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Organ-on-a-chip (OOC) models are based on microfluidics and can recapitulate the healthy and diseased microstructure of organs 1  and tissues and the dynamic microenvironment inside the human body. However, the use of OOC models to evaluate the safety and efficacy of nanoparticles (NPs) is still in the early stages. The different design parameters of the microfluidic chip and the mechanical forces generated by fluid flow play a pivotal role in simulating the human environment. This review discusses the role of different key parameters on the performance of OOC models. These include the flow pattern, flow rate, shear stress (magnitude, rate, and distribution), viscosity of the media, and the microchannel dimensions and shape. We also discuss how the shear stress and other mechanical forces affect the transport of NPs across biological barriers, cell uptake, and their biocompatibility. We describe several good practices and design parameters to consider for future OOC research. We submit that following these recommendations will help realize the full potential of the OOC models in the preclinical evaluation of novel therapies, including NPs.

Critical design parameters to develop biomimetic organ-on-a-chip models for the evaluation of the safety and efficacy of nanoparticles