Nerve guides made of natural or synthetic materials are an important surgical tool for nerve repair. These are tubes that are sutured to both ends of an injured nerve and guide the growth of nerve fibers and cells across the gap. Currently, however, these can only be used to bridge very small gaps. It was thought that a key reason for this limitation was a combination of tube properties and the lack of an internal framework to act as a “handrail” along which the regenerating tissue can orient itself and grow.
In this new study, the research team developed a novel type of nerve guide using two different types of natural silk. The tube wall was manufactured from silk produced by silkworms (Bombyx mori), and the inside filled with dragline silk fibers from golden orb-web spiders (Trichonephila edulis). The tubes were tested in rats whose right sciatic nerve had been cut, creating a 10 mm gap, which for a rat is of significant length. The researchers found that the damaged nerves adapted to the novel silk nerve guides and grew along the silk threads until the severed endings were successfully reconnected.
The research team used advanced microscopy techniques to analyse the healing process in detail. These showed that the silk tubes had a highly porous structure; an essential feature for nerve regeneration since this allows nutrients and waste materials to be exchanged. In addition, Schwann cells, the key drivers of peripheral nerve regeneration, adhered strongly to both the tube walls and the dragline silk fibers, and migrated with remarkable speed (over 1.1 mm per day).
The study further demonstrated that both types of silk played an important part in nerve regeneration. When nerve injuries were repaired using empty silk tubes, without the spider silk filling, the nerve fibers grew more slowly and were less organized.
Newrotex technology and how it works: the Newrotex nerve guide and tubes bridge the gap between two nerve endings. Credit: Newrotex
The silkworm silk tubes were supplied by Oxford Biomaterials, a company that was spun out of Oxford University in 2001 to exploit the biomimetic spinning technology developed by the Oxford Silk Group, part of the Department of Biology. Professor Fritz Vollrath, a co-founder of Oxford Biomaterials and a co-author on this study, said:
‘Animal silks offer exceptional mechanical and biological properties and versatile manufacturing possibilities to assist the re-engineering of tissue. Our advanced silk-in-silk nerve guides combine the excellent ability of silkworm silk to be processed into three dimensional structures with the outstanding cell adhesion qualities of spider dragline silk.’
‘These findings are a great step forward towards producing next-generation nerve guides that emulate the nervous architecture and possess advanced biological and mechanical features that support regeneration.'
A video of spider silk harvesting, which can be done without causing harm to the spider.
He added that using natural materials for nerve guides has many advantages over synthetic substances. Spider silk, for instance, degrades over time and produces hardly any immune response in animal models. They can also be highly abundant: a single harvest from an orb web spider can yield around 10m of silk, enough to fill a 10mm long nerve guide. Meanwhile, the porous structure of the tube walls made from silkworm silk presents versatile possibilities to incorporate bioactive molecules, such as growth factors, to promote nerve regeneration over longer distances.
Ultimately, the team hope to develop the silk nerve guides into an ‘off-the-shelf’ solution to treat nerve injuries in humans. Currently, most human nerve injuries are treated either using short synthetic hollow tubes or indeed re-deploying longer real nerves harvested from other areas of the patient’s body (called autografts). However, this latter process has many drawbacks, including a limited availability of donor nerves, lengthy operations, and the possibility of further harm for the patient. In this study, nerve regrowth and functional regain was similar for injuries repaired using the silk nerve guides or grafted nerves.
Newrotex Ltd, a spin-out company from Oxford Biomaterials, are developing silk technology for treating nerve injuries and are completing final pre-clinical studies with the aim of bringing a functional device suitable for humans to the market. Its CEO and founder, Dr Alex Woods, is a trauma orthopaedic surgeon at Oxford University Hospitals and holds a D.Phil in Zoology and a Bachelor of Medicine, Bachelor of Surgery from Oxford University. He said:
‘Peripheral nerve injuries have a devastating impact on patients world-wide. This study provides further evidence of the incredible regenerative properties of silk within the nervous system and demonstrates it’s exciting utility and potential as a material to meet the unmet clinical need for an “off-the-shelf” technology to treat nerve injuries.’
‘At Newrotex, we have developed silk nerve repair devices to bring to market for the first time a truly practical, sustainable, and effective treatment for large gap nerve injuries. This will improve the care that can be offered for patients, with a really accessible alternative to harmful autograft surgery, and will significantly increase the number of patients who can now hope to have their sensation and function restored after suffering injuries from trauma, or as a side effect of cancer surgery.’
The study ‘Silk-in-silk nerve guidance conduits enhance regeneration in a rat sciatic nerve injury model’ has been published in Advanced Healthcare Materials.