Towards establishing human body-on-a-chip systems

Abstract

Body-on-a-chip (BoC) platforms are established from multiple organs-on-chips (OoCs) to recapitulate the interactions between different tissues. Recently, Vunjak-Novakovic and colleagues reported the creation of a BoC system comprising four fluidically linked OoCs. Herein, the major innovations in their BoC system are discussed, followed by our future perspectives on enhancing the physiological relevance and scalability of BoCs for applications in studying disease mechanisms, testing potential therapeutics, and developing personalized medicine.

Animal Model Alternatives in Filovirus and Bornavirus Research

“…Advanced multi-organ-chips- (MOCs) or bodies-/humans-on-a-chip (BOCs) represent microengineered models that reconstitute the human body by functionally integrating multiple chips of organs of the human body or a systematic unit into one fabrication [ 165 , 185 , 193 , 194 ]. This means that single OOCs are fluidically coupled to a physiological multi-organ unit to model tissue–tissue crosstalk [ 123 , 184 , 195 , 196 , 197 ]. Such fluidical coupling itself leads to the phenotypic modulation of the cells as well as metabolic coupling of the compartments [ 196 ], potentially moving further towards physiological conditions.…”

“…Indeed, effects already found were reproduced in this system [ 196 ]. As disease initiation and progression involves many compartments of a body, shared medium flow where tissue–tissue communication is enabled without hampering the individual tissue identity is required [ 197 ]. As a result, different metabolic and nutritional requirements must be met [ 197 ].…”

“…Their endothelial lining of the channels allows for systemic flow of a blood substitute which can be quantified for blood and plasma concentrations of applied drugs [ 198 ]. Semi-permeable endothelial separation of compartments further ensures that the connected parenchymal compartments remain specific to their desired target tissue, especially when stem cell-derived lineages are used [ 197 ]. A shared vascular channel generally provides an environment for a functional human immune MOC with circulating immune cells such as monocytes, making it a platform that can be used to analyze tissue-specific immune-responses to drugs and damage [ 197 , 199 , 200 ].…”

“…Advanced MPSs include tissue-tissue interfaces, mechanical cues, interstitial flow, circulating immune cells, or vascularization with flow, adequate shear force, spatiotemporal gradients, or torsion [ 122 , 165 ]. Consequently, they may be more optimal in modeling viral kinetics and pharmacological aspects of ADMET and PK/PD of a candidate drug not possible in human patients [ 123 , 197 ]. The compatibility of MPS and organoids with innovative real-time imaging allows monitoring if respective recombinant surrogate viruses are available such as the recombinant EBOV-GFP.…”

“…At the same time, MPS microfabrication requires down-scaling of physiological parameters to chips [ 197 ]. The accurate adaptation of channel size, compartment distance, matrix, and medium formulation crucially determine tissue integrity, differentiation, and function.…”