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Empa - Biomaterials: Looking for made-to-measure materials

Since the end of July 2008, the "Biomaterials" laboratory of the Empa (Swiss Materials Testing and Research Institute) in St. Gallen has been an official member of the BioLAGO BioRegion. Three teams of researchers from the Biomaterials department are looking into the development of biomolecules and biomaterials for medical and industrially interesting applications. We talked with the laboratory’s deputy head, Dr. Manfred Zinn, about how the researchers find materials with the desired properties.

Dr. Zinn, what biomaterials and biomolecules is your department investigating?

Dr. Manfred Zinn is head of the “Bioprocesses” research group at Empa. (Photo: BioLAGO)
We deal with the development and made-to-measure production of polyhydroxyalkanoates (PHAs), biopolyesters of microbial origin, but we also use other substances and materials, for example starch and polylactide (PLA). The new “Biomolecules” research group, which was set up in autumn 2007 and which is coordinated by Dr. Linda Thöny-Meyer, deals with the production and modification of enzymes (laccase, tyrosinase, microperoxidase) and chiral constituents ([R]-3-hydroxyalkanoates). Protein expression is another important part of our work.
Background:
Dr. Manfred Zinn studied and did his doctorate (1998) on PHA biosynthesis at the ETH Zurich before spending three years at the Center for Environmental Biotechnology in Knoxville, USA, and Prof. Ralph Mitchell’s biofilm laboratories at Harvard University. Zinn teaches at the ETH Zurich and the Zurich University of Applied Sciences in Wädenswil. Since 2002, he has been head of the 8-member “Bioprocesses” research group in the “Biomaterials” department.

How can these substances be used in medicine?

We use the aforementioned materials to produce thermoplasts, i.e. plastics that can be easily shaped - when kept within a certain temperature range - for use in tissue culture involving bone cells or nerve cells. Insights into biopolyesters provide us with important information about the physico-chemical properties of the material, its long-term stability and biodegradation. The latter is becoming more and more important. These properties are of great importance for medical applications, for example implants, and care has to be taken that the degradation products of biomaterials do not lead to new problems for human health. International research teams have already been extremely successful. The first material produced with microbes is a biopolyester (poly-4-hydroxyalkanoate), which has recently been approved as a biologically degradable suture thread. Further research projects focusing on artificial cardiac valves, tendons and filling material for critical bone fractures as well as biodegradable screws place heavy demands on the materials. However, initial results suggest that these degradable implants promote self-healing of the injured parts and lead to a reduction in expensive follow-up operations.

Biological degradation is certainly also important for industry?

Biomaterials such as polyhydroxyalkanoates can be effectively used in industrial applications, for example for packaging and coating. They can also be used in agriculture as regrowable foil or fertiliser capsules. Crosslinking enables the production of biologically degradable rubbers, and chemical modifications change the properties of the materials (e.g., water-soluble polymers can be produced through the oxidation of side chains). We are mainly focused on the production of surfaces that help prevent biofilm formation and which can be used to coat materials. Biologically degradable biopolyesters can in general lead to a reduction in the quantities of petrol-based plastics and thus contribute to solving acute waste problems in developing countries.
Microbial expression systems are used in materials research. (Photo: BioLAGO)
Microbial expression systems are used in materials research. (Photo: BioLAGO)

What does biomaterials development involve and which kinds of devices are you using?

The development and production of biopolyesters requires a large number of different devices. The production of a specific type of polyhydroxyalkanoate involves the screening of optimal production strains and the identification of suitable growth conditions. Laboratory-scale batch and continuous cultures (chemostat) are used to determine higher cell density conditions. Chemostat production is an optimal method for achieving constant polymer compositions. At present, about one kilogramme polyhydroxyalkanoate can be produced after four to six weeks in a 20-litre bioreactor. The work of the “Biomolecules” division also depends a great deal on the issue in hand. In general, the bioconversion of substances involves screening methods combined with metabolic engineering.

How can PHA be isolated from bacteria and turned into bioplastics for use in medical applications?

The PHA-containing cells are concentrated by centrifugation, freeze-dried and then treated with an organic solvent (e.g., chloroform, methylenechloride or acetone). PHA is dissolved and filtered before it is precipitated with methanol. However, further steps are necessary to achieve PHA with reduced pyrogenic activity. In general the advantages of PHA are the production of controllable material properties, biocompatibility and biodegradability.

You are looking for conditions under which certain biosynthesis enzymes can be stimulated to produce product yields that are as high as possible. What are these conditions?

Higher activity and stability and improved substrate specificity are the primary goals in our effort to improve the conditions for synthesis, which will eventually lead to a reduction in production costs for biomaterials. We are working with different, well-established microbial expression systems. Theoretically, also unconventional, different induction systems of cell physiological importance can be taken into account. These include contact with surfaces, pH, oxygen, limitation of nutrients, temperature or substrates. Our work is based on literature and patent research in which similar processes are taken into account. After sufficient information has been collected, then the first experiments will be carried out as feasibility studies, and projects are then set up based on whether the feasibility studies are positive.

Is your search for certain properties in materials always fairly straightforward?

Empa, St. Gallen, Switzerland has six departments. (Photo: BioLAGO)
Usually, the consistence of biopolymers is a major problem when working with materials. For example, slow production processes and high temperatures lead to breaks in the chain or a rapid decrease in the molecular weight of the polymers. Lower temperatures, however, slow down the crystallisation or polymerisation processes and impede them enormously. This is a problem not only observed when working with thermoplastic polymers, but also when working with elastomers made from PHA.

Surface coatings have to be treated specifically in order to reduce adhesiveness. This can be achieved by the addition of additives or optimised process control. However, great care has to be taken that the additives do not affect the material’s biodegradability or biocompatibility, which would limit the possibilities of use considerably. The method is based on special experiments.

Do you work in cooperation with industrial partners?

Our department, as well Empa as a whole, sees itself as a bridge between industry, society and science. Empa is a research institution of the ETH Domain that combines the Swiss universities in Zurich and Lausanne with other research institutions. Many projects receive funding through the Commission for Technology and Innovation (KTI), so that SMEs can also benefit from the new findings. In some cases, development projects involving industrial partners are kept secret. Apart from such research projects, our work also involves pure services such as biodegradation, biofilm, fermentation or PHA biosynthesis. Our research projects are aimed at obtaining new know-how and patenting it. This also involves the Empa technology transfer office which awards licences or gets us involved in the patent applications of industrial partners.

What are your future research goals?

We are working to raise our international profile in biomaterials and bioconversion skills. We hope that the BioLAGO membership opens up interesting possibilities for cooperation with new industrial partners.

mst – 26 August 2008 © BIOPRO Baden-Württemberg GmbH
Further information:
Dr. Manfred Zinn
Materials Science and Technology (Empa)
Abt. Biomaterials
Lerchenfeldstraße 5
9014 St. Gallen
Tel.: +41 71 274 76 98
Fax: +41 71 274 77 88
E-mail: Manfred.Zinn@empa.ch
Website address: https://www.biooekonomie-bw.de/en/articles/news/empa-biomaterials-looking-for-made-to-measure-materials