The aim of this study was to evaluate longitudinal outcomes of recombinant human fibroblast growth factor (rhFGF)-2 plus deproteinized bovine bone mineral (DBBM) therapy in comparison with rhFGF-2 alone for treating periodontal intrabony defects. This study describes 4-year follow-up outcomes of the original randomized controlled trial. Intrabony defects in periodontitis patients were treated with rhFGF-2 (control) or rhFGF-2 plus DBBM (test). Clinical, radiographic, and patient-reported outcome (PRO) measures were used to evaluate the outcomes. Thirty-two sites were able to be followed up. At 4 years postoperatively, clinical attachment level (CAL) gains in the test and control groups were 3.5 ± 1.4 mm and 2.7 ± 1.4 mm, respectively, showing significant improvement from preoperative values but no difference between groups. Both groups showed an increase in radiographic bone fill (RBF) over time. At 4 years, the mean value for RBF in the test group (62%) was significantly greater than that in the control group (42%). In 1–2-wall defects, the test treatment yielded significantly greater RBF than the control treatment. No significant difference in PRO scores was noted between the groups. Although no significant difference in CAL gain was found between the groups at the 4-year follow-up, the combination treatment significantly enhanced RBF. Favorable clinical, radiographic outcomes, and PRO in both groups can be maintained for at least 4 years.

To date, enamel matrix derivative (EMD) has been considered to be one of the few biomaterials for clinical use capable of demonstrating true periodontal regeneration. The aim of this two-center prospective clinical study was to evaluate 2-year outcome of periodontal regenerative therapy using EMD in the treatment of intrabony defects, performed as an ‘advanced medical treatment’ under the national healthcare system in Japan. Patients with chronic periodontitis who have completed initial periodontal therapy at either of the two dental school clinics were enrolled. Each contributed at least one intrabony defect of ≥3 mm in depth. During surgery, EMD was applied to the defect following debridement. Twenty-two participants (mean age 55.2 years old, 9 men and 13 women) completed 2-year reevaluation, and a total of 42 defects were subjected to data analysis. Mean gains in clinical attachment level (CAL) at 1 and 2 years were 2.9 mm (38% of baseline CAL) and 3.1 mm (41%), respectively, both showing a significant improvement from baseline. There was also a significant reduction in probing depth (PD): mean reductions at 1 and 2 years were 3.2 and 3.3 mm, respectively. There was a progressive improvement in the mean percentages of bone fill from 26% at 1 year to 36% at 2 years. No significant difference in CAL gain at 2 years was found between 3-wall bone defects and other defect types combined. In multiple regression analysis, the baseline PD was significantly associated with CAL gain at 2 years. In this population of patients, the treatment of intrabony defects with EMD yielded clinically favorable outcomes, as assessed by periodontal and radiographical parameters, over a period of 2 years.

The aim of this study was to investigate the effects of fibroblast growth factor (FGF)-2 used in combination with deproteinized bovine bone mineral (DBBM) on the healing of experimental periodontal defects. Periodontal defects created in rats were treated by FGF-2, DBBM, FGF-2 + DBBM, or left unfilled. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing. In vitro cell viability/proliferation on DBBM with/without FGF-2 was assessed by WST-1. Cell behavior was analyzed using scanning electron and confocal laser scanning microscopy. Osteogenic differentiation was evaluated by staining with alkaline phosphatase and alizarin red. Bone volume fraction was significantly greater in FGF-2 and FGF-2 + DBBM groups than in other groups at 2 and 4 weeks postoperatively. In histological assessment, newly formed bone in FGF-2 and FGF-2 + DBBM groups appeared to be greater than other groups. Significantly greater levels of proliferating cell nuclear antigen-, vascular endothelial growth factor-, and osterix-positive cells were observed in FGF-2 and FGF-2 + DBBM groups compared to Unfilled group. In vitro, addition of FGF-2 to DBBM promoted cell viability/proliferation, attachment/spreading, and osteogenic differentiation. The combination therapy using FGF-2 and DBBM was similarly effective as FGF-2 alone in the healing of experimental periodontal defects. In certain bone defect configurations, the combined use of FGF-2 and DBBM may enhance healing via promotion of cell proliferation, angiogenesis, and osteogenic differentiation.

The aim of this study was to investigate in vivo and in vitro the effectiveness of the use of fibroblast growth factor (FGF)-2 with carbonate apatite (CO₃Ap) on periodontal healing. Periodontal defects created in the maxillary first molars in rats were treated with FGF-2, CO₃Ap, FGF-2 + CO₃Ap or left unfilled. Healing was evaluated using microcomputed tomography, histological, and immunohistochemical analyses. In vitro experiments were performed to assess cellular behaviors and the expression of osteoblastic differentiation markers in MC3T3-E1 cells. At 4 weeks, the bone volume fraction in the FGF-2 + CO₃Ap group was significantly greater than that in the CO₃Ap group, but there was no significant difference from the FGF-2 group. The FGF-2 + CO₃Ap group demonstrated greater new bone compared with the FGF-2 or CO₃Ap group. The FGF-2 + CO₃Ap group showed greater levels of osteocalcin-positive cells compared with the CO₃Ap group, but there was no significant difference from the FGF-2 group. In vitro, the FGF-2 + CO₃Ap group exhibited a greater extent of cell attachment and more elongated cells compared with the CO₃Ap group. Compared with the CO₃Ap group, the FGF-2 + CO₃Ap group showed significantly higher viability/proliferation, but the expressions of Runx2 and Sp7 were reduced. The results indicated that the use of FGF-2 with CO₃Ap enhanced healing in the periodontal defects. FGF-2 promoted cell attachment to and proliferation on CO₃Ap and regulated osteoblastic differentiation, thereby contributing to novel bone formation.

This report describes a case of generalized chronic periodontitis requiring periodontal regenerative therapy. The patient was a 56-year-old woman visiting the Tokyo Dental College Suidobashi Hospital with the chief complaint of swelling in the maxillary right gingiva. An initial examination revealed 34.0% of sites with a probing depth (PD) of ≥4 mm. The prevalence of sites with bleeding on probing was 32.7%. The plaque control record (PCR) score was 65.7%. Radiographic examination revealed angular bone resorption at #18 and 48. Horizontal absorption was also observed in other areas. The percent bone loss/age at #48 was 1.07. A clinical diagnosis of generalized chronic periodontitis (Stage III, Grade C) was made. Based on the clinical diagnosis of severe chronic periodontitis, initial periodontal therapy was performed. An improvement was observed in periodontal conditions at re-evaluation. The PCR score was 16.7%. Periodontal surgery was performed for teeth with a residual PD of ≥4 mm. Periodontal regenerative therapy using rhFGF-2 were performed on intrabony defects in #18 and 48. Open flap debridement was performed on #16, 26, and 27. Following evaluation, oral function was restored using all-ceramic crowns (#46). At 6 months postoperatively, the patient was transitioned to supportive periodontal therapy (SPT). During the 6-month SPT, stable periodontal conditions that facilitated a favourable level of plaque control were maintained.