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.
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.
Authors: Aaron W James; Jia Shen; Rebecca Tsuei; Alan Nguyen; Kevork Khadarian; Carolyn A Meyers; Hsin Chuan Pan; Weiming Li; Jin H Kwak; Greg Asatrian; Cymbeline T Culiat; Min Lee; Kang Ting; Xinli Zhang; Chia Soo Journal: JCI Insight Date: 2017-06-15
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Authors: Andrew L Alejo; Scott McDermott; Yusuf Khalil; Hope C Ball; Gabrielle T Robinson; Ernesto Solorzano; Amanda M Alejo; Jacob Douglas; Trinity K Samson; Jesse W Young; Fayez F Safadi Journal: J Orthop Sports Med Date: 2022-09-05
Authors: F Liu; E Ferreira; R M Porter; V Glatt; M Schinhan; Z Shen; M A Randolph; C A Kirker-Head; C Wehling; M S Vrahas; C H Evans; J W Wells Journal: Eur Cell Mater Date: 2015-09-21 Impact factor: 3.942
Authors: Choon G Chung; Aaron W James; Greg Asatrian; Le Chang; Alan Nguyen; Khoi Le; Georgina Bayani; Robert Lee; David Stoker; Xinli Zhang; Kang Ting; Bruno Péault; Chia Soo Journal: Stem Cells Transl Med Date: 2014-08-25 Impact factor: 6.940
Authors: Motasem Refaat; Eric O Klineberg; Michael C Fong; Tanya C Garcia; J Kent Leach; Dominik R Haudenschild Journal: Spine (Phila Pa 1976) Date: 2016-07-15 Impact factor: 3.241