Since early 2013, the Helmholtz Graduate School for Macromolecular Bioscience has been offering PhD students a structured, interdisciplinary training program at the Institute of Biomaterial Science of the Helmholtz-Zentrum Geesthacht in Teltow (HZG). In this joint project with the Freie Universität Berlin and the University of Potsdam, young researchers are developing biocompatible polymers that could be used in implants, for instance in artificial blood vessels or cardiac valves. Unique to this graduate school is the close collaboration between chemists, physicists, engineers, physicians, biologists and biotechnologists.
Simple bone fractures heal on their own; smaller cuts and abrasions heal spontaneously. However, these natural selfhealing capabilities are not sufficient in cases of complicated fractures, extensive wounds like an “ulcerated leg”, or defects of the blood vessels or heart valve. This is where regenerative medicine comes in. Biomaterials temporarily or permanently adopt the function of the missing tissue and may serve as a guiding structure for self-healing.
The future belongs to synthetic polymers. Depending on what kind of chemical components are linked to form polymers – long chains, networks or three-dimensional structures – they exhibit characteristic properties. The possibilities are virtually endless.
The Graduate School for Macromolecular Bioscience that started in early 2013 focuses on research and development in polymer-based biomaterials, the interaction of cells with these novel biomaterials as well as on developing the necessary methods to explore these interactions. With 17 research groups, the joint project of the Helmholtz-Zentrum Geesthacht in Teltow with the Freie Universität Berlin, the University of Potsdam, and the Helmholtz-Zentrum Berlin as an associated partner offers PhD students a structured program in this innovative field. The Helmholtz Graduate School has been established to combine the existing manifold skills of the partners from various disciplines in Berlin and Brandenburg, focusing competences, and enhancing international visibility.
In the near future, about 80 students will be part of the graduate school. The 55 PhD students who are already part of the school are a diverse group in every respect. They come from various European countries but also from Russia, Iran, India, and China as well as from very different disciplines. Here it becomes apparent that biomaterial research is a prime example of interdisciplinary collaboration. Chemists develop suitable synthetic polymers for medical applications. Physicists and engineers process them to achieve novel properties. Biologists, biotechnologists, and physicians focus on the complex interplay at the biomaterial/tissue interface.
At the Graduate School, biomaterial researchers communicate exclusively in English during colloquia, courses and the annual summer school. However, their scientific exchange requires far more than mere English skills. “The students also have to understand the language of the other disciplines,” says chemist Dr. Marc Behl, head of the Department “Active Polymers”. As if to prove that no discipline can do without the other, he sits together with physico-chemist Dr. Karl Kratz, head of the Department “Polymer Engineering”. “We need the feedback of biologists and physicians,” he hands over to Chinese physician and biologist Prof. Nan Ma, head of the Depart-ment “Biocompatibility”. She adds, “Our graduates have to think far beyond their own disciplines.”
The project “Inducing Memory Effects in Polymers by Physical Treatment” by Kratz’s team of PhD students at the Graduate School demonstrates how the interplay works. Physicists, chemists, and engineers need active polymers, and Behl’s group specializes in their design and synthesis. These materials are called ‘active’ because they react on external stimuli taking a different shape, for instance. After another signal, they return to their original shape; they “remember” it. Biologists, together with physicists, chemists and engineers, consider physical treatment methods they can use as a stimulus without damaging tissue: light, temperature changes or applying a magnetic field.
This leads to further specific requirements for the chemists. The polymer’s composition decides how sensitively the future material will react on the selected signal. This demands an exact analysis of the internal molecular architecture, spatial positioning, and flexibility of the components. “We know the natural properties of the components and different materials,” Behl says. “Combining them in an unexpected way yields new functions.”
Physicians, chemists, and engineers test and manipulate the active synthetic polymers in their laboratories until they react in the desired way. Kratz demonstrates a few perplexing examples of biomaterials with shape-memory developed during this collaboration. A thin plastic rod about the length of a finger, initially stretched out, rolls up into a little “pigtail” at the lower end when affected by an alternating magnetic field. As if by magic, a plastic rod takes three different shapes under different temperatures. From the stretched shape, it folds or rolls into a z-shape and stretches again an unlimited number of times. This could be developed into “intelligent” catheters that can be inserted pain-free into the ureter in a compressed shape, where it would unfold and release a specific medicine.
The novel degradable polymers, Behl’s department is working with in the project “Depsipeptides”, do move less but are multifunctional. The chemical constitution of these special polymers is somewhat similar to those of proteins and of synthetic polymers known as polyesters. The researchers are working to optimize the components’ constitution so the implant inserted into the body adjusts to the defect as a result of body temperature and is then populated by somatic cells before being gradually broken down into its components by endogenous enzymes and finally metabolized. Since this disintegration is linked to biological processes, it is clear that the chemists and biologists have to work very closely during the development process. Of course, the biologists thoroughly test each biomaterial that meets the expectations of the chemists and physicists on cells first in petri dishes and later in selected animal models to ensure there are no side effects.
In a separate project “Geometry of Biomaterials and their Influence on Stem Cell Development”, PhD students in the group of physician and biologist Nan Ma try to understand how the natural ability for regeneration can be pushed with so-called induced stem cells. These are perfectly normal somatic cells that can be cultivated in the lab. Under controlled conditions, they can be put into a state, in which they are able to regenerate a certain type of tissue. The researchers want to develop a kind of polymer “Band-Aid” covered with such cells. When inserted into damaged or occluded blood vessels, it could trigger a kind of natural repair of vascular walls. Nan Ma is already thinking ahead. “Depending on the application, such an implant might be equipped with a memory-effect.”
“The PhD program of the Graduate School ensures optimal interdisciplinary training due to the subjectspecific orientation of the research field,” summarizes Prof. Dr. Andreas Lendlein, Director of the HZG-Institute in Teltow and Professor of Materials in Life Sciences at the Institute of Chemistry and the Institute of Biochemistry and Biology of the University of Potsdam. Apart from the specialist training in their respective disciplines, PhD students also receive training in key skills and management qualities at the Dahlem Research School and the Potsdam Graduate School. The school’s spokesperson, Prof. Beate Koksch from the Institute of Chemistry and Biochemistry at the Freie Universität Berlin, regards this research association as a unique hub both spatially and scientifically. “The interdisciplinary thinking and research necessary for the development of modern biomaterials is not an essential part of existing university programs because it requires a specific scientific infrastructure, which is unique in Berlin and Brandenburg,” Koksch says. “With the Graduate School for Macromolecular Bioscience, the Helmholtz Association has established a cutting-edge training program that will not only expand and stabilize the existing numerous activities of the three partner institutions but also increase the international visibility of biomaterial research in Berlin and Brandenburg. The school’s graduates will be able to begin their career as preeminent specialists in the modern development of biomaterials with management skills.”
THE PROJECT
The Helmholtz Graduate School for Macromolecular Bioscience is a collaboration between the Institute of Biomaterial Science of the Helmholtz-Zentrum Geesthacht in Teltow (HZG), the Freie Universität Berlin, and the University of Potsdam. Prof. Andreas Lendlein, Director of the HZG-Institute in Teltow and Professor of Materials in Life Sciences at the University of Potsdam, played a leading role in establishing the school. The project is funded with 2.4 million Euros over a period of 6 years by the Helmholtz Association, complemented by stipends from the partners. Prof. Beate Koksch from the Institute of Chemistry and Biochemistry at the Freie Universität Berlin is the spokesperson of the Graduate School. Prof. Nan Ma from the Institute of Chemistry and Biochemistry at the Freie Universität Berlin and head of the Department “Biocompatibility” at the Institute of Biomaterial Science is the deputy spokesperson.
Contact
Dr. Anja Günther, Coordinator
Institute of Biomaterial Science
Helmholtz-Zentrum Geesthacht
Kantstr. 55, 14513 Teltow
macrobiouhzgpde
www.macrobio.hzg.de
Text: Sabine Sütterlin, Online-Editing: Julia Schwaibold, Translation: Susanne Voigt