Tools of the trade: leveraging 3D in vitro models to advance silicosis research

Silicosis is an occupational fibrotic lung disease representing a major public health crisis, and places a significant burden on patients and healthcare systems. There are no curative treatments for patients with silicosis, and available anti-fibrotic agents have not been shown to reduce disease progression. Enhanced understanding of the cellular mechanisms governing silicosis is required to establish biomarkers of disease onset and progression to allow for early detection, timely intervention, and development of improved therapeutics. Physiologically relevant 3D in vitro models enable investigation into mechanisms driving disease onset and progression, offering robust platforms for biomarker identification and drug screening, as well as toxicological assessments of silica-containing materials. Importantly, different models can be leveraged to recapitulate the various features of disease, depending on the specific research objective. This review highlights the current landscape of 3D models applied to silicosis research, highlighting innovative tools that can be harnessed to deepen our understanding of disease pathobiology, improve the drug development pipeline, and ultimately improve patient outcomes. We explore the limitations and opportunities of different modelling platforms specific to silicosis, and highlight translational opportunities for using human-centered modelling systems to evaluate the hazards of silica-containing materials and in representing varied occupations and exposure cohorts.