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Novel hydrogels as functional materials

In the ”NanoBioMater”project house, researchers from the University of Stuttgart are working to develop novel hydrogels with integrated biocompatible scaffold structures. Their aim is to make the materials suitable for producing innovative components for environmental and food analytics as well as medical applications. The hydrogels could potentially be used in diagnostic biosensors and the controlled release of medical compounds.

Organigramme of the “NanoBioMater” project house highlighting the outstanding interdisciplinary cooperation between researchers from different scientific fields. The work revolves around four pillars: molecular/nanocomponents, material synthesis, material processing and structural analytics / biocompatibility. © NanoBioMater, University of Stuttgart

Research is increasingly focussing on hybrid materials with biological and inorganic components. Scientists at the University of Stuttgart are working with the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, also in Stuttgart, on the development of innovative, robust hydrogels for extremely diverse applications. The scientists first began pooling their skills in the natural and engineering sciences, chemistry, material sciences and physics in spring 2014 when the "NanoBioMater" project house was launched.

Hydrogels owe their soft consistency to high water content, making them similar to many human and animal tissues. The researchers are hoping to use biobased scaffold structures and biominerals to make hydrogels that are suitable for a broad range of applications, including sensors and docking options for different substances that can be released at the site where the hydrogel is used. The idea of hydrogels that are so robust that they can be dried and rehydrated is another exciting possibility that will expand the range of applications enormously. The Carl Zeiss Foundation in Stuttgart was so convinced about the project's potential that, to date, it has provided funding of 750,000 euros. The University of Stuttgart is injecting around 250,000 euros into the interdisciplinary venture.

Glossary

  • Antigens are foreign substances that stimulate the immune system to produce antibodies.
  • Antibodies are blood proteins (immunoglobulins) which are produced by the B lymphocytes in response to disease. They recognise foreign substances that have entered the body (e.g. bacteria) and help the body fight against a particular disease and develop an immunity to that disease.
  • Biotechnology is the study of all processes involving life cells or enzymes for the transformation and production of certain substances.
  • Enzymes are catalysts in the living cells. They allow the execution of chemical transformations of the metabolism at body temperature.
  • Ribonucleic acid (abbr. RNA) is a normally single-stranded nucleic acid, which is very similar to DNA. It also consists of a sugar-phosphate backbone and a sequence of four bases. However, the sugar is a ribose and instead of thymine, RNA contains uracil. RNA has got various forms and functions; e.g. it serves as template during protein synthesis and it also constitutes the genome of RNA viruses.
  • A virus is an infectious particle (no cell!) consisting of a protein envelope and a genome (DNA or RNA). To be able to reproduce it depends entirely on the metabolism of living cells of host organisms (e.g., bacteria for phages, liver cells for Hepatitis A-virus).
  • A cell culture is a pool of uniform cells which were isolated from multicellular organisms and are cultivated on an artificial nutrition medium (in vitro) for experimental research.
  • The toxicity is the poisonousness of a substance.
  • Biocompatibility means in a literal translation: consistent with the living. It describes the two-way combatibility between a technical and biological system. Materials are biocompatible, when they don't have any negative influence on the organisms in their environment. Biocompatibility is also a measure for the biodegradability of substances in the sewage.
  • Bioactive compounds are substances in food that show health promoting biological activity in the human body but do not provide any nutrients or energy.
Various forms of life such as these Halomonas bacteria can excrete crystalline precipitates. The Halomonas principle is being used as a model for developing hydrogels. © NanoBioMater, University of Stuttgart

Prof. Dr. Christina Wege from the Institute of Biomaterials and Biomolecular Systems at the University of Stuttgart is coordinating NanoBioMater together with Prof. Dr. Günter Tovar from the Fraunhofer IGB. Wege explains: "The Carl Zeiss Foundation supports basic projects that have the potential to lead to a larger research alliance, and we hope to use the most successful NanoBioMater projects to apply for funds in order to establish an alliance in 2017. In the meantime, the projects continue in a kind of 'natural evolution'. Next year, we will evaluate the project in an overall university context, and select the most promising approaches to move forward with them on a regional level." The project house involves research groups from the Stuttgart-Vaihingen University campus as well as researchers from the Institute of Textile Technology and Process Engineering in Denkendorf (ITV), the NMI Natural and Medical Sciences Institute at the University of Tübingen as well as numerous cooperation partners at other Baden-Wüttemberg universities, Max Planck institutes and companies.

