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Wired tissue brings promise of smart cells

Nanoelectronic scaffold may be 3-D marvel

The nanoelectronic scaffold folded in three dimensions, with the circuits visible as loops.

Charles Lieber and Daniel Kohane

The nanoelectronic scaffold folded in three dimensions, with the circuits visible as loops.

A team of Harvard and MIT researchers has created the first three-dimensional piece of artificial tissue that’s wired with electronics.

The breakthrough brings promise that one day such wired tissue could act as sensors, detecting looming problems deep inside the body, and either fixing them directly or sending a message that help is needed. It could also be used to make “smart” prosthetics or replacement body parts.

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That’s still far in the future, of course. So far, the researchers have shown that their tiny electronic circuits can detect changes in pH balance in an artificial blood vessel, and measure real-time electrical activity and the effect of drugs on a patch of heart cells.

A tissue scaffold and the nanoelectronic wires that run through it.

CHARLES LIEBER AND DANIEL KOHANE

A tissue scaffold and the nanoelectronic wires that run through it.

The scientists, who published their work in August in the journal Nature Materials, call their creation a “nanoelectronic scaffold,” because the wiring is so small that it can slip undetected between cells, and is integrated into a scaffold used to grow artificial tissue.

“The ultimate goal is to replace the damaged tissue or organ with synthetic biological parts,” said Bozhi Tian, one of the original collaborators on the project who is now an assistant professor at the University of Chicago.

Previously, researchers have embedded wires in a flat layer of tissue, but the new work marks the first time anyone has ever thought to wire a three-dimensional clump of cells — which is much more difficult and potentially much more useful.

The wires will enable researchers to “see” deep inside living tissue, which is not possible today.

“It just opens a whole new field,” said Bianxiao Cui, a chemist at Stanford University who has reviewed the research.

Inside the body, clumps of cells behave very differently than they do lying in a flat sheet in a petri dish. Cui said scientists have not been able to clearly see that 3-D behavior without dissecting the tissue or examining one cell at a time.

“You understand the tissue from a totally different point of view,” if you can perceive what’s going on inside a clump of living cells, Cui said.

This ability to see inside tissue could prove highly useful in drug development, said Daniel Kohane, an anesthesiologist at Boston Children’s Hospital and one of three senior researchers involved in the nanoelectronic scaffold project. Now, drug developers have to test their drugs on flat layers of cells, which isn’t realistic, or in animals, which is expensive and poses ethical concerns.

The nanoelectronic scaffolds, or nanoES for short, are made by laying a flat, wire grid of silicon — the minimum building block of a computer chip — on a thin sheet of nickel. When the sheet is chemically dissolved, the wires fold up like origami into a three-dimensional scaffold shape that can be as small as the width of a human hair, Tian said. The scaffold is then seeded with cells that grow into artificial, sensing tissue.

“In our body, everything can be electronic,” said Tian, the lead author on the paper.

Other authors on the paper include Kohane, Harvard chemistry professor Charles Lieber, a founder of the field of nanotechnology, and Robert S. Langer, an institute professor at the Massachusetts Institute of Technology, himself a founder in the field of tissue engineering.

The scientists showed they could make cells grow into an artificial blood vessel, wired with nanoelectronics.

Charles Lieber and Daniel Kohane

The scientists showed they could make cells grow into an artificial blood vessel, wired with nanoelectronics.

The group has patented their technology, but have yet to attempt to commercialize it.

The crux of their invention is the ability to read the body’s electrical signals, which is crucial to understanding how cells in the heart, muscles, nerves, bone, and blood supply communicate. Heart cells, for instance, start beating at three weeks’ of gestation, and electrical signals drive heart function throughout a person’s life.

So, “investigating heart cells in the absence of electrical signals doesn’t make too much sense,” said Gordana Vunjak-Novakovic, a professor of biomedical engineering at Columbia University. Even so, that’s often how researchers have to study them today.

Wiring the cells via a nanoelectronic scaffold allows them to communicate with each other, Vunjak-Novakovic said, and to provide feedback to neighboring cells.

“We know this electrical activity is an excellent indicator of the state and health of cells,” she said.

Electrical signals are also profoundly important in the functioning of the brain. Lieber said he would love to use nanoelectric scaffolds to help restore motor control to people who have been paralyzed or who suffer brain damage from Parkinson’s or Alzheimer’s disease. The current devices used to stimulate the brain and read its electrical signals are too big, Lieber said; shrink them to the nano-level and he believes they would be much more effective.

“We’re making connections to neural systems at the level the brain can connect to itself,” Lieber said. “There’s essentially a whole world opened up as soon as one can take the power of electronics and merge it in a way that doesn’t perturb the biology.”

Here again, size is key; at the nano-level the scaffolding is small enough that it does not trigger an immune response, the researchers said, so it should be able to be safely used inside the body. Kohane said he hopes to begin testing the scaffolding in animals within a few years, and then in patients inside a decade.

Before then, the team needs to make sure the material can survive in the body’s challenging environment, Kohane said; moreover the group wants to figure out how to use the nanoelectronics to stimulate tissue and send messages, and not just sense what’s going on.

“We absolutely want to push this as far as we can,” Langer said.

Tian, meanwhile, now has his own lab, where he hopes to scale down the project even further — to build artificial parts that can operate inside a single cell.

Karen Weintraub can be reached at Karen@KarenWeintraub.com.

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