title: A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/β-TCP for periodontal regeneration.
abstract: OBJECTIVE
  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 β-tricalcium phosphate (β-TCP) carrier rhGDF-5/β-TCP into periodontal defects in man.
  
  
  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/β-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 β-TCP.
  
  
  RESULTS
  Sites receiving rhGDF-5/β-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/β-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/β-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 β-TCP occupied 8.4 ± 11.5% of the area of interest in biopsies of patients receiving rhGDF-5/β-TCP. Five biopsies (one rhGDF-5/β-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/β-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.
authors.affiliation: Department of Periodontology, School of Dentistry, University of Aarhus, Aarhus, Denmark. stavropoulos@odont.au.dk
authors.forename: Andreas
authors.initials: A
authors.lastname: Stavropoulos
authors.forename: Peter
authors.initials: P
authors.lastname: Windisch
authors.forename: Istvan
authors.initials: I
authors.lastname: Gera
authors.forename: Björn
authors.initials: B
authors.lastname: Capsius
authors.forename: Anton
authors.initials: A
authors.lastname: Sculean
authors.forename: Ulf M E
authors.initials: UM
authors.lastname: Wikesjö
mesh_terms: D000328:Adult; D016301:Alveolar Bone Loss / Q000188:drug therapy / Q000601:surgery; D001861:Bone Regeneration; D002130:Calcium Phosphates; D055113:Chronic Periodontitis / Q000188:drug therapy* / Q000601:surgery*; D003739:Dental Cementum / Q000502:physiology; D004337:Drug Carriers; D005260:Female; D055428:Growth Differentiation Factor 5 / Q000008:administration & dosage*; D016557:Guided Tissue Regeneration, Periodontal / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010513:Periodontal Ligament / Q000502:physiology; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012038:Regeneration; D018709:Statistics, Nonparametric
chemical_list: D002130:Calcium Phosphates; D004337:Drug Carriers; D055428:Growth Differentiation Factor 5; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate