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Tissue-Engineered Heart Steps Closer with Embedded Nanowires

By adding tiny nanowire electronic sensors into engineered 3D tissue structures, scientists have developed a way to monitor cell behavior that could advance the treatment of cardiac and neurological diseases and speed up the development of tissue-engineered hearts.

Researchers already know how to control the three-dimensional shape of engineered tissue: they grow the cells on miniscule, sponge-like scaffolds. These are then implanted into patients or used to study the effect of new drugs in the lab.

And they have also been able to incorporate electronic sensors into two-dimensional tissue, grown as flat layers. But these don't replicate the true 3D nature of tissue.

Now in a new US study published online in Nature Materials this week, researchers from MIT, Harvard University and Boston Children's Hospital, explain how they have taken this technology a step further to create true 3D engineered tissue embedded with electronic sensors in the underlying scaffold.

In a recent press statement, senior author Robert Langer, the David H. Koch Institute Professor at MIT, says they are very excited by the achievement:

"It brings us one step closer to someday creating a tissue-engineered heart, and it shows how novel nanomaterials can play a role in this field," says Langer.

The sensors are made of silicon nanowires and can be used to monitor electrical activity in the tissue around the scaffold, say the researchers.

They could also be used to control the release of drugs, or test the effect of new drugs, for example, on the beating of heart tissue. 3D Epoxy Scaffold with Silicon Nanowires The researchers made the 3D scaffold out of epoxy, a non-toxic material, and embedded it with silicon nanowires that carry electrical signals to and from the cells grown in the structure.

The nanowires are between 30 and 80 nanometers thick, which is about 1,000 times thinner than human hair.

Once the nanowires are in place, the scaffold is seeded with cells and the whole eventually grows into 3D engineered tissue embedded with multiple tiny sensors.

The team chose silicon for the nanowire electrodes because they are stable, small enough, and can be implanted safely. They are also more electrically sensitive than metal wires. They can detect electrical activity of less than one-thousandth of a watt, which is about the level of a single cell. Monitoring Cells and Blood Vessels In the Nature Materials paper, the researchers describe how they grew cardiac, neural and muscle tissue using their electrode-embedded scaffolds.

In the cardiac tissue experiment they also monitored cell response to noradrenalin, a neurotransmitter that is released by neurons of the heart to typically stimulate heart rate.

In another experiment the team used the nanowire-embedded scaffolds to grow blood vessels and showed the embedded sensors were able to monitor changes in pH levels inside and outside the vessels.

Implanting such a device in patients could help doctors monitor inflammations and other biochemical events.

The researchers say they want to engineer tissue that not only monitors electrical and chemical events, but also responds to them, for instance by releasing a drug.

Such a device would behave like a closed feedback loop, in a similar way to the autonomous nervous system. The system detects a change in the body and sends a corrective action in response.

Gordana Vunjak-Novakovic, a professor of biomedical engineering at Columbia University, says there is a great need for engineered cells that respond to electrical stimuli. For example it would be a big step toward new ways to treat heart and neurological diseases.

"This is a beautiful example of how nanoelectronics can be combined with tissue engineering to monitor the behavior of cells," says Vunjak-Novakovic, who was not involved in the study.

The team is now going to test the mechanical properties of the scaffold before proceeding with animal trials.

Funds from the National Institutes of Health, the McKnight Foundation and Boston Children's Hospital helped pay for the study.

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