Kurzfassung

Recent results from our group showed that an evolutionary "old" molecule, inorganic polyphosphate (polyP), provides an extracellular system for the transport and supply of energy. PolyP is a linear polymer consisting of up to hundreds of phosphate residues linked by high-energy phosphoric anhydride bonds. Platelets serve as vehicles to transport these energy-rich polymers to their target sites. The incorporation of polyP into the "dense granula" of the thrombocytes allows a "long-distance...Recent results from our group showed that an evolutionary "old" molecule, inorganic polyphosphate (polyP), provides an extracellular system for the transport and supply of energy. PolyP is a linear polymer consisting of up to hundreds of phosphate residues linked by high-energy phosphoric anhydride bonds. Platelets serve as vehicles to transport these energy-rich polymers to their target sites. The incorporation of polyP into the "dense granula" of the thrombocytes allows a "long-distance transport" of the polymer within the extracellular space without being exposed to the enzymatic attack by extracellular phosphatases - quite the contrary to extracellular ATP, which is only very short-lived and therefore only present there in very low concentrations. We were able to show that Ca-polyP, which is also found in bone tissue, as well as in blood platelets, plays a crucial role as a calcium and phosphate donor in the formation of hydroxyapatite. Recently, we have been able to develop Ca-polyP nanoparticles that facilitate the entry of the polymer into cells. The particles are taken-up by receptor-mediated endocytosis. Several metabolic pathways are induced by Ca-polyP, including the mTOR pathway, which triggers an increase in the number of mitochondria. The discovery of polyP as a "metabolic fuel" and signaling molecule with morphogenetic activity that stimulates differentiation, proliferation and mineralization of bone-forming cells as well as the development of new techniques for encapsulating polyP in nanoparticles that mimic the function of platelets open up new possibilities for regenerative medicine, e.g. for bone repair.
The aim of this project is the development of new strategies and - based on this - of scaffolds/implants for regenerative medicine, which induce vascularization. Morphogenetically active amorphous Ca-polyP microparticles are combined with a suitable hydrogel. The Ca-polyP microparticles are produced according to the technology developed by us. In this case, amorphous particles with a size of 150 to 250 nm are obtained.
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