Current methods for repairing injured nerves can be hit-and-miss and are restricted to repair over short distances. For the first time, researchers have combined two kinds of silk to create a promising biocompatible method of regenerating injured nerves over longer distances.
Peripheral nerves send messages from the brain and spinal cord to the rest of the body to, for example, move your muscles when you walk or let you know that your feet are cold. Peripheral nerves are easily damaged, interrupting the brain’s ability to communicate with muscles and organs.
The standard treatment for repairing an injured peripheral nerve is an autograft, where surgeons excise the damaged section and replace it with a nerve from elsewhere in the body. The graft nerve is taken from a sensory nerve, usually the sural nerve, that provides sensation to an area of the skin where sensation is not vital. But the success rate of nerve grafts can be hit-and-miss.
Nerve guides, the tubular structures sutured to both ends of a severed nerve to bridge the gap, have been around for about 30 years. However, they can only be used to bridge small gaps. Currently, FDA-approved nerve guides are restricted to short-distance nerve defects of up to 1.2 in (3 cm). Longer distances require an internal framework that provides the requisite structural and cellular support.
Enter researchers from the University of Oxford and the Medical University of Vienna, who’ve created a novel nerve guide by combining two different kinds of natural silk taken from silkworms (Bombyx mori) and golden orb weaving spiders (Trichonephila edulis) that has the potential to regenerate nerves over longer distances.
Previous studies have demonstrated the benefits of using silk as a biomaterial. Silkworm cocoon silk is composed of fibroin and sericin proteins. Both are biocompatible, elastic, and tough. Silk fibroin has been shown to induce wound healing by increasing cell proliferation and growth. Dragline silk from the orb weaving spider has remarkable mechanical properties, including high tensile strength and flexibility.
For the first time, the researchers combined the features of silk fibroin reconstituted into tubes and natural spider silk filaments to create a silk-in-silk conduit. The conduit wall was made from silkworm silk fibroin, filled with orb weaving spider dragline silk fibers that acted as an internal guiding structure, kind of like a handrail for the nerves.
The nerve guide was tested on rats whose right sciatic nerves had been severed, resulting in a significant gap of 0.4 in (10 mm). The researchers found that the damaged nerves adapted to the silk nerve guides and grew along the silk threads, successfully reconnecting the severed endings.
“In our study, it turned out that peripheral nerves function well when such threads are made of silk, with spider silk apparently being preferred for the guide rails,” said Lorenz Semmler, first author of the study.
The researchers also gained a greater understanding of the molecular structure of the silkworm silk tubes, finding that their porosity allows for the exchange of nutrients and waste products that is vital to the healing process. Moreover, the cells that are responsible for nerve regeneration were seen to adhere to both types of silk.
“As part of our study, we not only succeeded in nerve repair, we were also able to analyze the components of the healing process in detail,” Semmler said.
Using natural materials for nerve guides has obvious advantages over synthetic substances. Spider silk is biodegradable and produces only a very small immune response in animal models. It’s also scalable. A single harvest from an orb weaving spider can yield around 33 ft (10 m) of silk, enough to fill a 0.4 in (10 mm) long nerve guide. The porous nature of silkworm silk could allow for the incorporation of bioactive molecules to promote nerve regeneration over longer distances.
“Animal silks offer exceptional mechanical and biological properties and versatile manufacturing possibilities to assist the re-engineering of tissue,” said Fritz Vollrath, a co-author of the study. “Our advanced silk-in-silk nerve guides combine the excellent ability fo silkworm silk to be processed into three-dimensional structures with the outstanding cell adhesion qualities of spider dragline silk.”
The researchers hope that their discovery will pave the way for the development of “off-the-shelf” nerve guides to treat peripheral nerve injuries in humans.
The study was published in the journal Advanced Healthcare Materials.