Periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 in combination with carbonate apatite granules or rhFGF-2 alone: 12-month randomized controlled trial.

OBJECTIVES: This randomized controlled trial compared the outcomes of recombinant human fibroblast growth factor (rhFGF)-2 plus carbonate apatite (CO3Ap) granules with rhFGF-2 alone in the treatment of intrabony periodontal defects. MATERIALS AND METHODS: Patients with Stage III Grade B/C periodontitis who had completed initial periodontal therapy and had intrabony defects with a depth of ≥ 3 mm were included. Defects were treated solely with rhFGF-2 (control) or rhFGF-2 plus CO3Ap (test). Periodontal parameters and a patient-reported outcome measure (PROM) were assessed at baseline, at 6, 9 and 12 months postoperatively. The primary outcome was the change in clinical attachment level (CAL) from baseline to 12 months postoperatively. Using the Friedman test with Dunn's post-test, intragroup data were compared over time, and Mann-Whitney U test was used to assess intergroup data at each time point. RESULTS: Forty-eight sites in 38 patients were subjected to analysis. At 12 months postoperatively, CAL in both groups showed a significant improvement from baseline (p < 0.001). CAL gain was 3.4 ± 1.3 mm in the test group and 3.2 ± 1.2 mm in the control group, with no significant intergroup difference (p = 0.567). Radiographic bone fill in the test group (67.2%) was significantly greater than in the control group (32.4%) (p < 0.001). PROM scores showed no difference between groups. CONCLUSIONS: At 12 months, the outcomes including CAL gain and PROM showed no significant differences between groups, although the combination treatment enhanced radiographic bone fill. CLINICAL RELEVANCE: The use of rhFGF-2 (with/without CO3Ap) could lead to significant improvement in clinical parameters in the treatment of intrabony periodontal defects. The benefit of adding CO3Ap to rhFGF-2 therapy needs further evaluation. CLINICAL TRIAL REGISTRATION NUMBER: The University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) : UMIN000040783.

A Case Report of Periodontal Regenerative Therapy Using Recombinant Human Fibroblast Growth Factor 2 and Deproteinized Bovine Bone Mineral with Non-incised Papillae Surgical Approach (NIPSA) for Angular Bone Defect in Patient with Stage III Grade C Periodontitis.

This report describes a case of Stage III Grade C periodontitis requiring periodontal regenerative therapy. The patient was a 19-year-old woman who presented with the chief complaint of gingival recession in the incisor region. An initial examination revealed that 45.3% of sites had a probing depth of ≥4 mm and 45.8% bleeding on probing. Radiographic examination showed angular bone resorption in #25, 26, 31, 36, and 46 and horizontal resorption in other regions. Initial periodontal therapy was implemented based on a clinical diagnosis of Stage III Grade C periodontitis (generalized aggressive periodontitis). Occlusal adjustment was also performed at sites showing premature contact (#26 and 36) after suppression of inflammation. Periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF) -2 was performed on #25, 26, and 46. Combination therapy with rhFGF-2 and deproteinized bovine bone mineral (DBBM) was performed on #31 and 36. A non-incised papillae surgical approach (NIPSA) was used on #31. Periodontal conditions were then re-evaluated and the patient placed on supportive periodontal therapy. Regenerative therapy using rhFGF-2 and DBBM with NIPSA yielded an improvement in clinical parameters and bone resorption. This improvement has been adequately maintained over a 12-month period. Continued care is needed to maintain stable periodontal conditions.

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.

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.

Periodontal Regenerative Therapy with Recombinant Human Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral in Patient with Chronic Periodontitis: An 18-month Follow-up Report.

