title: Effect of recombinant human bone morphogenetic protein-4 dose on bone formation in a rat calvarial defect model.
abstract: BACKGROUND
  Bone morphogenetic proteins (BMPs) are being evaluated for periodontal and bone regenerative therapy. The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-4 (rhBMP-4) dose on local bone formation in a rat calvaria defect model.
  
  
  METHODS
  Calvarial, 8 mm diameter, critical-size osteotomy defects were created in 140 male Sprague-Dawley rats. Seven groups of 20 animals each received either 1) rhBMP-4 (2.5 microg) in an absorbable collagen sponge (ACS) carrier, 2) rhBMP-4 (5 microg)/ACS, 3) rhBMP-4 (2.5 microg) in a beta-tricalcium phosphate (beta-TCP) carrier, 4) rhBMP-4 (5 microg)/beta-TCP, 5) ACS or 6) beta-TCP carrier controls, or 7) a sham-surgery control, and were evaluated by histologic and histometric parameters following a 2- or 8-week healing interval (10 animals/group/healing interval).
  
  
  RESULTS
  Surgical implantation of rhBMP-4/ACS and rhBMP-4/beta-TCP resulted in enhanced local bone formation at both 2 and 8 weeks. Within the dose range examined, rhBMP-4 did not exhibit an appreciable dose-dependent response. Defect closure was not significantly different between the rhBMP-4/ACS and rhBMP-4/beta-TCP groups. New bone area of the rhBMP-4/ beta-TCP group was significantly greater than that of the rhBMP-4/ ACS group; however, bone density in the rhBMP-4/ACS group was significantly greater than that in the rhBMP-4/beta-TCP group at 8 weeks (P < 0.05).
  
  
  CONCLUSIONS
  rhBMP-4 combined with ACS or beta-TCP has a significant potential to induce bone formation in the rat calvaria defect model. Within the selected rhBMP-4 dose range and observation interval, there appeared to be no meaningful differences in bone formation.
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Korea.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Pang
authors.forename: Se-Ung
authors.initials: SU
authors.lastname: Im
authors.forename: Chang-Sung
authors.initials: CS
authors.lastname: Kim
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Jung-Kiu
authors.initials: JK
authors.lastname: Chai
authors.forename: Chong-Kwan
authors.initials: CK
authors.lastname: Kim
authors.forename: Soo-Boo
authors.initials: SB
authors.lastname: Han
authors.forename: Kyoo-Sung
authors.initials: KS
authors.lastname: Cho
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001847:Bone Diseases / Q000473:pathology / Q000601:surgery*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D002130:Calcium Phosphates; D003094:Collagen; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005781:Gelatin Sponge, Absorbable; D006801:Humans; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012886:Skull / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
chemical_list: C525809:BMP4 protein, human; D001672:Biocompatible Materials; C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; D004337:Drug Carriers; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate; D003094:Collagen