How inkjet printers help transform stem cells

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Inkjet printers and lasers are parts of a new way to produce cells important to research on nerve regeneration.

Schwann cells, for example, form sheaths around axons, the tail-like parts of nerve cells that carry electrical impulses. They promote regeneration of those axons and secrete substances that promote the health of nerve cells. But they’re hard to come by in useful numbers.

“This technology could lead to a better way to differentiate stem cells.”

So researchers have been taking readily available mesenchymal stem cells (also called bone marrow stromal stem cells that can form bone, cartilage, and fat cells) and using a chemical process to differentiate them into Schwann cells. But it’s an arduous and expensive process.

Researchers at Iowa State University have developed a nanotechnology that uses inkjet printers to print multi-layer graphene circuits and also uses lasers to treat and improve the surface structure and conductivity of those circuits.

It turns out mesenchymal stem cells adhere and grow well on the treated circuit’s raised, rough, and 3D nanostructures. Add small doses of electricity—100 millivolts for 10 minutes per day over 15 days—and the stem cells become Schwann-like cells.

“This technology could lead to a better way to differentiate stem cells,” says co-first author Metin Uz, a postdoctoral research associate in chemical and biological engineering. “There is huge potential here.”

Electrodes for injuries

The electrical stimulation is very effective, differentiating 85 percent of the stem cells into Schwann-like cells compared to 75 percent by the standard chemical process, according to the paper. The electrically differentiated cells also produced 80 nanograms per milliliter of nerve growth factor compared to 55 nanograms per milliliter for the chemically treated cells.

The researchers report the results could lead to changes in how nerve injuries are treated inside the body.

“These results help pave the way for in vivo peripheral nerve regeneration where the flexible graphene electrodes could conform to the injury site and provide intimate electrical stimulation for nerve cell regrowth,” the researchers write in a summary of their findings.

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The paper reports several advantages to using electrical stimulation to differentiate stem cells into Schwann-like cells:

  • doing away with the arduous steps of chemical processing
  • reducing costs by eliminating the need for expensive nerve growth factors
  • potentially increasing control of stem cell differentiation with precise electrical stimulation
  • and creating a low maintenance, artificial framework for neural damage repairs.

Problem solved

A key to making it all work is a graphene inkjet printing process that takes advantages of graphene’s wonder-material properties—it’s a great conductor of electricity and heat, it’s strong, stable, and biocompatible—to produce low-cost, flexible, and even wearable electronics.

But there was a problem: once graphene electronic circuits were printed, they had to be treated to improve electrical conductivity. That usually meant high temperatures or chemicals. Either could damage flexible printing surfaces including plastic films or paper.

The research group of lead author Jonathan Claussen, assistant professor of mechanical engineering and an associate of the US Department of Energy’s Ames Laboratory, solved the problem by developing computer-controlled laser technology that selectively irradiates inkjet-printed graphene oxide.

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The treatment removes ink binders and reduces graphene oxide to graphene—physically stitching together millions of tiny graphene flakes. The process makes electrical conductivity more than a thousand times better.

That led to experimental attempts to grow stem cells on printed graphene and then to electrical stimulation experiments.

“We knew this would be a really good platform for electrical stimulation,” says Suprem Das, a postdoctoral research associate in mechanical engineering and an associate of the Ames Laboratory. “But we didn’t know it would differentiate these cells.”

But now that it has, the researchers say there are new possibilities to think about. The technology, for example, could one day be used to create dissolvable or absorbable nerve regeneration materials that could be surgically placed in a person’s body and wouldn’t require a second surgery to remove.

The findings appear in Advanced Healthcare Materials. Funding came from the Roy J. Carver Charitable Trust, the US Army Medical Research and Materiel Command, and Iowa State.

Source: Iowa State University