Making Medical Miracles With Inkjet Printers
Bioprinting allows researchers to create replacement human tissue and output it on equipment similar to what came free in your desktop bundle.
You’ve probably owned an inkjet printer or two — one of those homely plastic boxes that performs mundane functions like scanning pictures and spitting out boarding passes while running through pricy ink cartridges like nobody’s business.
Where most of us behold an unremarkable piece of office equipment, Tao Xu sees a mechanical marvel. He has helped to pioneer ways to use those same inkjet devices to “print” cardiac tissue to repair a sick heart or create precise micro-assays that will slash the cost of testing new drugs.
Xu, an assistant engineering professor at the University of Texas at El Paso, is one of a growing number of scientists experimenting with the technique known as bioprinting. Researchers at the Medical University of South Carolina are trying to grow kidneys with printers, for example, while a team at Wake Forest University is developing a printer-based method to grow new tissue in burn wounds.
Xu recently received a three-year $423,000 grant from the National Institutes of Health to perfect cardiac patches containing cells cultured from a patient’s own tissue and tiny oxygen-releasing particles that should promote their growth. If they work, these patches could be an important new treatment for people suffering from cardiomyopathy, a disease process that weakens the heart’s pumping ability.
Damaged heart cells don’t regenerate well on their own, so they need an external cell source, Xu explains. Earlier research that involved injecting stem cells directly into the heart didn’t work because there wasn’t enough oxygen or nutrients for them to thrive, he says.
Enter the cardiac patch (which, Xu hastens to add, is still in the testing stage).
“We’re trying to fabricate the patch with a scaffold,” he says, explaining that inkjet heads can precisely deposit tiny droplets containing stem cells and oxygen particles onto a biodegradable substrate woven from nanofibers spun out of polylactic acid.
After the inkjet deposits a layer of cells and oxygen, another layer of substrate is added, then more cells and so on, creating a multilayer sandwich of organic material that could be implanted in a patient suffering from heart failure.
“We can keep going to however many layers you want,” Xu says, noting that a 10-by-10-by-2-millimeter cardiac patch might contain 5 million stem cells. Having an adequate supply of cells is important, “otherwise it won’t work at all.”
Xu hopes to have a patch available for animal testing by the end of his three-year grant. If all goes well, he plans to mount human trials in collaboration with researchers at Texas Tech University.
Biomedical researchers first saw the potential of thermal inkjet technology as it came into widespread use back in the 1990s, Xu says. But early experiments focused on printing organic molecules like DNA, not living cells.
When he arrived at Clemson University for his Ph.D. study nine years ago, Xu used ordinary off-the-shelf printers made by Hewlett Packard and Canon. Some inkjet nozzles can pass droplets as small as 10 microns (a micron is one-millionth of a meter), but most cells are in the 40- to 50-micron range, so different size nozzles are used for different purposes.
A key proof of concept, Xu recalls, came when the Clemson team showed that most of the cells could survive being squeezed through the ink jet heads, which can fire 15,000 times per second and operate at temperatures of 250-350 degrees Celsius.
Cells show “a little bit of heating, but it’s only on the surface,” he says. About 90 percent of cells remain viable after they are deposited on the substrate.
Researchers start with ordinary ink-filled cartridges, which are emptied, cleaned and sterilized before being refilled with cell-rich liquid solutions — a kind of “bio-ink.” Meanwhile, Xu confesses to prowling eBay looking for used, older-model printers suitable for his experiments.
After earning his doctorate, Xu did post-graduate research at Wake Forest University’s Institute of Regenerative Medicine, headed by Anthony Atala.
There, “we advanced the technology and tested quite a lot with animals,” Xu remembers. He also figured out how to print stem cells taken from amniotic fluid. “I demonstrated it was able to form bone tissue in animal models,” Xu says.
Atala, who has made headlines with his lab’s bold efforts to engineer replacement organs, such as bladders and heart valves, is developing a bio-printing method to repair burned skin. This approach starts with an infrared scanner that hovers over the wound, measuring the depth and dimensions of the crater-like injury.
Burn wounds need daily debriding for the first few weeks to remove dead and dying tissue, Atala says. Meanwhile, samples of the patient’s skin cells are cultured to make new cells. “Within two to three weeks you can have enough cells to cover the patient,” he says. “You can cover large areas with it.”
Once the wound’s healthy edges are apparent, the printing device deposits new cells in discrete layers. “We’ve actually already done it in rodents,” Atala says of the technique. Their wounds take three weeks to heal, whereas it takes five weeks to heal from a conventional skin graft.
He estimates the technology could be commercially available for human use within five years.
Meanwhile, Atala is also using the scan-and-print method to reconstruct solid organs. “That’s where this technology is very amenable to its application,” he says.
UTEP’s Xu sees other potential applications for bioprinting, such as screening new pharmaceutical compounds for their efficacy.
Current approaches to testing promising-but-expensive new compounds (which might cost as much as $100,000 a nanogram) employ a robotic system that deposits microliter-sized droplets onto cells to see whether it has any effect.
But because inkjet nozzles are so small, they can deliver candidate drugs in picoliters — billionths of a liter — onto equally small cell samples.
The cost comparison: $200 per dot using the robotic method versus mere pennies per sample using bio-printing, Xu says. He says he has received inquiries from printer manufacturers about commercializing the technology. “We know each other pretty well. They know what we are doing.”