Neurotransmitters In Biopolymers Stimulate Nerve Regeneration

[Guest guest]

Neurotransmitters In Biopolymers Stimulate Nerve Regeneration

http://www.sciencedaily.com/releases/2007/12/071211233410.htm

Research reported December 11 in the journal Advanced Materials

describes a potentially promising strategy for encouraging the

regeneration of damaged central nervous system cells known as

neurons.

The technique would use a biodegradable polymer containing a

chemical group that mimics the neurotransmitter acetylcholine to

spur the growth of neurites, which are projections that form the

connections among neurons and between neurons and other cells. The

biomimetic polymers would then guide the growth of the regenerating

nerve.

There is currently no treatment for recovering human nerve function

after injury to the brain or spinal cord because central nervous

system neurons have a very limited capability of self-repair and

regeneration.

" Regeneration in the central nervous system requires neural

activity, not just neuronal growth factors alone, so we thought a

neurotransmitter might send the necessary signals, " said Yadong

Wang, assistant professor in the Coulter Department of Biomedical

Engineering at Georgia Tech and Emory University, and principal

investigator of the study. The research was supported by Georgia

Tech, the National Science Foundation and the National Institute of

Biomedical Imaging and Bioengineering (NIBIB).

Chemical neurotransmitters relay, amplify and modulate signals

between a neuron and another cell. This new study shows that

integrating neurotransmitters into biodegradable polymers results in

a biomaterial that successfully promotes neurite growth, which is

necessary for victims of central nervous system injury, stroke or

certain neurodegenerative diseases to recover sensory, motor,

cognitive or autonomic functions.

Wang and graduate student Christiane Gumera developed novel

biodegradable polymers with a flexible backbone that allowed

neurotransmitters to be easily added as a side chain. In its current

form, the polymer would be implanted via surgery to repair damaged

central nerves.

" One of our ultimate goals is to create a conduit for nerve

regeneration that guides the neurons to regenerate, but gradually

degrades as the neurons regenerate so that it won't constrict the

nerves permanently, " explained Wang.

For the experiments, the researchers tested polymers with different

concentrations of the acetylcholine-mimicking groups. Acetylcholine

was chosen because it is known to induce neurite outgrowth and

promote the formation and strengthening of synapses, or connections

between neurons. They isolated ganglia nervous tissue samples,

placed them on the polymers and observed new neurites extend from

the ganglia.

Since these neuron extensions must traverse a growth inhibiting

material in the body, Wang and Gumera tested the ability of the

biomaterial to enhance the extension of sprouted neurites. More

specifically, they assessed whether the ganglia sprouted at least 20

neurites and then measured neurite length and neurite length

distribution with an inverted phase contrast microscope.

" We found that adding 70 percent acetylcholine to the polymer

induced regenerative responses similar to laminin, a benchmark

material for nerve culture, " said Wang. Seventy percent

acetylcholine also led to a neurite growth rate of up to 0.7

millimeters per day, or approximately half the thickness of a

compact disc.

Laminin is a natural protein present in the nervous tissues, but it

dissolves in water, making it difficult to incorporate into a

conduit that needs to support nerves for months. A synthetic polymer

with acetylcholine functional groups, on the other hand, can be

designed to be insoluble in water, according to Wang.

Since functional restoration after nerve injury requires synapse

formation, the researchers also searched for the presence of

synaptic vesicle proteins on the newly formed neurites. With

fluorescence imaging, they found that neurons cultured on these

acetylcholine polymers expressed an established neuronal marker

called synaptophysin.

To provide insights to new approaches in functional nerve

regeneration, the researchers are currently investigating the

mechanisms by which the neurons interact with these polymers. Since

neurons that remain intact after severe injury have only a limited

capacity to penetrate the scar tissue, these new findings in nerve

regeneration could help compensate for the lost connections.

" This polymer and approach aren't limited to nerve regeneration

though, they can probably be used for other neurodegenerative

disorders as well, " added Wang.

This work was funded by grant number R21EB008565 from the NIBIB of

the National Institutes of Health (NIH). The content is solely the

responsibility of the authors and does not necessarily represent the

official view of the NIBIB or the NIH.