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Platform Devised for 3-D Engineered Heart, Liver Tissue

Milica Radisic

Milica Radisic (NSERC, University of Toronto)

8 March 2016. An engineering team at University of Toronto designed and tested in lab animals a technology for growing synthetic heart and liver tissue for drug testing and eventual clinical use. Researchers led by chemical engineering professor Milica Radisic published their findings yesterday (7 March) in the journal Nature Materials; paid subscription required.

Radisic and graduate student Boyang Zhang, the paper’s first author, are co-founders of Tara Biosystems, a company in New York commercializing their work on tissue models for toxicology testing and drug discovery. The company, started in October 2014 with backing from the venture capital company Harris & Harris Group, is co-founded by researchers from Columbia University and MIT.

The researchers are seeking a better process for creating more realistic tissue models outside the body. Their technology, called AngioChip, creates a biodegradable polymer scaffold that enables functioning organ cells to grow into three-dimensional tissue. This approach, say the authors, results in stronger, more realistic tissue — including blood vessels — than most current lab methods growing tissue as flat surfaces.

“In the last few years,” says Radisic in a university statement, “it has become possible to order cultures of human cells for testing, but they’re grown on a plate, a two-dimensional environment. They don’t capture all the functional hallmarks of a real heart muscle, for example.”

AngioChip builds on the lab’s earlier work that developed single strands of biocompatible fiber called Biowire for growing synthetic heart tissue. Zhang designed the AngioChip with a biodegradable polymer material known as POMaC for the scaffold, that’s also soft, elastic, and can respond to an electric current. As reported in Science & Enterprise in August 2015, the lab first developed a simple mesh framework with this type of material.

In AngioChips, thin — 50 to 100 micron wide — POMac sheets are stacked into layers with micro- and nanoscale channels designed in the structure for blood vessels. UV light then bonds together each succeeding layer into a scaffold that’s bathed in live cells, which seeds the structure for tissue to grow.

In this proof-of-concept study, Radisic, Zhang, and colleagues built AngioChips with heart and liver tissue and showed in lab cultures that drug compounds circulate through the channels. The team, which includes medical researchers, then implanted engineered tissue in lab rats, and found blood could flow easily through the implanted samples.

The authors believe AngioChip tissue can provide a more reliable, less expensive, and less ethically-challenged alternative to current animal tests for drug toxicity, as well as some early-stage safety trials. Engineered tissue samples could also be used in drug discovery to screen potential compound libraries. In addition, engineered tissue from AngioChips could eventually be implanted to repair organ damage, using genetically similar cells to reduce chances for rejection, with the biocompatible scaffold degrading after a few months.

The team wants to develop the process further so AngioChips can be produced by machines rather than by hand, which will make it possible to employ manufacturing methods to produce engineered tissue.

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