Shell super glue for medicines

They are firmly anchored on the seafloor. Even whip surf on the shores can't hurt – mussels. The secret of their resilience lies in their feet: the shells produce a protein there that is better kept underwater than any other material. Whether it is stone, metal or plastic, the adhesive for the shell is very effectively glued to different surfaces.

Such an adhesive is a popular tool, especially in surgery and regenerative medicine. Due to biocompatible adhesives, complex fractures can be treated quickly rather than straightened with screws, nails or tiles. But also skin wounds and other tissue injuries can be sealed with such a wet glue.

Frequent extraction of proteins from mussels is too elastic

Therefore, the superglue of mussel foot protein has long been the target of material researchers and medical device manufacturers. However, it is very expensive to obtain marine proteins in larger quantities than marine animals. Attempts at chemical synthesis of the substance have either failed or not been cost-effective. Another challenge: Once mixed together, the clamshell adhesive begins to glue immediately. It's so hard to deal with him.

As part of the BMBF Ideas Competition Financing Initiative “New Products for Bioeconomics”, a team led by Nediljko Budis of the Technical University of Berlin is developing a biotechnology process for the production of more user-friendly super glue in the laboratory.

The bacteria were reprogrammed

Biotechnologists have a bacterium for it Escherichia coli converted so that it can now produce mussel protein. Chemical analyzes revealed that the amino acid L-DOPA was responsible for the super-adhesive power of the adhesive. However, L-DOPA is a non-proteinogenic amino acid – it is not inherently part of cellular protein synthesis. In natural proteins, L-DOPA is produced only in downstream steps through a biochemical process called post-rotational modification. However, L-DOPA is also very reactive, so the protein would be kept everywhere from the beginning. To avoid this, chemists still hung the ortho-nitrobenzene (oNB) protecting group on L-DOPA.

To convert bacteria into shellfish factories capable of exploiting the natural (xeno) amino acid oNB-DOPA, researchers have expanded the genetic makeup of their organisms – an approach also known as xenobiology or synthetic biology.

From now on, microbes can use the amino acid directly in their protein synthesis. The trick: Because Berlin scientists have been displaying the reactive catechol group L-DOPA with a protecting group, oNB-DOPA acts like a photoactivation switch. Only when the shell protein is irradiated with UV light does its sticky property activate. "This protection group makes the adhesive suitable for practical use," says project employee Christian Schipp.

Funding under the Call for Ideas

The "New Bioeconomy Products" contest offers people original ideas for bio-based economy products, a simple startup promotion. Promotion takes place in two stages. In the research phase, stakeholders can explore their ideas, develop a project plan and find the right partners. In the approximately two-year feasibility phase, the Federal Ministry of Research supports project partners so that the idea can actually become a product or venture.

"Without BMBF funding, our ambitious project would certainly not continue. The research phase offered us the opportunity to put together the widest possible consortium to implement our idea, "says Schipp. For the feasibility phase of the XenoGlue project, he formed a consortium with six partners so that the idea could soon become a marketing medical product. BMBF supports the project in the feasibility phase with a total of € 1.2 million.

Optimize production process and clinical trials

"We want to push a milligram to a gram in terms of production volume," Schipp explains. Together with TU Berlin's bioprocess engineers and EloSystems GbR, Xenoglue develops manufacturing processes that meet clinical quality standards. In addition, wet adhesive for the treatment of superficial wounds in veterinary medicine is being tested. Partner Cellbricks GmbH develops skin models where biotechnologists can extensively test the adhesive strength of their product. Dendropharm, in turn, develops the correct adhesive composition for shellfish and then tests it on small animals. Convinced of the glue here, biotechnologists also want to start the first clinical trials and have set up a company called "XenoGlue".

The team around Schipp has already mastered the first steps in that direction. Last year, Berliners were among the winners of the Science4Life business plan competition. The Germany – the Land of Ideas initiative has also become aware of the project. In 2018, the project team was rewarded as a great place in the land of ideas.

Author: Philipp Graf