Accelerated postero-lateral spinal fusion by collagen scaffolds modified with engineered collagen-binding human bone morphogenetic protein-2 in rats.

Accelerated postero-lateral spinal fusion by collagen scaffolds modified with engineered collagen-binding human bone morphogenetic protein-2 in rats.
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用工程胶原蛋白结合人骨形态发生蛋白 2 修饰的胶原蛋白支架加速大鼠后侧脊柱融合

DOI:
10.1371/journal.pone.0098480
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Shi Q
Shi Q
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Han X;Zhang W;Gu J;Zhao H;Ni L;Han J;Zhou Y;Gu Y;Zhu X;Sun J;Hou X;Yang H;Dai J;Shi Q

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骨形态发生蛋白-2(BMP-2)是一种有效的骨诱导细胞因子,在骨再生和修复中起着关键作用。然而,其分布和副作用是其成功作为治疗性治疗的主要障碍。已经报道了使用胶原递送基质的治疗的改进。为了研究后外侧脊柱融合的递送系统,开发了具有胶原结合结构域的工程化人BMP-2(CBD-BMP-2)和胶原支架,并将它们的组合植入Sprague-Dawley(SD)大鼠中以研究腰椎4-5(L4-L5)后外侧脊柱融合。将SD大鼠分为假手术组(G1,n = 20)、胶原支架组(G2,n = 20)和BMP-2负载胶原支架组(G3,n = 20)。      手术后16周,通过X射线照片、高分辨率显微计算机断层扫描(micro-CT)、手动触诊和苏木精和伊红(H&E)染色来评估大鼠的脊柱。结果显示,G2(40%)和G3(100%)组发生了脊柱L4-L5融合,而假手术组的结果不一致。此外,G3的结果优于G2,包括更高的融合效率(X评分,G2 = 2.4±0.163,G3 = 3.0±0,p<0.05)、更高的骨密度(BMD,G2:0.3337±0.0025g/cm 3,G3:0.4353±0.0234g/cm 3)。    P<0.05)和更多的骨小梁形成。结果表明,BMP-2具有位点特异性的胶原结合结构域,低至0.02mg CBD-BMP-2/cm 3胶原支架的剂量可以促进大鼠横突间后外侧融合。这表明,联合给药可作为脊柱融合术的一种替代方法,可显著降低大剂量BMP-2引起的副作用。
Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive cytokine that plays a critical role in bone regeneration and repair. However, its distribution and side effects are major barriers to its success as therapeutic treatment. The improvement of therapy using collagen delivery matrices has been reported. To investigate a delivery system on postero-lateral spinal fusion, both engineered human BMP-2 with a collagen binding domain (CBD-BMP-2) and collagen scaffolds were developed and their combination was implanted into Sprague-Dawley (SD) rats to study Lumbar 4–5 (L4–L5) posterolateral spine fusion. We divided SD rats into three groups, the sham group (G1, n = 20), the collagen scaffold-treated group (G2, n = 20) and the BMP-2-loaded collagen scaffolds group (G3, n = 20). 16 weeks after surgery, the spines of the rats were evaluated by X-radiographs, high-resolution micro-computed tomography (micro-CT), manual palpation and hematoxylin and eosin (H&E) staining. The results showed that spine L4–L5 fusions occurred in G2(40%) and G3(100%) group, while results from the sham group were inconsistent. Moreover, G3 had better results than G2, including higher fusion efficiency (X score, G2 = 2.4±0.163, G3 = 3.0±0, p<0.05), higher bone mineral density (BMD, G2: 0.3337±0.0025g/cm3, G3: 0.4353±0.0234g/cm3. p<0.05) and more bone trabecular formation. The results demonstrated that with site-specific collagen binding domain, a dose of BMP-2 as low as 0.02mg CBD-BMP-2/cm3 collagen scaffold could enhance the posterolateral intertransverse process fusion in rats. It suggested that combination delivery could be an alternative in spine fusion with dramatically decreased side effects caused by high dose of BMP-2.
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发表时间: 2011-12
期刊: Acta orthopaedica
影响因子: 3.7
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发表时间: 2013-01
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DOI: 10.1002/jor.20735
发表时间: 2009-03
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影响因子: 3
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