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基于负载骨形态发生蛋白-2的三维纤维聚乳酸-羟基乙酸共聚物/羟基磷灰石复合支架缓释实现的优化骨再生

Optimized bone regeneration based on sustained release from three-dimensional fibrous PLGA/HAp composite scaffolds loaded with BMP-2.

作者信息

Fu Yin-Chih, Nie Hemin, Ho Mei-Ling, Wang Chih-Kuang, Wang Chi-Hwa

机构信息

Orthopaedic Research Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

出版信息

Biotechnol Bioeng. 2008 Mar 1;99(4):996-1006. doi: 10.1002/bit.21648.

DOI:10.1002/bit.21648
PMID:17879301
Abstract

Contemporary treatment of critical bone defect remains a significant challenge in the field of orthopedic surgery. Engineered biomaterials combined with growth factors have emerged as a new treatment alternative in bone repair and regeneration. Our approach is to encapsulate bone morphogenetic protein-2 (BMP-2) into a polymeric matrix in different ways and characterize their individual performance in a nude mouse model. The main objective of this study is to examine whether the PLGA/HAp composite fibrous scaffolds loaded with BMP-2 through electrospinning can improve bone regeneration. The hypothesis is that different loading methods of BMP-2 and different HAp contents in scaffolds can alternate the release profiles of BMP-2 in vivo, therefore modify the performance of scaffolds in bone regeneration. Firstly, mechanical strength of scaffolds and HAp nanoparticles distribution in scaffolds were investigated. Secondly, nude mice experiments extended to 6 weeks were carried out to test the in vivo performance of these scaffolds, in which measurements, like serum BMP-2 concentration, ALP activity, X-ray qualification, and H&E/IHC tissue staining were utilized to monitor the growth of new bone and the changes of the corresponding biochemical parameters. The results showed that the PLGA/HAp composite scaffolds developed in this study exhibited good morphology/mechanical strength and HAp nanoparticles were homogeneously dispersed inside PLGA matrix. Results from the animal experiments indicate that the bioactivity of BMP-2 released from the fibrous PLGA/HAp composite scaffolds is well maintained, which further improves the formation of new bone and the healing of segmental defects in vivo. It is concluded that BMP-2 loaded PLGA/HAp composite scaffolds are promising for bone healing.

摘要

在骨科手术领域,关键骨缺损的现代治疗仍然是一项重大挑战。工程生物材料与生长因子相结合已成为骨修复和再生的一种新的治疗选择。我们的方法是以不同方式将骨形态发生蛋白-2(BMP-2)封装到聚合物基质中,并在裸鼠模型中表征它们各自的性能。本研究的主要目的是检验通过静电纺丝负载BMP-2的PLGA/HAp复合纤维支架是否能促进骨再生。假设是BMP-2的不同负载方法和支架中不同的HAp含量可以改变BMP-2在体内的释放曲线,从而改变支架在骨再生中的性能。首先,研究了支架的机械强度和HAp纳米颗粒在支架中的分布。其次,进行了长达6周的裸鼠实验以测试这些支架的体内性能,其中利用血清BMP-2浓度、碱性磷酸酶(ALP)活性、X射线鉴定以及苏木精-伊红(H&E)/免疫组化(IHC)组织染色等测量方法来监测新骨生长和相应生化参数的变化。结果表明,本研究中开发的PLGA/HAp复合支架具有良好的形态/机械强度,并且HAp纳米颗粒均匀地分散在PLGA基质内。动物实验结果表明,从纤维状PLGA/HAp复合支架释放的BMP-2的生物活性得到了良好维持,这进一步促进了体内新骨形成和节段性缺损的愈合。结论是负载BMP-2的PLGA/HAp复合支架在骨愈合方面具有前景。

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