Scientists have developed a new technique that produces a user friendly, low cost, tissue-engineered pseudo-organ. The chip-based model produces a faithful mimic of the in vivo liver inside a scalable fluid-handling device, demonstrating proof of principle for toxicology tests and opening up potential use in drug testing and personalised medicine.
The results are published today, Friday 11th September, in the journal Biofabrication.
The work was done by researchers based at the Wake Forest Institute for Regenerative Medicine and the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences. They created a device architecture within which were a series of 3D liver cell constructs enclosed in a biopolymer that closely mimics the extra-cellular matrix (ECM). Surrounding the printed cells with this ECM - which the body uses to support cells in the liver - makes this model a more realistic model of the cells in vivo.
The technique uses photopatterning to produce defined 3D constructs in a microfluidic system to probe the construct quickly. "It's basically scaled-down pluming" explains Adam Hall, an author on the paper. "This paper describes fairly hefty devices - a few mm - but we're working to scale this down considerably."
Collaboration proved to be the key to success; "The challenges were not too significant once Adam and I merged our areas of expertise." adds Aleksander Skardal, another author on the paper. "With his background in devices and microfabrication, and my background in biomaterials and biofabrication, the two technologies integrated rather well."
The 3D construct device offers a new tool in the development of drug treatments. At present, 2D testing in vitro doesn't replicate the activity of the cells, and until now 3D systems have not provided adequate interactions of cells with the ECM, or offered particularly high-throughput testing.
This is where the combination of technologies has proven vital. "3D constructs are less effective if you can't probe them quickly" continues Hall. "And without some important task, microfluidics are just a fun party trick."
The researchers were also happy how quickly the techniques fell into place.
"The first time we attempted to perform the in situ photopatterning - it just worked" says Skardal. "Science isn't always that easy, so we knew we might be onto something."
"Yes - this was one of those rare occasions where things seemed to fall into place" adds Hall.
The researchers are now working to reduce the size of the system allowing for multiple constructs that could be tested individually. This would open potential usage in drug testing and personalised medicine.
"Imagine being able to put, for example, tumor cells from a patient on a chip and test different drug cocktails on them" they conclude. "You could determine the effectiveness and side effects of different treatments on an individual basis without endangering the patient."
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In situ patterned micro 3-D liver constructs for parallel toxicology testing in a fluidic device
The published version of the paper 'In situ patterned micro 3-D liver constructs for parallel toxicology testing in a fluidic device' (Biofabrication 3 031001 ) will be freely available online from Friday 11 September. It will be available at http://iopscience.iop.org/1758-5090/7/3/031001 (DOI: 10.1088/1758-5090/7/3/032001)
Biofabrication focuses on using cells, proteins, biomaterials and/or other bioactive elements as building blocks to fabricate advanced biological models, medical therapeutic products and non-medical biological systems.
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