title: Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: histologic observations.
abstract: BACKGROUND
  Studies using ectopic rodent, orthotopic canine, and non-human primate models show that bone morphogenetic proteins (BMPs) coated onto titanium surfaces induce local bone formation. The objective of this study was to examine the ability of recombinant human BMP-2 (rhBMP-2) coated onto a titanium porous oxide implant surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge.
  
  
  METHODS
  Bilateral, critical-size, 5 mm, supra-alveolar, peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml, and six animals received implants coated with rhBMP-2 at 3.0 mg/ml or uncoated control. Treatments were randomized between jaw quadrants. The mucoperiosteal flaps were advanced, adapted and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7 and 8 post-surgery when they were euthanized for histologic evaluation.
  
  
  RESULTS
  Jaw quadrants receiving implants coated with rhBMP-2 exhibited gradually regressing swelling that became hard to palpate disguising the contours of the implants. The histologic evaluation showed robust bone formation reaching or exceeding the implant platform. The newly formed bone exhibited characteristics of the adjoining resident Type II bone including cortex formation for sites receiving implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml. Sites receiving implants coated with rhBMP-2 at 3.0 mg/ml exhibited more immature trabecular bone formation, seroma formation and peri-implant bone remodelling resulting in undesirable implant displacement. Control implants exhibited minimal, if any, bone formation. Thus, implants coated with rhBMP-2 at 0.75, 1.5 and 3.0 mg/ml exhibited significant bone formation (height and area) compared with the sham-surgery control averaging (+/-SD) 4.4+/-0.4, 4.2+/-0.7 and 4.2+/-1.2 versus 0.8+/-0.3 mm; and 5.0+/-2.2, 5.6+/-2.2 and 7.4+/-3.5 versus 0.7+/-0.3 mm(2), respectively (p<0.01). All the treatment groups exhibited clinically relevant osseointegration.
  
  
  CONCLUSIONS
  rhBMP-2 coated onto titanium porous oxide implant surfaces induced clinically relevant local bone formation including vertical augmentation of the alveolar ridge and osseointegration. Higher concentrations/doses were associated with untoward effects.
authors.affiliation: Laboratory for Applied Periodontal and Craniofacial Regeneration, Medical College of Georgia, School of Dentistry, Augusta, GA 30912, USA. uwikesjo@mcg.edu
authors.forename: Ulf M E
authors.initials: UM
authors.lastname: Wikesjö
authors.forename: Mohammed
authors.initials: M
authors.lastname: Qahash
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Polimeni
authors.forename: Cristiano
authors.initials: C
authors.lastname: Susin
authors.forename: Richard H
authors.initials: RH
authors.lastname: Shanaman
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rohrer
authors.forename: John M
authors.initials: JM
authors.lastname: Wozney
authors.forename: Jan
authors.initials: J
authors.lastname: Hall
mesh_terms: D016301:Alveolar Bone Loss / Q000139:chemically induced; D000540:Alveolar Ridge Augmentation / Q000009:adverse effects / Q000379:methods*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000009:adverse effects / Q000494:pharmacology*; D015921:Dental Implants; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020007:Implants, Experimental; D008297:Male; D016348:Osseointegration / Q000187:drug effects*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D049291:Seroma / Q000139:chemically induced; D013499:Surface Properties; D014025:Titanium; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020099:Coated Materials, Biocompatible; D015921:Dental Implants; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C009495:titanium dioxide; D014025:Titanium