Indiana University Researchers Pioneer Use of Innovative 3D Bioprinter

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Here's a new recipe for creating living tissue: Impale tiny clumps of cells onto needles, much like miniature shish kebab skewers. Instead of heading to a tiny BBQ grill, you wait while the cells grow together to form the tissue you want -- perhaps skin, or a section of blood vessel.

Researchers at Indiana University are among the first in the United States to have direct access to a 3D bioprinter using that innovative technology to create living tissue, now for use in research laboratories, and potentially for use in humans.

Traditional 3D printers create objects in layers by applying a fluid cell-embedding substance ("bio-ink") through a nozzle. The new machine uses a robot to place the tiny spheres of cells on the needles, carefully arranging them by cell type and location. The spheroids are assembled snugly against each other, enabling them to fuse together into the desired form of tissue.

Scientists will be using the instrument, distributed by the Japanese firm Cyfuse, to conduct research in tissue engineering and regenerative medicine projects in fields ranging from vascular and musculoskeletal biology to dermatology, ophthalmology and cancer, said David B. Burr, Ph.D., associate vice chancellor for research at Indiana University-Purdue University Indianapolis, professor of anatomy and cell biology at the IU School of Medicine and of biomedical engineering at IUPUI.

"We have a large and robust group of investigators in these fields who are interested in 3D bioprinting for aspects of their work," Dr. Burr said. "Having this device positions us, and these investigators, to conduct research and obtain grant funding in new areas that many universities are simply not able to compete for yet."

The Cyfuse printer, named Regenova, uses a small robot to place the tiny spheroids -- each containing about 20,000 cells -- onto the needle array. The types of cells, and their arrangements, vary depending on the tissue needed. Once assembled, the cells "know" how to do the rest, organizing themselves into the tissue needed. When ready, the tissue is removed from the spines.

Cyfuse calls its methodology "kenzan," a reference to the plate with needles -- also called the spiky frog -- used to affix plants in ikebana, the Japanese art of flower arrangement.

"Putting the printer in our hands immensely empowers us to do constructs no one has done before," said Nicanor Moldovan, Ph.D., an adjunct associate professor of biomedical engineering and of ophthalmology and a member of the Biocomplexity Institute at IU Bloomington.

Dr. Moldovan, whose interest is in tissue engineering, argues that by enabling the cells to create their own external structure -- extracellular matrix – rather than adding it as "bio-ink," the resulting tissues are much more likely to gain approval from the Food and Drug Administration for human use in the future.

Bioprinting from traditional 3D printers creates some issues. It requires the use of gels to carry cells through the printer nozzle that are compatible with the cells and the tissue being created. Fragments of the biogel remain, which would be seen as foreign, if not toxic, agents. Moreover, Dr. Moldovan said, forcing the gel mixture through the printing tip creates shear forces that can damage the cells.

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