C. O. Fok, BSc(PT), a Ahmed Jan, DDS, b Sean A. F. Peel, PhD, c A. Wayne Evans, MD, d Cameron M. L. Clokie, DDS, PhD, FRCDC, e George K. B. Sándor, MD, DDS, PhD, FRCDC, FRCSC, FACS, f London and Toronto, Canada, Tampere and Oulu, Finland UNIVERSITY OF WESTERN ONTARIO, UNIVERSITY OF TORONTO, UNIVERSITY OF TAMPERE, AND UNIVERSITY OF OULU Background. Hyperbaric oxygen therapy (HBO) promotes osseous healing, however the mechanism by which this occurs has not been elucidated. HBO may promote angiogenesis, which is vital for bone healing. Vascular endothelial growth factor (VEGF) is one of the key factors that stimulates angiogenesis. Objective. The objective of this study was to investigate whether HBO altered VEGF expression during bone healing. Methods and materials. Archived samples from calvarial defects of rabbits exposed to HBO (2.4 ATA, 90 minutes a day, 5 days a week for 4 weeks) and normobaric oxygen controls (NBO) were analyzed by immunohistochemistry. Results. VEGF expression in 6-week HBO samples was elevated compared to NBO (P = .012). Staining of the 12- week HBO samples was reduced compared to 6-week HBO (P = .008) and was similar to 6- and 12-week NBO control samples. Conclusion. HBO therapy resulted in increased VEGF expression in the defects even 2 weeks after the termination of treatment (6 weeks postsurgery). (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:417-22) A critical-sized osseous defect is defined as the mini- mum dimension of a bony lesion that cannot repair itself to its preinjured state without intervention during an individual’s life span. 1 In the rabbit calvarium this is defined as a defect 15 mm in diameter. Critical-sized osseous defects may lead to numerous complications including fracture, non-union and pseudo-arthrosis. 2 Surgical treatments prevent further complications, which may involve the use of a fixation device and autogenous bone graft material to bridge the gap in the defect. All such reconstructive procedures that require a second surgical site for the harvesting of tissue are associated with potential morbidity. 3,4 Synthetic bio- materials have been used in place of autogenous bone grafts. 5 Recently, Jan et al., 6 using the rabbit critical- sized calvarial defect model, showed that 20 treatments of 90 minutes of hyperbaric oxygen (HBO) at 2.4 atmospheres could heal both critical-sized and supra- critical-sized calvarial defects when compared to nor- mobaric oxygen controls (NBO). This suggests that HBO has the potential to augment bony healing. HBO’s mode of action in the treatment of decompres- sion sickness and carbon monoxide poisoning is well understood based on its effects on reducing gas emboli a Resident in Oral and Maxillofacial Surgery, Schulich School of Medicine and Dentistry, University of Western Ontario. b Resident in Oral and Maxillofacial Surgery and Anesthesia, Univer- sity of Toronto. c Assistant Professor, Orthobiologics Group, University of Toronto. d Hyperbaric Medicine Unit, Department of Anesthesia, Faculty of Medicine, University of Toronto. e Professor, Discipline Head, Oral and Maxillofacial Surgery and Anesthesia, Director, Orthobiologics Group, University of Toronto. f Professor, Oral and Maxillofacial Surgery and Anesthesia, Univer- sity of Toronto; Regea Institute, University of Tampere, Tampere, Finland; and Dosent, University of Oulu, Oulu, Finland. Received for publication Dec 7, 2006; returned for revision Jul 13, 2007; accepted for publication Jul 13, 2007. 1079-2104/$ - see front matter © 2008 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2007.07.015 417 Vol. 105 No. 4 April 2008 ORAL AND MAXILLOFACIAL SURGERY Editor: James R. Hupp