Abstract
INTRODUCTION: There has been an increasing desire for the development of predictive periodontal regenerative therapy for severe periodontitis. In this study, we investigated the effect of the combined use of fibroblast growth factor-2 (FGF-2), a drug for periodontal regeneration approved in Japan, and carbonated apatite (CO(3)Ap), bioresorbable and osteoconductive scaffold, on periodontal regeneration in beagle dog model of one-wall periodontal defect (severe intraosseous defect) for 24 weeks in comparison with CO(3)Ap or vehicle alone. METHODS: One-wall periodontal defects were created (mesiodistal width × depth: 4 × 4 mm) on the mesial portion of the mandibular first molar (M1) of beagle dogs on both side. Mixture of FGF-2 and CO(3)Ap, vehicle and CO(3)Ap, or vehicle alone were administered to the defects and designated as groups FGF-2+CO(3)Ap, CO(3)Ap, and control, respectively. To assess the periodontal regeneration, radiographic analysis over time for 24 weeks, and micro computed tomography (μCT) and histological evaluation at 6 and 24 weeks were performed. RESULTS: For the regenerated tissue in the defect site, the mineral content of the FGF-2+CO(3)Ap group was higher than that of the CO(3)Ap group in the radiographic analysis at 6-24 weeks. In the context of new bone formation and replacement, the FGF-2+CO(3)Ap group exhibited significantly greater new bone volume and smaller CO(3)Ap volume than the CO(3)Ap group in the μCT analysis at 6 and 24 weeks. Furthermore, the density of the new bone in the FGF-2+CO(3)Ap group at 24 weeks was similar to those in the control and CO(3)Ap groups. Histological evaluation revealed that the length of the new periodontal ligament and cementum in the FGF-2+CO(3)Ap group was greater than that in the CO(3)Ap group at 6 weeks. We also examined the effect of the combined use of the FGF-2 and CO(3)Ap on the existing bone adjacent to the defect and demonstrated that the existing bone height and volume in the FGF-2+CO(3)Ap group remained significantly greater than those in the CO(3)Ap group. CONCLUSION: This study demonstrated that the combination of FGF-2 and CO(3)Ap was effective not only in enhancing new bone formation and replacing scaffold but also in maintaining the existing bone adjacent to the defect site in a beagle dog model of one-wall periodontal defect. Additionally, new periodontal tissues induced by FGF-2 and CO(3)Ap may follow a maturation process similar to that formed by spontaneous healing. This suggests that the combined use of FGF-2 and CO(3)Ap would promote periodontal regeneration in severe bony defects of periodontitis patient.