title: Evaluation of an injectable rhGDF-5/PLGA construct for minimally invasive periodontal regenerative procedures: a histological study in the dog.
abstract: OBJECTIVE
  To evaluate the injectability, biocompatibility, safety, and periodontal wound healing/regeneration following application of a novel bioresorbable recombinant human growth/differentiation factor-5 (rhGDF-5)/poly(lactic-co-glycolic acid) (PLGA) construct.
  
  
  METHODS
  Periodontal pockets (3 x 6 mm, width x depth) were surgically created over the buccal roots of the second and fourth mandibular pre-molars in eight adult Hound Labrador mongrel dogs. Surgeries including injection of the rhGDF-5/PLGA construct into the pockets were sequenced that four animals provided 2-/4-week and four animals 6-/8-week observations of sites receiving rhGDF-5/PLGA or serving as sham-surgery control.
  
  
  RESULTS
  The rhGDF-5/PLGA construct was easy to prepare and apply. Approximately 0.2 ml (93 microg rhGDF-5)/tooth was used. Clinical and radiographic healing was exemplary without adverse events. Healing was characterized by a non-specific connective tissue attachment, acellular/cellular cementum, periodontal ligament (PDL), bone regeneration, and a junctional epithelium. PLGA fragments were observed in 4/7, 2/8, and 1/8 sites at 2, 4, and 6 weeks, respectively. Associated inflammatory reactions exhibited no limiting effect on periodontal wound healing/regeneration. Root resorption/ankylosis was not observed. Bone formation showed apparent increased maturity (lamellar bone) at 6 weeks in sites receiving rhGDF-5/PLGA compared with the control. Both protocols exhibited significant increases in PDL, cementum, and bone regeneration over time, without significant differences between treatments. In time, PDL and cementum regeneration was twofold greater for the control at 4 weeks (p=0.04) while increased bone formation was observed at sites receiving rhGDF-5/PLGA (p<0.01).
  
  
  CONCLUSIONS
  In conclusion, the rhGDF-5/PLGA construct appears to be a safe technology for injectable, ease-of-use application of rhGDF-5-stimulated periodontal wound healing/regeneration. Additional work to optimize the polymer carrier and rhGDF-5 release kinetics/dose might be required before evaluating the efficacy of this technology in clinical settings using minimally invasive approaches.
authors.affiliation: US Army Advanced Education Program in Periodontics, Ft. Gordon, GA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Kwon
authors.forename: William
authors.initials: W
authors.lastname: Bennett
authors.forename: Samuel
authors.initials: S
authors.lastname: Herberg
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bastone
authors.forename: Susanne
authors.initials: S
authors.lastname: Pippig
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; D016301:Alveolar Bone Loss / Q000209:etiology / Q000628:therapy; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D004195:Disease Models, Animal; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage; D055428:Growth Differentiation Factor 5 / Q000008:administration & dosage / Q000502:physiology*; D016557:Guided Tissue Regeneration, Periodontal / Q000379:methods*; D006801:Humans; D015552:Injections, Intralesional; D019344:Lactic Acid / Q000008:administration & dosage; D008297:Male; D008334:Mandible / Q000187:drug effects / Q000601:surgery; D010514:Periodontal Pocket / Q000150:complications / Q000188:drug therapy*; D010519:Periodontium / Q000187:drug effects* / Q000502:physiology; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011994:Recombinant Proteins; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D055428:Growth Differentiation Factor 5; D011994:Recombinant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid