Improved spinal fusion efficacy by long-term delivery of bone morphogenetic protein-2 in a rabbit model.

Improved spinal fusion efficacy by long-term delivery of bone morphogenetic protein-2 in a rabbit model.
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DOI:
10.3109/17453674.2011.636675
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发表时间:
2011-12
期刊:
影响因子:
3.7
通讯作者:
Kim BS
Kim BS
中科院分区:
医学2区
文献类型:
--
作者:
Lee JW;Lee S;Lee SH;Yang HS;Im GI;Kim CS;Park JH;Kim BS

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为了提高重组人骨形态发生蛋白-2(rhBMP-2)的成骨效率,各种新的给药系统被引入。其中,我们之前已经开发了肝素偶联PLGA纳米球(HCPN)作为BMP-2的长期输送系统。体外研究表明,BMP-2长期给药系统可提高骨形成水平。然而,BMP-2对脊柱融合的长期影响还没有被评估。因此,我们现在在兔融合模型中验证了这样的假设:与短期注射相比,使用HCPN长期注射BMP-2可以改善脊柱融合。成年新西兰大白兔24只(4组6只)行后外侧融合术。自体骨移植组接受自体髂骨碎屑植骨作为阳性对照。骨形态发生蛋白-2-PN组给予重组人骨形态发生蛋白-2(每个种植体20μg)和纤维蛋白凝胶悬浮聚乳酸纳米球(PN),作为短期释药组。HCPN组给予不含BMP-2的纤维蛋白凝胶悬浮液作为阴性对照。骨形态发生蛋白-2-羟基喜树碱组植入重组人骨形态发生蛋白-2(每个种植体20μg),悬浮于纤维蛋白凝胶中,作为长期释药组。术后12周处死动物。然后进行手动触诊、轴向拉伸试验、X线片和组织学评估。在同等剂量下,BMP-2长期给药组的脊柱融合率和融合块的杨氏模数均好于短期给药组。然而,长期分娩的结果不如自体移植组。HCPN系统作为一种有效的载体有望提高BMP-2在脊柱融合中的成骨效率。
Various new delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2) have been introduced to improve its efficacy in osteogenesis. Of these, we have previously developed heparin-conjugated PLGA nanospheres (HCPN) as a long-term delivery system for BMP-2. In vitro studies have shown that the BMP-2 long-term delivery system enhances the level of bone formation. However, the long-term effects of BMP-2 on spinal fusion have not been assessed. Therefore, we now tested the hypothesis that the long-term delivery of BMP-2 using HCPN improves spinal fusion compared to short-term delivery in a rabbit fusion model. 24 adult New Zealand White rabbits underwent posterolateral fusion (6 animals in 4 groups). The autograft group received an autologous iliac chip bone graft as a positive control. The BMP-2-PN group received rhBMP-2 (20 μg per implant) and PLGA nanospheres (PN) suspended in fibrin gel, and served as a short-term release group. The HCPN group received HCPN suspended in fibrin gel without BMP-2 as a negative control. The BMP-2-HCPN group received rhBMP-2 (20 μg per implant)-bound HCPN suspended in fibrin gel and served as a long-term release group. All animals were killed 12 weeks after surgery. Manual palpation, axial tensile tests, radiography, and histological evaluations were then performed. The spinal fusion rate and Young's modulus of the fusion mass were better in the BMP-2 long-term delivery group than in the short-term delivery group at an equivalent dose. However, the outcome of the long-term delivery was inferior to that of the autograft group. The HCPN system showed potential as an effective carrier that might improve the osteogenic efficacy of BMP-2 for spinal fusion.
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