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

• Published in: Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2013-07, Vol.18 (4), p.646-657
• Main Authors: Dong, Jian, Yuan, Wei, Shen, Jia, Tian, Hai Jun, Wang, Jeffrey C., Zhang, Xinli, James, Aaron W., Zara, Janette N., Asatrian, Greg, Siu, Ronald K.
• Format: Article
• Language: English
• Subjects: Animals; Bone Demineralization Technique; Bone Morphogenetic Protein 2 - therapeutic use; Bone Transplantation; Male; Medicine; Medicine & Public Health; Nerve Tissue Proteins - therapeutic use; Original Article; Orthopedics; Rats; Rats, Nude; Recombinant Proteins - therapeutic use; Rheumatology; Spinal Fusion - methods
• ISSN: 0949-2658; 1436-2023
• DOI: 10.1007/s00776-013-0390-5

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. Twenty-six skeletally mature athymic rats underwent posterolateral spine fusion of L4/L5 vertebrae. Treatment groups included NELL-1 (10 and 50μg) in a demineralized bone matrix (DBX), as compared to BMP-2 (90μg) in an absorbable collagen sponge (ACS) or morselized iliac crest bone. Scaffolds without recombinant protein were used as controls. Animals were sacrificed at 4weeks 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 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. 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.