[tt] More nano-neural regeneration

[Hughes, James J.]

http://www.eurekalert.org/pub_releases/2007-05/ehs-not051707.php

Nanomedicine opens the way for nerve cell regeneration
2 research groups present results at NSTI Nanotech 2007

The ability to regenerate nerve cells in the body could reduce the
effects of trauma and disease in a dramatic way. In two presentations at
the NSTI Nanotech 2007 Conference, researchers describe the use of
nanotechnology to enhance the regeneration of nerve cells. In the first
method, developed at the University of Miami, researchers show how
magnetic nanoparticles (MNPs) may be used to create mechanical tension
that stimulates the growth and elongation of axons of the central
nervous system neurons. The second method from the University of
California, Berkeley uses aligned nanofibers containing one or more
growth factors to provide a bioactive matrix where nerve cells can
regrow.

It is known that injured neurons in the central nervous system (CNS) do
not regenerate, but it is not clear why. Adult CNS neurons may lack an
intrinsic capacity for rapid regeneration, and CNS glia create an
inhibitory environment for growth after injury. Can these challenges be
overcome even before we fully understand them at a molecular level "why
axons in central nervous system do not regenerate"" Dr. Mauris N. De
Silva describes the novel nanotechnology based approach designed that
includes the use of magnetic nanoparticles and magnetic fields for
addressing the challenges associated with regeneration of central
nervous system after injury. "By providing mechanical tension to the
regrowing axon, we may be able to enhance the regenerative axon growth
in vivo". This mechanically induced neurite outgrowth may provide a
possible method for bypassing the inhibitory interface and the tissue
beyond a CNS related injury. Using optic nerve and spinal cord tissues
as in vivo models and dissociated retinal ganglion neurons as an in
vitro model, De Silva and his colleagues are currently investigating how
these magnetic nanoparticles can be incorporated into neurons and axons
at the site of injury. Although, this study is at a very preliminary
stage to explore the possibility of using magnetic nanoparticles for
enhancing in vivo axon regeneration, this work may have significant
implications for the treatment of spinal cord injuries, and is a vital
"next step" in bringing this new technology to clinical use.

The second presentation focuses on peripheral nerve injury, which
affects 2.8% of all trauma patients and quite often results in lifelong
disability. Since peripheral nerves relay signals between the brain and
the rest of the body, injury to these nerves results in loss of sensory
and motor function. Upper extremity paralysis alone affects more than
300,000 individuals annually in the US. The most serious form of
peripheral nerve injury is complete severance of the nerve. The severed
nerve can regenerate; the nerve fibers from the nerve end closest to the
spinal cord have to grow across the injury gap, enter the other nerve
segment and then work their way through to their end targets (skin,
muscle, etc). Usually, when the gap between the severed nerve endings is
larger than a few millimeters, the nerve does not regenerate on its own.
If left untreated, the end result is permanent sensory and motor
paralysis. A few hundred thousand people suffer from this debilitating
condition annually in the US.

Currently, the most successful form of treatment is to take a section of
healthy nerve (autograft) from another part of the patient's body to
bridge the damaged one. This autograft then serves as a guide for nerve
fibers to cross the injury gap. Although successful, this autograft
procedure has major drawbacks including loss of function at the donor
site, multiple surgeries and, quite often, it's just not possible to
find a suitable nerve to use as a graft. Various synthetic nerve grafts
are currently available but none work better than the autograft and
can't bridge gaps larger than 4 centimeters.

Researchers at the University of California, Berkeley have developed a
technology that has the potential to serve as a better alternative than
currently available synthetic nerve grafts. The graft material is
composed entirely of aligned nanoscale polymer fibers. These polymer
fibers act as physical guides for regenerating nerve fibers. They have
also developed a way to make these aligned nanofibers bioactive by
attaching various biochemicals directly onto the surfaces of the
nanofibers. Thus, the bioactive aligned nanofiber technology mimics the
nerve autograft by providing both physical and biochemical cues to
enhance and direct nerve growth.

This technology has been tested by culturing rat nerve tissue ex vivo on
our bioactive aligned nanofiber scaffolds. When the nerve tissue was
cultured on unaligned nanofibers there was no nerve fiber growth onto
the scaffolds. However, on aligned nanofiber scaffolds, they not only
observed nerve fibers growing from the tissue but the nerve fibers were
aligned in the same orientation as the nanofibers. Furthermore, when
there were biochemicals present on the nanofibers, the nerve fiber
growth was enhanced 5 fold. In a matter of just 5 days, nerve fibers had
extended 4 millimeters from the nerve tissue in a bipolar fashion on the
bioactive aligned nanofiber scaffolds. Thus, this technology can induce,
enhance and direct nerve fiber regeneration in a straight and organized
manner.

In order to make the technology clinically viable, they have also
developed a novel graft fabrication technology in their laboratory. The
most common method for fabricating polymer nanofibers is to use an
electrical field to "spin" very thin fibers. This technique is called
electrospinning and can be used to make nanofiber scaffolds in various
shapes such as sheets and tubes. They have made a key innovation to this
technology that enables us to fabricate tubular nerve grafts composed
entirely of polymer nanofibers aligned along the length of tubes. This
technology also allows customization of the length, diameter and
thickness of the aligned tubular nanofiber grafts. The group will
evaluate the performance of these aligned nanofiber nerve grafts in
small animal pre-clinical studies starting in mid-May.

The technology presented herein is being patented by the University of
California, Berkeley and has been licensed to NanoNerve, Inc.

According to Principal Investigator, Shyam Patel, "Speed is the key to
successful nerve regeneration. Our aligned nanofiber technology takes
full advantage of the fact that the shortest distance between damaged
nerve endings is a straight line. It directs straightforward nerve
growth and never lets them stray from the fast lane."

###

The presentation on magnetic nanoparticles is "Developing
Super-Paramagnetic Nanoparticles for Central Nervous System Axon
Regeneration" by M.N. De Silva, M.V. Almeida and J.L. Goldberg, from the
University of Miami. The talk on aligned nanofibers is "Bioactive
Aligned Nanofibers for Nerve Regeneration" by S. Patel and S. Li, from
the University of California, Berkeley, CA. Both will be given on May
24, 2007 at the NSTI Nanotech 2007 conference in Santa Clara, CA, at
2:10 PM and 2:50 PM, respectively, both in Grand Ballroom D of the Santa
Clara Convention Center.


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