Decoupling the Direct and Indirect Biological Effects of ZnO Nanoparticles Using a Communicative Dual Cell‐Type Tissue Construct

While matter at the nanoscale can be manipulated, the knowledge of the interactions between these nanoproducts and the biological systems remained relatively laggard. Current nanobiology study is rooted on in vitro study using conventional 2D cell culture model. A typical study employs monolayer cell culture that simplifies the real context of which to measure any nanomaterial effect; unfortunately, this simplification also demonstrated the limitations of 2D cell culture in predicting the actual biological response of some tissues. In fact, some of the characteristics of tissue such as spatial arrangement of cells and cell–cell interaction, which are simplified in 2D cell culture model, play important roles in how cells respond to a stimulus. To more accurately recapitulate the features and microenvironment of tissue for nanotoxicity assessments, an improved organotypic‐like in vitro multicell culture system to mimic the kidney endoepithelial bilayer is introduced. Results showed that important nano‐related parameters such as the diffusion, direct and indirect toxic effects of ZnO nanoparticles can be studied by combining this endoepithelial bilayer tissue model and traditional monolayer culture setting.