A technique has been developed to produce synthetic spider silk so medics can use it as a scaffold in wounds that promotes healing.
The medicinal use of spider’s webs in the treatment of wounds was first recognised by the ancient Greeks and Romans.
Spider silk is a strong, biocompatible, biodegradable, protein-based material that does not seem to cause a strong immune, allergic or inflammatory reaction which is unusual for non-human proteins.
These qualities are now being harnessed following five years of research by scientists of different disciplines.
Scientists developed a technique to create a biodegradable mesh, which can replace the extra cellular matrix generated by human body cells, accelerating growth of new tissue. It can also be used for the slow release of antibiotics.
In research funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the team from the University of Nottingham demonstrated for the first time how ‘click-chemistry’ (see below) can be used to attach molecules to artificially produced spider silk synthesised by E.coli bacteria.
Professor Neil Thomas, the study’s team leader, explained: “The spider silk provides a good biocompatible scaffold for new human cell growth.
“Our technology allows the decoration of the silk with drugs or other molecules and these can be slowly released to impart their therapeutic activity. Because the silk fibres self-assemble we can control the ratio of different antibiotics added to it to help combat resistant bacteria.
“Initially we think [it could be used for] things like dressings for external diabetic ulcers and other slow-healing wounds that are easily infected.
“Using our technique, infection could be prevented over weeks or months by the controlled release of antibiotics. At the same time tissue regeneration is accelerated by silk fibres functioning as a temporary scaffold before being biodegraded.”
How it started
Dr Goodacre, who heads up the SpiderLab in the School of Life Sciences, was addressing a discipline-bridging university ‘sandpit’ meeting five years ago when the discussion turned to understanding how spider silk works and the possibility of making some.
Goodacre explained what happened next.
“At the end of the session Neil came up to me and said ‘I think my group could make that’. He also suggested that there might be more interesting ‘tweaks’ one could make so that the silk could be ‘decorated’ with different, useful, compounds either permanently or which could be released over time due to a change in the acidity of the environment.”
A SpiderLab PhD student, David Harvey, conducted a study on synthetic spider silk providing ground work for development. Harvey worked on making silk fibres, incorporating the unusual amino acid, but also decorated it and demonstrated its antibiotic activity.
Why E-coli bacteria?
“The silk proteins are expressed as fusions with a solubilising protein in the E. coli. All of the methionine amino acids are replaced by the unnatural amino acid L-Azidohomoalanine. The molecules that decorate the silk (such as drugs, antibiotics, fluorophores) are then covalently attached using a ‘click’ reaction, a very selective, high yield reaction between the azide groups on the silk and an alkyne group on the molecules that will be attached to it.”
The solubilising protein is then removed and the spider silk fibres self-assemble.
Thomas said that protein production in E. coli is easier to scale up and mutagenesis of the silk proteins is much easier to achieve compared with using yeast or mammalian systems such as goats.
Spider silk itself presents its own problems because spiders are territorial and cannibalistic and so cannot be farmed in the same way as silkworms.