Investigators at Georgia Tech believe that a newly developed biodegradable polymer containing an acetylcholine-like substance can be used to encourage the regeneration of damaged central nervous system neurons. The research is being reported in the December 11 issue of the journal Advanced Materials:
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)…
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…
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.