Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Cancer Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Tissue Eng Part A. 2019 Dec;25(23-24):1677-1689. doi: 10.1089/ten.TEA.2019.0124. Epub 2019 Sep 11.
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 . 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 . 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. Impact Statement In this study, polyelectrolyte complex was used to absorb neural epidermal growth factor like-like molecule-1 (NELL-1) and bone morphogenetic protein 2 (BMP-2) to achieve controlled dual release. The addition of NELL-1 significantly reduced the effective dose of BMP-2 to 2.5% of its conventional dose in absorbable collagen sponge, to produce solid spinal fusion without significant adverse effects. This study was the first to identify the efficacy of combination NELL-1 and BMP-2 in a control release carrier in spinal fusion, which could be potentially used clinically to increase fusion rate and avoid the adverse effects commonly associated with conventional BMP-2.
骨形态发生蛋白 2（BMP-2）广泛用于脊柱融合，但它会引起异位骨和脂肪组织等不良反应。神经表皮生长因子类似物 1（NELL-1）已被证明能抑制 BMP-2 诱导的不良反应。然而，尚未开发出既能控制 NELL-1 又能控制 BMP-2 释放以产生长期生物活性的最佳载体。在这项研究中，我们采用聚电解质复合物（PEC）作为 NELL-1 和 BMP-2 的控制释放载体。超低位 BMP-2 与 NELL-1 协同作用于骨髓间充质干细胞成骨分化，具有更大的矿化作用。在大鼠后路脊柱融合中，研究了 PEC 中 NELL-1 和超低位 BMP-2 的成骨能力。我们的研究结果表明，与 NELL-1 或 BMP-2 单独使用相比，联合组在术后 8 周时融合率、骨结构和骨刚度均增加。此外，在所有 PEC 组中，异位骨和脂肪组织的形成可忽略不计。总之，PEC 控制释放载体中 NELL-1 和超低位 BMP-2 的双重递送与单独使用 BMP-2 相比具有更高的融合效率，可能是目前用于脊柱融合的 BMP-2 治疗的更好替代方案。
影响陈述在这项研究中，聚电解质复合物被用于吸收神经表皮生长因子类似物 1（NELL-1）和骨形态发生蛋白 2（BMP-2）以实现控制双重释放。在可吸收胶原海绵中，NELL-1 的添加使 BMP-2 的有效剂量减少到其常规剂量的 2.5%，从而产生无明显不良反应的固体脊柱融合。这项研究首次确定了控制释放载体中组合的 NELL-1 和 BMP-2 在脊柱融合中的疗效，这可能在临床上用于增加融合率并避免与常规 BMP-2 相关的不良反应。
