Bioprinting of a human neuron model for quantifying pollutant toxicity
Although pesticides are widely used in modern agriculture, growing evidence indicates that chronic exposure to these environmental contaminants contributes to the development of neurodegenerative disorders. This concern is amplified by the global rise in aging populations and the corresponding increase incidence in neurodegenerative diseases. Among the most widely used pesticides, organophosphates, particularly chlorpyrifos (CPF), are of significant concern due to their extensive agricultural use and well-established neurotoxic effects. Here, we present a 3-dimensional (3D) human neuron progenitor cell (hNPC) tissue model, fabricated using digital light processing (DLP)-based bioprinting. This platform enables precise spatial control over the cell density, geometry, and mechanical properties within a gelatin methacrylate (GelMA) scaffold, providing a tunable and biomimetic extracellular matrix. Using this system, we evaluated hNPC response to CPF exposure within a physiologically relevant 3D context. We further investigated CPF-induced neurotoxicity, specifically exploring acetylcholinesterase gene expression as a primary mechanistic etiology. Our findings demonstrate that our engineered 3D bioprinted constructs offer a more physiologically relevant and cost-effective platform for studying pollutant-induced neurotoxicity compared to conventional 2-D and in vivo rodent models, respectively. This work establishes a scalable 3D bioprinted system for mechanistic toxicology studies and advances predictive modeling of human neurological responses to environmental toxicants.
