The Hereon Participates in a New Project: Biomaterials for Heart Implants in Children
Interview with Dr Axel Neffe
More than a third of all congenital heart defects in children require the reconstruction of the heart's right ventricular outflow tract. Because the implant does not grow along with the child, the risky operation must be repeated several times. This could change in the distant future:
The EU project TEH-Tube is to develop an implant that will be absorbed with time and will simultaneously be replaced by the body's own tissue. The implant is based on a bioabsorbable biomaterial. While it remains a dream of the future, the intention, however, is to also carry out this research over a period of decades.
The development of innovative polymer-based biomaterials for medical applications presents considerable challenges for researchers. Very few polymer systems, for example, have been established for clinical use to date. This particularly applies to those materials which are meant to remain in the body only for a certain period of time before being absorbed by the body.
Such a project can only fully succeed if the entire chain of development – from design, synthesis, testing and approval – is taken into consideration. The challenge is closing the gap between the fundamental research and clinical application. This project therefore takes particular care, even at the early stages, in regards to questions of quality management relevant to certification.
TEH-Tube is an EU-funded research project, which began in January 2014 and will initially run for four years. Seven European organisations and research institutions are participating, among them the Institute of Biomaterial Science at the Helmholtz-Zentrum Hereon in Teltow. Dr. Axel Neffe leads the Department of Biomimetic Materials at the Hereon.
"The operation must therefore be repeated in affected children as long as the heart is still growing. That’s precisely what TEH-Tube is about: to develop a new material system so that these additional surgeries can be avoided." Photo: Hereon/ E. Fesseler
Dr. Neffe, what is the particular expertise in Teltow? Why are you involved in this EU project?
On the one hand, we are one of Europe’s leaders in the area of polymer synthesis and polymer characterisation, not only in physicochemical but also in biological characterisation. In addition, we possess the special in-house capability to carry out research within what is referred to as GMP conditions (Good Manufacturing Process) and to produce the first prototypes. This means that the process and documentation is GMP compliant, which is important for approval preparation and for carrying out clinical trials. It serves to ensure that the research results can actually be carried over to the clinical realm. In Germany and in Europe there are very few research institutions in which this can be done, and we are one of those facilities.
What is the goal of the TEH-Tube project?
The goal is the curative treatment of children with a congenital heart defect in which the right ventricular outflow tract of the heart fails to function properly due to a malformation, so the heart vessels as well as the valves must be reconstructed. In contrast to adult patients, the heart grows in children but the material does not grow along with it. The operation must therefore be repeated in aff ected children as long as the heart is still growing. That’s precisely what TEH-Tube is about: to develop a new material system so that these additional surgeries can be avoided.
How do you expect to achieve this goal of avoiding operations every two years?
We focus on using a bioabsorbable material, which means a material that will fulfil its function within the body only for a certain period of time and will then slowly be replaced by the body’s own material. It should, therefore, be dissolved in the body during the same period in which the new cells are growing in the correct location. This should then result in fully functioning bodily tissue.
What kind of material are we talking about?
It is a bioabsorbable polymer from the polyester class. The special thing about this project is that either seeding the cells on the material within the body should be specially supported or we first seed the cells on the material outside the body.
What kind of cells should be seeded on the polymer?
We use mesenchymal stem cells, which are also known as adult stem cells.
The supporting skeleton of the implant slowly dissolves in the body then?
Right. This will occur over a period adapted to the regeneration. If the material is absorbed too quickly, then it couldn't perform its necessary function long enough. If it were slower, then the material itself would prevent the growth of the body’s own tissue.
What are the greatest challenges of this project?
TEH-Tube is a large interdisciplinary project. This means that various chemical, physical and biological experiments must converge, and they must bring about the correct results in all aspects. A major challenge is that we need to recognize as early as the preparation phase which key parameters are essential for the implantation to be a success. This means that we must ask: what material properties must be fulfilled? How should the design look? How should it be processed in order for the project to actually be implemented successfully? The special challenges for our institute in Teltow are the surface functionalization of the polymers and the question concerning how the polymer synthesis can be adjusted to the requirements.
What are the special roles for the Institute of Biomaterial Science?
The first objective for the Institute of Biomaterial Science is the surface functionalization of commercially available polymers. Our second task is to produce new polymers because not all commercially available polymers may be perfectly suited to our needs. These objectives are undertaken while also taking into account the quality management requirements.
Surface functionalization of clinically established polymers – can you explain that?
We don’t change the basic properties of the polymers, but rather their surfaces only. For example, a material might be suitable in regards to its bioabsorption rates and its mechanical properties, but the body's cells might not bind well to this material. This means that we want to enable the cells to better adhere to the surface. One way to achieve our goal is to apply peptides that bind the cells to this polymer.
What are the roles of the partners?
A total of seven partners are participating in this project. One partner is mainly responsible for the administration side while three partners from the industrial sector and three academic partners are also involved.
The two other academic partners are the General Hospital in Paris (APHP) and University College in London. The group led by Prof. David Kalfa in Paris is concerned with studying suitable animal models in order to investigate the subject as a whole. The group also produces the stem cells required for the project. The University College London researches polymer preparation so that the polymers can be developed into the correct form. The partner roles include biological and mechanical testing as well as preparation for clinical translation and approval.
How does the TEH-TUBE project fi t into the overall research activities of the institute?
The idea that biomaterials can be replaced by the body’s own material in order to achieve complete regeneration is a goal towards which we work at this institute as a whole. This particular EU project fits precisely into the strategic focus of the institute.
Thank you very much for the interview!
Author: Erich Wittenberg
Published in in2science #1 (December 2014)