Physiologically relevant organs on chips

Abstract

Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and pharmaceutical research. Here we review the recent development of microengineered physiological systems, or organs on chips, that reconstitute the physiologically critical features of specific human tissues and organs and their interactions. This technology uses microengineering approaches to construct organ-specific microenvironments, reconstituting tissue structures, tissue–tissue interactions and interfaces, and dynamic mechanical and biochemical stimuli found in specific organs, to direct cells to assemble into functional tissues. We first discuss microengineering approaches to reproduce the key elements of physiologically important, dynamic mechanical microenvironments, biochemical microenvironments, and microarchitectures of specific tissues and organs in microfluidic cell culture systems. This is followed by examples of microengineered individual organ models that incorporate the key elements of physiological microenvironments into single microfluidic cell culture systems to reproduce organ-level functions. Finally, microengineered multiple organ systems that simulate multiple organ interactions to better represent human physiology, including human responses to drugs, is covered in this review. This emerging organs-on-chips technology has the potential to become an alternative to 2D and 3D cell culture and animal models for experimental medicine, human disease modeling, drug development, and toxicology.

Organoids, organs-on-chips and other systems, and microbiota

“…To mimic key aspects of living organs, such as the multicellular structures, cell-cell and tissue-tissue interactions, and the native microenvironment, organ-on-a-chip systems have been developed to incorporate microfluidic and microengineering technology [7,108]. The benefit of developing such systems is that it provides a platform to study the complex physiological and pathophysiological responses of tissues at an organ level, to provide patients with quicker access to new medication.…”

Tissue engineered organoids for neural network modelling

“…15,16 Due to this complexity, it has been difficult to develop living artificial neural networks that are reproducible, can be scaled-up and are low-cost, reliable, as well as efficient, robust, and reproducible, 1,2 both during standard physiological situations and abnormal pathological situations during disease. 17,18 Some of the many design considerations for neural models are highlighted in Table 1. …”

Current approaches and future role of high content imaging in safety sciences and drug discovery

“…An even more complex acquisition technology includes the "organ on a chip approach," which uses a 3D microfluidic cell culture chip that can both measure and simulate the activities, mechanics and physiological responses of entire organs or organ systems (Huh et al, 2011;Baker, 2011). Using this approach, multiple biological processes, e.g., in the liver, kidney, lung or heart can be stimulated (pharmacologically or mechanically) during the imaging data acquisition, which allows the investigation of biological mechanisms and responses in organ specific microenvironments (Yum et al, 2014). the obtained imaging datasets are analyzed using imaging analysis algorithms for the automated unbiased extraction of quantitative information.…”