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Title: Synergistic Effect of NELL-1 and an Ultra-Low Dose of BMP-2 on Spinal Fusion
Authors: Liu, L 
Lam, WMR 
Naidu, M 
Yang, Z 
Wang, M 
Ren, X 
Hu, T
Kumarsing, R 
Ting, K
Goh, JCH 
Wong, HK 
Keywords: NELL-1
control release
dual delivery
polyelectrolyte complex
spinal fusion
ultra-low dose of BMP-2
Biomechanical Phenomena
Bone Morphogenetic Protein 2
Calcium-Binding Proteins
Cell Differentiation
Drug Liberation
Drug Synergism
Rats, Sprague-Dawley
Spinal Fusion
Tissue Scaffolds
X-Ray Microtomography
Issue Date: 1-Dec-2019
Publisher: Mary Ann Liebert Inc
Citation: Liu, L, Lam, WMR, Naidu, M, Yang, Z, Wang, M, Ren, X, Hu, T, Kumarsing, R, Ting, K, Goh, JCH, Wong, HK (2019-12-01). Synergistic Effect of NELL-1 and an Ultra-Low Dose of BMP-2 on Spinal Fusion. Tissue Engineering - Part A 25 (23-24) : 1677-1689. ScholarBank@NUS Repository.
Abstract: Copyright © 2019 Mary Ann Liebert, Inc. Bone morphogenetic protein 2 (BMP-2) is widely used in spinal fusion but it can cause adverse effects such as ectopic bone and adipose tissue in vivo. Neural epidermal growth factor like-like molecule-1 (NELL-1) has been shown to suppress BMP-2-induced adverse effects. However, no optimum carriers that control both NELL-1 and BMP-2 releases to elicit long-term bioactivity have been developed. In this study, we employed polyelectrolyte complex (PEC) as a control release carrier for NELL-1 and BMP-2. An ultra-low dose of BMP-2 synergistically functioned with NELL-1 on bone marrow mesenchymal stem cells osteogenic differentiation with greater mineralization in vitro. The osteoinductive ability of NELL-1 and an ultra-low dose of BMP-2 in PEC was investigated in rat posterolateral spinal fusion. Our results showed increased fusion rate, bone architecture, and improved bone stiffness at 8 weeks after surgery in the combination groups compared with NELL-1 or BMP-2 alone. Moreover, the formation of ectopic bone and adipose tissue was negligible in all the PEC groups. In summary, dual delivery of NELL-1 and an ultra-low dose of BMP-2 in the PEC control release carrier has greater fusion efficiency compared with BMP-2 alone and could potentially be a better alternative to the currently used BMP-2 treatments for spinal fusion.
Source Title: Tissue Engineering - Part A
ISSN: 19373341
DOI: 10.1089/ten.tea.2019.0124
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