Researchers at New York University and the Massachusetts Institute of Technology 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. The main authors of the article are Todd C. Holmes, assistant professor of biology at NYU and Shuguang Zhang, research scientist at MIT.
This peptide-based scaffold, on which neurons grow fibers to communicate with each other and establish functional synapses, may be the long-sought ideal for growing replacement nerve cells for victims of spinal cord injuries and other forms of nerve damage.
Holmes and Zhang said, "Nerve cells are notoriously fussy. This problem becomes even more acute in regions of damaged nervous system. The nervous system actually produces factors that prevent re-growth and repair. That's what makes this newly discovered biomaterial so exciting. It supports nerve cell attachment, neurite outgrowth, and the establishment of new functional connections between nerve cells that allow the nerve cells to communicate with each other. These are important considerations for the design of new materials for repairing the damaged nervous system. Future potential therapeutic targets include repair of injured peripheral nerve, and perhaps, even repair of injured spinal cord."
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.
"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 at the Center for Molecular Neurobiology at the University of Hamburg in Germany. Schachner wrote a "News and Views" article about this work in the journal Nature.
Synthetic scaffolds have been used to grow skin, livers and cartilage, but researchers have made little progress until now on developing scaffolds for the generation of nerve cells.
The new biomaterial developed by Holmes and colleagues seems to be an ideal 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.
This discovery began when Holmes tested one of the peptides as a "control" while studying the nerve cell toxicity of peptide fragments found in the brains of Alzheimer's disease patients. Holmes did not expect the control peptide to have any biological effect. Much to the surprise of the scientists, the peptides self-assembled into thin, wavy films that look a little like Saran Wrap under a microscope. More powerful microscopes showed that the peptide-based film contained a network of fibers. Not only were the peptides not toxic, nerve cells seemed to thrive in culture in the presence of the peptides.
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 comprehensively in the brain, spinal cord and peripheral nerves.
This work was supported by Hercules, Inc., the U.S. Army Research Office, the National Institutes of Health and the Whitaker Foundation.
Journal
Proceedings of the National Academy of Sciences