Journal ArticleDOI
A microfluidic device for a pharmacokinetic–pharmacodynamic (PK–PD) model on a chip
TLDR
Combination of a mathematical modeling approach (PK-PD modeling) and an in vitro experimental approach (microCCA) provides a novel platform with improved predictability for testing drug toxicity and can help researchers gain a better insight into the drug's mechanism of action.Abstract:
Drug discovery is often impeded by the poor predictability of in vitro assays for drug toxicity. One primary reason for this observation is the inability to reproduce the pharmacokinetics (PK) of drugs in vitro. Mathematical models to predict the pharmacokinetics-pharmacodynamics (PK-PD) of drugs are available, but have several limitations, preventing broader application. A microscale cell culture analog (microCCA) is a microfluidic device based on a PK-PD model, where multiple cell culture chambers are connected with fluidic channels to mimic multi-organ interactions and test drug toxicity in a pharmacokinetic-based manner. One critical issue with microfluidics, including the microCCA, is that specialized techniques are required for assembly and operation, limiting its usability to non-experts. Here, we describe a novel design, with enhanced usability while allowing hydrogel-cell cultures of multiple types. Gravity-induced flow enables pumpless operation and prevents bubble formation. Three cell lines representing the liver, tumor and marrow were cultured in the three-chamber microCCA to test the toxicity of an anticancer drug, 5-fluorouracil. The result was analyzed with a PK-PD model of the device, and compared with the result in static conditions. Each cell type exhibited differential responses to 5-FU, and the responses in the microfluidic environment were different from those in static environment. Combination of a mathematical modeling approach (PK-PD modeling) and an in vitro experimental approach (microCCA) provides a novel platform with improved predictability for testing drug toxicity and can help researchers gain a better insight into the drug's mechanism of action.read more
Citations
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Journal ArticleDOI
Microfluidic organs-on-chips
TL;DR: A microfluidic cell culture device created with microchip manufacturing methods that contains continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level physiology has great potential to advance the study of tissue development, organ physiology and disease etiology.
Journal ArticleDOI
From 3D cell culture to organs-on-chips.
TL;DR: New advances in 3D culture that leverage microfabrication technologies from the microchip industry and microfluidics approaches to create cell-culture microen environments that both support tissue differentiation and recapitulate the tissue-tissue interfaces, spatiotemporal chemical gradients, and mechanical microenvironments of living organs are reviewed.
Journal ArticleDOI
Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow
Hyun Jung Kim,Dongeun Huh,Geraldine A. Hamilton,Donald E. Ingber,Donald E. Ingber,Donald E. Ingber +5 more
TL;DR: This gut-on-a-chip recapitulates multiple dynamic physical and functional features of human intestine that are critical for its function within a controlled microfluidic environment that is amenable for transport, absorption, and toxicity studies, and hence it should have great value for drug testing as well as development of novel intestinal disease models.
Journal ArticleDOI
25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine
Nasim Annabi,Nasim Annabi,Ali Tamayol,Ali Tamayol,Jorge Alfredo Uquillas,Jorge Alfredo Uquillas,Mohsen Akbari,Mohsen Akbari,Luiz E. Bertassoni,Luiz E. Bertassoni,Chaenyung Cha,Chaenyung Cha,Gulden Camci-Unal,Gulden Camci-Unal,Mehmet R. Dokmeci,Mehmet R. Dokmeci,Nicholas A. Peppas,Ali Khademhosseini,Ali Khademhosseini +18 more
TL;DR: The development of advanced hydrogel with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light‐sensitive, composite, and shape‐memory hydrogels, and a number of potential applications and challenges in the utilization in regenerative medicine are reviewed.
Journal ArticleDOI
Organs-on-chips at the frontiers of drug discovery
TL;DR: The new opportunities for the application of organ-on-chip technologies in a range of areas in preclinical drug discovery, such as target identification and validation, target-based screening, and phenotypic screening are examined.
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Journal Article
Clinical Pharmacokinetics of 5-Fluorouracil and Its Metabolites in Plasma, Urine, and Bile
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