An angiogenic hydrogel
Kofi
Bioengineered Materials Promote the Growth of Functional Vasculature
ScienceDaily (Dec. 23, 2009) � Georgia Tech researchers have shown that
they are able to induce significant functional vasculature growth in
areas of damaged tissue through the use of synthetic polymers called
hydrogels.
Regenerative medicine therapies often require the growth of functional,
stable blood vessels at the site of an injury. Using synthetic polymers
called hydrogels, researchers at the Georgia Institute of Technology
have been able to induce significant vasculature growth in areas of
damaged tissue.
"This study shows that bio-artificial materials are suitable for
promoting vasculature growth and remodeling," said lead author on the
study Andr�s Garc�a, professor and Woodruff Faculty Fellow in Georgia
Tech's Woodruff School of Mechanical Engineering and the Petit Institute
for Bioengineering and Bioscience. "Because hydrogels are very
compatible with biological tissues, they are a promising therapeutic
delivery vehicle to improve treatment of peripheral artery disease,
ischemic heart disease, and survival of cell and tissue transplants."
Details of the research were published in the early edition of the
journal Proceedings of the National Academy of Sciences on December 21,
2009.
As part of the research, Garc�a and Georgia Tech graduate student Edward
Phelps tailored the biochemical and mechanical properties of
polyethylene glycol-based hydrogel matrices to enable vasculature to
form in and around them. First, the researchers incorporated specific
chemical cross-links into the gels so that they would maintain their
structural integrity and only degrade in the presence of enzymes called
matrix metalloproteinases that are typically expressed by invading
cells. They also incorporated into the matrices a protein, vascular
endothelial growth factor (VEGF), which stimulates the growth of blood
vessels.
"Incorporating these cross-links controlled the release of VEGF from the
matrix so that VEGF was only released as the matrix was digested by
invading cells," explained Garc�a. "This was very important because if
you have something solid such as a matrix that cannot degrade, you will
not have any vasculature growth into that area."
Adhesive amino acid sequences were also added to the gel so that cells
could spread within the gel and interact with nearby endothelial cells
undergoing the blood vessel growth process called angiogenesis.
When the researchers implanted the pre-formed hydrogel constructs into
small animals, the matrix exhibited constant levels of VEGF for two days
followed by a gradual decrease during the following 12 days. When
animals were injected with soluble VEGF, a steady decline of VEGF was
recorded until 90 percent of the compound was lost within two weeks.
"With the degradable implant that included growth factors, after two
weeks we saw that new vessels were growing into and around the implant,"
noted Phelps.
Additional studies with micro-CT imaging showed a six-fold increase in
vascular density at two weeks and a 12-fold increase in vascular density
at four weeks with the degradable matrix compared to an injection of
soluble VEGF. In addition, the hydrogel degraded in a controlled fashion
and was replaced by normal tissue.
"We found that the vasculature was functional and connected to the host
circulatory system, which we saw when a contrast agent injected through
the aorta reached the vessels in the implant," added Garc�a.
To place the hydrogel deeper inside the body than the pre-formed matrix
construct would allow and to be able to fill in an injured area of any
shape, the researchers developed a liquid material that forms a gel
inside the body when exposed to ultraviolet light.
"In reality, most injuries are not well-defined defects so you can't
take a pre-formed construct and fill the irregular-sized site," added
Garc�a. "Instead, you want to be able to access the area in a minimally
invasive way and injecting this solution through the skin allows us to
do that without surgery."
The researchers injected the VEGF-containing matrix solution into mice
suffering from restricted blood flow, known as ischemia, in one leg.
After seven days, the animals exhibited a 50 percent increase in blood
perfusion to the affected leg and a 100 percent increase in perfusion to
the affected foot. The blood flow to the affected leg was greatly
enhanced compared to treatment with a non-degradable hydrogel and
injection of soluble growth factors alone.
"The engineered matrix containing VEGF performed much better than
injecting soluble VEGF, indicating that the delivery vehicle acted
synergistically to amplify the effect of the growth factor," noted
Phelps.
According to the researchers, the increased perfusion was due to growth
factor sequestration in the matrix, resulting in prolonged exposure that
persisted as the matrix was degraded and remodeled.
Additional studies are currently being conducted to determine the
clinical viability of these hydrogels as therapeutic vascularization
therapies to treat peripheral artery disease and ischemic heart disease,
and cell transplantation to treat diabetes. Future studies may
incorporate more or different growth factors to achieve even more robust
healing effects.
Other researchers involved in the study include W. Robert Taylor, a
professor in the Wallace H. Coulter Department of Biomedical Engineering
at Georgia Tech and Emory University, Emory's Division of Cardiology,
and the Atlanta Veterans Affairs Medical Center; Peter Thul�, an
associate professor in Emory University's Division of Endocrinology,
Metabolism and Lipids, and the Atlanta Veteran's Affairs Medical Center;
and Natalia Land�zuri, a postdoctoral fellow in the Emory University
Division of Cardiology.
The work was supported by the National Institutes of Health, the Atlanta
Clinical and Translational Science Institute (ACTSI) through the Georgia
Tech/Emory Center (GTEC) for the Engineering of Living Tissues, the
Juvenile Diabetes Research Foundation, and the American Heart
Association.
Maier Yancov
enironment that fosters the creation/growth of cancer...?
Kofi
<6493d8e6-6090-422f...@v25g2000yqk.googlegroups.com>,
Maier Yancov <mya...@gmail.com> wrote:
> doesn't anything angiogenic always carry a danger of creating an
> enironment that fosters the creation/growth of cancer...?
Yes. It's always a risk in regenerative medicine.