Applicability of organ-on-chip systems in toxicology and pharmacology

Abstract

Organ-on-chip (OoC) systems are microfabricated cell culture devices designed to model functional units of human organs by harboring an in vitro generated organ surrogate. In the present study, we reviewed issues and opportunities related to the application of OoC in the safety and efficacy assessment of chemicals and pharmaceuticals, as well as the steps needed to achieve this goal. The relative complexity of OoC over simple in vitro assays provides advantages and disadvantages in the context of compound testing. The broader biological domain of OoC potentially enhances their predictive value, whereas their complexity present issues with throughput, standardization and transferability. Using OoCs for regulatory purposes requires detailed and standardized protocols, providing reproducible results in an interlaboratory setting. The extent to which interlaboratory standardization of OoC is feasible and necessary for regulatory application is a matter of debate. The focus of applying OoCs in safety assessment is currently directed to characterization (the biology represented in the test) and qualification (the performance of the test). To this aim, OoCs are evaluated on a limited scale, especially in the pharmaceutical industry, with restricted sets of reference substances. Given the low throughput of OoC, it is questionable whether formal validation, in which many reference substances are extensively tested in different laboratories, is feasible for OoCs. Rather, initiatives such as open technology platforms, and collaboration between OoC developers and risk assessors may prove an expedient strategy to build confidence in OoCs for application in safety and efficacy assessment.

Culture of vibrating microtome tissue slices as a 3D model in biomedical research

“…Organ-on-chip models integrate mechanical (such as shear or strain stress) and chemical (growth factors, cytokines) cues and include tailored sensing of the culture environment regarding aspects as medium flow rate, temperature, pH, partial pressure of gases, and mechanical forces, among many others [ 7 – 9 ]. Organ-on-chip are a particularly promising strategy for assessing the safety and efficacy of chemicals and pharmaceuticals [ 10 ]; the devices can harbor simple (cell lines) or complex (organoids) biological structures [ 11 ], and can be designed to allow communication between cell types of different organs, in what has been called multiorgan chips. Another recent advance is bioprinting, in which 3D printing-like techniques are used to combine cells, growth factors, and/or biomaterials to create 3D cell aggregates resembling tissues or organs [ 12 , 13 ].…”

A narrative review of organoids for investigating organ aging: opportunities and challenges

“…The organ-on-a-chip technology uses microfabricated cell culture devices that combine biomaterial technologies, microfluidic systems, and tissue engineering and can simulate the crosstalk between different tissues and organs. [89] Despite its current limitations, [90] the organ-on-chip technology has been employed to study several aging-related diseases, such as rheumatoid arthritis, [91] hypertensive nephropathy, [92] diabetes, [71] and neuromuscular diseases [93] (Fig. 3C).…”

Developer’s Guide to an Organ-on-Chip Model

“…The final step of the OoC development process is the functional validation: Only through a comprehensive characterization of the model’s capability to recreate in vivo functions and mechanisms as well as of its limitations, it is possible to build confidence in its predictivity and the translatability of results. ,, This functional validation can encompass different types of case studies depending on its specific intended use, for example, (i) the assessment of its response to sets of training and validation compounds, (ii) the recapitulation of known physiological mechanisms and responses to defined stimuli, or (iii) the recreation of defined pathogenesis processes and pathophysiological responses. In addition to the validation of the function, it is crucial to also define the window of functional stability, i.e., the time frame during which studies can be conducted.…”