Critical Considerations for the Design of Multi-Organ Microphysiological Systems (MPS)

Abstract

Identification and approval of new drugs for use in patients requires extensive preclinical studies and clinical trials. Preclinical studies rely on in vitro experiments and animal models of human diseases. The transferability of drug toxicity and efficacy estimates to humans from animal models is being called into question. Subsequent clinical studies often reveal lower than expected efficacy and higher drug toxicity in humans than that seen in animal models. Microphysiological systems (MPS), sometimes called organ or human-on-chip models, present a potential alternative to animal-based models used for drug toxicity screening. This review discusses multi-organ MPS that can be used to model diseases and test the efficacy and safety of drug candidates. The translation of an in vivo environment to an in vitro system requires physiologically relevant organ scaling, vascular dimensions, and appropriate flow rates. Even small changes in those parameters can alter the outcome of experiments conducted with MPS. With many MPS devices being developed, we have outlined some established standards for designing MPS devices and described techniques to validate the devices. A physiologically realistic mimic of the human body can help determine the dose response and toxicity effects of a new drug candidate with higher predictive power.

Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

“…In addition, single-cell in vitro models, as reported in the literature reviewed here, may not adequately reflect the pathogenesis of diseases in vivo . A multi-organ in vitro model based on microfluidic technology may be more helpful models of vascular diseases for the evaluation of the safety and efficacy of berberine ( Rothbauer et al, 2018 ; Malik et al, 2021 ). For the clinical trial of berberine on vascular disease, many factors limit its clinical application, including the low methodological quality and drug–drug interactions ( Imenshahidi and Hosseinzadeh, 2019 ).…”

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.…”

Liver organ-on-chip models for toxicity studies and risk assessment

“…79,82,85 Using microfluidic devices can also efficiently reproduce physiological multiorgan interactions, where the multiple organ models cultured in separate biochips or multi-OoC platform are connected together through microfluidic tubing or microchannels. [86][87][88] Moreover, microfluidic technology offers the advantages of incorporating biosensors and bio-actuators to control the cultures, provide rapid analysis, and apply electrical or mechanical stimuli. 84,85,87 Selecting appropriate materials for the microfluidic device is one of the fundamental steps in OoC development.…”