title: NELL-1 based demineralized bone graft promotes rat spine fusion as compared to commercially available BMP-2 product.
abstract: BACKGROUND
  Spinal fusion is among the most commonly performed orthopaedic procedures. Unfortunately, current treatments such as autologous bone grafting or recombinant proteins (BMP-2) have numerous clinical shortcomings. Here, we directly compare the efficacy of NELL-1, a novel osteoinductive growth factor, to two currently available treatments, (1) recombinant BMP-2 and (2) iliac crest bone grafting, in a spinal fusion model.
  
  
  METHODS
  Twenty-six skeletally mature athymic rats underwent posterolateral spine fusion of L4/L5 vertebrae. Treatment groups included NELL-1 (10 and 50 μg) in a demineralized bone matrix (DBX), as compared to BMP-2 (90 μg) in an absorbable collagen sponge (ACS) or morselized iliac crest bone. Scaffolds without recombinant protein were used as controls. Animals were sacrificed at 4 weeks post-operative and fusion was assessed by manual palpation, radiography [high-resolution X-ray, micro-computed tomography (microCT)], histology (hematoxylin and eosin, Masson's trichrome) and immunohistochemistry (osteocalcin).
  
  
  RESULTS
  Results showed 100 % fusion in all NELL-1- and BMP-2-treated samples. In contrast, lower rates of fusion were observed in scaffold-only and bone graft treatment groups. MicroCT scans revealed radiographic evidence of fusion among spines treated with NELL-1. Bone bridging was also observed with BMP-2 treatment, but was accompanied by inner radiolucency, suggesting cyst-like bone formation. Histologically, NELL-1-treated grafts showed increased bone formation, endochondral ossification and vascularization. Although BMP-2 treated grafts exhibited increased bone formation and angiogenesis, numerous adipocytes were also observed.
  
  
  CONCLUSIONS
  NELL-1-based bone grafts are comparable to BMP-2 + ACS in spinal fusion efficacy. Histological differences were observed however, including robust endochondral ossification with NELL-1 treatment as compared to lipid-filled bone with BMP-2 treatment. These findings suggest NELL-1 based bone grafts show promise for future efforts in skeletal tissue engineering.
authors.affiliation: Department of Orthopaedic Surgery, Zhongshan Hospital, FudanUniversity, 180 Fenglin Road, Shanghai 200032, China.e-mail: dong.jian@zs-hospital.sh.cn
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.forename: Aaron W
authors.initials: AW
authors.lastname: James
authors.forename: Greg
authors.initials: G
authors.lastname: Asatrian
authors.forename: Jia
authors.initials: J
authors.lastname: Shen
authors.forename: Janette N
authors.initials: JN
authors.lastname: Zara
authors.forename: Hai Jun
authors.initials: HJ
authors.lastname: Tian
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Siu
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Dong
mesh_terms: D000818:Animals; D018775:Bone Demineralization Technique; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D016025:Bone Transplantation; D008297:Male; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*; D051381:Rats; D011923:Rats, Nude; D011994:Recombinant Proteins / Q000627:therapeutic use; D013123:Spinal Fusion / Q000379:methods*
chemical_list: D055396:Bone Morphogenetic Protein 2; C484480:Nell1 protein, rat; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins