NELL-1 based demineralized bone graft promotes rat spine fusion as compared to commercially available BMP-2 product

Wei Yuan, Aaron W. James, Greg Asatrian, Jia Shen, Janette N. Zara, Hai Jun Tian, Ronald K. Siu, Xinli Zhang, Jeffrey C. Wang, Jian Dong

Research output: Contribution to journalArticlepeer-review


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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)646-657
Number of pages12
JournalJournal of Orthopaedic Science
Issue number4
StatePublished - Jul 2013
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine


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