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In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device.

ABSTRACT: 3D tissue models are increasingly being implemented for drug and toxicology testing. However, the creation of tissue-engineered constructs for this purpose often relies on complex biofabrication techniques that are time consuming, expensive, and difficult to scale up. Here, we describe a strategy for realizing multiple tissue constructs in a parallel microfluidic platform using an approach that is simple and can be easily scaled for high-throughput formats. Liver cells mixed with a UV-crosslinkable hydrogel solution are introduced into parallel channels of a sealed microfluidic device and photopatterned to produce stable tissue constructs in situ. The remaining uncrosslinked material is washed away, leaving the structures in place. By using a hydrogel that specifically mimics the properties of the natural extracellular matrix, we closely emulate native tissue, resulting in constructs that remain stable and functional in the device during a 7-day culture time course under recirculating media flow. As proof of principle for toxicology analysis, we expose the constructs to ethyl alcohol (0-500 mM) and show that the cell viability and the secretion of urea and albumin decrease with increasing alcohol exposure, while markers for cell damage increase.

SUBMITTER: Skardal A

PROVIDER: S-EPMC5704969 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device.

Skardal Aleksander A Devarasetty Mahesh M Soker Shay S Hall Adam R AR

Biofabrication 20150910 3

3D tissue models are increasingly being implemented for drug and toxicology testing. However, the creation of tissue-engineered constructs for this purpose often relies on complex biofabrication techniques that are time consuming, expensive, and difficult to scale up. Here, we describe a strategy for realizing multiple tissue constructs in a parallel microfluidic platform using an approach that is simple and can be easily scaled for high-throughput formats. Liver cells mixed with a UV-crosslinka ...[more]

PMID: 26355538

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Project description:INTRODUCTION:Microfluidic reactionware allows small volumes of reagents to be utilized for highly controlled flow chemistry applications. By integrating these microreactors with onboard analytical systems, the devices change from passive ones to active ones, increasing their functionality and usefulness. A pressing application for these active microreactors is the monitoring of reaction progress and intermediaries with respect to time, shedding light on important information about these real-time synthetic processes. OBJECTIVE:In this multi-disciplinary study the objective was to utilise advanced digital fabrication to research metallic, active microreactors with integrated fibre optics for reaction progress monitoring of solvent based liquids, incompatible with previously researched polymer devices, in combination with on-board Ultraviolet-visible spectroscopy for real-time reaction monitoring. METHOD:A solid-state, metal-based additive manufactured system (Ultrasonic Additive Manufacturing) combined with focussed ion beam milling, that permitted the accurate embedment of delicate sensory elements directly at the point of need within aluminium layers, was researched as a method to create active, metallic, flow reactors with on-board sensing. This outcome was then used to characterise and correctly identify concentrations of UV-active water-soluble B-vitamin nicotinamide and fluorescein. A dilution series was formed from 0.01-1.75 mM; which was pumped through the research device and monitored using UV-vis spectroscopy. RESULTS:The results uniquely showed the in-situ ion milling of ultrasonically embedded optical fibres resulted in a metallic microfluidic reaction and monitoring device capable of measuring solvent solutions from 18 ?M to 18 mM of nicotinamide and fluorescein, in real time. This level of accuracy highlights that the researched device and methods are capable of real-time spectrographic analysis of a range of chemical reactions outside of those possible with polymer devices.

Dataset Information

In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device.

Publications

In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device.

Similar Datasets

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