The Bone-Forming Effects of HIF-1α-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-1α (HIF-1α) promotes osteogenesis in rat bone mesenchymal stem cells (BMSCs). In this study, the function of HIF-1α 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-1α (cHIF). The ectopic bone formation was evaluated in nude mice. The therapeutic potential of HIF-1α-overexpressing canine BMSCs in bone repair was evaluated in mesi-implant defects of immediate post-extraction implants in the canine mandible. HIF-1α 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-1α-overexpressing canine BMSCs. This study provides an important experimental evidence in a preclinical large animal model concerning to the potential applications of HIF-1α in promoting new bone formation as well as the osseointegration of immediate implantation for oral function restoration.

Bone tissue engineering in oral peri-implant defects in preclinicalin vivoresearch: A systematic review and meta-analysis

“…Recently, micro‐computed tomography (micro‐CT) has been proposed as an alternative method for assessing three‐dimensional peri‐implant bone microarchitecture with high resolution and accuracy, in a fast and non‐destructive manner. Only one study in the present review reported micro‐CT assessment of peri‐implant bone regeneration (Zou et al, ). A high correlation between micro‐CT and histomorphometry for assessing peri‐implant bone regeneration has been reported in recent preclinical (Kang et al, ; Vandeweghe et al, ) and clinical studies (de Lange et al, ; Johansson et al, ).…”

Clinical, radiological, and gene expression analyses in smokers and non‐smokers, Part 2: RCT on the late healing phase of osseointegration

“…52 HIF-1a promotes the osteogenesis of rat mesenchymal stem cells (MSCs) 53 and transduced MSCs enhance osseointegration in canine mandibular defects. 54 In a recent study, HIF-1a has also been implicated in osteoclast inhibition, in combination with estrogen. 55 Although the role of HIF-1a in osseointegration and homeostasis around oral implants remains to be established, we explored whether there are any differences in baseline, constitutive expression between the maxilla and mandible.…”

“…It has been suggested that HIF‐1α regulates bone formation and bone differentiation via VEGF and placenta growth factor . HIF‐1α promotes the osteogenesis of rat mesenchymal stem cells (MSCs) and transduced MSCs enhance osseointegration in canine mandibular defects . In a recent study, HIF‐1α has also been implicated in osteoclast inhibition, in combination with estrogen …”

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

“…Previous studies have confirmed that HIF‐1α can markedly enhance both vessel number and the bone regeneration area in ischemic tissue after a local injection of HIF‐1α vectors . Although HIF‐1α have not been used in angiogenesis and osteogenesis in tissue‐engineered bone using adenoviruses and a gelatin scaffold, Jiang et al .…”