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Abstract
Physiological bone formation and pathophysiological bone destruction are complex processes that are controlled by morphogenetically active signaling molecules that display a spatially and temporally precise pattern of expression. During differentiation of osteoblasts from their mesenchymal progenitor/stem cells and of osteoclasts from their hemopoietic precursor cells, a lineage-specific release of growth factors and a trans-lineage homeostatic cross-talk via signaling molecules take place. It is pressing and likewise challenging to develop bone substitution materials to heal bone defects. The major hurdle is to fabricate a template that is functioning in a way mimicking the morphogenetic, inductive role(s) of the physiological extracellular matrix. In the last few years, two naturally occurring polymers, biogenic polyphosphate (bio-polyP) and biogenic silica (bio-silica), have been identified to cause morphogenetic activity on both osteoblasts and osteoclasts. These polymers elicit, after exposure to bone cells, cytokines that affect bone mineralization (hydroxyapatite formation). In this manner, bio-silica and bio-polyP cause an increased release of BMP-2, the key mediator activating the anabolic arm of the hydroxyapatite forming cells, and of RANKL. In addition, bio-polyP inhibits the progression of the pre-osteoclasts to functionally active osteoclasts. Even more, the mature osteoblasts release an inhibitory factor which suppresses growth of osteoclasts. Based on these findings, new strategies for the fabrication of bone biomimetic templates have been developed applying 3D-printing techniques. Finally, a strategy is outlined by which these two morphogenetically active polymers might be used to develop a novel functionally active polymer with self-regulatory activity, accelerating on hydroxyapatite formation of bone cells.
CV
Univ.-Prof. Dr. W.E.G. Müller
Institute for Physiological Chemistry
Johannes Gutenberg University
- Medical School -
Duesbergweg 6, 55099 Mainz; Germany
P: +49-(6131)39-25910
F: +49-(6131)39-25243
Honorary Professor at the Chinese Academy of Sciences [Shanghai Institute of Materia Medica]
Professional career:
1977 Head of the Department "Applied Molecular Biology", Institute for Physiological Chemistry, University of Mainz (Germany)
1977, 1982: Research visitor at the Institute of Microbial Chemistry (Prof. Dr. H. Umezawa), Tokyo (Japan)
1986 - 1991: Visiting professor at the National Cancer Research Institute (Prof. Sugimura; Dr. Nishimura; Dr. Kuchino), Tokyo (Japan)
1993 - 1999: Visiting professor (Japanese Society for the Promotion of Science), Dept of Developmental Medical Sciences, Graduate School of Medicine (Prof. Ushijima), University of Tokyo
Since 2002 Coordinator German Center of Excellence “Marine Molecular Biotechnology”
Since 2008 Bilateral cooperation grants on Bio-materials between Germany and China
Since 2010 German-Chinese Joint Laboratory (until 2015): NanoBiomaterials;
European-Chinese Joint Laboratory (until 2015): IRSES- “MarBioTec”: EU 7th Framework
Since 1970 Editor or member of the Editorial Boards of numerous Journals and Book Series (Nucleic Acids Research; Progress in Molecular and Subcellular Biology [Editor-in-Chief]; Mechanism of Ageing and Development [Editor-in-Chief]; Cellular and Molecular Biology [Co-Editor])
Professional posts and awards:
1972 Boehringer Award for Excellence in Pathophysiology Research
1977 Johann-Georg-Zimmermann Award for Excellence in Cancer Research
1980 Max-Bürger Award for Gerontology
1986 Kani-Medal of the Foundation for Promotion of Cancer Research, Tokyo
1986 Institut Ruder Boskovic-Medal in Gold; Zagreb
1990 Senator of the "Akademie gemeinnütziger Wissenschaften zu Erfurt"
1996 Research Award from the "International Human Frontier Science Program"
1996 Croatian Award for Science and Research, Croatian Academy of Science and Arts
1996 Member of the “Croatian Academy of Science and Arts”
1998 Member of the “Belarus Medical Academy”
2002 Coordinator of the German Center of Excellence “Marine Molecular Biotechnology”
2002 Innovation prize of the state of Rhineland-Palatinate, Germany
2005 “Spiridion Brusina” Award from the Croatian Genetic Society.
2007 Award in Marine Biotechnology “Paul-Scheuer-Preis”
2010 Honorary Professor at the Chinese Academy of Sciences [Shanghai Institute of Materia Medica]
2010 Honorary Research Fellow at the Chinese Academy of Geological Sciences
2010 “Land of Ideas” Award from the President of the State
2011 Friendship Award from Chinese Government
Main research areas:
The research is focused on marine biotechnology. In 1978 we succeeded to bring a sponge bioproduct to commercial use [Ara-A (Arabinofuranosyladenine)]. At present, our main focus is in the field of biomineralization, using sponge enzymes which are able to form and to degrade polymeric biosilica. These data are patented worldwide and published in leading journals. In the last years we cooperate with Prof. Dr. Qingling Feng (Qinghua University), Prof. Dr. Xiaohong Wang (National Research Center for Geoanalysis, Chinese Academy of Geological Sciences, Beijing) and Prof. Jinhe Li (Institute of Oceanology, Chinese Academy of Sciences, Qingdao), and Prof. Dr. Yuewei Guo (Shanghai Institute of Materia Medica; Chinese Academy of Sciences) on the elucidation of the chemical – biochemical – and molecular biological elucidation of the body plan as well as the spicule composition of the giant sponge Monorhaphis chuni. Major emphasis is the study on characteristics of sponge spicules and bionic applications. We own the patents which are granted on cell culture techniques of sponges and corals. With these tools in hand our group is able to use the sponges in a sustainable manner for biotechnological purposes. In addition, we study the symbiotic relationship between sponges and bacteria on molecular level.
Besides these biotechnological achievements we work in the field of molecular evolution; our results contributed to the understanding by which driving forces the transition to Metazoa took place. Besides these activities in “Molecular Genomics of Invertebrates” we have been involved in the elucidation of the mode of action of a series of antitumor compounds used in clinics, e.g. Bleomycin. For these achievements I got several awards in internal medicine and medical life science. As the head of the Department we have a P3-facility where we conduct HIV and Prion experiments.
Our contributions can be read in over 1000 publications and 20 patents. Since 2002 I am the leader of the German Center of Excellene “BIOTECmarin” which has been established for 9 years. My Department of Applied Molecular Biology includes 2 Professors and 30 Post-Docs and Graduate Students. In December 2010 I got the “Innovation Award for Research” from the State.
In the last evaluation on the German Scientists working in Molecular Marine Biotechnology I had been ranked on the first place with 58 points, number of citations in 2011: 1100.
Publications: > 1000 peer reviewed publications
350 published presentations from international conferences |