A Randomized Clinical Trial Evaluating rh-FGF-2/β-TCP in Periodontal Defects

Abstract

Biological mediators have been used to enhance periodontal regeneration. The aim of this prospective randomized controlled study was to evaluate the safety and effectiveness of 3 doses of fibroblast growth factor 2 (FGF-2) when combined with a β-tricalcium phosphate (β-TCP) scaffold carrier placed in vertical infrabony periodontal defects in adult patients. In this double-blinded, dose-verification, externally monitored clinical study, 88 patients who required surgical intervention to treat a qualifying infrabony periodontal defect were randomized to 1 of 4 treatment groups-β-TCP alone (control) and 0.1% recombinant human FGF-2 (rh-FGF-2), 0.3% rh-FGF-2, and 0.4% rh-FGF-2 with β-TCP-following scaling and root planing of the tooth prior to a surgical appointment. Flap surgery was performed with EDTA conditioning of the root prior to device implantation. There were no statistically significant differences in patient demographics and baseline characteristics among the 4 treatment groups. When a composite outcome of gain in clinical attachment of 1.5 mm was used with a linear bone growth of 2.5 mm, a dose response pattern detected a plateau in the 0.3% and 0.4% rh-FGF-2/β-TCP groups with significant improvements over control and 0.1% rh-FGF-2/β-TCP groups. The success rate at 6 mo was 71% in the 2 higher-concentration groups, as compared with 45% in the control and lowest treatment groups. Percentage bone fill in the 2 higher-concentration groups was 75% and 71%, compared with 63% and 61% in the control and lowest treatment group. No increases in specific antibody to rh-FGF-2 were detected, and no serious adverse events related to the products were reported. The results from this multicenter trial demonstrated that the treatment of infrabony vertical periodontal defects can be enhanced with the addition of rh-FGF-2/β-TCP (ClinicalTrials.gov NCT01728844).

Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three-Dimensional Woven-Fabric Scaffold for Periodontitis

“…Previous clinical studies incorporated growth factors into their scaffold to stimulate periodontal regeneration, but they consistently yielded lower LBG values compared to those observed in the present study: rhPDGF-BB/ β -TCP (3.3 mm at 24 months) [19], rh-FGF-2/ β -TCP (3.7 mm at 6 months) [20], rh-FGF2/hydroxypropyl cellulose (1.9 mm at 9 months), or EMD (1.3 mm at 9 months) [21]. Altogether, these data demonstrate the importance of stem cell therapy for an effective periodontal regeneration.…”

Evaluation of Recombinant Human FGF-2 and PDGF-BB in Periodontal Regeneration: A Systematic Review and Meta-Analysis

“…Four of the RCTs evaluated the efficacy of rhFGF-2 in treating periodontal infrabony defects (Cochran 24 , Kitamura 30 , Kitamura 31 and Kitamura 32 ), while the rest evaluated the efficacy of rhPDGF-BB on either periodontal infrabony defects (Mishra 22 , Jayakumar 27 , Maroo and Murthy 28 , Nevins 33 , Thakare 36 ) or gingival recession (Carney 23 , Deshpnade 25 , McGuire 29 ). In the four RCTs that dealt with the efficacy of rhFGF-2, a total of 5 different concentrations were utilized to assess their differential impact on several dependent variables, including bone fill percentage (BF%), linear bone growth(LBG) and gains in clinical attach levels (CAL-G).…”

“…Some included patients with periodontal osseous defects 22, 27, 28, 33, 36 while others selected a sample of patients who suffered from gingival recession 23, 25, 29 . As for research into rhFGF-2, as many as five distinct doses were used in four of the RCTs, creating clinical ambiguity concerning the most effective concentration of rhFGF-2 24, 30–32 . Such ambiguities created the need for a critical review to develop quantifiable evidence-based guidelines for clinical utilization.…”

“…Unfortunately, each of these studies suffered from limitations that weakened their clinical value (The problems will be identified and discussed below). Subsequent to these studies, several later RCTs were reported 24, 28, 32 , which significantly enlarged the overall sample size for our meta-analysis. This permitted us to independently evaluate the clinical efficacy of rhFGF-2 and rhPDGF-BB with different specific concentrations in periodontal repair.…”

Absorbable collagen sponges loaded with recombinant bone morphogenetic protein 9 induces greater osteoblast differentiation when compared to bone morphogenetic protein 2

“…Examples of these include the use of platelet‐derived growth factor for periodontal and peri‐implant defects (Kaigler et al, 2011), enamel matrix derivative for periodontal intrabony defects (Miron et al, 2016), and fibroblast growth factor two for periodontal defects (Cochran et al, 2016). One growth factor that has received widespread use for the regeneration of pure bone defect is that of bone morphogenetic protein 2 (BMP2) utilized across many fields of medicine (Carreira et al, 2015; Lin, Lim, Chan, Giannobile, & Wang, 2015; Schroeder et al, 2016).…”