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'Liver-on-chip' designed to predict drug toxicity

Posted: 18 Mar 2013 ?? ?Print Version ?Bookmark and Share

Keywords:medical devices? testing? processors?

Drugs that cannot be detoxified by the liver may cause poisoning or other lethal side effects. Thus, researchers from the A*STAR Institute of Bioengineering and Nanotechnology (IBN) have engineered a device that mimics the natural tissue environment of the liver and test new drugs introduced to it to predict the level of toxicity.

IBN Group Leader Professor Hanry Yu elaborated, "Most materials and devices have been designed with little attention to what the cells need. By using a cell-centred approach and translating our basic understanding of tissue behaviour, we have developed liver tissue models that can simulate conditions outside the body with striking similarity to organs inside the body."

IBN HepaTox chip

HepaTox / liver-on-chip. Source: IBN

IBN’s liver tissue models for drug toxicity testing comprise of patented technologies such as the 'liver-on-chip' or HepaTox, 3D cellulosic scaffold and microporous membrane sandwich culture.

HepaTox is a ‘liver-on-chip? that allows researchers to test the effect of drugs on the liver. By seeding liver cells within a microfluidic system, the micro device is used to screen the liver’s capacity to process different drugs and other compounds. HepaTox features eight channels, which enable multiple drug screening in parallel. With miniaturization, the amount of liver cells and drugs can also be significantly reduced, saving cost without comprising efficiency.

IBN 3D cellulosic scaffold

Three-dimensional cellulosic scaffold. Source: IBN

Using hydroxypropyl cellulose, an FDA-approved plant-based material that is the basic building block of cotton and paper, IBN fabricated a biocompatible porous scaffold that enables liver cells to spontaneously assemble into three-dimensional liver spheroids. These spheroids strongly resemble liver tissue, hence facilitating drug testing. This technology was licensed in 2010 to Taiwan-based Bio-Byblos Biomedical for manufacturing.

A typical drug screening platform requires liver cells for testing, and conventionally the cells are cultured within a collagen-based gel. However, the gel can trap drugs and limit access to nutrients and oxygen, leading to variable and inconsistent results.

IBN microporous membrane sandwich culture

Microporous membrane sandwich culture. Source: IBN

Using IBN’s microfabricated microporous membrane, the liver cells are sandwiched between the membranes, which can control the transfer of drugs, nutrients and oxygen to the cells, and provide more reliable and reproducible screening results. The membrane surface has been engineered to simulate liver cell interaction with matrix and promote formation of liver tissues after the cells are seeded. Experiments have shown that the microporous membranes can maintain long-term liver cell functions for more than two weeks and will be useful for chronic liver toxicity testing, and industry-scale drug screening.

If commercialized, IBN's liver tissue models can be developed into test kits to support drug development and pre-clinical research. In January this year, IBN collaborated with Janssen, a pharmaceutical company of Johnson & Johnson, to produce liver cells from human stem cells for drug testing. This new research project leverages on IBN's expertise in liver tissue engineering to develop an alternative source of human liver cells that are limited in supply. IBN is also working with global healthcare company Hoffman La-Roche on a new drug screening method for hepatitis viruses, which are leading causes of liver cancer.





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