title: Optimal condition of heparin-conjugated fibrin with bone morphogenetic protein-2 for spinal fusion in a rabbit model.
abstract: OBJECTIVE
  Heparin-conjugated fibrin (HCF) is a carrier for long-term release of bone morphogenetic protein-2 (BMP-2) and has been shown to promote bone formation in animal models. We performed an experimental study to determine the optimal dose of BMP-2 with an HCF carrier that promotes bone formation comparable to that of autograft while minimizing complications in spinal fusion.
  
  
  METHODS
  Twenty-four rabbits underwent posterolateral fusion of the L5-6 spinal segments. Different concentrations of HCF BMP-2 (1/10, 1/20, 1/30 or 1/40) were implanted in the spines of experimental rabbits, and autograft or INFUSE was implanted in the spines of control animals. Eight weeks after treatment, spinal fusion efficacy was evaluated by plain radiography, micro-computed tomography (micro-CT), mechanical testing and histomorphometry.
  
  
  RESULTS
  Similar to autograft, the 1/40 HCF BMP-2 showed significant bone formation on micro-CT and histomorphometry with mechanical stability. However, the other HCF BMP-2 concentrations did not show significant bone formation compared with autograft. Although conventional BMP-2 (INFUSE) led to higher bone formation and stability, it also led to excessive ectopic bone and fibrous tissue formation.
  
  
  CONCLUSIONS
  This study suggests the optimal concentration of BMP-2 using HCF for spinal fusion, which may decrease the complications of high-dose conventional BMP-2.
authors.affiliation: Department of Orthopedics, Korea University Ansan Hospital, Ansan, South Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Hong
authors.affiliation: Next-Generation Pharmaceutical Research Center, Korea Institute of Toxicology, Daejeon, Republic of Korea.
authors.forename: Sun-Woong
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Orthopedics, Korea University Ansan Hospital, Ansan, South Korea.
authors.forename: Jung-Wook
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Scoliosis Research Institute, Department of Orthopedics, Korea University Guro Hospital, Seoul, South Korea.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Suh
authors.affiliation: Department of Orthopedics, Korea University Ansan Hospital, Ansan, South Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Ko
authors.affiliation: Department of Orthopedics, Korea University Ansan Hospital, Ansan, South Korea. Electronic address: canall@korea.ac.kr.
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004343:Drug Implants; D005337:Fibrin / Q000008:administration & dosage* / Q000737:chemistry; D006493:Heparin / Q000008:administration & dosage* / Q000737:chemistry; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D013123:Spinal Fusion / Q000379:methods*; D013131:Spine / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D004343:Drug Implants; D005337:Fibrin; D006493:Heparin
keywords: BMP-2; autograft; heparin-conjugated fibrin; spinal fusion