MIT engineers have devised 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
is adhered to skin that has been exposed to the same compounds,
corresponding regions of the tree light up in response.
The researchers, 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, say that their 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
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.
Zhao, Lu, and their colleagues have published their results today in the
journal Advanced Materials. The paper’s co-authors are graduate students
Xinyue Liu, Hyunwoo Yuk, Shaoting Lin, German Alberto Parada, Tzu-Chieh
Tang, Eléonore Tham, and postdoc Cesar de la Fuente-Nunez.
A hardy alternative
In recent years, scientists have explored a variety of responsive
materials as the basis for 3D-printed inks. For instance, scientists
have used inks made from temperature-sensitive polymers to print
heat-responsive shape-shifting objects. Others have printed
photoactivated structures from polymers that shrink and stretch in
response to light.
Zhao’s team, working with bioengineers in Lu’s lab, 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,” Yuk says.
“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.
“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.”
From tattoos to living computers
Lu provided the team with bacterial cells engineered to light up in
response to a variety of chemical stimuli. The researchers then came up
with a recipe for their 3-D ink, using a combination of bacteria,
hydrogel, and nutrients to sustain the cells and maintain their
“We found this new ink formula works very well and can print at a high
resolution of about 30 micrometers per feature,” Zhao says. “That means
each line we print contains only a few cells. We can also print
relatively large-scale structures, measuring several centimeters.”
They printed the ink using a custom 3-D printer that they built using
standard elements combined with fixtures they machined themselves. To
demonstrate the technique, the team printed a pattern of hydrogel with
cells in the shape of a tree on an elastomer layer. After printing, they
solidified, or cured, the patch by exposing it to ultraviolet radiation.
They then adhere the transparent elastomer layer with the living
patterns on it, to skin.
To test the patch, the researchers smeared several chemical compounds
onto the back of a test subject’s hand, then pressed the hydrogel patch
over the exposed skin. Over several hours, branches of the patch’s tree
lit up when bacteria sensed their corresponding chemical stimuli.
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
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.
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 ingestibles should be possible.”
This research was supported, in part, by the Office of Naval Research,
National Science Foundation, National Institutes of Health, and MIT
Institute for Soldier Nanotechnologies.