Spider silk fibers enhance nerve regeneration

Peripheral nerve injury is one of the greatest challenges in reconstructive surgery. Severe trauma, tumor infiltration or even neuroma resection may lead to irreversible nerve damage. While surgical intervention remains the gold standard, sometimes suturing of the nerve is not possible. Then transplantation is being taken into consideration. Apart from conventional autografting, clinicians may one day be equipped with artificial nerve grafts made from an extraordinary material, spider web. In spring 2011 scientists from the Department of Plastic, Hand and Reconstructive Surgery in Hannover constructed and tested special so called “nerve conduits”.

They seem to facilitate communication between the proximal and distal nerve ends, as well as they provide physical guidance, essential for axonal regeneration. These revolutionary findings have been recently published in an open access journal PLoS ONE (1).

The development of effective treatment for peripheral nerve defects seems to be of considerable medical interest. The need for new techniques comes from a dissatisfaction with these available. Conventional grafting involves harvesting nerve segments from another body part of the patient. Partial deinnervation in the so called “donor site” is often observed. In vast injuries such as brachial plexus lesion, the number of available autografts is insufficient to repair all nerve defects. The situation is even more dramatic as far as long nerve damage is concerned. The clinical outcome of such procedures leaves a lot to be desired, whereas transplanted autograft works as nothing more than a scaffolding for regenerating axons. Therefore it could be easily replaced by an artificial equivalent.

Such tunnels can be built of non ­ resorbable materials such as silicone or polyethylene, but they cause long-term complications due to substantial toxicity and tendency to constrict the nerve. Bioresorbable materials present a promising alternative. NeuraGen (2) is an example of artificial nerve graft, made of collagen, commercially available for treating short nerve defects. Attempts are made to create an environment for regenerating nerve as similar to the natural as possible. It can be achieved by biomimetic nerve guidance channels, which provide the release of neurotrophic factors (3) and cell ­ binding domains.

The application of spider silk is a novel and unique technique. It was described for the first time in 2006 by the same group of researchers from Hannover (4). Schwann cells were cultivated on spider silk fibers and it was established that the biomaterial promotes remarkable cellular adhesion, proliferation and vitality. The first spider silk construct was made of decellularized pig venules and sterilized spider dragline, which was cut and put inside the tube. A species of spider used for harvesting silk was Nephila clavipes, which is thought to be the least immunogenic. Average length of 150 m of silk is possible to be harvested per hour. In 2008 (5) researchers successfully used spider silk constructs for 20mm sciatic nerve defects in rats. New biomaterial turned out to be long­term degradable by proteolytic enzymes, but no inflammation was observed. Constructs did not swell and seem to be resistant to bacterial and fungal decomposition.

This year’s study describes reparations of large defects of 60mm, on a large animal model – sheep. It seems to be a breakthrough, because it brings the discovery closer to clinical application in reconstructive surgery. During the trial nerve defects were induced by surgical resection of tibial nerve and either spider silk constructs (based on the same method as this in 2006) or autologous nerve grafts were implanted for bridging the nerve lesion sites. Both groups were compared by means of various tests, including in vivo electromyography and electroneurography. After 10 months animals were euthanized and post mortem histological examination and immunostaining were conducted. Morphological results and functional tests did not show any significant difference in the regeneration process in both groups. If spider silk constructs had enhanced nerve regeneration as effectively as animalsˈ own nerves, in future we may avoid donor site morbidity and engraft artificial constructs. This discovery has a very large potential to become a basis for future trials on humans. And let us hope, that thanks to spider silk we will soon be able to treat peripheral nerve defects.

Written by: Natalia Neumann

1.LoS One. 2011 Feb 25;6(2):e16990. Spider silk constructs enhance axonal regeneration and remyelination in long nerve defects in sheep. Radtke et al. Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany
3.Int Rev Neurobiol 87: 173–98.Chiono V, Tonda-Turo C, Ciardelli G (2009) Chapter 9: Artificial scaffolds for peripheral nerve reconstruction.
4.J Cell Mol Med. 2006 Jul-Sep;10(3):770-7.Use of spider silk fibres as an innovative material in a biocompatible artificial nerve conduit. Allmeling C. et al. Department of Plastic, Hand- and Reconstructive Surgery, Medical School Hannover, Hannover, Germany
5.Cell Prolif. 2008 Jun;41(3):408-20. Epub 2008 Apr 2. Spider silk fibres in artificial nerve constructs promote peripheral nerve regeneration. Allmeling C. et al, Department of Plastic, Hand- and Reconstructive Surgery, Medical School Hannover, Hannover, Germany.

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