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The bone-forming effects of HIF-1?-transduced BMSCs promote osseointegration with dental implant in canine mandible.


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

SUBMITTER: Zou D 

PROVIDER: S-EPMC3293808 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

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