Nanomedicine Opens The Way For Nerve Cell Regeneration: Two Research Groups Pres

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Nanomedicine Opens The Way For Nerve Cell Regeneration: Two Research

Groups Present Results At NSTI Nanotech 2007

http://www.medicalnewstoday.com/medicalnews.php?newsid=71453

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.

The mission of Nanomedicine: Nanotechnology, Biology & Medicine, the

international peer-reviewed journal published by Elsevier, is to

communicate new nanotechnology findings, and encourage collaboration

among the diverse disciplines represented in nanomedicine. Because

this closely mirrors NSTI's charter to seek the " promotion and

integration of nano and other advanced technologies through

education, technology and business development, " Elsevier is pleased

to be working in collaboration with NSTI to bring this presentation

to the attention of the scientific community.