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van de Steeg, E.

Publications and source records attributed to van de Steeg, E..

2 recordsLinked to original sources

STARTER : A Stand-Alone Reconfigurable and TranslationalOoC Platorm based on Modularity and Open Design Principles

Organ-on-Chips (OoC) have the potential to revolutionize drug testing. However, the fragmented ecosystem of available OoC systems leads to wasted resources and collaboration barriers, slowing uptake. To address this, there is a need for OoC platforms based on interoperability standards, modularity, and reconfigurability. Technology platforms based on open designs would enable seamless integration of diverse OoC models and components, facilitating translation. Our study introduces a modular microfluidic platform that integrates swappable modules for pumping, sensing, and OoCs, all within the ANSI/SLAS microplate footprint. Sub-components operate as microfluidic building blocks (MFBBs) and can interface with the demonstrated Fluidic Circuit Board (FCB) universally as long as the designs adhere to ISO standards. The platform architecture allows tube-less inter-module interactions via arbitrary and reconfigurable fluidic circuits. We demonstrate two possible fluidic configurations which include in-line sensors and furthermore demonstrate biological functionality by running both in-vitro and ex-vivo OoC models for multiple days. This platform is designed to support automated multi-organ experiments, independent of OoC type or material. All designs shown are made open source to encourage broader compatibility and collaboration.

bioengineering↗

A hollow fiber membrane-based liver organoid-on-a-chip model for examining drug metabolism and transport

Liver-on-a-chip models predictive for both metabolism as well as canalicular and blood transport of drug candidates in humans are lacking. Here, we established an advanced, bioengineered and animal component-free hepatocyte-like millifluidic system based on 3D hollow fiber membranes (HFMs), recombinant human laminin 332 coating and adult human stem cell-derived organoids. Organoid fragments formed polarized and tight monolayers on HFMs with improved hepatocyte-like maturation, as compared to standard 3D organoid cultures in Matrigel from matched donors. Gene expression profiling and immunofluorescence revealed that hepatocyte-like monolayers expressed a broad panel of phase I (e.g., CYP3A4, CYP2D6) and II (UGTs, SULTs) drug-metabolizing enzymes and drug transporters (e.g., OATP1B3, MDR1 and MRP3). Moreover, statically cultured monolayers displayed phase I and II metabolism of a cocktail of six relevant compounds, including midazolam and 7-hydroxycoumarin. We also demonstrated the disposition of midazolam in the basal/blood-like circulation and apical/canalicular-like compartment of the millifluidic chip. Finally, we connected the system to the other two PK/ADME-most relevant organ systems, i.e. small intestine- and kidney proximal tubule-like to study the bioavailability of midazolam and coumarin, and excretion of metformin. In conclusion, we generated a proof-of-concept liver organoid-on-a-chip model for examining metabolism and transport of drugs, which can be further developed to predict PK/ADME profiles in humans.

pharmacology and toxicology↗