Lung Microtissue Array to Screen the Fibrogenic Potential of Carbon Nanotubes.
Lung Microtissue Array to Screen the Fibrogenic Potential of Carbon Nanotubes.
复制标题
DOI：
10.1038/srep31304
复制
发表时间：
2016-08-11
影响因子：
4.6
通讯作者：
Zhao R
中科院分区：
文献类型：
--
作者：
Chen Z;Wang Q;Asmani M;Li Y;Liu C;Li C;Lippmann JM;Wu Y;Zhao R
由于其优异的物理和化学特性，多壁碳纳米管（MWCNT）在结构复合材料、导电材料、传感器、药物输送和医学成像等领域具有潜在的应用前景。然而，由于其体积小、重量轻，MWCNT的应用也引起了健康问题。体内动物研究表明，MWCNT引起肺组织的生物力学和遗传改变，从而导致肺纤维化。为了筛选特定类型MWCNT的纤维化风险因素，我们开发了一种人肺微组织阵列设备，可以实时和原位读取MWCNT损伤后工程肺微组织的生物力学特性。我们发现MWCNT浓度越高，细胞毒性越严重。更重要的是，低浓度50 ng/ml的短型MWCNT刺激了微组织的形成和收缩力的产生，并引起了纤维化标志物miR-21表达的大幅增加，表明这种特定碳纳米管类型和浓度具有高的成纤维潜力。所提出的微组织阵列系统为在现实组织环境中高通量检测靶化合物的治疗和毒理学效应提供了强有力的工具。
Due to their excellent physical and chemical characteristics, multi-wall carbon nanotubes (MWCNT) have the potential to be used in structural composites, conductive materials, sensors, drug delivery and medical imaging. However, because of their small-size and light-weight, the applications of MWCNT also raise health concerns. In vivo animal studies have shown that MWCNT cause biomechanical and genetic alterations in the lung tissue which lead to lung fibrosis. To screen the fibrogenic risk factor of specific types of MWCNT, we developed a human lung microtissue array device that allows real-time and in-situ readout of the biomechanical properties of the engineered lung microtissue upon MWCNT insult. We showed that the higher the MWCNT concentration, the more severe cytotoxicity was observed. More importantly, short type MWCNT at low concentration of 50 ng/ml stimulated microtissue formation and contraction force generation, and caused substantial increase in the fibrogenic marker miR-21 expression, indicating the high fibrogenic potential of this specific carbon nanotube type and concentration. The presented microtissue array system provides a powerful tool for high-throughput examination of the therapeutic and toxicological effects of target compounds in realistic tissue environment.