title: Improved spinal fusion efficacy by long-term delivery of bone morphogenetic protein-2 in a rabbit model.
abstract: OBJECTIVE
  Various new delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2) have been introduced to improve its efficacy in osteogenesis. Of these, we have previously developed heparin-conjugated PLGA nanospheres (HCPN) as a long-term delivery system for BMP-2. In vitro studies have shown that the BMP-2 long-term delivery system enhances the level of bone formation. However, the long-term effects of BMP-2 on spinal fusion have not been assessed. Therefore, we now tested the hypothesis that the long-term delivery of BMP-2 using HCPN improves spinal fusion compared to short-term delivery in a rabbit fusion model.
  
  
  METHODS
  24 adult New Zealand White rabbits underwent posterolateral fusion (6 animals in 4 groups). The autograft group received an autologous iliac chip bone graft as a positive control. The BMP-2-PN group received rhBMP-2 (20 μg per implant) and PLGA nanospheres (PN) suspended in fibrin gel, and served as a short-term release group. The HCPN group received HCPN suspended in fibrin gel without BMP-2 as a negative control. The BMP-2-HCPN group received rhBMP-2 (20 μg per implant)-bound HCPN suspended in fibrin gel and served as a long-term release group. All animals were killed 12 weeks after surgery. Manual palpation, axial tensile tests, radiography, and histological evaluations were then performed.
  
  
  RESULTS
  The spinal fusion rate and Young's modulus of the fusion mass were better in the BMP-2 long-term delivery group than in the short-term delivery group at an equivalent dose. However, the outcome of the long-term delivery was inferior to that of the autograft group.
  
  
  CONCLUSIONS
  The HCPN system showed potential as an effective carrier that might improve the osteogenic efficacy of BMP-2 for spinal fusion.
authors: Orthopaedic Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Republic of Korea.
authors: Jae-Wook
authors: JW
authors: Lee
authors: Saehyoung
authors: S
authors: Lee
authors: Sun Hwa
authors: SH
authors: Lee
authors: Hee Seok
authors: HS
authors: Yang
authors: Gun-Ii
authors: GI
authors: Im
authors: Chang-Sung
authors: CS
authors: Kim
authors: Jung-Ho
authors: JH
authors: Park
authors: Byung Soo
authors: BS
authors: Kim
mesh_terms: D000328:Adult; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D016025:Bone Transplantation; D016503:Drug Delivery Systems; D006801:Humans; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D013123:Spinal Fusion / Q000379:methods* / Q000592:standards; D013718:Tensile Strength; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D055396:Bone Morphogenetic Protein 2