A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/β-TCP for periodontal regeneration

Aim: The primary objective of this study was to clinically and histologically evaluate periodontal wound healing/regeneration following surgical implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a particulate beta-tricalcium phosphate (beta-TCP) carrier rhGDF-5/beta-TCP into periodontal defects in man. Material & Methods: Twenty chronic periodontitis patients, each with at least one tooth scheduled for extraction exhibiting a probing depth >= 6 mm and an associated intra-bony defect > 4 mm participated in the study upon written informed consent. Subjects (one defect/patient) were randomized to receive open flap debridement (OFD) + rhGDF-5/beta-TCP (n = 10) or OFD alone (control; n = 10). Block biopsies of the defect sites were collected at 6 months post-surgery and prepared for the histological evaluation. Two masked examiners evaluated the deepest aspect of each defect site relative to bone (height/area), periodontal ligament (PDL) and cementum regeneration, and residual beta-TCP. Results: Sites receiving rhGDF-5/beta-TCP showed numerically greater PD reduction (3.7 +/- 1.2 versus 3.1 +/- 1.8 mm; p = 0.26), less gingival recession (0.5 +/- 0.8 versus 1.4 +/- 1.0 mm; p < 0.05) and greater clinical attachment level (CAL) gain (3.2 +/- 1.7 versus 1.7 +/- 2.2 mm; p = 0.14) at the deepest aspect of the defect compared with OFD alone. One biopsy in the rhGDF-5/beta-TCP and four biopsies in the OFD group were deemed as not evaluable. Histologically, bone regeneration height was almost threefold greater for the rhGDF-5/beta-TCP treatment compared with OFD alone (2.19 +/- 1.59 versus 0.81 +/- 1.02 mm; p = 0.08). Similarly an almost twofold increase was observed for PDL (2.16 +/- 1.43 versus 1.23 +/- 1.07 mm; p = 0.26), cementum (2.16 +/- 1.43 versus 1.23 +/- 1.07 mm; p = 0.26) and bone regeneration area (0.74 +/- 0.69 versus 0.32 +/- 0.47 mm(2); p = 0.14). Root resorption/ankylosis was not observed. Residual beta-TCP occupied 8.4 +/- 11.5% of the area of interest in biopsies of patients receiving rhGDF-5/beta-TCP. Five biopsies (one rhGDF-5/beta-TCP, four OFD) were deemed unsuitable to allow a meaningful histological or histometrical evaluation. Conclusions: Descriptive statistics showed greater PD reduction and CAL gain, and greater alveolar bone regeneration and periodontal regeneration at sites that received rhGDF-5/beta-TCP compared to control. However, these differences were not statistically significant. Future studies with larger sample sizes will have to be conducted to verify these findings.