Capillaries of artificial, resilient polymer with a diameter of 20 µm. Image: Fraunhofer Institute for Laser Technology ILT, Aachen

Tissue engineering pursues the aim of replacing natural tissue after
injuries and illnesses with implants which enable the body to regenerate
itself with the patient’s own cells. So that tissue can be produced to
replicate the body’s natural tissue, knowledge of the interaction
between cells in a three-dimensional framework and the growth conditions
for complete regeneration is essential. Using a special laser
technique, research scientists at the Fraunhofer Institute for Laser Technology ILT
and other Fraunhofer Institutes have succeeded in producing hybrid
biomimetic matrices. These serve as a basis for scaffold and implant
structures on which the cells can grow effectively.

If
tissue has been badly damaged by disease or due to an accident or if
parts of the tissue have been completely removed, the body is often
unable to regenerate this tissue itself. What’s more, in many cases no
endogenous material is available for transplants. As a result, demand in
the medical field is increasing for implants which enable complete
regeneration to take place. But the current artificially produced
implants are often not adequately adapted to the environment in the
patient’s body and are therefore of limited use as a tissue replacement.
           

The
main reason for this lack is the missing knowledge on how cells react
to a three-dimensional environment. Scientists at Fraunhofer ILT in
cooperation with other Fraunhofer Institutes, however, have developed a
process for producing biomimetic scaffolds which closely emulates the
endogenous tissue. This process allows the fabrication of specialized
model systems for the study of threedimensional cell growth, for the
future generation of optimal conditions for the cells to colonize and
grow. For this purpose the Aachen-based research scientists have
transferred the rapid prototyping technique to endogenous materials.
They combine organic substances with polymers and produce
three-dimensional structures which are suitable for building artificial
tissue.

Laser light converts liquid into 3-D solids

As
the basis the research scientists use dissolved proteins and polymers
which are irradiated with laser light and crosslinked by photolytic
processes. For this they deploy specially developed laser systems which
by means of ultra-short laser pulses trigger multiphoton processes that
lead to polymerization in the volume. In contrast to conventional
processes, innovative and low-cost microchip lasers with pulse durations
in the picosecond range are used at Fraunhofer ILT which render the
technique affordable for any laboratory.

Test matrix consisting of a polymer support structure and a protein functional structure. Image: Fraunhofer Institute for Laser Technology ILT, Aachen

The
key factors in the process are the extremely short pulse durations and
the high laser-beam intensities. The short pulse duration leads to
almost no damage by heat to the material. Ultra-fast pulses in the
megawatt range drive a massive amount of protons into the laser focus in
an extremely short time, triggering a non-linear effect. The molecules
in the liquid absorb several photons simultaneously, causing free
radicals to form which trigger a chemical reaction between the
surrounding molecules. As a result of this process of multiphoton
polymerization, solids form from the liquid. On the basis of CAD data
the system controls the position of the laser beam through a microscope
with a precision of a few hundred nanometers in such a way that
micrometer-fine, stable volume elements of crosslinked material
gradually form.            

“This
enables us to produce scaffolds for cell scaffolds with a resolution of
approximately one micrometer directly from dissolved proteins and
polymers to exactly match our construction plan,« explains Sascha
Engelhardt, project manager at the ILT. “These biomimetic scaffolds will
enable us to answer many aspects of threedimensional cell growth.”

For
this purpose the team of research scientists uses various endogenous
proteins, such as albumin, collagen and fibronectin. As pure protein
structures are not very shape-stable, however, the Aachen-based
researchers combine them with biocompatible polymers. These polymers are
used to generate a scaffold which in a subsequent step provides a
framework for the protein structures that have been produced. This new
process makes it possible to create structures offering much greater
stability. The scaffold can be seeded with the patient’s own cells in a
medical laboratory. The colonized scaffolds can then be expected to
produce good implant growth in the patient’s body. The long-term aim is
to use the process to produce not only individual cell colonies but also
complete artificial tailor-made organs. That would represent a huge
medical advance!

The
Fraunhofer ILT research scientists are currently engaged in work to
optimize the process. For example, they want to greatly increase the
production speed by combining the fabrication process with other rapid
prototyping methods, in order to reduce the time and cost involved in
producing tailor-made supporting structures for synthetic tissue.

Fraunhofer-Institut für Lasertechnik ILT