Textile products used for the treatment of wounds are increasingly being coupled with bioactive functions. A growing number of biocompatible and absorbable high-tech materials are used on and in the human body for therapy, diagnosis and measurements. Michael Doser, Director of Medical Engineering/Biomedical Process Engineering at the ITV Denkendorf, is working on innovative wound management products and processes.
Prof. Dr. Michael Doser proves that a life sciences career is possible without long-term research stays abroad. Doser grew up in Stuttgart where he studied biology at the University of Hohenheim and did his doctorate on mistletoe lectins in the late 1980s. “Plant lectins can act as antibodies and have a particularly high specificity for sugar moieties on cell surfaces. When I was doing my studies, we analysed mistletoe lectins and their impact on tumour cells. Lectins do not just target cancer cells, but they also inhibit their growth and kill them. This is why mistletoe extracts are used therapeutically. Currently used mistletoe extracts are usually standardised in terms of mistletoe lectins,” explains Doser who also says that from the word go his interest was not just limited to biology-related topics, but, although initially more as a hobby, also in engineering-related topics such as process control.
He owed it to this inclination that, as a young scientist, he got a job at the ITV Denkendorf, which gave him the opportunity to participate in a BMBF-funded project focused on the development of a biohybrid pancreas. The former head of the ITV Denkendorf’s Department of Biomedical Engineering and later director of the institute, Prof. Dr.-Ing. Heinrich Planck, was instrumental in establishing the field of medical engineering at the ITV and attached great importance to developing innovative products with new properties through the biological functionalisation of textile materials. “We developed a vascular prosthesis that contained islets of Langerhans in the vascular wall. The construct was designed for use in diabetes therapy and worked well in vitro, i.e. produced insulin. However, the prosthesis did not work as desired in vivo, i.e. in contact with blood, and we decided to discontinue the project,” says Doser.
Although the project was put on the backburner, it was far from falling into oblivion. At present, Doser is thinking about using advances in knowledge and technology to restart the project. The BMBF-funded project became nevertheless a strategic success. The cooperation with the Department of Transplantation Medicine at the University Hospital in Tübingen (Director: Prof. Dr. Becker) led to the establishment of BMOZ (German Centre for Biomaterials and Organ Replacement) by Planck and Becker. Doser also contributed to the establishment of this new centre. “The centre was in fact a pioneer for competence centres and clusters as we know them today. Suprathel®, an innovative skin substitute for the treatment of dermal wounds, was probably one of the most successful products developed by BMOZ researchers. Suprathel® is similar to the human skin with which it shares properties such as elasticity, permeability to water vapour, impermeability to bacteria, as well as stimulating the healing process.
The development of products for the treatment of dermal wounds paved the way towards further developments in the innovative field of regenerative medicine in which Doser developed a growing interest from the turn of the millennium. Initially, within the context of BMOZ, Doser focused on the development of a polymer that could be used as guidance channel for the promotion of the directed growth of nerves. The invention was based on the finding that severed peripheral nerves, for example nerves in limbs, were able to regrow. However, the extent and quality of regeneration is poor if the nerves are left to themselves. The researchers therefore aimed to develop an encasing structure that prevented the axons from growing in a disoriented manner and that was absorbed by the body once it had fulfilled its task.
The research and development work was a big challenge. “Until then, absorbable, biocompatible polymers were mainly made from polylactic acid, and their application in regenerative medicine was therefore a big problem. Polylactic acid degrades in the human body into small units that are absorbed by the body virtually simultaneously. This leads to the local accumulation of lactic acid, resulting in inflammation and scarring of the surrounding tissue. This is also the reason why big polylactic acid plates are unsuitable for bone repair,” says Doser. Scar tissue would impede the growth of the nerve and needs to be avoided. Doser’s research group therefore set out to look for alternatives.
The researchers have since developed a material that consists of caprolactone and trimethylen carbonate. Doser and his team have set up a BMBF-funded REGiNA project with the aim of developing a membrane that does not lead to the aforementioned complications. “In cooperation with the BG Casualty Hospital in Tübingen and the NMI Natural and Medical Sciences Institute in Reutlingen, we have been able to show in animal models that the nerves grew across a distance of up to two centimetres and that the guidance channel dissolved completely after a period of six months or so,” says Doser summarising the current state of development. The nerve guidance polymers have since been patented and are now used for developing channels that promote the growth of nerves across greater distances. The new nerve guidance channels consist of a capillary membrane with integrated filaments that are coated with a range of growth factors.
Doser is convinced that regenerative biomaterials like Suprathel® have a promising future: “As far as guided tissue engineering is concerned, we are developing biomaterial-based methods for controlling regenerative processes in the body at the same time as preventing adverse side effects. The skin substitute Suprathel® is an excellent example of biomaterials with an excellent regenerative capacity. It also shows that regenerative implants can cope without cells, in particular as the use of cells and the approval of cell-based products has become a regulatory nightmare,” said Doser. Doser will in future focus on materials that are suitable for the development of regenerative and drug delivery systems.
Another functional medical material was also developed in the context of the REGiNA health region: a synthetic sealing plug that ensures that the vessel opening is sealed quickly and safely when a catheter is removed. This plug consists of caprolactone, trimethylene carbonate and glycolide. The combination of these three monomers produces a block copolymer that is absorbed completely by the body as the natural vascular wall regenerates. “We are currently testing the material in animal models and the first results will be available in summer 2014. If everything goes as planned, then we will be able to fine-tune the design and start an extensive clinical trial for approval of the material as a medical device,” says Doser.
In addition to his research and development activities, Doser also teaches students at the universities of Stuttgart and Tübingen where he is involved in the two universities’ first interuniversity medical engineering course. He is in charge of integrating classes on regulatory affairs into the course and also lectures on polymeric biomaterials. He is also involved in the master’s course on process engineering at the University of Stuttgart, and has taken over the coordination of the “Biomedical Process Engineering” course following Professor Planck’s retirement. This course is also extremely popular with mechanical engineering and technical biology students.
Prof. Dr. Michael DoserITV DenkendorfKörschtalstraße 2673770 DenkendorfTel.: +49 (0)711 9340-263E-mail: michael.doser(at)itv-denkendorf.de