New Method of 3D Cell Printing Ups Brain Cell Survival Rate: What Is Block-Cell Printing?

By Gabrielle Jonas on February 11, 2014 5:39 PM EST

A Lot Can Change in 18 Centuries, Like Going From Printing in Ink to Living Cells
cells printed in a grid pattern by block cell printing technology and woodblocks used in ancient Chinese printing (Photo: Lidong Qin lab and Digital Mus)

Researchers in Houston have developed a way to print living cells in virtually any shape onto any surface. Unlike recent, similar work using 3D printing, almost all cells survive the process, say scientists in this week's Proceedings of the National Academy of Sciences. "The current technologies are inadequate," said Dr. Lidong Qin, a specialist in nanomedicine at the Houston Methodist Research Institute, one of the new method's inventors. "Inkjet-based cell printing leaves many of the cells damaged or dead. We wanted to see if we could invent a tool that helps researchers obtain arrays of cells that are alive."

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So far, Qin and his co-inventor have printed out cancer cells, neurons, fibroblasts, and immune cells.

Until now, attempts to print cells in two and three dimensions have employed a technology using specialized inkjet printers. The survival rate cells shot out of; the nozzles of such inkjet printers has been as high as 80 percent. "We are seeing close to 100 percent of cells in BloC-Printing survive the printing process," Qin, said.

Qin's approach, dubbed Block-Cell-Printing ("BloC-Printing"), prints the cells within five micrometers of each other. The technique is quite impressive considering most animal cells are 10 to 30 micrometers wide. His team has been able to print out many different cell types, including breast cancer cells and neurons. He is able to print 2-D cell arrays in about half an hour, which he considers slow. While the fidelity of BloC-Printing is high, Qin said inkjet printing remains faster, and BloC-Printing cannot yet print multi-layer structures as inkjetting can

In December; a 3-D inkjet printer in the UK has successfully printed out ocular cells, making it the first time the technology has been used successfully to print mature central nervous system cells. The "ink" was made from retinal cells derived from adult rat retinas suspended in a special culture medium. The printed retinal ganglion cells, which transmit information from the eye to the brain, and glial cells, which support and protect neurons, retained their ability to survive and grow in culture. The breakthrough, detailed in a paper published in the journal Biofabrication, elevated the use of 3-D biomedical printing to arranging cells into highly defined patterns and structures.

There, the printers used a piezoelectric inkjet printer, made in Texas that ejected the cells through a sub-millimeter-diameter nozzle in response to specific electrical pulses. Those researchers plan to make living tissues using multiple nozzles which each have a piezoelectric driver that can be individually addressed, so that potentially different types of cells could be printed from different nozzles at the same time as part of a tissue-engineering protocol.

"The technology has low requirement. We were sick of using inkjet printing and started to think for other approaches to prepare a cell pattern," Qin told the International Science Times.  "We were one day, suddenly inspired by the little stamps kids are playing with. The technical mechanism for the kids' stamps is the same as the ancient woodblock printing."

One of the advantages of Qin's lower-tech methodology is that his "print-outs" will survive on any surface. "We tried glass and a few plastic surfaces," he said. "They all work with BloC-Printing. Many cell printing applications will require cells to stay on certain surfaces. For example, if you run electro-physiology measurements, you want the cells to stay on an electrode array. If you do tissue regeneration, you want the cells to stay on scaffold materials."

The dangers posed by the ability to print out cancer cells, which could be imbibed by accident did not concern Qin. "People need to be cautious when handling bio-hazardous materials. We won't persuade lay people to use the device. Instead, the device is ideal for research labs to generate cell arrays. The BloC-Printing won't create additional risks to the existing cell handling protocols for researchers in their labs."

If I Only Had a Brain

Qin, who is also a Weill Cornell Medical College assistant professor, printed a grid of brain cells and gave the cells time to form synaptic and autaptic junctions. "The cell junctions we created may be useful for future neuron signal transduction and axon regeneration studies," he said. "Such work could be helpful in understanding Alzheimer's disease and other neurodegenerative diseases." He doesn't think they'll be able to print out a whole organ, though. "Printing multilayers of cells is still a big challenge for BloC printing," he said. "This is too ambitious. I'll say impossible." His ambition will remain to "seek more practical applications for the technology" including drug-screening, when combined with molecular printing, as well as cancer diagnosis. "

The reason the technology is so promising in the area of cancer diagnosis is that arrangement of metastatic cancer cells in a grid allowed Qin and his team to determine the metastatic potential of cancer cells. The longer the protrusion a cancer cell generated, the more malignant it was. "The measurement may help to diagnose a cancer's stage." he said. "When cancer cells are trapped by the BloC printing hooks, their membrane can be extended along the device channel. The elongated length correlates to cancer cells' migration/invasion capability. Such elongation behavior is caused by the channel width and cells extend through the narrow 3-micron channel."

While making the molds, Qin configured the position and spacing of the traps and shape of the channel navigated by the cells. Dr. Qin and his team guided living cells into miniscule hook-like traps in the silicone mold. Successive cells flowed down a column inside the mold, past trapped cells to the next available slot, eventually creating a line of cells in a grid of lines. When he lifted the mold away, the living cells remained by adhering to the growth medium or other substrate, in prescribed formation.

At the cost of about one dollar per single BloC mold versus a $10,000 to $200,000 inkjet cell printer, the invention comes out as a money-saver. Then there's the nominal costs of a syringe, a carefully prepared suspension of living cells, a Petri dish, a steady hand, and, one hopes, quite a bit of good will and know-how.

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