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图案化钛涂层对巨噬细胞极化和骨髓干细胞成骨分化的影响。

Influence of patterned titanium coatings on polarization of macrophage and osteogenic differentiation of bone marrow stem cells.

作者信息

Zhang Zequan, Xie Youtao, Pan Houhua, Huang Liping, Zheng Xuebin

机构信息

1 Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, PR China.

2 University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, PR China.

出版信息

J Biomater Appl. 2018 Feb;32(7):977-986. doi: 10.1177/0885328217746802. Epub 2017 Dec 13.

Abstract

Biomaterial surface topography plays a vital role in the osteointegration of implants by regulating the early cell responses and tissue growth-in. However, most of the previous researches focused on the effects of osteogenic cells, only a little is known about the immune cells which dominate osteogenesis after implanting. In this paper, patterned titanium coatings were fabricated and the effects of surface topography on the macrophage behaviors were investigated. On patterned titanium surface, macrophages preferred to polarize to M2, while macrophages on traditional titanium coatings presented higher M1 polarization. Nearly 70% higher expression of anti-inflammatory genes, including interleukin-4, interleukin-10, interleukin-1ra, and arginase, were detected on the patterned titanium coatings. While the pro-inflammatory genes, such as interleukin-1β, interleukin-6, tumor necrosis factor-α, interferon-γ, and inducible nitric oxide synthase were notably depressed. Up-regulation of the osteoinductive cytokines were also detected on the patterned coatings, which indicated advantageous osteogenic microenvironment provided by macrophages. Immunomodulation effect on osteogenesis was also investigated in this study. Stimulated with RAW cells/patterned coatings conditioned medium, bone marrow stem cells presented nearly 1.5 fold higher expression of osteogenic genes and more mineralization nodules than the traditional sprayed Ti coatings. All these results suggested that modulating materials with a patterned surface might be a valuable strategy to endow the implants with favorable osteoimmunomodulatory properties.

摘要

生物材料表面形貌通过调节早期细胞反应和组织向内生长,在植入物的骨整合中起着至关重要的作用。然而,以往的大多数研究都集中在成骨细胞的作用上,对于植入后主导骨生成的免疫细胞却知之甚少。本文制备了图案化钛涂层,并研究了表面形貌对巨噬细胞行为的影响。在图案化钛表面,巨噬细胞更倾向于极化为M2型,而传统钛涂层上的巨噬细胞则呈现出更高的M1极化。在图案化钛涂层上检测到抗炎基因(包括白细胞介素-4、白细胞介素-10、白细胞介素-1受体拮抗剂和精氨酸酶)的表达提高了近70%。而促炎基因,如白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α、干扰素-γ和诱导型一氧化氮合酶则显著下调。在图案化涂层上还检测到骨诱导细胞因子的上调,这表明巨噬细胞提供了有利的成骨微环境。本研究还探讨了对骨生成的免疫调节作用。用RAW细胞/图案化涂层条件培养基刺激后,骨髓干细胞的成骨基因表达比传统喷涂钛涂层高出近1.5倍,矿化结节也更多。所有这些结果表明,用图案化表面调节材料可能是赋予植入物良好骨免疫调节特性的一种有价值的策略。

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