The inkjet printer technology often seen in offices is now finding use in research that uses suspensions of living cells as their ink to explore ways to manufacture complex tissues and organs. However, inkjet-based cell printing leaves many cells damaged or dead. Now researchers have developed a technique akin to ancient Chinese woodblock printing wherein nearly all cells survive. The findings are detailed in the Proceedings of the National Academy of Sciences.
Bio-printing may not only find use in manufacturing tissues and organs, but also in laying down patterns of cells on surfaces for a wide variety of experiments, such as testing if a molecule could find use in medicine, or analyzing how cells function and communicate with other cells. Previous inkjet-based cell printing typically can leave up to half the printed cells dead, lacks precision when it comes to depositing cells on surfaces, and overall can be expensive and difficult to operate.
“We were sick of using inkjet printing and started to think for other approaches to prepare a cell pattern,” says biomedical researcher Lidong Qin at Houston Methodist Research Institute.
Qin recalled that one day he and his colleagues were inspired by rubber stamps children play with. The way these stamps print letters and other images works much like the ancient Chinese woodblocks that revolutionized the printing world more than 1,800 years ago.
The blocks in question are made of silicone. Cells flow down columns in the blocks. The way in which these columns are arranged is fully configurable during the creation of the blocks. There are hook-like traps within these columns that help control the rate at which cells get deposited onto surfaces. When the block is lifted away, the cells remain behind in precise formations.
“As long as cells are suspended well enough, clogging won’t happen,” Qin says. “The hook-shaped traps are not sharp at their edges; tearing won’t happen either.”
This approach produces 2-D arrays of cells in as little as a half-hour. It prints the cells as close together as 5 microns — in comparison, most animal cells are 10 to 30 microns wide. It can simultaneously handle multiple cell types, and results in close to 100 percent cell survival. The researchers have named this method Block-Cell-Printing, or BloC-Printing.
The scientists demonstrated they could print metastatic cancer cells in a grid and examine their growth in comparison with non-metastatic cells to characterize the metastatic potential of those cells. This could help diagnose the stage of a cancer.
The researchers also printed a grid of brain cells and got them to form connections with each other. These cell junctions might be useful in future studies of neuron communication and regeneration for understanding Alzheimer’s and other neurodegenerative diseases.
“We found printing neuron cells was extremely challenging — it took us more than three months to figure out the right conditions,” Qin says.
The scientists noted the materials to make each block cost only about $1, and that each block is reusable for hundreds of printings. The approach does not require sophistical equipment — after a block has been fabricated, a researcher only needs a syringe, a suspension of living cells, a Petri dish and a steady hand, Qin says. In comparison, inkjet-based cell printers can cost between $10,000 and $200,000.
Qin does note that inkjet-based cell printing remains faster. Also BloC-Printing cannot yet print multi-layer structures as inkjets can. Still, Qin notes it could still find use for many types of experiments involving drug screening, RNA interference, and other molecule-cell and cell-cell interaction studies.