Hyperbaric Oxygen Therapy Promotes Bone Healing in Patients with Maxillary Sinus Lateral Augmentation and Diabetic Mice Potentially through the Nrf2 Pathway.

OBJECTIVE: To assess the impact of hyperbaric oxygen (HBO) therapy on bone healing in dia-betic patients and explore potential mechanisms in an animal experiment.

METHODS: Four non-diabetic patients undergoing maxillary sinus lateral augmentation were assigned to either standard care (control group) or HBO treatment for 5, 6 or 9 weeks. Bone core samples were collected for immunochemistry during the preparation for implant insertion. Additionally, 12 db/db diabetic mice and 12 control mice with tibia defects were subjected to HBO treatment. After 7 days, the bone repair process was assessed using microcomputed tom-ography (microCT), histology, immunohistochemistry and Western blot analyses.

RESULTS: HBO improved bone formation in the implant areas of patients treated for 5, 6 and 9 weeks, increasing local vascular endothelial growth factor, bone morphogenetic protein-2 and osteocalcin expression. Diabetic mice exhibited impaired bone healing, but HBO-treated groups (diabetic or non-diabetic) showed enhanced new bone formation. Increased osteocalcin and runt-related transcription factor 2 and decreased tartrate-resistant acid phosphatase expression were detected. The nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway and its downstream proteins catalase and heme oxygenase-1 were upregulated after HBO.

CONCLUSION: HBO enhances bone healing in both patients and diabetic mice, and is potentially mediated through the Nrf2 pathway.