title: Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primates.
abstract: BACKGROUND
  Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone.
  
  
  METHODS
  rhBMP-2-coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP-2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP-2 (0.2 mg/ml). Contra-lateral jaw quadrants received three TPO implants without rhBMP-2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis.
  
  
  RESULTS
  Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP-2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone-implant contact pattern regardless of rhBMP-2 concentration resulting in significant osseointegration; rhBMP-2 (2.0 mg/ml): 43% and rhBMP-2 (0.2 mg/ml): 37%. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone-implant contact ( approximately 75%; p<0.05). There were no statistically significant differences between rhBMP-2-coated and control implants relative to any other parameter including peri-implant and intra-thread bone density.
  
  
  CONCLUSIONS
  rhBMP-2-coated TPO implants enhanced/accelerated local bone formation in Type IV bone in a dose-dependent fashion in non-human primates resulting in significant osseointegration. rhBMP-2-induced de novo bone formation did not reach the level of osseointegration observed in native resident bone within the 16-week interval.
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: Yi-Hao
authors.initials: YH
authors.lastname: Huang
authors.forename: Andreas V
authors.initials: AV
authors.lastname: Xiropaidis
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Sorensen
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rohrer
authors.forename: Hari S
authors.initials: HS
authors.lastname: Prasad
authors.forename: John M
authors.initials: JM
authors.lastname: Wozney
authors.forename: Jan
authors.initials: J
authors.lastname: Hall
mesh_terms: D000818:Animals; D015519:Bone Density; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D001842:Bone and Bones / Q000033:anatomy & histology; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003758:Dental Implantation, Endosseous; D015921:Dental Implants; D003764:Dental Materials; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020007:Implants, Experimental; D008251:Macaca; D008297:Male; D008437:Maxilla / Q000601:surgery; D008856:Microscopy, Fluorescence; D016348:Osseointegration / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D013499:Surface Properties; D014025:Titanium; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020099:Coated Materials, Biocompatible; D015921:Dental Implants; D003764:Dental Materials; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C009495:titanium dioxide; D014025:Titanium