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Anita Ignatius makes biomaterials smart

Anita Ignatius is not interested in knowledge just for the sake of knowledge. “I have always been interested in the practical application of knowledge,” said the 45-year-old veterinarian. Highly theoretical courses she had to attend during her studies put an end to her dreams of opening her own practice after university. But this experience also had its advantages, because it helped her realise what she really wanted – namely doing research of practical relevance. And she has been actively involved in applied research since 1993 when she started to work at the Institute of Orthopaedic Research and Biomechanics at Ulm University Hospital.

Prof. Dr. Anita Ignatius, Director of the Institute of Orthopaedic Research and Biomechanics. © Pytlik

The young scientist quickly became a renowned biomaterials researcher, making a huge contribution to the success of the strongly interdisciplinary institution. In 2009, Anita Ignatius achieved her greatest success so far: at the end of 2008 she was given the chair of orthopaedic research and biomechanics at the Institute of Orthopaedic Research and Biomechanics at Ulm University Hospital, subsequently becoming the institute's director in 2009 following the retirement of her scientific supervisor Lutz Claes. Accepting this post meant refusing attractive offers from other universities. The research done by "her institute", Anita Ignatius reported with a note of satisfaction in her voice, is of huge relevance to national health policy. According to the latest report from the Health Research Council in 2007, diseases and injuries of the locomotor system generate huge healthcare costs and require the kind of research that the Ulm researchers have been focussing on for many years.

Interdisciplinary approach

For Ignatius, this confirms that what she refers to “mainstream research” does not always cover the most needed areas of research. Her team at the Ulm-based institute, which now has 42 scientists, has always been immune to falling into the trap of involvement in mainstream research. The institute’s engineers, physicians, (molecular) biologists, physicians and computer scientists have always been part of mainly international research consortia. This is one of the reasons why Ignatius does not regret not having undertaken a postdoctoral research stay abroad, unlike many other German students after their doctorate. “This interdisciplinary aspect has made my work exciting and attractive and we have always worked in cooperation with many international organisations.”

Not only replacement, but also regeneration

The electron microscope image shows polymer fibres with mesenchymal stem cells.<br />
Mesenchymal stem cells on a matrix consisting of polymer fibres. © Ignatius

In Ulm, Anita Ignatius quickly got involved in biomaterials research and the establishment of a cell laboratory. Her particular focus is on replacement materials for bones, such as ceramics, absorbable polymers based on polylactides (PLA) or polyglycolides or metals. This research has led to the development of an absorbable bone pin to fix bone fractures.

Anita Ignatius explains that her goal has always remained the same, namely to optimise biomaterials and implants. However, the requirements now made on materials and devices are much greater than before; implants need to be compatible with tissue and need to be able to interact with cells and tissue. The developments clearly point towards regeneration, and no longer on purely replacing old or damaged tissue.

How to make biomaterials like their new environment

Ignatius’ team, in cooperation with orthopaedists from the University of Ulm, has discovered that specifically coated metals prevent the attachment of undesired proteins and promote the attachment of wanted ones, for example stem cells. The scientists hope to use these coatings as scaffolding in tissue and tendon replacements. Working with chemists and scientists from the department of transfusion medicine in Ulm, Ignatius and her team of researchers are developing bioactive coatings that specifically release biologically active factors and promote tissue regeneration.

Functional replacement tissue

Anita Ignatius and her team of researchers also use natural scaffolding materials (silk or collagen) for culturing mesenchymal stem cells and osteoblasts as well as spinal disc and anterior cruciate ligament cells. They are investigating the effect of mechanical stimuli on three-dimensionally cultured cells. Ignatius intends to use mechanical stimuli in regenerative therapy in order to produce functional tissue grafts, i.e. grafts with biological functions.

Mechanical stimuli to reach the goal

Newly formed bone, labelled with fluorescent dyes, in the pores of a tissue engineering scaffold. © Ignatius

Ignatius and her team are also working on other projects in order to test the affect of mechanical stress on mesenchymal stem cells, tenocytes and osteoblasts in collagen scaffolds or newly developed synthetic matrices. These investigations are based on the idea that it is possible to control cell function through the application of mechanical stimuli. There is evidence that bone in the tissue is very responsive to this type of stimuli.  

Ignatius pursues this approach on the cell biological level where she investigates the effects of mechanical stimuli on cells of the locomotor system, and how the cells recognise and process certain stimuli. According to Ignatius, the efficient cure and regeneration of musculoskeletal tissue depends largely on such mechanical stimuli.

Deciphering the secret of mechanotransduction

Electron microscope pictures of osteoblasts in a collagen gel exposed to mechanical stress. The photo shows how fibres and cells orient themselves in the direction of expansion.
Electron microscope pictures of osteoblasts in a collagen gel exposed to mechanical stress. The photo shows how fibres and cells orient themselves in the direction of expansion. © Ignatius

Based on these findings, the scientists hope to develop new therapeutic strategies for the treatment of defective healing processes and degenerative diseases. The focus of the Ulm researcher has increasingly been on regeneration processes in degenerative and injured tissues, particularly in elderly patients. This focus seems to fit in well with Ignatius’ concepts as she describes herself as someone to whom: “Relevant topics are highly important.”

Which mechanisms lead to osteoporosis?

Newly developed tissue engineering scaffold for bone tissue developed in the EU project STEPS. © Ignatius

Such relevant topics are ongoing cooperative projects that focus on osteoporosis and polytraumatised patients. With colleagues from Würzburg, Hamburg and Munich, Anita Ignatius is working on the clarification of mechanisms that lead to defective bone regeneration in osteoporosis patients.

In many trauma surgery and orthopaedic hospitals, physicians are often faced with the problem of osteoporotic fractures being difficult to treat, of porous bones that can only be stabilised with great difficulty, and osteoporotic bones that heal badly.

In another project undertaken in cooperation with trauma surgeons at the University of Ulm, Ignatius hopes to find out whether factors that are systemically released after injury affect the function of stem and bone cells. This might explain why fractures heal badly in polytraumatised patients.

Joint combat against diseases of the locomotor system

As the head of an institute, Anita Ignatius is highly unlikely to ever become a research project manager. Nevertheless, she is very interested in coordinating and bringing together apparently different disciplines that deal with disorders of the locomotor system. As a result of the interdisciplinary approach of the Ulm-based institute, Anita Ignatius is part of the Centre of Musculoskeletal Research at Ulm University, bringing together the research departments of trauma surgery and orthopaedics and her own department.

Hope for help from materials researchers

Despite making progress in the areas of biomaterials and tissue engineering, Anita Ignatius is aware that many surgeons are still faced with the unsolved challenge of vascularising large bone defects. “Ideal” scaffold materials are still lacking and Ignatius is hoping for input from material scientists. She is convinced that cell-based therapies will not be able to achieve a breakthrough on their own, and that this can only be achieved in cooperation with other disciplines. And the Ulm-based Institute for Orthopaedic Research and Biomechanics has a great deal of experience in exactly this area.

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/anita-ignatius-makes-biomaterials-smart