Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/hydroxyapatite composite

Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/hydroxyapatite composite
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DOI:
10.1016/j.biomaterials.2004.02.010
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发表时间:
2005-01-01
期刊:
影响因子:
14
通讯作者:
Yoshikawa, H
Yoshikawa, H
中科院分区:
工程技术1区
文献类型:
--
作者:
Kaito, T;Myoui, A;Yoshikawa, H

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骨形态发生蛋白(BMPs)是一种具有诱导新骨形成的生物活性分子,在临床骨缺损修复中具有潜在的应用价值。然而,一个理想的系统,用于提供骨形成蛋白,可以加强他们的骨诱导能力,并提供初始的机械强度和支架骨长入尚未开发。在这项研究中,构建骨形成蛋白的载体/支架系统,我们结合了两种生物材料:互连多孔羟基磷灰石钙陶瓷(IPCHA),和合成的可生物降解聚合物聚D,L-乳酸-聚乙二醇嵌段共聚物(PLA-PEG)。我们采用兔桡骨模型评价rhBMP-2/PLA PEG/IP-CHA复合材料的骨再生效果。在植入后8周,用5 μ g或20 μ g BMP处理的组中的所有骨缺损完全修复,具有足够的强度。此外,使用这种载体支架系统,我们将这种结果所需的BMP的量减少到以前研究中所需量的约十分之一,这可能是由于IP-CHA的上级骨传导能力和PLA-PEG提供的最佳药物递送系统,在互连孔中诱导新骨形成。本研究结果表明,合成的可生物降解聚合物/IP-CHA复合物是一种优良的rhBMP-2载体/支架组合递送系统,并强烈促进rhBMP-2在骨组织再生中的临床效果。(C)2004爱思唯尔有限公司保留所有权利。
Bone morphogenetic proteins (BMPs) are biologically active molecules capable of inducing new bone formation, and show potential for clinical use in bone defect repair. However, an ideal system for delivering BMPs that can potentiate their bone-inducing ability and provide initial mechanical strength and scaffold for bone ingrowth has not yet been developed. In this study, to construct a carrier/scaffold system for BMPs, we combined two biomaterials: interconnected-porous calcium hydroxyapatite ceramics (IPCHA), and the synthetic biodegradable polymer Poly D,L,-lactic acid-polyethyleneglycol block co-polymer (PLA-PEG). We used a rabbit radii model to evaluate the bone-regenerating efficacy of rhBMP-2/PLA PEG/IP-CHA composite. At 8 weeks after implantation, all bone defects in groups treated with 5 or 20 mug of BMP were completely repaired with sufficient strength. Furthermore, using this carrier scaffold system, we reduced the amount of BMP necessary for such results to about a tenth of the amount needed in previous studies, probably due to the superior osteoconduction ability of IP-CHA and the optimal drug delivery system provided by PLA-PEG, inducing new bone formation in the interconnected pores. The present findings indicate that the synthetic biodegradable polymer/IP-CHA composite is an excellent combination carrier/scaffold delivery system for rhBMP-2, and that it strongly promotes the clinical effects of rhBMP-2 in bone tissue regeneration. (C) 2004 Elsevier Ltd. All rights reserved.