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Harald Krug is investigating the use of new materials

Prof. Dr. Harald Krug, a toxicologist who runs the "Materials-Biology Interaction" division at Empa - Swiss Federal Laboratories for Materials Testing and Research in St. Gallen, Switzerland, and his team are investigating the interactions of synthetic materials with biological systems. The team of 25 researchers is focusing in particular on the effect of particles and nanomaterials such as CNT on human and animal cells. The division has been an official member of the BioLAGO BioRegion since July 2008.

Prof. Harald Krug has been head of the Materials-Biology Interactions department of Empa in St. Gallen since 2007. (Photo: BioLAGO)
The organism can interact with synthetic surfaces in many different ways; sometimes, severe problems are observed. Implants, cardiac pacemakers or prostheses to replace bones contain a broad range of different materials, including metals and carbon modifications, that might have a range of, sometimes damaging, side effects in the body. Undesired contacts, for example through the absorption of synthetic substances through the lungs, the intestinal tract or the skin, frequently lead to adverse health effects.

“We are focusing our efforts on trying to understand these reactions in order to be able to control or prevent them in the case of undesired interactions occurring,” said Prof. Dr. Harald Krug highlighting the goals of his research. Besides the reduction of side effects, Krug and his team are aiming to optimise materials used in the human body to achieve a better and longer tolerability. In addition, the team’s focus on the potential risks of nanomaterials will take into account the responsible and sustainable use of nanotechnology.
Prof. Dr. Harald Krug was born in 1952 in Edermünde-Besse and studied biology and chemistry at the University of Kassel before receiving his PhD from the University of Göttingen and going on to work for several years at the Karlsruhe Research Centre. In 1996, Krug habilitated at the University of Karlsruhe in the field of environmental toxicology. He is currently the coordinator of NanoCare, a BMBF-funded project dealing with the systematic investigation of the potential risks of nanomaterials. He has been with Empa since 2007, where he heads up the Materials-Biology Interactions department.

Analysis of different cell species

Krug and his team focus on the investigation of different biological test systems, involving both human and animal cell lines (e.g., mouse and rat). Primary cells from humans and chickens (bone marrow stem cells from donors as well as embryonic neuronal stem cells from chicken embryos) and human tissue (for example, placenta, which is regarded as a key barrier tissue) are all used as part of their research. The cells are tested for their reaction with solid composite materials in connection with implants and their surface finishing. Additional investigations are focusing on micro- and nanosize surface structures as well as on nanoparticles. Krug’s research involves a broad range of different materials, including metals (gold and silver particles), metal oxides, polymers and carbon modifications (fullerenes, CNTs, carbon black).

“We use the entire range of molecular biology and cell biology methods in our measurements and analyses, and our work here is rather like that of a normal biology laboratory,” said Prof. Dr. Harald Krug. In addition to these methods, the researchers also use electron microscopy, confocal laser scanning microscopy (CLSM), fluorescence microscopy and fluorescence-assisted cell sorting (FACS). The scientists also use genetically engineered cells that provide them with insights into ongoing cell processes such as differentiation and proliferation. Such investigations are carried out using, amongst other things, reporter genes that express a fluorescent protein. The analysis is done online and on the living tissue. Krug’s work group also has the equipment to carry out patch-clamping techniques as well as being able to use other analysis methods in other Empa departments, including key methods relating to nanoparticles, for example TOF-SIMS or Raman spectroscopy. TOF-SIMS is an abbreviation of "Time-of-flight-secondary mass spectroscopy". Particles are removed from the surface of the sample and accelerated into a flight tube where their mass is determined with a mass spectrometer. Raman spectroscopy is a well-known spectroscopic method in which an excited molecule sends out characteristic wavelengths.

Made-to-measure in vitro models

The researchers have developed made-to-measure in vitro models to control cell behaviour. These models are used to investigate the interaction between materials that are used for medical purposes and the organism. For example, the structuring of the surface of synthetic substances with what are known as micro- and nanosize pillars or wells has an important effect on the behaviour of cells. “This has a decisive impact on the ingrowth of implants,” said Prof. Harald Krug highlighting the importance of using primary human material from hospitals since this does not require the use of cell lines.
Human macrophages with iron oxide particles (coloured red) on their surface. (Photo: Dr. Hellmuth Zöltzer)
Human macrophages with iron oxide particles (red) on their surface. (Photo: Dr. Hellmuth Zöltzer)

Dangerous carbon nanotubes (CNT)

One of Prof. Krug’s specialisations is the interaction of biological systems with carbon nanotubes (CNT) incorporating the effects of nanomaterials on cells. CNTs are currently used in composite materials, for example as reinforcement for the plastics in glass heater coatings for car windows. “CNTs are currently a subject of controversy, as it is suspected that the catalyst metals contained in the CNTs may be toxic and also that the CNT fibres themselves may have a similar effect to asbestos,” said the nanotoxicologist. A broad variety of CNTs are available (for example, CNTs with a single wall or with several walls, insulating CNTs, semiconducting or electrically conducting CNTs), thus making the use of CNTs very interesting. So far, the exact influence of carbon nanotubes on biological processes has yet not been clarified.

Due to the catalytic metals they contain, CNTs and the pure metal particles (including silver and gold particles) are not only catalytically active, but may also be oxidising due to the transition metals contained. This leads to both oxygen radicals and oxidative stress in cells. This could also lead to DNA damage, which would accumulate over time, build in intensity and potentially have a serious effect. Additional risks are inflammations of the lung when the substances are inhaled as well as effects on protein activity. The Materials-Biology Interactions department uses animal and human cell lines to investigate the reactions of CNTs on cells as well as any damage that may be caused. “It is important to produce suitable suspensions, something that is not always done to required quality standards,” said Krug highlighting that the analyses at Empa are carried out with a three-dimensional cell model in close cooperation with researchers at the University of Berne. The scientists also work in cooperation with nanotoxicologists at the Institute of Nanotechnology in Karlsruhe.

Goal: safe nanotechnology

Asked about his future research goals, Krug refers to improving the safety of nanotechnologies. “The early identification of the risks of using nanomaterials is a huge challenge that will help prevent severe consequences for the environment and for human health and has benefits for society as a whole,” said Prof. Krug who sees the Empa as a bridge between science and research on the one hand and between society and industry on the other hand. He also sees his research as an excellent starting point for the interaction with the BioLAGO network. He hopes to be able to work closely and effectively with industry, as future nanotechnology research will to a growing extent depend on financial support from industry and funding organisations. “Public funds will fall away and this will considerably weaken an important pillar of the societal function of scientific institutions,” said Krug.

mst – 29 Sept. 2008
© BIOPRO Baden-Württemberg GmbH

More Information:
Prof. Dr. Harald Krug
Materials, Science and Technology (Empa)
Abt. Materials-Biology Interactions
Lerchenfeldstrasse 5
9014 St. Gallen
Tel.: +41 (0)71 274 7 274
E-Mail: harald.krug@empa.ch

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/harald-krug-is-investigating-the-use-of-new-materials