Engineers 3-D print a ‘living tattoo’

MIT engineers have developed a 3-D printing technique that uses a new kind of ink made from genetically programmed living cells.

The cells are engineered to light up in response to a variety of stimuli. When mixed with a slurry of hydrogel and nutrients, the cells can be printed, layer by layer, to form three-dimensional, interactive structures and devices.

The team has then demonstrated its technique by printing a “living tattoo” — a thin, transparent patch patterned with live bacteria cells in the shape of a tree. Each branch of the tree is lined with cells sensitive to a different chemical or molecular compound. When the patch adheres to skin that has been exposed to the same compounds, corresponding regions of the tree light up in response.

This technique can be used to fabricate “active” materials for wearable sensors and interactive displays. Such materials can be patterned with live cells engineered to sense environmental chemicals and pollutants as well as changes in pH and temperature.

What’s more, the team developed a model to predict the interactions between cells within a given 3-D-printed structure, under a variety of conditions. The team says researchers can use the model as a guide in designing responsive living materials.

MIT engineers have devised a 3-D printing technique that uses a new kind of ink made from genetically programmed living cells. Credit: MIT researchers

MIT researchers realized that live cells might also serve as responsive materials for 3D-printed inks, particularly as they can be genetically engineered to respond to a variety of stimuli. The researchers are not the first to consider 3-D printing genetically engineered cells; others have attempted to do so using live mammalian cells, but with little success.

“It turns out those cells were dying during the printing process because mammalian cells are basically lipid bilayer balloons,” says one of the co-author Hyunwoo Yuk. “They are too weak, and they easily rupture.”

Instead, the team identified a hardier cell type in bacteria. Bacterial cells have tough cell walls that are able to survive relatively harsh conditions, such as the forces applied to ink as it is pushed through a printer’s nozzle. Furthermore, bacteria, unlike mammalian cells, are compatible with most hydrogels — gel-like materials that are made from a mix of mostly water and a bit of polymer. The group found that hydrogels can provide an aqueous environment that can support living bacteria.

The researchers carried out a screening test to identify the type of hydrogel that would best host bacterial cells. After an extensive search, a hydrogel with pluronic acid was found to be the most compatible material. The hydrogel also exhibited an ideal consistency for 3-D printing.

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“This hydrogel has ideal flow characteristics for printing through a nozzle,” Zhao says. “It’s like squeezing out toothpaste. You need [the ink] to flow out of a nozzle like toothpaste, and it can maintain its shape after it’s printed.”

The researchers also engineered bacteria to communicate with each other; for instance they programmed some cells to light up only when they receive a certain signal from another cell. To test this type of communication in a 3-D structure, they printed a thin sheet of hydrogel filaments with “input,” or signal-producing bacteria and chemicals, overlaid with another layer of filaments of an “output,” or signal-receiving bacteria. They found the output filaments lit up only when they overlapped and received input signals from corresponding bacteria.

Yuk says in the future, researchers may use the team’s technique to print “living computers” — structures with multiple types of cells that communicate with each other, passing signals back and forth, much like transistors on a microchip.

“This is very future work, but we expect to be able to print living computational platforms that could be wearable,” Yuk says.

For more near-term applications, the researchers are aiming to fabricate customized sensors, in the form of flexible patches and stickers that could be engineered to detect a variety of chemical and molecular compounds. They also envision their technique may be used to manufacture drug capsules and surgical implants, containing cells engineered produce compounds such as glucose, to be released therapeutically over time.

“We can use bacterial cells like workers in a 3-D factory,” Liu says. “They can be engineered to produce drugs within a 3-D scaffold, and applications should not be confined to epidermal devices. As long as the fabrication method and approach are viable, applications such as implants and in-gestibles should be possible.”

The work was led by Xuanhe Zhao, the Noyce Career Development Professor in MIT’s Department of Mechanical Engineering, and Timothy Lu, associate professor of biological engineering and of electrical engineering and computer science.

Reference:

Xinyue Liu, Hyunwoo Yuk, Shaoting Lin, German Alberto Parada, Tzu-Chieh Tang, Eléonore Tham, Cesar de la Fuente-Nunez, Timothy K. Lu, Xuanhe Zhao, 3D Printing of Living Responsive Materials and Devices. Advanced Materials, 2017, DOI: 10.1002/adma.201704821

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