Journal Article

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

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

2013

Overview

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.

• Publisher: Elsevier B.V,Springer Japan,Springer Nature B.V
• Subject: 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