title: Periodontal wound healing/regeneration following the application of rhGDF-5 in a beta-TCP/PLGA carrier in critical-size supra-alveolar periodontal defects in dogs.
abstract: OBJECTIVE
  The objective of this study was to evaluate the effect of a novel recombinant human GDF-5 (rhGDF-5) construct intended for onlay and inlay indications on periodontal wound healing/regeneration.
  
  
  METHODS
  Contralateral, surgically created, critical-size, 6-mm, supra-alveolar periodontal defects in five adult Hound Labrador mongrel dogs received rhGDF-5 coated onto beta-tricalcium phosphate (beta-TCP) particles and immersed in a bioresorbable poly(lactic-co-glycolic acid) (PLGA) composite or the beta-TCP/PLGA carrier alone (control). The rhGDF-5 and control constructs were moulded around the teeth and allowed to set. The gingival flaps were then advanced; flap margins were adapted 3-4 mm coronal to the teeth and sutured. The animals were euthanized at 8 weeks post-surgery when block biopsies were collected for histometric analysis.
  
  
  RESULTS
  Healing was generally uneventful. A few sites exhibited minor exposures. Three control sites and one rhGDF-5 site (in separate animals) experienced more extensive wound dehiscencies. The rhGDF-5 and control constructs were easy to apply and exhibited adequate structural integrity to support the mucoperiosteal flaps in this challenging onlay model. Limited residual beta-TCP particles were observed at 8 weeks for both rhGDF-5/beta-TCP/PLGA and beta-TCP/PLGA control sites. The rhGDF-5/beta-TCP/PLGA sites showed significantly greater cementum (2.34 +/- 0.44 versus 1.13 +/- 0.25 mm, p=0.02) and bone (2.92 +/- 0.66 versus 1.21 +/- 0.30 mm, p=0.02) formation compared with the carrier control. Limited ankylosis was observed in four of five rhGDF-5/beta-TCP/PLGA sites but not in control sites.
  
  
  CONCLUSIONS
  Within the limitations of this study, the results suggest that rhGDF-5 is a promising candidate technology in support of periodontal wound healing/regeneration. Carrier and rhGDF-5 dose optimization are necessary before further advancement of the technology towards clinical evaluation.
authors.affiliation: U.S. Army Advanced Education Program in Periodontics, Ft. Gordon, GA, USA. david.kwon@us.army.mil
authors.forename: David H
authors.initials: DH
authors.lastname: Kwon
authors.forename: Frederick C
authors.initials: FC
authors.lastname: Bisch
authors.forename: Robert W
authors.initials: RW
authors.lastname: Herold
authors.forename: Cornelius
authors.initials: C
authors.lastname: Pompe
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bastone
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Rodriguez
authors.forename: Cristiano
authors.initials: C
authors.lastname: Susin
authors.forename: Ulf M E
authors.initials: UM
authors.lastname: Wikesjö
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects; D002130:Calcium Phosphates; D025021:Cementogenesis / Q000187:drug effects*; D004285:Dogs; D004337:Drug Carriers; D055428:Growth Differentiation Factor 5 / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D010513:Periodontal Ligament / Q000502:physiology; D010519:Periodontium / Q000601:surgery*; D011091:Polyesters; 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; D011091:Polyesters; D011994:Recombinant Proteins; C471130:beta-tricalcium phosphate-poly-L-lactide copolymer