title: Growth/differentiation factor-5 significantly enhances periodontal wound healing/regeneration compared with platelet-derived growth factor-BB in dogs.
abstract: OBJECTIVE
  Recombinant human growth/differentiation factor-5 (rhGDF-5) in a particulate beta-tricalcium phosphate (beta-TCP) carrier is being evaluated to support periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following an established clinical (benchmark) protocol including surgical implantation of rhGDF-5/beta-TCP in comparison with that following implantation of recombinant human platelet-derived growth factor-BB (rhPDGF) combined with a particulate beta-TCP biomaterial using an established canine defect model.
  
  
  METHODS
  Bilateral, 4 x 5 mm (width x depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in five adult Beagle dogs. Defect sites were randomized to receive rhGDF-5/beta-TCP or the rhPDGF construct followed by wound closure for primary intention healing. The animals were sacrificed following an 8-week healing interval for histological and histometric examination.
  
  
  RESULTS
  Clinical healing was generally uneventful. Sites receiving rhGDF-5/beta-TCP exhibited a significantly enhanced cementum formation compared with sites receiving the rhPDGF construct, averaging (+/-SD) 4.49+/-0.48 versus 2.72+/-0.91 mm (p<0.001). Similarly, bone regeneration height and area were significantly enhanced at sites receiving rhGDF-5/beta-TCP versus that of the rhPDGF construct averaging, 3.08+/-0.74 versus 1.29+/-0.78 mm (p<0.001) and 6.03+/-1.28 versus 2.98+/-2.61 mm(2) (p<0.01), respectively. Cementum regeneration included cellular/acellular mixed (extrinsic/intrinsic) fibre cementum at sites receiving rhGDF-5/beta-TCP; sites receiving the rhPDGF/beta-TCP showed a pre-dominantly acellular cementum. Newly formed cementum generally extended above the adjoining alveolar bone. Both protocols displayed beta-TCP residues apparently undergoing resorption. Application of both materials appears safe, as they were associated with limited, if any, adverse events.
  
  
  CONCLUSIONS
  rhGDF-5/beta-TCP shows a significant potential to support/accelerate periodontal wound healing/regeneration. Application of rhGDF-5/beta-TCP appears safe and should be further evaluated in human clinical trials.
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Korea.
authors.forename: Hyuk-Rak
authors.initials: HR
authors.lastname: Kwon
authors.forename: Ulf M E
authors.initials: UM
authors.lastname: Wikesjö
authors.forename: Jung-Chul
authors.initials: JC
authors.lastname: Park
authors.forename: Young-Taek
authors.initials: YT
authors.lastname: Kim
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bastone
authors.forename: Susanne D
authors.initials: SD
authors.lastname: Pippig
authors.forename: Chong-Kwan
authors.initials: CK
authors.lastname: Kim
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy*; D000818:Animals; D000077214:Becaplermin; D001861:Bone Regeneration / Q000187:drug effects; D002130:Calcium Phosphates; D025021:Cementogenesis / Q000187:drug effects; D003739:Dental Cementum / Q000187:drug effects; D004285:Dogs; D004337:Drug Carriers; D055428:Growth Differentiation Factor 5 / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D017622:Periodontal Attachment Loss / Q000188:drug therapy*; D010513:Periodontal Ligament / Q000187:drug effects; D010519:Periodontium / Q000601:surgery; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology* / Q000627:therapeutic use; D020574:Proto-Oncogene Proteins c-sis; D011897:Random Allocation; D011994:Recombinant Proteins; D012038:Regeneration / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D002130:Calcium Phosphates; D004337:Drug Carriers; D055428:Growth Differentiation Factor 5; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate; D000077214:Becaplermin