Periodontal Regenerative Therapy Using rhFGF-2 and Deproteinized Bovine Bone Mineral versus rhFGF-2 Alone: 4-Year Extended Follow-Up of a Randomized Controlled Trial.

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.

Healing of Experimental Periodontal Defects Following Treatment with Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral.

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.

Surgical Periodontal Therapy with Recombinant Human Fibroblast Growth Factor-2 in Treatment of Chronic Periodontitis: A Case Report with 2-year Follow-up.

We report a case of generalized chronic periodontitis requiring periodontal regenerative therapy. The patient was a 53-year-old woman who presented with the chief complaint of gingival swelling. An initial examination revealed 31.5% of sites with a probing depth of ≥4 mm and 46.3% with bleeding on probing. Radiographic examination showed vertical bone resorption in tooth #33. Horizontal adsorption was also observed in other areas. Based on a clinical diagnosis of severe generalized chronic periodontitis, initial periodontal therapy consisting of plaque control, scaling and root planing, occlusal adjustment, caries treatment, and splint placement was performed. After re-evaluation, surgical periodontal treatment was performed at selected sites. Periodontal regeneration therapy with recombinant human fibroblast growth factor (rhFGF)-2 was performed at #33. Two other sites (#14, 15), which had residual periodontal pockets, were treated by open-flap debridement. After re-evaluation, the patient was placed on a maintenance program. Periodontal regenerative therapy with rhFGF-2 resulted in an improvement in angular bone resorption, which has been properly maintained for 2 years. Continued care is needed to maintain stable periodontal conditions.

Periodontal surgery using rhFGF-2 with deproteinized bovine bone mineral or rhFGF-2 alone: 2-year follow-up of a randomized controlled trial.

AIM: To compare outcomes of rhFGF-2 + DBBM therapy with rhFGF-2 alone in the treatment of intrabony defects. This study provides 2-year follow-up results from the previous randomized controlled trial. MATERIALS AND METHODS: Defects were randomly allocated to receive rhFGF-2 + DBBM (test) or rhFGF-2 (control). Treated sites were re-evaluated at 2 years postoperatively, using original clinical and patient-centred measures. RESULTS: Thirty-eight sites were available for re-evaluation. At 2 years, both groups showed a significant improvement in clinical attachment level (CAL) from baseline. A gain in CAL of 3.4 ± 1.3 mm in the test group and 3.1 ± 1.5 mm in the control group was found. No significant inter-group difference was noted. Both groups showed a progressive increase in radiographic bone fill (RBF). The test treatment yielded greater RBF (56%) compared with the control group (41%). The control treatment performed better in contained defects in terms of CAL and RBF. There was no significant difference in patient-reported outcomes between groups. CONCLUSIONS: At 2-year follow-up, the test and cotrol treatments were similarly effective in improving CAL, whereas the test treatment achieved a significantly greater RBF. In both treatments, favourable clinical, radiographic, and patient-reported outcomes can be sustained for at least 2 years. TRIAL REGISTRATION: The University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) 000025257.

Treatment with functionalized designer self-assembling peptide hydrogels promotes healing of experimental periodontal defects.

BACKGROUND/OBJECTIVES: It has been reported that self-assembling peptide (SAP) hydrogels with functionalized motifs enhance proliferation and migration of host cells. How these designer SAP hydrogels perform in the treatment of periodontal defects remains unknown. This study aimed to test the potential of local application of designer SAP hydrogels with two different functionalized motifs in the treatment of experimental periodontal defects. MATERIAL AND METHODS: In vitro, viability/proliferation of rat periodontal ligament-derived cells (PDLCs) cultured on an SAP hydrogel RADA16 and RADA16 with functionalized motifs, PRG (integrin binding sequence) and PDS (laminin cell adhesion motif), was assessed. Cell morphology was analyzed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In vivo, standardized periodontal defects were made mesially in the maxillary first molars of Wistar rats. Defects received RADA16, PRG, PDS or left unfilled. At 2 or 4 weeks postoperatively, healing was assessed by microcomputed tomography, histological and immunohistochemical methods. RESULTS: Viability/proliferation of PDLCs was significantly greater on PRG than on RADA16 or PDS at 72 hours. rPDLCs in the PRG group showed enhanced elongations and cell protrusions. In vivo, at 4 weeks, bone volume fractions in the PRG and PDS groups were significantly greater than the RADA16 group. Histologically, bone formation was more clearly observed in the PRG and PDS groups compared with the RADA16 group. At 4 weeks, epithelial downgrowth in the hydrogel groups was significantly reduced compared to the Unfilled group. In Azan-Mallory staining, PDL-like bundles ran in oblique direction in the hydrogel groups. At 2 weeks, in the area near the root, proliferating cell nuclear antigen (PCNA)-positive cells were detected significantly more in the PRG group than other groups. At 4 weeks, in the middle part of the defect, a significantly greater level of vascular endothelial growth factor (VEGF)-positive cells and α-smooth muscle actin (SMA)-positive blood vessels were observed in the PRG group than in other groups. CONCLUSION: The results indicate that local application of the functionalized designer SAP hydrogels, especially PRG, promotes periodontal healing by increasing cell proliferation and angiogenesis.

Combined effects of systemic parathyroid hormone (1-34) and locally delivered neutral self-assembling peptide hydrogel in the treatment of periodontal defects: An experimental in vivo investigation.

AIM: To evaluate in vivo combination therapy of systemic parathyroid hormone (PTH) and locally delivered neutral self-assembling peptide (SAP) hydrogel for periodontal treatment. MATERIALS AND METHODS: Viability/proliferation of rat periodontal ligament cells in a neutral SAP nanofibre hydrogel (SPG-178) was evaluated using WST-1 assay. Periodontal defects were created mesially to the maxillary first molars in 40 Wistar rats. Defects were filled with 1.5% SPG-178 or left unfilled. Animals received PTH (1-34) or saline injections every 2 days. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing at 2 or 4 weeks postoperative. RESULTS: At 72 hr, cells in 1.5% SPG-178 showed increased viability/proliferation compared to cells in 0.8% SPG-178 or untreated controls. In vivo, systemic PTH resulted in significantly greater bone volume in the Unfilled group at 2 weeks (p = .01) and 4 weeks (p < .0001) than in the saline control. At 4 weeks, a significantly greater bone volume was observed in the PTH/SPG-178 (p = .0003) and PTH/Unfilled (p = .004) groups than in Saline/SPG-178 group. Histologically, greater bone formation was observed in PTH/SPG-178 at 4 weeks than in other groups. In the PTH/SPG-178 group, increased proportions of PCNA-, VEGF-, and Osterix-positive cells were observed in the treated sites. CONCLUSIONS: These findings suggest that intermittent systemic PTH and locally delivered neutral SAP hydrogel enhance periodontal healing.

Treatment of intrabony periodontal defects using rhFGF-2 in combination with deproteinized bovine bone mineral or rhFGF-2 alone: A 6-month randomized controlled trial.

AIM: To evaluate the use of recombinant human fibroblast growth factor (rhFGF)-2 in combination with deproteinized bovine bone mineral (DBBM) compared with rhFGF-2 alone, in the treatment of intrabony periodontal defects. MATERIALS AND METHODS: Patients with periodontitis who had received initial periodontal therapy and had intrabony defects of ≥ 3 mm in depth were enrolled. Sites were randomly assigned to receive a commercial formulation of 0.3% rhFGF-2 + DBBM (test) or rhFGF-2 alone (control). Clinical parameters and a patient-reported outcome measure (PROM) were evaluated at baseline and at 3 and 6 months postoperatively. RESULTS: Twenty-two sites in each group were evaluated. A significant improvement in clinical attachment level (CAL) from baseline was observed in both groups at 6 months postoperatively. CAL gain was 3.16 ± 1.45 mm in the test group and 2.77 ± 1.15 mm in the control group, showing no significant difference between groups. Radiographic bone fill was significantly greater in the test group (47.2%) than in the control group (29.3%). No significant difference in PROM between groups was observed. CONCLUSIONS: At 6 months, no significant difference in CAL gain or PROM between the two treatments was observed, although combination therapy yielded an enhanced radiographic outcome.