Left without a trellis, vines will grow in any direction toward
the sun. Much like climbing plants, new blood vessels need a
guide too. In regenerative medicine research funded by
Institute of Biomedical Imaging and Bioengineering (NIBIB)
3D printed scaffolds have proved a useful tool for helping
to grow small blood vessels.
The 3D-printed vascular networks are undergoing study for
their potential to treat ischemia – a medical condition
responsible for restricting blood flow to parts of the body.
At its most effective, the regenerative blood vessel treatment
is capable of encouraging the regrowth of 70% of the vessels in
the ischemic foot of a mouse model.
The global burden of disease
Ischemia can occur in the heart, the brain, bowel, limbs and
the skin. If left untreated, the condition kills tissue, and
may lead to death. According to the World Health Organization’s
global burden of disease report, ischemic heart disease
ranks within the top 20 most prevalent disabilities in the
One possible treatment for ischemia is to remove the affected
part, and encourage the body to grow new, functioning blood
vessels. For large vessels, such as arteries and veins, this is
relatively simple. But with smaller vessels, it becomes
significantly harder to treat.
The various 3D
printed scaffold patterns (left) and and their growth rate when
implanted in a mouse. In this experiment, one foot (as viewed on
the left in each image) was left without ischemia. Image via
nature biomedical engineering
Channeling blood vessels with 3D printing
When vessels are removed in a procedure, new ones are grown by
applying growth factors to the tissue. Christopher Chen,
Professor of Biomedical Engineering at Boston University and lead author of
the NIBIB study,
explains, “We know that when growth factors are injected
into a tissue, they do induce the sprouting of new blood
vessels, but in a disorganized pattern unable to deliver oxygen
to ischemic tissues,”
“Our goal was to use engineering to direct the growth of new
vessels into an orderly, functional network.”
To guide the growth of new vessels, Chen et al. proposed
the use of 3D printing to trial a number of scaffold designs.
These designs were 3D printed as a mold, and cast for implant
in the body using a fibrin gel solution, then patterned
with endothelial cells.
Of the 4 different designs tried, a pattern forming tracks
proved to be the most effective at regrowing vessels – after 5
days inside the ischemic foot of a mouse, 70% of blood vessels
had grown back into the foot.
A “no pattern” patch, without the careful placement of
endthelial cells inside the designed channels proved to be the
least effective after 5 days.
A challenge to medicine
Reproducing vascular structures is one of the chief challenges
in modern medicine. Ischemic diseases are also undergoing
a study at Korea’s Pohang University of Science and
Technology (POSTECH). And
neurovascular research at the University of
Manchester in the UK recently succeeded in replicating the
bloood-brain barrier using 3D printing.
Commenting on the NIBIB project, Chen says, “Although we are
still at the very early stages of this project, we are
encouraged by the initial results.”
Rosemarie Hunziker, Director of the NIBIB Program in Tissue
Engineering, concludes, “The results of this collaboration are
an excellent example of how engineers can take what biologists
and physicians know about how our bodies work and use the
information to create practical, innovative medical
vascular networks direct therapeutic angiogenesis in
ischaemia‘ is published online in nature
biomedical engineering journal. The paper is
co-authored by T. Mirabella, J. W. MacArthur, D. Cheng, C.
K. Ozaki, Y. J. Woo, M. T. Yang & C. S. Chen.
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Featured image shows the gradual regrowth of blood vessels
after the implant of the study’s’ scaffolds. Image via nature