3D Printed Stackable Titer Plate Inserts Supporting Three Interconnected Tissue Models for Drug Transport Studies.
Current in vitro drug screening methods often rely on single-cell models and are therefore imprecise in predicting drug absorption, distribution, metabolism, excretion, and toxicity. This study presents a method to fabricate 3D printed inserts that are compatible with commercially available titer plates. Hydrogels can be casted into the inserts and cells can be cultured either in or on the hydrogels. Once individual cell cultures are fully differentiated, the three different cell cultures are stacked on top of each other for biological experiments. To show the possibilities of this approach, three tissue models representing the first pass metabolism is used. The three tissue models are based on gelatin hydrogels and Caco-2, HUVEC, and HepG2 cells to simulate the small intestine, vascular endothelium, and liver, respectively. The device is simple to fabricate, user friendly, and an alternative to microfluidic-based organ on a chip systems. The presented first pass metabolism study allows for gaining information on drug absorption, distribution, metabolism, and, in the future, excretion in one compact device complying the micro titer plate format.
['Leth Jepsen|Morten|M|0000-0001-9023-8706', 'Willumsen|Andreas|A|', 'Mazzoni|Chiara|C|0000-0002-0988-3108', 'Boisen|Anja|A|0000-0002-9918-6567', 'Hagner Nielsen|Line|L|0000-0002-3789-4816', 'Dufva|Martin|M|0000-0001-5449-0189']
D018938:Caco-2 Cells D004353:Drug Evaluation, Preclinical D056945:Hep G2 Cells D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D020100:Hydrogels D056656:Lab-On-A-Chip Devices D046210:Microfluidic Analytical Techniques D008954:Models, Biological D010599:Pharmacokinetics D066330:Printing, Three-Dimensional D054457:Tissue Scaffolds
first pass metabolism HepG2 cells Caco-2 cells HUVEC cells tissue engineering