Implementing organ-on-chip in a next-generation risk assessment of chemicals: a review

Abstract

Organ-on-chip (OoC) technology is full of engineering and biological challenges, but it has the potential to revolutionize the Next-Generation Risk Assessment of novel ingredients for consumer products and chemicals. A successful incorporation of OoC technology into the Next-Generation Risk Assessment toolbox depends on the robustness of the microfluidic devices and the organ tissue models used. Recent advances in standardized device manufacturing, organ tissue cultivation and growth protocols offer the ability to bridge the gaps towards the implementation of organ-on-chip technology. Next-Generation Risk Assessment is an exposure-led and hypothesis-driven tiered approach to risk assessment using detailed human exposure information and the application of appropriate new (non-animal) toxicological testing approaches. Organ-on-chip presents a promising in vitro approach by combining human cell culturing with dynamic microfluidics to improve physiological emulation. Here, we critically review commercial organ-on-chip devices, as well as recent tissue culture model studies of the skin, intestinal barrier and liver as the main metabolic organ to be used on-chip for Next-Generation Risk Assessment. Finally, microfluidically linked tissue combinations such as skin–liver and intestine–liver in organ-on-chip devices are reviewed as they form a relevant aspect for advancing toxicokinetic and toxicodynamic studies. We point to recent achievements and challenges to overcome, to advance non-animal, human-relevant safety studies.

Reanalysis of Trichloroethylene and Tetrachloroethylene Metabolism to Glutathione Conjugates Using Human, Rat, and Mouse Liver in Vitro Models to Improve Precision in Risk Characterization

“… 34 A number of such models have been developed by researchers in academia and the private sector, 57 and their use in chemical risk assessment has been proposed in next-generation risk assessments. 58 Although the opportunities are many, the challenges are also formidable, including the cost, complexity, and low throughput of most of the available models. 38 , 59 , 60 …”

Proof-of-Concept Organ-on-Chip Study: Topical Cinnamaldehyde Exposure of Reconstructed Human Skin with Integrated Neopapillae Cultured under Dynamic Flow

“…Our study is a stepping stone towards future multi-organ on chip platforms which interconnect complex barrier organoids and internal organoids required to adequately mimic human physiology and disease. Microfluidic platforms containing several culture compartments interconnected with micro channels already exist [ 37 , 38 ]. These platforms are showing potential as a prediction tool for compound metabolism in target organs and in pharmacokinetic studies.…”

Advances in Organ-on-a-Chip Materials and Devices

“…A holistic model describes absorption and metabolism to study the effect of chemicals as an ADME tool. 45 Relevant tissue study and drug discovery occurred based on ADME optimization. 46 Importantly, ADME parameters can be used to calculate parameters relevant to the OoC platform.…”

“…Using the previously developed design criteria, the group devised a simple set of design requirements that could be utilized to construct an OoC platform. A holistic model describes absorption and metabolism to study the effect of chemicals as an ADME tool . Relevant tissue study and drug discovery occurred based on ADME optimization .…”