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原代成骨细胞和纤维母细胞对锐钛矿型二氧化钛纳米颗粒的反应不同:细胞毒性和炎症研究。

Preosteoblasts and fibroblasts respond differently to anatase titanium dioxide nanoparticles: a cytotoxicity and inflammation study.

机构信息

Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CNRS UMR 6600, Compiègne, France.

出版信息

Colloids Surf B Biointerfaces. 2012 Feb 1;90:68-74. doi: 10.1016/j.colsurfb.2011.09.044. Epub 2011 Oct 5.

DOI:10.1016/j.colsurfb.2011.09.044
PMID:22019048
Abstract

There is a bundle of proofs suggesting that some industrial nanoparticles (NPs) can provoke diseases and pollute the environment durably. However, these issues still remain controversial. In the biomedical field, TiO(2) NPs were recently proposed to serve as fillers in polymeric materials to improve bone prostheses and scaffolds. Submicrometer TiO(2) particles could also result from wear debris of prostheses. Thus, it appears to be of the highest importance to elucidate the effects of well-characterized TiO(2) NPs on the behaviour of osteoblasts. In this work, we have measured the toxicity of anatase TiO(2) NPs with two different cell types, on L929 fibroblasts and for the first time on MC-3T3 pre-osteoblasts, with the aim to determine the level of cellular toxicity and inflammation. Our results clearly show that these NPs provoke different dose-response effects, with the pre-osteoblasts being much more sensitive than fibroblasts. Furthermore, we observed that anatase TiO(2) NPs had no effect on cell adhesion. By contrast, both cell types had their morphology and LDH release modified in the presence of NPs. Their DNA was also found to be fragmented as analyzed by quantifying the sub-G1 cell population with flow cytometry. By measuring the production of IL-6 and TNF-α proinflammatory cytokines, we have shown that TNF-α was never produced and that MC-3T3 cells were secreting IL-6. Most importantly, our results highlight the necessity of evaluating the toxicity of prostheses wear debris, and of NP coatings of medical implants, to determine if they can possibly provoke inflammation and inhibit bone reconstruction.

摘要

有大量证据表明,某些工业纳米颗粒(NPs)可能会持久地引发疾病并污染环境。然而,这些问题仍然存在争议。在生物医学领域,TiO(2) NPs 最近被提议用作聚合物材料中的填充物,以改善骨假体和支架。亚微米 TiO(2) 颗粒也可能是假体磨损的结果。因此,阐明经过良好表征的 TiO(2) NPs 对成骨细胞行为的影响显得尤为重要。在这项工作中,我们使用两种不同的细胞类型(L929 成纤维细胞和首次使用的 MC-3T3 前成骨细胞)测量了锐钛矿 TiO(2) NPs 的毒性,目的是确定细胞毒性和炎症水平。我们的结果清楚地表明,这些 NPs 引起了不同的剂量反应效应,前成骨细胞比成纤维细胞敏感得多。此外,我们观察到锐钛矿 TiO(2) NPs 对细胞黏附没有影响。相比之下,两种细胞类型在存在 NPs 的情况下都会改变其形态和 LDH 释放。通过流式细胞术定量分析亚 G1 细胞群,我们还发现它们的 DNA 被片段化。通过测量促炎细胞因子 IL-6 和 TNF-α 的产生,我们表明 TNF-α 从未产生,并且 MC-3T3 细胞分泌 IL-6。最重要的是,我们的结果强调了评估假体磨损碎片和医疗植入物 NP 涂层的毒性的必要性,以确定它们是否可能引发炎症并抑制骨重建。

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