Delivering treatments directly to the moist tissues that line many parts of our bodies is notoriously difficult. Can genetically-engineered spider silk proteins provide building blocks for new materials that stick more effectively onto these slippery surfaces?
Our bodies have around 300 to 400 square metres of mucous membranes, lining areas such as the inside of our mouth, stomach and bowels. Covered with a mucus gel, these moist tissues help protect us from foreign invaders such as bacteria and viruses.
Mucous membranes offer an excellent route for the non-invasive delivery of drugs around the body, due to their excellent blood supply. But they are also vulnerable to diseases and wounds themselves – including cancer, ulcers and chronic inflammation – which affect millions of people around the world and are increasing along with the rise of other chronic diseases, like diabetes.
But delivering localised treatments to mucous membranes is difficult as their good hydration and lubrication make it difficult to anchor any material in position – and they are also very dynamic with a rapid turnover rate, removing any foreign objects in the process.
Researchers are aiming to develop new transmucosal drug delivery systems, mucosal wound dressings and mucosal tissue engineering scaffolds that can stick more effectively to these moist tissues. They have already created a range of different materials using synthetic polymers and biopolymers with so-called ‘mucoadhesive’ properties, including micro and nanoparticles, gel slabs, patches and capsules. But their hunt continues for new, more effective materials.
Spider silk is strong, biocompatible, biodegradable and lightweight, therefore providing an excellent base for the development of materials for a range of medical applications. Scientists are using genetic engineering with the aim of creating enhanced spider silk proteins with added benefits, such as with improved mucoadhesive, anti-inflammatory or wound-healing properties.
In a new study, researchers in Sweden produce and characterise two new partial spider silk protein variants, which they designed specifically to improve their mucoadhesive properties.1
Improving the mucoadhesive properties of implanted materials depends largely on increasing their interactions with a family of large proteins called mucins, which are the main gelling component of mucus. So the scientists engineered their two new silk protein variants, one of which was designed to enhance non-specific interactions with mucins and the other to boost specific binding with these proteins.
During their investigations, the researchers used a range of techniques to examine different properties of their two new silk variants and test their mucin-binding abilities, for which they relied on ultrapure water prepared using a PURELAB Option-Q system.
They successfully demonstrated that both of their newly engineered variants can readily be made into a range of potentially useful materials including coatings, fibres, meshes and foams – and importantly, they also showed they are both better at binding to mucin proteins than the original partial silk protein.
These two new spider silk protein variants could lay the foundations for the development of a range of new silk protein-based materials that could help improve the delivery of local treatments to mucosal membranes.
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Petrou, G. et al., Genetically engineered mucoadhesive spider silk. Biomacromolecules 2018 Jul 16. doi: 10.1021/acs.biomac.8b00578.