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用于人骨髓间充质干细胞成骨分化的载地塞米松磷酸钙纳米颗粒的制备

Preparation of dexamethasone-loaded calcium phosphate nanoparticles for the osteogenic differentiation of human mesenchymal stem cells.

作者信息

Chen Ying, Li Jingchao, Kawazoe Naoki, Chen Guoping

机构信息

Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

出版信息

J Mater Chem B. 2017 Sep 7;5(33):6801-6810. doi: 10.1039/c7tb01727h. Epub 2017 Aug 3.

Abstract

As an earliest known and readily available osteogenic inducer for stem cells, dexamethasone (DEX) plays a key role in affecting cell functions and cellular processes, especially for cell proliferation and differentiation. However, the clinical application of DEX has been limited because of its uncontrolled release. An ideal carrier is desired to control the DEX release for the osteogenic differentiation of stem cells and bone tissue engineering. Biphasic calcium phosphate nanoparticles (BCP-NPs) should be potential carriers for DEX due to their osteoconductive properties and good biocompatibility as a bone graft biomaterial. In this study, DEX-loaded BCP-NPs were prepared by two methods: (1) immersion of BCP-NPs in a DEX solution (denoted DEX/BCP-NPs), (2) DEX incorporation during BCP-NP formation in a calcifying solution (denoted DEX@BCP-NPs). The DEX@BCP-NPs showed a higher DEX loading amount and more sustainable DEX release than did the DEX/BCP-NPs. The DEX@BCP-NPs were used for the culture of human bone marrow-derived mesenchymal stem cells (hMSCs) and showed a promotive effect on the proliferation of hMSCs. Furthermore, the DEX@BCP-NPs significantly increased the alkaline phosphatase (ALP) activity, calcium deposition and gene expressions of the osteogenic markers of hMSCs when compared to BCP-NPs without DEX loading. The results demonstrated BCP-NPs were good carriers for DEX loading and the DEX@BCP-NPs should be useful for bone tissue engineering.

摘要

作为最早被发现且易于获取的干细胞成骨诱导剂,地塞米松(DEX)在影响细胞功能和细胞进程中发挥着关键作用,尤其是对细胞增殖和分化。然而,由于其释放不受控制,DEX的临床应用受到了限制。人们期望有理想的载体来控制DEX的释放,以用于干细胞的成骨分化和骨组织工程。双相磷酸钙纳米颗粒(BCP-NPs)因其具有骨传导特性且作为骨移植生物材料具有良好的生物相容性,应是DEX的潜在载体。在本研究中,通过两种方法制备了负载DEX的BCP-NPs:(1)将BCP-NPs浸泡在DEX溶液中(记为DEX/BCP-NPs),(2)在钙化溶液中形成BCP-NP的过程中掺入DEX(记为DEX@BCP-NPs)。与DEX/BCP-NPs相比,DEX@BCP-NPs显示出更高的DEX负载量和更可持续的DEX释放。DEX@BCP-NPs用于培养人骨髓间充质干细胞(hMSCs),并对hMSCs的增殖具有促进作用。此外,与未负载DEX的BCP-NPs相比,DEX@BCP-NPs显著提高了hMSCs的碱性磷酸酶(ALP)活性、钙沉积和成骨标志物的基因表达。结果表明BCP-NPs是负载DEX的良好载体,DEX@BCP-NPs应可用于骨组织工程。

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