This report describes a case of generalized chronic periodontitis requiring periodontal regenerative therapy. The patient was a 62-year-old man who presented with the chief complaint of gingival swelling in the molar region. An initial examination revealed that 31.6% of sites had a probing depth of ≥4 mm and 18.5% bleeding on probing. Radiographic examination revealed vertical bone resorption in #14, 25, 26, 27, 32, 37, 45, and 47, and horizontal resorption in other regions. Based on a clinical diagnosis of moderate chronic periodontitis, initial periodontal therapy consisting of plaque control and scaling and root planing was performed. Occlusal adjustment of premature contact sites was performed after inflammation was suppressed. Surgical periodontal therapy was subsequently performed at selected sites. Periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 was performed on #14, 25, 26, 32, and 37. Combination therapy with rhFGF-2 and deproteinized bovine bone mineral (DBBM) was performed on #45 and 47. Other sites with residual periodontal pockets were treated by open flap debridement, and #27 was extracted due to a bone defect exceeding the root apex. Progress was then reevaluated and the patient placed on supportive periodontal therapy. Periodontal regenerative therapy using rhFGF-2 in combination with DBBM resulted in an improvement in clinical parameters and vertical bone resorption. This improvement has been adequately maintained over an 18-month period. The periodontal treatment provided resulted in a marked improvement in the patient's oral health-related quality of life.

Surgical Treatment of Furcation Involvement Associated with Recurrence of Aggressive Periodontitis: A Case Report.

Here, we report a case of generalized chronic periodontitis with furcation involvement that was treated successfully by means of surgical intervention. The patient was a 43-year-old man requesting treatment for periodontal disease. An initial examination revealed 42% of sites with a probing depth of ≥4 mm and 42.9% of sites with bleeding on probing. The maxillary molars showed varying degrees of furcation involvement. Radiographic examination revealed bone resorption in the molar and mandibular anterior teeth regions. Microbiological examination of subgingival plaque revealed the presence of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia. The patient's oral health-related quality of life (OHRQL) was also assessed. Based on a clinical diagnosis of severe chronic periodontitis, initial periodontal therapy was performed. Plaque control, scaling and root planing, extraction, temporary fixed restoration, occlusal adjustment, and root canal treatment were implemented. Following reevaluation, open flap debridement was performed at selected sites. Root resection was performed on the distal root of #16. Prosthetic treatment was then initiated for recovery of oral function. After confirmation of appropriate occlusion and cleanability, the patient was placed on supportive periodontal therapy. Root resection improved cleanability. This clinical improvement has been adequately maintained over a 2-year period. The patient's OHRQL score showed a slight deterioration during the supportive periodontal therapy OK period, however. This indicates the need for further careful monitoring of periodontal conditions, as well as of how they are perceived by the patient themselves.

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.

Periodontal Regenerative Therapy with Enamel Matrix Derivative in Patient with Chronic Periodontitis: A 3.5-year Follow-up Report.

Here, we report periodontal treatment including regenerative therapy in a patient with generalized chronic periodontitis. The patient was a 53-year-old woman who presented with the chief complaint of gingival swelling and tooth mobility in the right maxillary molar region. An initial examination revealed 36% of sites with a probing depth of ≥4 mm and 15.5% with bleeding on probing. Radiographic examination revealed vertical bone resorption in #15, 24, 27, 34, 37, 45, and 47. Horizontal resorption was noted in other regions. The clinical diagnosis was moderate chronic periodontitis. Initial periodontal therapy consisted of plaque control, scaling, and root planing together with treatment for caries. Occlusal adjustment of premature contact sites was performed after suppression of inflammation. Periodontal regenerative therapy using enamel matrix derivative was performed on #15, 24, 34, 45, and 47. Other sites with residual periodontal pockets were treated by open flap debridement. Tooth #27 was extracted due to a bone defect exceeding the root apex; #37 was extracted due to frequent acute symptoms following periodontal surgery. Following re-evaluation, the patient was placed on supportive periodontal therapy. Periodontal regenerative therapy improved vertical bone resorption. This improvement has been adequately maintained over a 3 years 6 months period. Additional care is necessary, however, to further improve the patient's oral health-related quality of life during supportive periodontal therapy.

Enhanced healing of surgical periodontal defects in rats following application of a self-assembling peptide nanofibre hydrogel.

