The presence of insufficient bone volume remains a major clinical problem for dental implant placement to restore the oral\r\nfunction. Gene-transduced stem cells provide a promising approach for inducing bone regeneration and enhancing\r\nosseointegration in dental implants with tissue engineering technology. Our previous studies have demonstrated that the\r\nhypoxia-inducible factor-1? (HIF-1?) promotes osteogenesis in rat bone mesenchymal stem cells (BMSCs). In this study, the\r\nfunction of HIF-1? was validated for the first time in a preclinical large animal canine model in term of its ability to promote\r\nnew bone formation in defects around implants as well as the osseointegration between tissue-engineered bone and dental\r\nimplants. A lentiviral vector was constructed with the constitutively active form of HIF-1? (cHIF). The ectopic bone formation\r\nwas evaluated in nude mice. The therapeutic potential of HIF-1?-overexpressing canine BMSCs in bone repair was evaluated\r\nin mesi-implant defects of immediate post-extraction implants in the canine mandible. HIF-1? mediated canine BMSCs\r\nsignificantly promoted new bone formation both subcutaneously and in mesi-implant defects, including increased bone\r\nvolume, bone mineral density, trabecular thickness, and trabecular bone volume fraction. Furthermore, osseointegration\r\nwas significantly enhanced by HIF-1?-overexpressing canine BMSCs. This study provides an important experimental\r\nevidence in a preclinical large animal model concerning to the potential applications of HIF-1? in promoting new bone\r\nformation as well as the osseointegration of immediate implantation for oral function restoration.
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