Life in print: cell by cell, ink-jet printing builds living tissues

Science News,  Jan 26, 2008  by Sarah Webb

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Almost as soon as ink-jet printers hit the market in the 1980s, materials researchers realized that the machines could be used to deposit droplets of substances other than ink. In principle, anything that could squeeze through the printhead--including plastics, silicon, or dissolved metals--could be laid out in some precise pattern. And when printed in layers to create three-dimensional structures, such "inks" could allow the rapid design and even production of plastic or electronic parts for a variety of devices (SN: 3/27/04, p. 196).

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If ink-jet technology could work for printing plastic and electronic components, researchers suggested, it could also work for custom designing structures built with living cells.

"One of our goals, in a sense, always was to build a mechanical rat--if we can have moving parts, structural parts, and electrical parts all in one unit, then it's kind of like an animal," says Paul Calvert of the University of Massachusetts Dartmouth. "If I can build a mechanical rat, then maybe I could build a real rat."

Ink-jet printers won't start out by mass-producing living rats, though. Instead, researchers are setting their sights on producing skin, heart-muscle patches, and perhaps even organs.

Although researchers can create intricate structures with inkjet printing, organs built in this way might not perform perfectly, because engineered tissues do not go through a natural development process, says Thomas Boland of Clemson University in South Carolina. Natural tissues follow a bottom-up design, developing through the growth and differentiation of various progenitor cells. Engineered tissues instead conform to a top-down design template, based on what a final tissue should look like. Though the designs provide an overall structure, researchers rely on the cells' biology to fill in that template and signal to each other to produce an organized tissue.

Even though ink-jet-printed tissues might not have the same properties as their natural counterparts, such structures could prove useful in medicine and even in novel devices. Ink-jet-tissues could provide new cell-based materials for drug testing, new ways to probe cellular communication, living sensors, or even fuel cell-type batteries.

PRINTING CELLS Most inexpensive home printers signal a tiny nozzle to heat the ink just enough to build up pressure so that it releases a droplet that falls onto the page. More expensive industrial printers deposit an ink droplet when a piezoelectric crystal within the nozzle vibrates in response to an electric current. Because of the sensitivity of cells to heat, electricity, and other stresses, it might seem that cells couldn't survive such arduous treatment.

In fact, experiments show that at least 90 percent of cells can survive the printing process and remain viable. Boland and his colleagues have used modified thermal ink-jet printers to print mammalian cells, including human neurons and cardiac cells, onto biopaper, a hydrated gel surface made of collagen. Other groups, including Brian Derby's at the University of Manchester in the United Kingdom, use piezoelectric printers. Derby and his colleague, cell biologist Julie Gough, recently demonstrated survival rates of 95 percent or better when they printed human fibroblasts.

Such systems allow researchers to place cells individually and precisely. For example, Derby's ink drops are 10 to 50 micrometers ([micro]m) across and have a volume of roughly 10 picoliters, or one lO0-billionth of a liter, With cells measuring approximately 8 to 10gm across, each drop probably contains one cell on average, he says. Simple modifications can tweak a conventional office printer to print those individual cells in layers, one on top of another, to produce 3-D structures, Boland says.

Arranging cells in three dimensions is only the first step, however. Such structures need materials around the cells that will support and sustain them, and a major challenge is producing inks with the appropriate properties for building robust 3-D structures. These inks, separate from the ones that deposit cells, have to be liquid within the printer but then solidify once they're released in drops from the printer. They also need to mimic the natural rigidity and flexibility of tissues. Researchers are investigating materials that are compatible with the cells and that switch their properties depending on temperature or some other controllable factor. To boost cell survival in the scaffolds, they may o need additional proteins such as growth factors and agents that prompt cells to specialize. "We still have a long way to go to optimize the ink for these materials," Boland says. Several groups are teaming with printer manufacturers to develop printers tailored to cell-based applications.

CELLULAR COMMUNICATION Although cells suspended in a medium can move through a printer just like any other ink, introducing a living ingredient produces a dynamic material. The cells respond to each other as well as to chemicals included in the printing mixture to influence cell behavior. Chemical signals between cells are critical for organizing and maintaining complex tissues, but researchers know relatively little about how extracellular signals work together. Scientists understand how certain signals lead cells to grow, divide, and produce the complex patterns within living tissues, Calvert says, but they don't know "how this allows different cell types to wind up in the right structure."