Application of HIF-1α by gene therapy enhances angiogenesis and osteogenesis in alveolar bone defect regeneration

Background: A successful clinical outcome for implanted tissue-engineered bone is dependent on the establishment of a functional vascular network. Gene-enhanced tissue engineering represents a promising approach for vascularization and osteogenesis. In the present study, we tested the angiogenesis and osteogenesis efficacy of gelatin as the scaffold carrier in combination with a virus encoding the HIF-1α gene in a rat alveolar bone defect model. Methods: Three groups of 10 rats each were either left untreated, treated with adenovirus encoding hypoxia-inducible factor-1α (AdHIF-1α)/gelatin sponge or treated with gelatin sponge with adenovirus encoding red fluorescence protein, respectively. At 4 weeks, all samples were determined by micro-computed tomography, histological analyses and immunohistochemical studies. Results: Scaffolds loaded with AdHIF-1α were able to sustain the release of AdHIF-1α for up to 21 days and alveolar bone defects treated with scaffolds containing AdHIF-1α significantly induced new bone and new vessel formation in vivo. Conclusions: Overexpression of HIF-1α by gene therapy may be a useful method for enhancing alveolar bone defect osteogenesis and angiogenesis.