title: Experimental spinal fusion with recombinant human bone morphogenetic protein-2 delivered by a synthetic polymer and beta-tricalcium phosphate in a rabbit model.
abstract: METHODS
  An experimental animal study to achieve posterolateral intertransverse process spine fusion with recombinant bone morphogenetic protein in combination with a new delivery system.
  
  
  OBJECTIVE
  To evaluate the efficacy of a new synthetic biodegradable bone-inducing material containing recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone-graft substitute for posterolateral intertransverse process fusion in a rabbit model.
  
  
  BACKGROUND
  rhBMP-2, a powerful bone-inducing cytokine, has been used as a bone graft substitute in combination with animal-derived collagen to achieve spinal fusion in animal models. However, the minimum dose of rhBMP-2 required to obtain solid posterolateral intertransverse process fusion was high on the basis of previous reports (>100 microg in rabbit models). To improve the efficacy, performance of rhBMP-2, and the safety of the delivery system for this protein, a more sophisticated system is required.
  
  
  METHODS
  To fabricate one implant for one-side L4-L5 intertransverse process fusion, beta-tricalcium phosphate (beta-TCP) powder (300 microg), a polymer gel (PLA-DX-PEG block copolymer; 300 microg) and rhBMP-2 (7.5, 15, or 30 microg) were mixed and manually shaped to resemble a rod. Through a posterolateral approach, two implants were placed on both sides (1 per side) by surgery so as to bridge the transverse processes of adult New Zealand white rabbits (n = 27). In control animals, implants without rhBMP or autogenous cortico-cancellous bone chips from the iliaccrest were placed in a similar location. The lumbar vertebrae were recovered 6 weeks after surgery. The posterolateral fusion was examined by manual palpation, radiography, biomechanical testing, and histology.
  
  
  RESULTS
  Rabbits that received 15 or 30 microg of rhBMP-2 showed consistent fusion. However, solid fusion was seen in 2 of 5 rabbits with autografting and rabbits that received 7.5 microg of rhBMP-2. Fusion was not observed in the rabbits that did not receive rhBMP-2.
  
  
  CONCLUSIONS
  Consistent spinal fusion was obtained by implanting a biodegradable bone-inducing implant composed of beta-TCP, PLA-DX-PEG, and rhBMP-2 within a period of 6 weeks. The rhBMP-2 doses required for the spinal fusion were significantly lower than those reported previously.
authors.affiliation: Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Namikawa
authors.forename: Hidetomi
authors.initials: H
authors.lastname: Terai
authors.forename: Eisuke
authors.initials: E
authors.lastname: Suzuki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hoshino
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Toyoda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Shimpei
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Kunio
authors.initials: K
authors.lastname: Takaoka
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage; D002130:Calcium Phosphates / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery; D023421:Models, Animal; D011108:Polymers / Q000008:administration & dosage*; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins / Q000008:administration & dosage; D013123:Spinal Fusion / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C485817:beta-tricalcium phosphate