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3-D model replicates liver cells, may expedite drug testing

Researchers have developed a 3-D device for replicating liver cells that could expedite drug testing, according to published findings in Biofabrication.

“We have demonstrated a microfluidic device featuring individually addressable tissue constructs photopatterned using an accurate mimic of the [extracellular matrix (ECM)],” researchers Aleksander Skardal, PhD, and Adam R. Hall, PhD, assistant professors at Wake Forest Institute for Regenerative Medicine and Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences wrote.

Aleksander Skardal

Skardal, Hall and colleagues created a 3-D device enclosing liver cells in a biopolymer that mimicked ECM. Liver cells were mixed with a UV-crosslinkable hydrogel solution, placed into the device and photopatterned to produce the tissue constructs in situ. The hydrogel was used because it “specifically mimics the properties of the natural ECM,” according to the research. The constructs remained stable in the device for 7 days.

The researchers then used between 0 mM and 500 mM of ethyl alcohol to mix with the constructs for a toxicology analysis.

Adam R. Hall

“We found that ethanol dosing … results in a systematic effect on cell viability,” the researchers wrote. “Additionally, analytical assessment of liver function showed that the output of both human serum albumin and urea are significantly reduced under increasing ethanol exposure.”

According to a press release, this device may serve as a new tool for developing drug therapies. Currently, 2-D testing in vitro does not replicate cell activity, and other 3-D devices have not provided sufficient interactions of cells with the ECM, the release said.

“3-D constructs are less effective if you can’t probe them quickly,” Hall said in the release. “And without some important task, microfluidics are just a fun party trick.”

“The first time we attempted to perform the in situ photopatterning, it just worked,” Skardal said in the release. “Science isn’t always that easy, so we knew we might be onto something.”

The ramifications of the researchers’ work may provide a broad range for drug testing and individualized medicine, according to the release.

“We expect that our overall approach will be useful in a wide range of applications that will benefit from the use of 3-D models as opposed to traditional 2-D cell cultures, including drug development, complex toxicology testing and personalized medicine,” they said. – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.