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Once a nerve cord is severed, for example after an accident, there is usually no cure. Only surgery can occasionally repair the damage. If at all. In some operations, nerve cords are removed from another part of the body and inserted at the point where it has been severed. This reconnects the nerve endings and enables that part of the body to recover its functionality, at least partially. If this is not possible, the limb or the whole body part remains paralyzed and rigid. Scientists at the Max Planck Institute for Polymer Research have now developed substances that stimulate damaged nerves to grow. Initial tests on mice have already shown that nerve cords can regenerate themselves this way.

Although nerves are capable of eventually spanning a severed area themselves, this process takes time. In addition, damaged nerve fibers need an intact framework of proteins like the ones that surround healthy nerves. However, this framework is often also damaged in accidents. This so-called extracellular matrix forms the adhesive base for the nerve cords, the researchers explain. Just as tomato plants need a trellis, nerve cells need this matrix in order to be able to grow alongside it. “This is why we at the Max Planck Institute for Polymer Research have developed a material made of the body’s own building blocks that can be used as a substitute for this matrix,” explain researchers Tanja Weil and Christopher V. Synatschke. “And as has been shown, the artificial framework can help damaged nerves to regenerate.”

Modular system

The building blocks of a natural, biological matrix are specialized proteins, i.e. long chains of molecules shaped like a ball of wool. These small balls then form long protein strings in the mass that in turn form the extracellular matrix. Like a kind of lattice that the nerve cells can entwine themselves across. However, the processes that take place in the body are very complex and therefore cannot be duplicated in a test tube.

“This is why we are taking a slightly different approach to our research. Although we use the same basic materials that make up the extracellular matrix of nerve fibers, we put them together in a more simplified form,” the scientists said while describing their study. “To do this, we use short molecule chains, known as peptides, which, like proteins, consist of amino acid building blocks. We specifically produce these peptides chemically in such a way that the exact position of each building block can be fixed.“

Figuratively speaking, they would then create a synthesis of nubs and corresponding holes on the molecules. Something like Lego bricks: “Two peptide molecules synthesized like this will probably attach themselves to each other in such a way that the nubs and holes match up. It is only then that a stable structure is created. This is how we are able to make long fibers, whose microscopic structure differs from the proteins found in the extracellular matrix of the nerve cords. However, they are very similar to natural proteins in terms of their dimensions and chemical composition.”

How damaged nerves are able to grow again © matt white, based on models from the MPI for Polymer Research

Successful tests with mice

The researchers had to go one step further in order to find out how nerve cells behave when designed to grow on this artificial extracellular matrix and how these growth characteristics change with the help of various chemical peptides. In cooperation with their partner Bernd Knöll, professor at the Institute of Physiological Chemistry at the German University of Ulm, the researchers have produced a broad range of diverse peptide structures, applied them to glass slides, and cultivated nerve cells on these structures too. The researchers found that the nerve cells on some of these fibrous structures did not grow at all. “However, after a short time, axons formed in others – these are thin protrusions that establish connections to other nerve cells.”

The fibrous structure on which the nerve cells grew best was then tested in animal experiments at the University of Ulm. A mouse had its facial nerve (which controls the movement of the whiskers) severed surgically on one side. “The peptides were injected at the nerve breakage point that was created that way after they had formed the fibrous structure. The mouse was already able to move its whiskers again after just 18 days. The nerve cords had apparently grown back together.”

Since the peptides of these synthetic fibers are very similar to the natural proteins that make up the extracellular matrix, the researchers now hope “that the material will remain in place for the time it takes to heal, but that the body will then be able to break it down. So far, the scientists have observed that the amount of material at the injection site gradually disappears.” Whether this is due to biodegradation or because it gets distributed through the body is something that requires much more research.”

Optimism among researchers

It will be some time before this new method can be used on humans. Further optimizations are necessary because the nerve cells on the material do not yet grow as well as they do on a natural, biological matrix, “plus they also tend to grow quite randomly in all directions,” the researchers admit. “Therefore, in the next step, we want to incorporate other growth elements into the artificial matrix in order to further accelerate the healing process. We also want to align the injected fibrous structures so that the nerve cells are able to grow in one direction.”

However, the scientists assume that their artificial extracellular matrix could at least help to heal minor injuries to nerve cords and therefore avoid surgery in the future. “And perhaps, after some more research, it will one day be possible to treat not only injuries to the peripheral nervous system but also to the central nervous system,” they hope.