Lung Microtissue Array to Screen the Fibrogenic Potential of Carbon Nanotubes

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.

Microclot array elastometry for integrated measurement of thrombus formation and clot biomechanics under fluid shear

“…1). We fabricated the middle PDMS layer using a multilayer photolithography and soft-lithography technique as previously described 21,28 . An array of submillimeter-size microwells (13 columns by 6 rows) were cast in the middle PDMS layer, and each microwell contains a pair of flexible PDMS micropillars that serve as force sensors to report clot-generated contractile forces (Fig.…”

21st Century Tools for Nanotoxicology: Transcriptomic Biomarker Panel and Precision‐Cut Lung Slice Organ Mimic System for the Assessment of Nanomaterial‐Induced Lung Fibrosis

“…In the context of ENMs exposure, lung fibrosis is one of the routinely observed pathologies in animals and thus is of high interest and relevance to regulatory scientists. [9,[13][14][15]18,47,[52][53][54][55][56] Lung fibrosis is a progressive interstitial lung disease marked by chronic scarring of the lungs. It is a widely investigated occupational hazard and is commonly observed in miners and welders exposed to metal dusts.…”

Design rules for a tunable merged-tip microneedle

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