Organ-on-a-chip platforms for evaluation of environmental nanoparticle toxicity

Abstract

Despite showing a great promise in the field of nanomedicine, nanoparticles have gained a significant attention from regulatory agencies regarding their possible adverse health effects upon environmental exposure. Whether those nanoparticles are generated through intentional or unintentional means, the constant exposure to nanomaterials can inevitably lead to unintended consequences based on epidemiological data, yet the current understanding of nanotoxicity is insufficient relative to the rate of their emission in the environment and the lack of predictive platforms that mimic the human physiology. This calls for a development of more physiologically relevant models, which permit the comprehensive and systematic examination of toxic properties of nanoparticles. With the advancement in microfabrication techniques, scientists have shifted their focus on the development of an engineered system that acts as an intermediate between a well-plate system and animal models, known as organ-on-a-chips. The ability of organ-on-a-chip models to recapitulate in vivo like microenvironment and responses offers a new avenue for nanotoxicological research. In this review, we aim to provide overview of assessing potential risks of nanoparticle exposure using organ-on-a-chip systems and their potential to delineate biological mechanisms of epidemiological findings.

Cardiac Organoids and Gastruloids to Study Physio-Pathological Heart Development

“…For the heart, morphogen gradients, lineage tracking, fate mapping in 3D, and spatial transcriptomics (i.e., in situ single cell-sequencing) are critical to dissect heart (micro-)chamber formation. Starting from gastruloid studies, the first proposed bioengineered mini-hearts further underline the necessity of building solid in vitro models of the myocardium at different developmental stages to address causes of cardiac congenital diseases [42,56], and also build efficient drug-screenings [45], in particular via 'organs on a chip' platforms (reviewed in [57,58]). Manipulating biomechanics coupled to biochemical inputs are key modulatory parameters to induce changes in signal transduction and downstream cellular processes for successful and directed tissue morphogenesis.…”

Organ-On-A-Chip: A Survey of Technical Results and Problems

“…An innovative idea is the use of multi-species liver-on-a-chip system which uses the liver cells from multiple animals, this is done to prove that each species can react differently to certain drugs. In the example given, the drug killed the human liver cells, but the rat cells remained alive ( Lu and Radisic, 2021 ).…”

“…Some of the problems occur due to the rapid advancements in technology and people not understanding how toxic can some of the newly developed fuels can be, should be considered for application on environmental toxicology. Most experiments regarding OoC are focused on either toxicity or diseases around the alveoli, only a fraction of the entire respiratory system, however there are different airway-on-a-chip models and even innovative approaches which use 3D printing and constructing in addition to the OoC concept ( Lu and Radisic, 2021 ).…”

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

“…Most importantly, the species-specific difference in drug kinetics and metabolism often limits the value of animal model studies in drug development experiments which can be surmounted by the species-specific organoid models ( Kratochvil et al, 2019 ). Apart from alleviating much of the aforementioned limitations, organoid models also extend the option for high-throughput toxicity evaluation, scaling-up, and relatively long-term adverse effect assessment of conventional as well as nano-drugs ( Nagy and Robbins, 2019 ; Kim et al, 2020 ; Liu et al, 2021 ; Lu and Radisic, 2021 ). The potential role of various organoid models as a reliable modality for drug toxicity assessments has been delineated hereunder.…”