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载 rhBMP-2 和地塞米松的 Zein/PLLA 支架在增强间充质干细胞体外成骨中的潜力。

Potential of rhBMP-2 and dexamethasone-loaded Zein/PLLA scaffolds for enhanced in vitro osteogenesis of mesenchymal stem cells.

机构信息

Norman Bethune First Hospital, Jilin University, Changchun 130021, China.

Alan G. MacDiarmid Laboratory, College of Chemistry, Jilin University, Changchun 130012, China.

出版信息

Colloids Surf B Biointerfaces. 2018 Sep 1;169:384-394. doi: 10.1016/j.colsurfb.2018.05.039. Epub 2018 May 19.

DOI:10.1016/j.colsurfb.2018.05.039
PMID:29803154
Abstract

Nanofibers fabricated by electrospinning simulate the extracellular matrix of bone cells and so researchers have taken a keen interest in them for regenerating bone tissue. The aim of this study was to fabricate ideal Zein/PLLA nanofibers by coaxial electrospinning and to load them with bone morphogenetic protein 2 (BMP-2) and dexamethasone (DEX) for dual controlled-release for bone tissue engineering applications. Morphology, surface hydrophilicity and core-shell construction were analyzed by environmental scanning electron microscopy (SEM), water contact angle and transmission electron microscopy (TEM). The properties of the scaffolds were studied in terms of the viability, morphology and osteogenic differentiation of mesenchymal stem cells (MSCs) that had been cultured on nanofiber mats of the Zein/PLLA and were determined using SEM, CCK-8 assay, quantitative ALP staining analysis, quantitative mineral deposition using Alizarin red staining (ARS), immunofluorescence staining and western blot analysis of osteogenic proteins. In vitro studies demonstrated that the biological activity of DEX and BMP-2 was retained in the dual-drug-loaded nanofiber scaffolds. A large quantity of DEX was released in the first three days, while the release of BMP-2 lasted for more than 21 days. In vitro osteogenesis studies showed that the drug-loaded nanofiber scaffolds induced osteogenic differentiation. Furthermore, the dual controlled-release of BMP-2 and DEX enhanced the osteogenic differentiation of MSCs resulting from synergistic effects. Therefore, Zein/PLLA nanofiber scaffolds loaded with BMP-2 and DEX have great potential in bone tissue engineering applications.

摘要

静电纺丝制备的纳米纤维模拟了骨细胞的细胞外基质,因此研究人员对其在骨组织再生方面非常感兴趣。本研究旨在通过同轴静电纺丝制备理想的玉米醇溶蛋白/聚乳酸(PLLA)纳米纤维,并负载骨形态发生蛋白 2(BMP-2)和地塞米松(DEX)以用于骨组织工程应用的双重控制释放。通过环境扫描电子显微镜(SEM)、水接触角和透射电子显微镜(TEM)分析形貌、表面亲水性和核壳结构。通过在玉米醇溶蛋白/PLLA 纳米纤维垫上培养间充质干细胞(MSCs),研究支架的性能,包括细胞活力、形态和成骨分化,使用 SEM、CCK-8 测定、定量碱性磷酸酶染色分析、茜素红染色(ARS)定量矿物质沉积、免疫荧光染色和碱性磷酸酶染色分析进行评估。体外研究表明,DEX 和 BMP-2 的生物活性在双载药纳米纤维支架中得以保留。大量 DEX 在头三天释放,而 BMP-2 的释放持续超过 21 天。体外成骨研究表明,载药纳米纤维支架诱导成骨分化。此外,BMP-2 和 DEX 的双重控制释放通过协同作用增强了 MSCs 的成骨分化。因此,负载 BMP-2 和 DEX 的玉米醇溶蛋白/PLLA 纳米纤维支架在骨组织工程应用中具有巨大潜力。

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