Writing cells with light
THE JOURNEY OF
1990s-
In the mid-1990s, David Odde, now a bioengineer at the University of
milestone
Minnesota, had just started his laboratory at Michigan Technological
3D BIOPRINTING
2000
University, working on nerve regeneration. Not long after, something
in the university news caught his eye. “I saw this little blurb that said,
‘physics professor develops atomic pencil,’” Odde recalled. “It went
on to describe Michael Renn’s work, which was using lasers to guide
atoms on surfaces.”
by CAROLYN WALSH, PHD
Renn was a physicist at Michigan Technological University and had
done his postdoctoral research with Eric Cornell and Karl Wieman, who
Scientists use 3D bioprinting to sculpt cells and biomaterials into 3D
used lasers to cool atoms to near absolute zero, a discovery that later
biological constructs. Over the last few decades, 3D bioprinting has matured
earned them the Nobel Prize. Inspired by their method, Renn realized
from an engineering curiosity to a widely used technique for disease
that light could not only cool atoms but also maneuver them, leading to
his development of the atomic pencil.
modeling and drug development, with the ultimate goal of fabricating
“It was our conversation that steered it toward using [laser technology]
1980s
transplantable organs.
to directly write cells and other biologicals,” explained Odde. He proposed
bringing cells from his lab to Renn’s laser setup to see whether they could
“write” cells onto surfaces.
It worked: Using a near-infrared laser, the two scientists guided indi
vidual
neurons suspended in culture medium and deposited them onto
a glass surface in precisely spaced clusters. The cells survived, adhered,
Breakthroughs
and extended neurites, demonstrating that light could position living cells
with high precision (4). “It contributed to the overall ethos or idea that
TOP IMAGE: David Odde was one of the first scientists to use lasers
IMAGE LEFT:
that set the stage
this was feasible and should be pursued,” said Odde. “In that sense, I
to bioprint cells. ABOVE: A laser beam can move and position living
Robert Klebe used
cells without harming them.
think it was stimulating to the field.
an inkjet printer to
precisely deposit
In the mid-1980s, engineer Charles Hull, who worked on fabricating
cell adhesion
Printing 3D tissues
proteins and guide
plastic devices from photopolymers at Ultra Violet Products, was
cells into define
frustrated by the lengthy, error-prone process of making prototypes.
patterns.
In the early 2000s, Thomas Boland, a bioengineer then at Clemson University, was
IMAGE BELOW:
Typically, it took months and multiple iterations to design a part and
Charles Hull
exploring how to use tissue engineering to develop transplantable organs. Like
invented
then painstakingly cast the material in a mold. To speed things up, Hull
Klebe, Boland was drawn to the precision and rapidity of standard office printers,
stereolithography,
built a device that used a computer-controlled ultraviolet laser to cure
a technique that
but instead of printing cell adhesion proteins, he and his team became the first to
uses ultraviolet
and solidify liquid photopolymer resin, creating each new layer on top
print living mammalian cells.
light to cure liquid
of the last to form a 3D object without the need for molds. In 1986, he
resin layer by layer.
Because mammalian cells are much larger and more delicate than ink
filed a patent for this technique, known as stereolithography, laying
2000s
droplets, Boland’s team replaced the printer’s ink system with wider chan
the foundation of 3D printing (1).
nels
connected to reservoirs of cell suspensions, enabling it to gently eject
Around the same time, Robert Klebe, a cell biologist at the University
droplets of cell suspension without damaging them.
Using this setup, they first demonstrated that they could arrange cells
of Texas, was looking for a way to precisely position cells so he could
in 2D patterns by printing blobs of bovine cells suspended in culture medium
study cell-cell interactions and how cellular adhesion proteins influ
onto a gel surface (5). To extend this to 3D — essential for artificial tissues — they
ence
morphogenesis. This led him to develop cytoscribing, in which
used thermo-reversible gels as scaffolds. These gels could be printed as liquids and
he loaded a standard Hewlett-Packard inkjet printer with a solution
then solidify, making sequential layers that provided structural support for the cells.
of cell adhesion protein and printed it onto a surface in specific pat
When they deposited droplets of cells in close proximity within this 3D gel matrix,
terns.
When cells were added, they attached to where the proteins
the cells fused, forming tissue-like constructs (6).
had been printed (2). To demonstrate the precision of this method,
A few years later, Gábor Forgacs, a biophysicist at the University of Missouri,
Klebe spelled out the word “fibronectin” with mouse fibroblast cells
took advantage of this natural process of cell fusion to take a step forward in bio
in his patent application (3).
printing
vasculature (7). His team built a robotic bioprinter that placed tiny cylinders
At the time, it may not have been obvious that Hull’s 3D printed struc
of living cells around removable agarose rods. The cylinders spontaneously fused
tures
and Klebe’s cellular writing had much in common. In the coming
into continuous tissues and allowed Forgacs’s group to create hollow tubes that
years, however, researchers would combine and build on these innova
mimicked blood vessels..
tions
to develop modern 3D bioprinting, typically defined as the precise
TOP RIGHT: Thomas Boland and his team modified a commercial inkjet printer
patterning of living cells and biological materials into 3D structures.
to print mammalian cells. BOTTOM RIGHT: Gábor Forgacs printed multicellular
spheroids or cylinders around removable agarose rods, allowing the cells to
fuse into hollow, vessel-like structures.
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CREDIT: ISTOCK.COM/DAVID ODDE
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