title: Comparative study of fusion rate induced by different dosages of Escherichia coli-derived recombinant human bone morphogenetic protein-2 using hydroxyapatite carrier.
abstract: BACKGROUND
  Hydroxyapatite (HA) is considered to be useful because of its high affinity for recombinant human bone morphogenetic protein (rhBMP), mechanical resistance to compressive force, and possible reduction of rhBMP dose.
  
  
  OBJECTIVE
  To evaluate the osteoinductivity of Escherichia coli-derived rhBMP-2 and the suitability of porous HA as an rhBMP-2 carrier.
  
  
  METHODS
  In vivo study using microcomputerized tomography (micro-CT) scanning.
  
  
  METHODS
  Seventy-six New Zealand white male rabbits were randomized into a single control group (n=14) without rhBMP-2 and four experimental groups (10 μg, 50 μg, 200 μg, and 500 μg of rhBMP-2; n=14 in each group). The subjects were divided into 3- and 6-week groups.
  
  
  METHODS
  Outcome was evaluated by radiography, bending test, three-dimensional micro-CT, and histologic examinations.
  
  
  METHODS
  Bilateral posterolateral fusion was carried out, and rhBMP-2 (0, 10, 50, 200, 500, 1,000, and 2,000 μg) was implanted into the bilateral transverse processes using HA as a carrier.
  
  
  RESULTS
  The fusion rates of the 3-week group were 83.3% for 50 and 200 μg of rhBMP-2 and 100% for 500 μg. The improved fusion rates of the 50 μg or higher groups compared with those of control were statistically significant. The fusion rates of the 6-week group were 75% for 10 μg of rhBMP-2 and 100% for 50 μg or higher. Similarly, the improved fusion rates of the 10 μg or higher groups compared with those of control were statistically significant. Significantly higher percent volumes were observed in the 3-week 200 μg of rhBMP-2 group and 6-week 200 μg of rhBMP-2 group than the 3-week HA group and 6-week HA group, respectively. Trabecular thickness was significantly higher in the 3-week 200 μg of rhBMP-2 group than the 3-week HA group. Histologic analysis of the 10 μg group showed bone tissues within the pores from 3 weeks, and this was observed more vividly in the 50, 200, and 500 μg groups. The 6-week 10 μg and 50 μg of rhBMP-2 groups had lower amounts of new tissue but higher portions of complete bone tissue within the HA specimen, along with higher formation of completely reconstituted bone tissues outside HA.
  
  
  CONCLUSIONS
  Injection of 50 μg or more of E. coli-derived rhBMP-2 into a HA carrier induced earlier bone fusion in the intertransverse process of rabbits, which confirms the excellent bone forming ability of E. coli-derived rhBMP-2 and the suitability of HA as a carrier of rhBMP-2.
authors.affiliation: Department of Orthopedic Surgery, College of Medicine, Seoul National University, SMG-SNU Boramae Medical Center, 41 Boramae-Gil, Dongjak-Gu, Seoul, 156-707, Korea. spinelee@snu.ac.kr
authors.forename: Jae Hyup
authors.initials: JH
authors.lastname: Lee
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Yu
authors.forename: Jae Jun
authors.initials: JJ
authors.lastname: Yang
authors.forename: Hae-Ri
authors.initials: HR
authors.lastname: Baek
authors.forename: Kyung-Mee
authors.initials: KM
authors.lastname: Lee
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Koo
authors.forename: Bong-Soon
authors.initials: BS
authors.lastname: Chang
authors.forename: Choon-Ki
authors.initials: CK
authors.lastname: Lee
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D004337:Drug Carriers / Q000494:pharmacology*; D017886:Durapatite / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy / Q000601:surgery; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage; D013123:Spinal Fusion / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D017886:Durapatite