Nerve injuries: wound healing with the power of peptides

Injuries to the nerves require prompt treatment to prevent permanent damage. The common nerve repair procedure involves carefully stitching the two endings of the wounded nerve together. Led by Dr. Christopher Synatschke, the research team of Professor Tanja Weil (Max Planck Institute for Polymer Research) has now developed a novel biomaterial that is designed to promote our body’s natural self-healing mechanisms.

In a conversation with COMPAMED-tradefair.com, Dr. Synatschke explains how the material is created, describes what it is meant to accomplish and reveals future steps!

Dr. Synatschke, you research nanofibers for wound healing. What are these fibers made of?

Dr. Christopher Synatschke: Our research team works with so-called "self-assembling peptides". These are short amino acid chains that we synthetically create in the laboratory. They are able to self-assemble into superstructures, hence their name. The fibers we studied include several types of superstructures. Some of them are able to create nanofibers. We were able to show that they are great candidates to accelerate wound healing. We use peptides with about 7 to 15 amino acids.

You first tested their effects in cell culture. How and why did you do that?

Synatschke: We collaborated with Professor Bernd Knöll and his team at the Institute of Physiological Chemistry at the University of Ulm for the tests. They specialize in neuronal cell cultures. The long-term goal of biomaterial development is to create a therapeutic application. This requires pretesting. You study the ability of different chains of amino acid to pass further tests, which is done in a cell culture and in this case peripheral nerve cells obtained from animals. Professor Knöll’s research team developed a computer-assisted assay that can analyze the cell adhesion of our materials. The aim of this pretest is to distinguish suitable materials out of the large quantities of materials we are able to generate. We have created a library of about 30 different chains of amino acid and subsequently selected two of them for further studies.

Which test was performed with the two peptide sequences?

Synatschke: This involved animal testing on a mouse. The facial nerve that controls the whisker movement was cut on one side to simulate a nerve problem that can be caused by an accident or trauma for example. Surgeons currently use a so-called nerve-grafting technique to restore the movement in humans. That means a segment of unrelated nerve is used to stitch together and bridge the injured portion of nerve. However, our material is not sewn, because it is liquid. As was the case in the animal test, it can be injected into the affected area and was detectable at the application site over three weeks. Since it works like a scaffold or grid for cell direction, it supports cell growth and bridges the defect. The researchers used video recordings to observe the mouse and document the results. This revealed whether and when the whiskers were able to move again. Without any treatment, full nerve regeneration can be detected within three weeks. Meanwhile, our injected material prompted faster regeneration and higher synchronization of whisker movement compared to non-treatment.

Will you test other scaffold structures?

Synatschke: We made a preselection because it is impossible to test all the peptides. This would be far too elaborate, costly and also unethical. Our next step is to study whether our material can aid growth factors in the defect. Growth factors are proteins made by cells that can accelerate the growth of neurons for example. Typically, these proteins are quickly "washed away" from defects, making the concentration at the local site not very high. That’s why we want to artificially add proteins to increase the local concentration. Another idea is to lab-create chemical molecules that can mimic the primary functions of the proteins. They could then be attached to our material, creating continuously high concentrations of a messenger substance, which would accelerate peripheral nerve cell growth in the damaged system. We hope that this results in further improvement. Having said that, these are steps we plan to take in the future.

Once you succeed in developing this “wound gel” for human use, how difficult will it be to produce?

Synatschke: The benefit of this material is that these are short amino acids that we can already produce on an industrial scale without difficulty. You might have to adapt the actual application because the sequence is able to form several structures. Strict adherence to certain processes is necessary to get the desired structure. The technical implementation is easy but you need to ensure that this makes sense at the physician level at a later point in time. After all, a doctor doesn’t have 24 hours to wait until the material changes into the right structure and is applicable. That’s why you have to create formulations that can be used immediately because nerve injuries must be treated as quickly as possible.

How large can the nerve defect be for treatment with your material?

Synatschke: The defects in the mouse were millimeter-sized. However, other approaches consider bridging larger sections by premixing cells for example. If this is successful, I believe larger defects can also be bridged.