WIRE)–In the emerging field of tissue engineering, scientists encourage
cells to grow on carefully designed support scaffolds. The ultimate goal is to create
living structures that might one day be used to replace lost or damaged tissue,
but the manufacture of appropriately detailed scaffolds presents a significant
challenge that has kept most tissue engineering applications confined to the
research lab. Now a team of researchers from the Laser Zentrum Hannover (LZH)
eV Institute in Hannover, Germany, and the Joint Department of Biomedical
Engineering at the University of North Carolina at Chapel Hill and North
Carolina State University has modified a manufacturing technique called
two-photon polymerization (2PP) to create finely detailed structures such as
tissue scaffolds more quickly and efficiently than was previously possible. The
new technique, which the team describes in a paper published this week in the
Optical Society’s (OSA) open-access journal Biomedical Optics Express, could help pave the way to more
wide-spread clinical use of microscale medical devices.
Many important biological functions take place on the
microscopic level and as medical research advances into this Lilliputian realm,
scientists have turned to precise techniques such as 2PP to create the tiny
tools necessary to manipulate cells and other miniscule structures. In
current-generation 2PP technology, a laser pulse that lasts approximately one
quadrillionth of a second sends a burst of energy into unset resin, causing the
molecules around the pulse to fuse together into two adjoining cone shapes. By
focusing on multiple points in succession, 2PP can build up complex 3D
structures, cone-shaped block by cone-shaped block.
2PP can be used to manufacture devices from a wide range of
base materials and does not require extreme temperatures, harsh chemicals, or
cleanroom facilities, but its main drawback is long fabrication times. Like in
a tiled mosaic, small 2PP building blocks can create a richly detailed design,
but if you want a large structure, like a tissue scaffold that could mimic
natural body parts, it can take a long time to lay all the pieces together.
“Blood vessel networks can be several centimeters in length,
but walls of the smallest branches (capillaries) are only a few micrometers
thick. The same applies with any tissue. Many tissues may be large, but they
all have important features on the microscale,” says team member Shaun Gittard
of the LZH. The team notes that using conventional 2PP to manufacture the
tissue scaffolds for such structures could be prohibitively slow. They address
the problem by using a computer-controlled hologram to split the 2PP laser into
multiple beams, creating up to 16 different focus points that can work
“As an example, take the time for fabricating a single
layered, 1-millimeter square with 100 nanometer resolution,” the authors write.
“With conventional single-focus 2PP at one millimeter per second, the
fabrication time would be 2 hours and 47 minutes. In contrast, with 16 foci
this same area could be scanned in merely 10 minutes.” Or, in other words, many
foci make light work.
The team first tested their multiple foci system by creating
16 miniature Venus statues, each so small as to be invisible to the human eye.
“The Venus is kind of a logo of our research group,” says Gittard. “We have
used it as a familiar demonstration structure for various fabrication
In addition to replicas of classic Greek artwork, the team
also used the new technique to manufacture cylindrical tissue scaffolds and an
array of microneedles. Less than a half millimeter wide, rocket-shaped microneedles
can be used to provide painless injections or take blood samples, notes Gittard
(see figure). “One of the biggest promises in the future is real-time,
pain-free glucose sensing and insulin delivery for treating diabetes,” he says.
For now the team has only used the multiple beams to create
multiple copies of the same structure. Their next goal is to use the system to
produce one large, complex 3-D structure, which is a more complicated task
since it requires moving the relative placement of the different foci during
the fabrication process, Gittard says.
“The ability to produce large-scale devices with sub-micron
features is exciting, as many cell features, such as organelles, are on this
size scale,” the authors write. Gittard explains that such detailed features
could be used to control cell attachment and alignment, which is important
since cell orientation affects function in a number of tissues, such as blood
vessels, nerves, bone, and muscle.
Paper: “Fabrication of microscale medical devices by two-photon
polymerization with multiple foci via a spatial light modulator,”
Shaun D. Gittard, Alexander Nguyen, Kotaro Obata, Anastasia Koroleva, Roger J.
Narayan, Boris N. Chichkov, Biomedical Optics Express, Volume 2, Issue 11, pp.
About Biomedical Optics Express
Biomedical Optics Express is OSA’s principal outlet for serving the biomedical
optics community with rapid, open-access, peer-reviewed papers related to
optics, photonics and imaging in the life sciences. The journal scope encompasses
theoretical modeling and simulations, technology development, and biomedical
studies and clinical applications. It is published by the Optical Society and
edited by Joseph A. Izatt of Duke
Optics Express is an open-access journal and is available at no cost to readers
online at www.OpticsInfoBase.org/BOE.
Uniting more than 130,000 professionals from 175 countries, the Optical Society
(OSA) brings together the global optics community through its programs and
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field, providing educational resources to the scientists, engineers and
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