A meta-transcriptomic assessment of chronic respiratory exposure to cobalt-based nanomaterials using a microfluidic three-dimensional lung model for determining potential predisposition to lung injury

Project summary The use of cobalt-based nanomaterials has increased recently since they have many of the same attractive properties as other metallic nanoparticles, but appear to be more inert when exposed to cell cultures. However, as many studies have shown, the use of single cell culture systems for the

assessment of toxicology needs to be advanced because cells do communicate and effect on each other in living organisms. This proposal focuses on determining the fate, translocation, and toxicology of cobalt and cobalt oxide nanomaterials using several advanced three-dimensional lung models. Respiratory exposure is believed to be one of the most likely exposure scenarios during both use and

development of these nanomaterials, so it is important to determine how they interact with respiratory epithelial and immune cells, as well as the endothelial cells of the gas exchange barrier. In addition, since studies have suggested that these materials may lead to fibrosis, a pulmonary fibroblast culture

has also been included in this assessment. The goal is to expose these cells for 4-6 weeks (depending on the stability of the cell culture) using a microfluidics-based artificial lung culture to ascertain potential long-term effects of chronic cobalt-based nanomaterial respiratory exposure using standard toxicology testing, microscopy, and RNA-Seq transcriptomics. The goal of this proposal is

two-fold: 1) determining if long-term exposure, or repeated exposures, to cobalt-based nanoparticles will cause respiratory damage, and 2) exposing undergraduate students from a rural University comprised heavily of first-generation students, to advanced technologies in the biomedical sciences. Completion of these goals will allow for a greater understanding to the overall safety concerns for the

use and fabrication of these materials, since inhalation of nanoparticles is the most likely portal of entry.