Integrating biological vasculature into a multi-organ-chip microsystem

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.A chip-based system mimicking the transport function of the human cardiovascular system has been established at minute but standardized microsystem scale. A peristaltic on-chip micropump generates pulsatile shear stress in a widely adjustable physiological range within a microchannel circuit entirely covered on all fluid contact surfaces with human dermal microvascular endothelial cells. This microvascular transport system can be reproducibly established within four days, independently of the individual endothelial cell donor background. It interconnects two standard tissue culture compartments, each of 5 mm diameter, through microfluidic channels of 500 μm width. Further vessel branching and vessel diameter reduction down to a microvessel scale of approximately 40 μm width was realised by a two-photon laser ablation technique applied to inserts, designed for the convenient establishment of individual organ equivalents in the tissue culture compartments at a later time. The chip layout ensures physiological fluid-to-tissue ratios. Moreover, an in-depth microscopic analysis revealed the fine-tuned adjustment of endothelial cell behaviour to local shear stresses along the microvasculature of the system. Time-lapse and 3D imaging two-photon microscopy were used to visualise details of spatiotemporal adherence of the endothelial cells to the channel system and to each other. The first indicative long-term experiments revealed stable performance over two and four weeks. The potential application of this system for the future establishment of human-on-a-chip systems and basic human endothelial cell research is discussed.BMBF, 0315569, GO-Bio 3: Multi-Organ-Bioreaktoren für die prädiktive Substanztestung im Chipforma

Dynamic culture of human liver equivalents inside a micro-bioreactor for long-term substance testing : From 23rd European Society for Animal Cell Technology (ESACT) Meeting: Better Cells for Better Health Lille, France. 23-26 June 2013

Published by BioMed Central: Materne, Eva-Maria et al.: Dynamic culture of human liver equivalents inside a micro-bioreactor for longterm substance testing. - In: BMC Proceedings. - ISSN 1753-6561 (online). - 7 (2012), suppl. 6, art. P72. - doi:10.1186/1753-6561-7-S6-P72

A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Current in vitro and animal tests for drug development are failing to emulate the systemic organ complexity of the human body and, therefore, to accurately predict drug toxicity. In this study, we present a multi-organ-chip capable of maintaining 3D tissues derived from cell lines, primary cells and biopsies of various human organs. We designed a multi-organ-chip with co-cultures of human artificial liver microtissues and skin biopsies, each a 1/100 000 of the biomass of their original human organ counterparts, and have successfully proven its long-term performance. The system supports two different culture modes: i) tissue exposed to the fluid flow, or ii) tissue shielded from the underlying fluid flow by standard Transwell® cultures. Crosstalk between the two tissues was observed in 14-day co-cultures exposed to fluid flow. Applying the same culture mode, liver microtissues showed sensitivity at different molecular levels to the toxic substance troglitazone during a 6-day exposure. Finally, an astonishingly stable long-term performance of the Transwell®-based co-cultures could be observed over a 28-day period. This mode facilitates exposure of skin at the air–liquid interface. Thus, we provide here a potential new tool for systemic substance testing.BMBF, 0315569, GO-Bio 3: Multi-Organ-Bioreaktoren für die prädiktive Substanztestung im Chipforma

Automated substance testing for lab-on-chip devices : From 23rd European Society for Animal Cell Technology (ESACT) Meeting: Better Cells for Better Health Lille, France. 23-26 June 2013

First published by BioMed Central: Kloke, Lutz ; Schimek, Katharina ; Brincker, Sven ; Lorenz, Alexandra ; Jänicke, Annika ; Drewell, Christopher ; Hoffmann, Silke ; Busek, Mathias ; Sonntag, Frank ; Danz, Norbert ; Polk, Christoph ; Schmieder, Florian ; Borchanikov, Alexey ; Artyushenko, Viacheslav ; Baudisch, Frank ; Bürger, Mario ; Horland, Reyk ; Lauster, Roland ; Marx, Uwe : Automated substance testing for lab-on-chip devices : From 23rd European Society for Animal Cell Technology (ESACT) Meeting: Better Cells for Better Health Lille, France. 23-26 June 2013. - In: BMC Proceedings. - ISSN 1753-6561 (online). - 7 (2013), suppl. 6, P28. - doi:10.1186/1753-6561-7-S6-P28