title: Recombinant human bone morphogenetic protein-2 stimulates bone formation during interfrontal suture expansion in rabbits.
abstract: BACKGROUND
  Suture expansion stimulates bone growth to correct craniofacial deficiencies but has a high potential of treatment relapse. The objective of this study was to investigate whether there is a dose-dependent relationship between the recombinant human bone morphogenetic protein-2 (rhBMP-2) and bone formation during suture expansion.
  
  
  METHODS
  Fifty 6-week-old male New Zealand white rabbits were randomly assigned to 5 groups to receive 0 (control), 0.01, 0.025, 0.1, or 0.4 mg/mL of rhBMP-2 delivered by absorbable collagen sponge placed over the interfrontal suture. The suture was expanded for 33 days by 200 g of constant force via a spring anchored with 2 miniscrew implants. Distance of suture expansion, suture volume, and cross-sectional area after expansion were measured using radiographs with bone markers and microcomputed tomography. Suture widths and mineralization appositional rates were calculated based on the widths between bone labels under an epifluorescent microscope. Software (Multilevel Win 2.0; University of Bristol, Bristol, United Kingdom) was used to model distance of suture expansion over time as polynomials to compare group differences. Wilcoxon signed rank tests were performed to compare the suture volume and cross-sectional area, mineral apposition rate, and suture width between groups. The significance level was set at P = 0.05.
  
  
  RESULTS
  Whereas the sutures were expanded in all groups, sutures were expanded by significantly greater amounts in the control and the 0.01 mg/mL groups without fusing the sutures than in the 0.025, 0.1, and 0.4 mg/mL groups with fusing sutures. Compared with the controls, the 0.01 mg/mL group showed significantly lower suture volumes, cross-sectional areas, and suture widths after expansion. The mineral apposition rate was significantly higher in the 0.01 mg/mL group than in the controls from days 10 to 30.
  
  
  CONCLUSIONS
  The 0.01 mg/mL dose of rhBMP-2 delivered by absorbable collagen sponge can stimulate bone formation at the bony edges of the suture during suture expansion; however, higher concentrations cause suture fusion. With an appropriate concentration, rhBMP-2 might facilitate suture expansion for clinical uses.
authors.affiliation: Department of Orthodontics, Texas A&M University, Baylor College of Dentistry, Dallas, TX, USA.
authors.forename: Sean Shih-Yao
authors.initials: SS
authors.lastname: Liu
authors.forename: Haisong
authors.initials: H
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.forename: Elias
authors.initials: E
authors.lastname: Kontogiorgos
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Whittington
authors.forename: Kenner G
authors.initials: KG
authors.lastname: Misner
authors.forename: Hee-Moon
authors.initials: HM
authors.lastname: Kyung
authors.forename: Peter H
authors.initials: PH
authors.lastname: Buschang
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Opperman
mesh_terms: D000497:Alloys / Q000737:chemistry; D019412:Anatomy, Cross-Sectional; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000627:therapeutic use*; D001863:Bone Screws; D001864:Bone Wires; D002113:Calcification, Physiologic / Q000187:drug effects; D003393:Cranial Sutures / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D057918:Fiducial Markers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005624:Frontal Bone / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005781:Gelatin Sponge, Absorbable; D021621:Imaging, Three-Dimensional / Q000379:methods; D008297:Male; D008856:Microscopy, Fluorescence; D009532:Nickel / Q000737:chemistry; D010012:Osteogenesis / Q000187:drug effects; D019857:Osteogenesis, Distraction / Q000295:instrumentation / Q000379:methods; D010118:Oxytetracycline; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013314:Stress, Mechanical; D013635:Tantalum / Q000737:chemistry; D014025:Titanium / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000627:therapeutic use*; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D000497:Alloys; D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C040654:titanium nickelide; D013635:Tantalum; D009532:Nickel; D014025:Titanium; C007740:fluorexon; D010118:Oxytetracycline