Scientists at the University of Illinois at Urbana-Champaign and the University of Wisconsin-Madison say they have created a microtube platform that could one day be implanted like stents to promote neuron regrowth at injury sites or to treat neurological diseases.
“This is a powerful three-dimensional platform for neuron culture,” said Xiuling Li, Ph.D., the U. of I. professor of electrical and computer engineering who co-led the study along with UW-Madison professor Justin Williams, Ph.D. “We can guide, accelerate, and measure the process of neuron growth, all at once.”
The team published the results (“Toward Intelligent Synthetic Neural Circuits: Directing and Accelerating Neuron Cell Growth by Self-Rolled-Up Silicon Nitride Microtube Array”) in ACS Nano.
“This work has clear implications toward building intelligent synthetic neural circuits by arranging the size, site, and patterns of the microtube array, for potential treatment of neurological disorders,” wrote the investigators.
“There are a lot of diseases that are very difficult to figure out the mechanisms of in the body, so people grow cultures on platforms so we can see the dynamics under a microscope,” explained U. of I. graduate student Paul Froeter, the first author of the study. “If we can see what's happening, hopefully we can figure out the cause of the deficiency and remedy it, and later integrate that into the body.”
The biggest challenge facing researchers trying to culture neurons for study is that it's difficult to recreate the three-dimensional environment of the brain. Other techniques have used glass plates or channels carved into hard slabs of material, but the nerve cells look and behave differently than they would in the body. The microtubes provide a three-dimensional, pliant scaffolding, the way that the cellular matrix does in the body.
The team uses an array of microtubes, made with a technique pioneered in Dr. Li's lab for electronics applications such as 3D inductors. Thin membranes of silicon nitride roll themselves up into tubes of precise dimensions. The tubes are about as wide as the cells, as long as a human hair is wide, and spaced apart about as far as they are long. The neurons grow along and through the microtubes, sending out exploratory arms across the gaps to find the next tube.
The microtubes not only provide structure for the neural network, guiding connections, but also accelerate the nerve cells' growth—and time is crucial for restoring severed connections in the case of spinal cord injury or limb reattachment.
“It's not surprising that the axons like to grow within the tubes,” said Dr. Williams. “These are exactly the types of spaces where they grow in vivo. What was really surprising was how much faster they grew. This now gives us a powerful investigative tool as we look to further optimize tube structure and geometry.”
For Dr. Li's group, the next step is to put electrodes in the microtubes so researchers can measure the electrical signals that the nerves conduct. “If we place electrodes inside the tube, since they are directly in contact with the axon, we will be able to study signal conduction much better than conventional methods,” said Dr. Li.
They also are working to stack the microtubes in multiple layers so that bundles of nerves can grow in a 3D network.
“If we can grow lines of neurons together in a bundle, we could simulate what's going down your spine or going to your limbs,” noted Froeter. “Then we can take mature cultures and sever them, then introduce the microtubes and see how they regrow.”
“Getting to the clinic will take a long time, but that is what keeps us motivated,” pointed out Dr. Li.