Abstract
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.
Highlights
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[1,2,3,4]
Based on the microtissue force gauge, we report in this study the development of an engineered human lung microtissue array system for the real-time, in situ monitoring of the biomechanical impacts of MWCNT on lung cells and tissues
We treated B2B normal lung bronchial epithelial cells before microtissue seeding with MWCNT and S-MWCNT-C at concentration of 50 ng/mL, which was calculated based on the dosages used in animal studies to mimic in vivo situation[26,27,28]
Summary
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[1,2,3,4]. Based on the microtissue force gauge, we report in this study the development of an engineered human lung microtissue array system for the real-time, in situ monitoring of the biomechanical impacts of MWCNT on lung cells and tissues. Short type carbon nanotube 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. These data demonstrated the screening capability of the microtissue array system.
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