>neural scaffold work

From: Spudboy100@aol.com
Date: Fri Jun 09 2000 - 08:59:48 MDT


CAMBRIDGE, Mass. -- Researchers at the Massachusetts Institute of Technology
and New York University report in the June 6 issue of the Proceedings of the
National Academy of Sciences (PNAS) that they have made a biomaterial that
supports living nerve cells.

This peptide-based scaffold, on which neurons grow fibers to communicate with
each other and establish functional synapses, may be the long-sought ideal
medium for growing replacement nerve cells for victims of spinal cord
injuries and other forms of nerve damage.

New biological materials based on the tiny protein linkages called peptides
"will become increasingly important in developing approaches for a wide range
of innovative medical technologies, including controlled drug release, new
scaffolds for cell-based therapies, tissue engineering and
biomineralization," predict authors Shuguang Zhang, associate director of the
Center for Biomedical Engineering at MIT; Todd C. Holmes (MIT PhD, 1994),
assistant professor of biology at NYU; and colleagues.

This is the first peptide-based biomaterial of its kind that can be designed
at the molecular level. Although parts of animal cells such as collagen can
be extracted as a basis for growing cells, such animal-derived materials may
carry and pass on viruses to the attached growing cells. In contrast, the new
peptide-based material is not extracted from animal cells.

And unlike other synthetic materials, these peptides are completely
biological. The peptides are composed of amino acids, which are the building
blocks of all proteins. The peptides do not evoke an immune response or
inflammation in living animals, and they can be used for a variety of
applications. "The reason this material is so interesting and unique is that
we can individually tailor it to grow virtually every type of cell in the
body," Zhang said.

"Further development of biological materials and related cell-based therapies
may bring us closer to the elusive goal of repairing the damaged nervous
system," wrote Melitta Schachner, a researcher in molecular neurobiology at
the University of Hamburg in Germany. Schachner wrote a "News and Views"
article about this work in the journal Nature.


Researchers are working to develop new biologically compatible scaffolds for
controlled drug release, tissue repair and tissue engineering.

Synthetic scaffolds have been used to grow skin, livers and cartilage, among
other tissues, but some cells can't tolerate these scaffolds, which tend to
be acidic.

While a successful scaffold has to be cell-friendly, it has to be
particularly hospitable to grow nerve cells. The brain seems to keep firm
control on the reproduction of its cells. Inhibitor molecules block
regenerating neurons. Neurons grown on the wrong substrate die. After an
initial period of development at the very beginning of life, very few new
neurons are produced by the adult central nervous system.

The new biomaterial developed by Zhang, Holmes and colleagues seems to be an
ideal substrate, or growing surface, for cells slated for replacing damaged
tissue in the nervous system. Neurons attach to it and grow axons, the long
tails through which they send signals. Active synapses -- the spaces through
which nerve cells communicate -- form and survive in these cultured cells.


Fragments of the 80,000-plus of kinds proteins in our body are called
peptides. Peptides transform themselves like tiny smart Legos into millions
of essential substances.

Zhang and other scientists have recently discovered that these same peptides
can be tweaked into forming completely new natural materials that may be able
to perform a variety of useful functions inside and outside the body.

Researchers have found that peptides can self-assemble into non-protein-like
structures such as fibers, tubules, sheets and thin layers. They can be made
responsive to changes in acidity, mechanical forces, temperature, pressure,
electrical and magnetic fields and light. They are stable at temperatures up
to 350 degrees Celsius and can be produced up to a ton at a time at
affordable cost. They can be programmed to biodegrade.

Out of scientific curiosity, Zhang asked Holmes to test one of his
self-assembling peptides for toxicity to nerve cells. Not only were they not
toxic, they seemed to thrive in culture in the presence of a salt. With the
salt, the peptides self-assembled into thin, wavy films that look a little
like Saran Wrap. Under a microscope, the film contained a network of fibers.

Further tests showed that nerve cells happily grew on these fibers. While no
immune response or inflammation was seen when the peptides were injected into
rat muscle tissue, they have not yet tested in the brain, spinal cord and
peripheral nerves.

Other authors are Sonsoles de Lacalle of California State University; Xing Su
of Affymetrix Inc. of Santa Clara, Calif.; Guosong Liu of the Department of
Brain and Cognitive Sciences at MIT and Alexander Rich of the Center for
Biomedical Engineering at MIT.

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