Human organs-on-chips for disease modelling, drug development and personalized medicine

Abstract

The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology with high fidelity. Here, I review how single and multiple human organ chip systems have been used to model complex diseases and rare genetic disorders, to study host–microbiome interactions, to recapitulate whole-body inter-organ physiology and to reproduce human clinical responses to drugs, radiation, toxins and infectious pathogens. I also address the challenges that must be overcome for organ chips to be accepted by the pharmaceutical industry and regulatory agencies, as well as discuss recent advances in the field. It is evident that the use of human organ chips instead of animal models for drug development and as living avatars for personalized medicine is ever closer to realization.

Modeling Neurodegenerative Diseases Using In Vitro Compartmentalized Microfluidic Devices

“…MPS have also found several applications in different organs modelling, such as gut (Raimondi et al, 2019), liver (Banaeiyan et al, 2017), retina (Achberger et al, 2019), skin (Sutterby et al, 2020) and others reviewed by D.E. Ingber (Ingber, 2022). The microbiota-neurodegeneration hypothesis can be study by the interface between individual organ-on-chip as brain and gut tissues creating a barrier model and study the penetration of neurotoxins through microbiota (Raimondi et al, 2019;Ambrosini et al, 2020;Ceppa et al, 2020).…”

Breakthroughs and Applications of Organ-on-a-Chip Technology

“…Despite all these challenges, OOAC has a promising future and is an actively pursued field. Readers are encouraged to read another recent review on the subject [ 142 ]. Microbiorobotics (MBR) can be deployed in an OOAC for multiple purposes, such as drug delivery, real-time monitoring of the physiology of tissues in the cellular environment, and as a testbed [ 143 ].…”

Flowmetering for microfluidics

“…8,9 Microfluidics has since then raised interest in a constantly increasing range of applications, taking advantage of several unique features: i/in direct inspiration from microelectronics, microfluidics allows to achieve high integration, automation, and parallelization of multiple steps (leading to the concept of "microfluidic processor" and "Micro-Total Analysis System", a term first coined by Widmer and Manz 10 ); ii/microfluidics allows the reliable manipulation of sub-microliter quantities of fluids, and thus a dramatic reduction in this device's sizes and the required sample and reagent quantities; iii/finally, microfluidics has also opened the route to intrinsically new concepts, such as "digital PCR" 11,12 or "organs on chip". [13][14][15] These intrinsic advantages have resonated with biological and medical markets, in which reagents and samples can be extremely limited and expensive, and the development of systems in biology and molecular medicine has called for massively parallel analyses. In 2013, the microfluidic market was valued at US$ 1.6 billion, 16 and is expected to reach US$ 44.0 billion by 2025.…”