This blog is and will mostly be about zoonotic diseases but I hope you will forgive me for every now and then straying off topic. Today the reason for my slight deviation from the norm is because this work is just so cool!
Researchers have regrown nerves using spider silk – it sounds more like science fiction than fact (although admittedly those two do tend to blur around the edges).
Why were they even doing this research in the first place?
Our peripheral nerves (those outside our central nervous system which is itself comprised of the brain and spinal cord) can become damaged for several reasons including severe trauma and cancer, sometimes leading to a length of nerve that is destroyed or has to be removed. Currently these deficits are repaired by either suturing the nerve ends either side of the gap back together or by transplanting a donor nerve into the gap which has its own problems with donor morbidity and sometimes a lack of availability if the deficit is too large.
Artificial agents for bridging (small) gaps and promoting nerve regrowth are commercially available but those grafts with non-resorbable material can lead to secondary problems, resulting in the necessity of a second operation to remove them and so researchers are now looking into making constructs that use bioresorbable materials. Researchers in Germany looked at the possibility of using spider silk.
What did they do?
To make the constructs the researchers took venules 6cm in length and 3-4mm diameter from the legs of pigs, washing and cleaning them. They then collected silk from adult female Nephilia clavipes spiders (basically by stimulating the silk gland and then pulling the silk onto spools as it left the gland over the lateral spinnerets). They cut the silk to 6cm in length and pulled it through the venules until it took up roughly a quarter of the diameter. (And yes, I’m afraid my abysmal artwork has returned once more.)
The researchers then anaesthetised some adult sheep and removed a 6cm long section of one of the tibial nerves. They then EITHER:
- placed the venule-spider silk construct into the gap
- flipped the removed section of nerve by 180 degrees so that the end that was nearest the foot was now nearest the hip and vice versa and placed it back into the gap (‘autologous nerve transfer’)
The animals were then observed closely for 10 months before being euthanised.
So what happened?
Immediately after the operation all of the sheep showed the signs that would be expected with tibial nerve transection – they couldn’t stand on the leg properly and it was held in an abnormal stance (with an over-flexed hock joint and a partially flexed fetlock). There was reduced pain sensation in the leg below the stifle (the knee).
After ~ 3 weeks the sheep appeared to start standing more normally and around 2 months after the operation the sheep were walking ‘with ease’ on the affected leg. After 4 months the researchers describe ‘co-ordinated stepping of the hindlimbs… during walking’. At this point there were no obvious differences in strength between the operated leg and the unoperated one, although there was some atrophy of the calf muscle of the leg which was operated on.
10 months later when the sheep were euthanised the researchers looked at the tibial nerves and constructs in great detail. They found that in both groups:
- the axons had regenerated across the repair site and along the entire length of the construct/lesion site
- the axons were aligned properly and under the microcope they were found to have normal anatomy (they were in fascicles – bundles -, were ensheathed by Schwann cells and had what looked like nodes of Ranvier)
-the researchers stained the sections for sodium channels found in normal healthy nerves and found that they were present in the regenerated axons and that they were present in the right place (in the apparent nodes of Ranvier)
- there was no significant difference between the number of regenerated axons in the autologous controls and the number in the spider silk construct nerves and overall the researchers found that there was no significant difference on the functionality of the nerve between the two methods of repair
- no traces of the spider silk were left
What does this mean? And does it matter?
In this sheep model the researchers demonstrated that the venule-spider silk construct is equally as good for large nerve deficits as an autologous nerve transplant. Obviously more research is needed before this construct can be tested in a clinical setting but if further work is successful it could eliminate the need for a donor nerve – a great step forwards in nerve repair.
I’m quite glad it’s not my lab that’s full of spiders for silk harvesting though…
Radtke, C., Allmeling, C., Waldmann, K., Reimers, K., Thies, K., Schenk, H., Hillmer, A., Guggenheim, M., Brandes, G., & Vogt, P. (2011). Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep PLoS ONE, 6 (2) DOI: 10.1371/journal.pone.0016990
Fields RD, Le Beau JM, Longo FM, Ellisman MH (1989). Nerve regeneration through artificial tubular implants. Prog Neurobiol 33(2): 87-134
Keeley R, Atagi T, Sabelman E, Padilla J, Kadlcik S et al. (1993). Peripheral nerve regeneration across 14-mm gaps: a comparison of autograft and entubulation repair methods in the rat. J Reconstr Microsurg 9(5): 349-58
Allmeling C, Jokuszies A, Reimers K, Kall S, Vogt PM (2006). Use of spider silk fibres as an innovative material in a biocompatible artificial nerve conduit. J Cell Mol Med 10 (3): 770-7 doi:10.1111/j.1582-4934.2006.tb00436.x