Nerve conduits made from the silk spun by spiders are as effective in promoting tissue regeneration as those formed from nerves located in a patient's own body, according to new research that could pave the way for use of the technology in humans.
For the study published Feb. 2 in Biomaterials, researchers induced autologous nerves, also called artificial nerve conduits or grafts, that were based on spider silk in live animals using a 6-centimeter-long nerve defect model. Nerve defects longer than 3 centimeters are usually considered to be critical, requiring different surgical intervention.
“Therefore, a product with potential to be used in larger nerve gaps extending 3 centimeters is highly desirable and clinically necessary,” the study authors wrote.
The longer model allowed them to investigate structural and anatomical regeneration in peripheral nerve tissue. Researchers concluded that regeneration of axons supported by the implant was comparable to that in an autologous nerve graft — the gold standard in nerve repair surgery — suggesting that a biomaterial-based spider silk nerve conduit is as effective as autologous nerve transplantation in promoting nerve regeneration.
The findings add to growing research on using spider silk nerve grafts as an alternative surgical intervention in nerve repair. Yet they differ from previous studies in that the researchers used a spider silk-based artificial nerve graft in order to make it possible to use this technology in a clinical setting, because it does not have “the potential morbidity of autologous nerve grafts, such as sensory loss or painful neuroma formation at the donor nerve site,” the authors note.
One author, Christine Radtke, has worked with spider silk for more than 15 years, focusing on repairing peripheral nerves. Radtke, a professor at the Department of Plastic and Reconstructive Surgery at the Medical School of Vienna, explains that a nerve in the arm or the neck can regenerate, while peripheral nerve injuries require replacing the nerve because cells residing outside the brain and spinal cord do not regenerate.
Some of the past studies Radtke has conducted in this research area include one published in PLoS ONE in 2011 that demonstrated that spider silk enhances migration of Schwann cells, which refers to any of the cells in the peripheral nervous system whose basement membrane provide for the critical process for nerve regeneration known as axon regrowth, in a 6 centimeter long tibial nerve defect model in adult sheep.
The nerve regeneration improvement showed a need for scientists to explore clinical implications, including reconstructive nerve surgery.
Yet to date, in vivo studies in this area have lagged.
“Although spider silk is a well-characterized biomaterial, data regarding spider silk degradation in an in vivo environment is scarce,” the new study notes. The authors’ work is an exception: They cite past studies in which they used spider silk to repair gaps that emerge as a result of damaged tissue and reported this silk being fully degraded after 11 months in vivo, noting that this material degradation “has a direct influence” on the length of the largest nerve gap.
Radtke’s latest is also an in vivo study. It compared the amount of time that axons took to regenerate when aided by the spider silk implants with the time required by autologous nerve graft using a 6-centimeter adult sheep tibial nerve defect model where artificial nerve grafts were induced in 28 German black-headed mutton sheep.
Examinations of axonal regrowth and spider silk degradation were done in narrowly defined time series — 20, 30, 40, 50, 90, 120, 150 and 180 days — as peripheral nerve regeneration is highly time-sensitive due to deterioration of the neuromuscular junction.
Another issue is the 3-centimeter gap size limitation of autologous nerve transplantation. Longer nerve defects are often critical and require surgical interventions different from the current gold-standard techniques. Radtke says this is why the research team decided to study spider silk material that the nerve is able to regenerate over a larger gap.
The next step calls for clinical translational research to support applying findings to new treatments.
The study, “Spider silk nerve graft promotes axonal regeneration on long distance nerve defect in a sheep model,” published Feb. 2 in Biomaterials, was authored by Christine Radtke, Tim Kornfeld, C.T. Peck, P. Hoffmann, G. Brandes and P.M. Vogt, Hannover Medical School; and Jasmin Nessler, Carina Helmer, Regina Hannemann and Karl-Heinz Waldmann, University of Veterinary Medicine Hannover.