Periodontal repair in dogs: evaluation of a bioabsorbable space-providing macroporous membrane with recombinant human bone morphogenetic protein-2.
BACKGROUND
Recombinant human bone morphogenetic protein-2 (rhBMP-2) technologies have been shown to significantly support alveolar bone formation. Biomaterial limitations, however, have restricted the biologic potential for onlay indications. The objective of this study was to evaluate regeneration of alveolar bone and periodontal attachment, and biomaterials reaction following surgical implantation of a space-providing, bioabsorbable, macroporous, polyglycolic acid-trimethylene carbonate (PGA-TMC) membrane combined with a rhBMP-2 construct in a discriminating onlay defect model.


METHODS
Routine supraalveolar periodontal defects were created at the mandibular premolar teeth in 9 beagle dogs. Contralateral jaw quadrants in subsequent animals were randomly assigned to receive the dome-shaped PGA-TMC (100 to 120 microm pores) membrane with rhBMP-2 (0.2 mg/mL) in a bioresorbable hyaluronan (Hy) carrier or the PGA-TMC membrane with Hy alone (control). The gingival flaps were advanced to submerge the membranes and teeth and sutured. Animals were euthanized at 8 and 24 weeks postsurgery for histologic observations.


RESULTS
Jaw quadrants receiving the PGA-TMC membrane alone experienced exposures at various time points throughout the study. Jaw quadrants receiving the PGA-TMC/rhBMP-2 combination remained intact, although one site experienced a late minor exposure. Newly formed alveolar bone approached and became incorporated into the macroporous PGA-TMC membrane in sites receiving rhBMP-2. The PGA-TMC biomaterial was occasionally associated with a limited inflammatory reaction. Residual PGA-TMC could not be observed at 24 weeks postsurgery. Residual Hy could not be observed at any time interval. Regeneration of alveolar bone height (means +/- SD) was significantly increased in sites receiving the PGA-TMC/rhBMP 2 combination compared to control (3.8 +/- 1.3 versus 0.7 +/- 0.5 mm at 8 weeks and 4.6 +/- 0.8 versus 2.1 +/- 0.4 mm at 24 weeks; P < 0.05). Limited cementum regeneration was observed for PGA-TMC/rhBMP-2 and PGA-TMC control sites. Ankylosis compromised regeneration in sites receiving PGA-TMC/rhBMP-2.


CONCLUSIONS
The bioabsorbable, space-providing, macroporous PGA-TMC membrane appears to be a compatible biomaterial for bone augmentation procedures. rhBMP-2 significantly enhances alveolar bone augmentation and soft tissue healing when combined with the PGA-TMC membrane.
Wikesjö
Ulf M E
UM
Laboratory for Applied Periodontal and Craniofacial Regeneration, Temple University School of Dentistry, Philadelphia, PA 19140, USA. uwikesjo@temple.edu
Lim
Won Hee
WH
Thomson
Robert C
RC
Cook
Alonzo D
AD
Wozney
John M
JM
Hardwick
W Ross
WR
D020341:Absorbable Implants; D016301:Alveolar Bone Loss / Q000601:surgery*; D000539:Alveolar Process / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000502:physiology*; D003739:Dental Cementum / Q000473:pathology / Q000503:physiopathology; D004146:Dioxanes; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D006820:Hyaluronic Acid; D008297:Male; D016555:Matched-Pair Analysis; D008567:Membranes, Artificial; D010513:Periodontal Ligament / Q000473:pathology / Q000503:physiopathology; D011100:Polyglycolic Acid; D011897:Random Allocation; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004146:Dioxanes; D008567:Membranes, Artificial; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D011100:Polyglycolic Acid; C443643:trimethylene carbonate; D006820:Hyaluronic Acid