Prof. Werner E. G. Müller is the Senator and the Academician of the Erfurt Academy of Sciences (Germany), as well as the Academician of the Croatian Academy of molecular biology, (bio)chemistry and tissue engineering. Based on his research achievements, he has been awarded with one ERC Advanced Investigator Grant and three ERC Proof of Concept Grants in the field of enzyme-based biomineralization and regenerative medicine. He was also a recipient of a grant in the frame of the "International Human Frontier Science Program". His work had been recognized by more than 20 national and international scientific awards, including the highest award from Germany “German Federal Cross Medal; 1st class” and the “Friendship Award” from China. He has more than 1,200 publications (Hirsch-index: 84; ISI Web of Science), 21 granted patents and 15 patent applications [DEPATISnet – Data base: 226 hits].
Topic title：Morphogenetically
active amorphous polyphosphate nanoparticles: A foundational breakthrough
invention for personalized and regenerative medicine
Abstract：Inorganic polyphosphate (polyP) is one of the oldest chemical
energy-providing molecules in biological systems. This polymer, containing a
much longer sequence of high-energy phosphate units than the universal energy
donor adenosine triphosphate (ATP), has attracted increasing attention for
potential biomedical applications because of its diverse metabolic and
regulatory functions and its ability to form biologically active
nano/microparticles.
In its particulate form, polyP is not
biologically active but these particles easily transform into a coacervate form
in which polyP is biologically active. polyP can be easily combined with other
materials used in tissue engineering, e.g. for the production of bioprintable
bioinks (even for cell printing) or stable polymers such as polymethacrylate of
polycaprolactone. In this way, the material could be applied not only as a
filler, but also for the fabrication of larger mechanically more stable implants.
In addition, together with other negative polyanions, polyP is able to
selforganize the presence of divalent cations to polymer bundles stabilized by
Ca2+ bridges, or polyP nano/microparticles can be created in situ
from polyP incorporated into certain hydrogels. Through the selection of
suitable hydrogel-forming polymers and controlled hardening via calcium ions,
hybrid biomaterials of defined porosity and mechanical properties can be
fabricated, which are not only morphogenetically active, i.e. capable of
promoting cell growth, differentiation and migration via specific gene
induction, but also provide the cells with the energy needed for their
function, including those processes which proceed in the extracellular space.
With the discovery of polyP and the
characterization of the multiple functions of this energy-rich biopolymer, a
new physiological molecule has been introduced into the growing group of
biomaterials of biomedical interest, which adds a novel principle: metabolic
energy-delivery in addition to morphogenetic/regenerative activity. There is no
other biomaterial that is provided with this property combination.
References
1. Wang X H, Schröder H C, Müller W E G.
Polyphosphate as a metabolic fuel in Metazoa: A foundational breakthrough
invention for biomedical applications. Biotechnol J 2016, 11: 11-30.
2. Wang X H, Schröder H C, Müller W E G.
Amorphous polyphosphate, a smart bioinspired nano-/bio-material for bone and
cartilage regeneration: Towards a new paradigm in tissue engineering. J Mat
Chem B 2018, 6: 2385-2412
3. Tolba E, Wang X H, Müller W E G. In situ
polyphosphate nanoparticle formation in hybrid poly(vinyl alcohol)/karaya gum
hydrogels: A porous scaffold inducing infiltration of mesenchymal stem cells.
Adv Sci 2019, 6: 1801452.
4. Müller W E G, Wang S, Wang X H.
Transformation of amorphous polyphosphate nanoparticles into coacervate
complexes: an approach for the encapsulation of mesenchymal stem cells. SMALL
2018, 14: e1801170. doi: 10.1002/smll.201801170.