Structuring is the key to functionalisation

The montage shows how tobacco mosaic virus-based scaffold and functional components (the latter presented with docking molecules) are integrated into the hydrogel structure. © NanoBioMater, University of Stuttgart

Wege and her team have brought a highly innovative approach from the field of plant virology into the project house: plant virus building blocks from the tobacco mosaic virus, TMV for short. The building blocks serve as structural components which give the hydrogels stability as well as sensory and bioactive properties. TMV is a hollow tube compound around 300 nanometres long where coat proteins are arranged around an RNA molecule. The researchers use synthetic RNA variants in place of viral RNA . "TMV-based constructs can be used to produce a broad range of different shapes. They can be of defined length, bent, branched or even star-shaped. The nanotubes can be equipped with different docking sites for a variety of molecules and are thus suitable for use in cell cultures and the human body. "The docking sites for peptides can be coupled with enzymes, antibodies or medical substances. We also believe that it is possible to use antibodies that trigger sensory functions when they detect certain antigens."

The researchers think it may also be possible to produce hydrogels containing enzymes that can be used to detect pollutants and toxins in liquid media. This would enable effective test systems to be developed. It would be particularly useful if these kinds of applications could dry, store and reactivate hydrogels by rehydration. The NanoBioMater project house researchers have already achieved initial success with these developments.

Enzyme-containing hydrogels are also of medical relevance: for example, oxidising enzymes could be used to develop novel glucose detection systems in blood sugar tests. Wege explains why they are better than conventional methods: "Due to their tubular structure, TMV scaffolds have such a large number of surface docking sites that they can be used in the hydrogel reaction matrix as scaffolds with high coupling density. This would enable us to develop highly sensitive systems. It has also already been shown that the nanotubes are able to stabilise enzymes, giving them a much longer storage time."

“Smart biomaterials“with huge future potential

Several teams are working on the development of hybrid hydrogel materials. One team deals with the molecular assembly and processing of the gel, another with the development of suitable tobacco mosaic virus structures, and a third with biomineralisation. Spray-drying enables the formation of microparticles and 3D printing expands application possibilities. © NanoBioMater, University of Stuttgart

The possible applications of hydrogels go far beyond those described in this article. Hydrogels are also excellent matrix models for biomineralisation models, with the gel matrix used as a template for crystallisation. This idea has been modelled on nature. A group of researchers led by Prof. Dr. Franz Brümmer from the Department of Zoology at the University of Stuttgart has chosen to use sea urchins, among other animals, as models. The animals mineralise their calcareous skeleton, teeth and needles. The results of research into peptide-mediated deposition processes of crystalline precipitates, carried out in cooperation with Prof. Dr. Joachim Bill's department at the University of Stuttgart's Institute for Material Sciences , are being used for developing mineralised hydrogels. One of the goals is to design peptides that enable the precipitation of solid products from dissolved mineral salts. By coupling the peptides to the viral nanostructures, the researchers can create superstructures that can be turned into materials of different rigidity, porosity and functionality.

The particular appeal of this approach is the use of 3D printers for producing the hydrogels. The goal is to print gels in layers – with or without biomineralisation peptides – and then biomineralise them if required. "We hope that this will lead to a stable, hierarchical structure and generate manageably sized materials with a defined nanostructure. We should then be able to produce encapsulations for cell-containing implants," says Dr. Alexander Southan, one of the interdisciplinary team leaders in the project house.

In 2015, the NanoBioMater team ran a summer school in the Black Forest to which external scientists were invited. The scientists discussed the range of possible applications for hydrogels with scaffold structures. "Around 80 students, PhD students and internationally reputed scientists accepted our invitation. There was an atmosphere of intense, open and joyful exchange, which led us to envisage similar events in the future. As a result, the first international NanoBioMater conference will be held from 27th to 30th June 2017," said Wege.

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