AIM: The aim of this study was to investigate the effects of a self-assembling peptide (SAP) nanofibre hydrogel on healing of surgical periodontal defects in rats. MATERIALS AND METHODS: In vitro interactions between rat periodontal ligament (PDL) cells and SAP hydrogel (2.5% RADA16) were assessed by cell proliferation assays. In vivo, maxillary first molars of 45 Wistar rats were extracted and after healing, bilateral periodontal defects were surgically created mesially in second molars. Defects were treated with RADA16, Matrigel, or left unfilled. After 2 and 4 weeks, defect healing was evaluated by microcomputed tomography, histological and immunohistochemical analyses. RESULTS: Periodontal ligament cells grown on RADA16 showed an gradual increase in proliferation up to 72 h. At 4 weeks post surgery, the bone volume fraction and trabecular thickness of defect areas in the RADA16 group were significantly greater than those in other groups. Histologically, enhanced new bone formation was observed in the RADA16 group. At 4 weeks, PDL-like collagen bundles ran oblique to the root surface in the RADA16 group. Expression levels of PCNA-positive cells, vascular endothelial growth factor and osteopontin in the RADA16 group were significantly greater than those in other groups. CONCLUSIONS: Within the limitations of the study, application of the SAP hydrogel promoted healing of surgical periodontal defects by enhancing cell recruitment and possibly angiogenesis.

Effect of poly (lactide-co-glycolide) (PLGA)-coated beta-tricalcium phosphate on the healing of rat calvarial bone defects: a comparative study with pure-phase beta-tricalcium phosphate.

OBJECTIVES: To investigate the effect of poly (lactide-co-glycolide) (PLGA)-coated ß-tricalcium phosphate (TCP) as a scaffold on bone regeneration in rat calvaria. MATERIAL AND METHODS: Bilateral critical-sized defects were created in the calvaria of 20 Sprague Dawley rats. Defects of each rat were filled with pure-phase ß-TCP or PLGA/ß-TCP, or left as unfilled control. The healing was evaluated by micro-computed tomography, histological, and immunohistochemical analyses. Tartrate-resistant acid phosphatase (TRAP) staining was also performed to assess the resorption activity. RESULTS: At 4 weeks, ingrowth of cells from the surrounding tissue into the ß-TCP and PLGA/ß-TCP biomaterials were observed in the defect area, and new bone formation had started. At 6 weeks, the value for defect closure in the ß-TCP group was significantly greater than that in the unfilled control (P < 0.01). A significantly greater level of new bone formation was found in the ß-TCP group (P < 0.01) and PLGA/ß-TCP group (P < 0.05) than that in the control group, while no significant difference was found between the ß-TCP and PLGA/ß-TCP groups. At both time points, the height of new tissue/biomaterial in the central third of the defect was significantly increased when the ß-TCP or PLGA/ß-TCP was used. Proliferating cell nuclear antigen -positive cells were observed around and inside the ß-TCP or PLGA/ß-TCP, and TRAP-positive cells were found at the surface of the biomaterials, suggesting that remodeling was occurring. CONCLUSION: The application of PLGA-coated ß-TCP could promote bone regeneration to similar extent as the ß-TCP biomaterial in this in vivo model.

Fibroblast growth factor-2 promotes healing of surgically created periodontal defects in rats with early, streptozotocin-induced diabetes via increasing cell proliferation and regulating angiogenesis.

AIM: To evaluate the effects of fibroblast growth factor (FGF)-2 on the healing of surgical periodontal defects in rats with early, streptozotocin-induced diabetes. MATERIALS AND METHODS: Fifty Wistar rats were assigned to streptozotocin-induced diabetes or non-diabetes group. Periodontal defects were surgically created at maxillary first molars. Defects were treated with hydroxypropyl cellulose (HPC) or FGF-2 with HPC. Defect fill was evaluated by microcomputed tomography. Histological and immunohistochemical analyses were performed. RESULTS: Compared to vehicle alone, FGF-2 treatment yielded significantly greater bone volume and trabecular thickness in diabetes group. Diabetes group displayed reduced new bone formation and significantly longer epithelial down-growth compared to non-diabetes group. In diabetes group, FGF-2 treatment increased PCNA-positive cells and new bone formation after 2 weeks and suppressed epithelial down-growth, but new cementum formation was minimal even after 4 weeks. In diabetes group, overexpression of vascular endothelial growth factor was evident in cells within connective tissue, and no significant enhancement was observed by FGF-2 treatment. FGF-2 increased the expression of α-smooth muscle actin in diabetes group. CONCLUSIONS: Treatment of surgical periodontal defects in diabetic rats with the single application of FGF-2 provided beneficial effects primarily on new bone formation via increasing cell proliferation and regulating angiogenesis.

Combined Effects of Fibroblast Growth Factor-2 and Carbonate Apatite Granules on Periodontal Healing: An In Vivo and In Vitro Study.

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.

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.