Modification of calcium phosphate bioceramics with biologically active metal ions for a specific control of cellular reactions

• Applicants: Professor Dr. Uwe Gbureck; Professor Dr. Michael Gelinsky; Professor Dr. Stefan Rammelt
• Subject Area: Dentistry, Oral Surgery ; Biomaterials ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 157820161

The aim of the research project is the modification of calcium phosphate ceramics with different metal ions (Co2+, Cu2+, Ni2+ etc.) for the stimulation of biological processes, e.g. the angiogenesis as a precondition for bony ingrowth of implants and the osteoclast activity for promoted in vivo resorption of the materials. Applied porous ceramic materials are made from calcium deficient hydroxyapatite respectively calcium hydrogen phosphate (brushite), which are obtained from cement setting reactions of alpha- or beta-tricalcium phosphate in aqueous solution respectively diluted phosphoric acid. The fabrication of model structures occurs either by manufacturing of the materials as cement paste in silicone moulds for simple geome-tries with relatively low porosities (for experiments with osteoclasts) or by 3D powder printing for the production of complexly shaped macroporous structures for studying the angiogene-sis in defined pore systems. The loading of the ceramics with metal ions is carried out by either addition of the respective salts during sintering as well as by subsequent adsorption from aqueous solutions to set cements. In vitro investigations of material resorption are per-formed with osteoclasts, obtained from human monocytes by addition of the differentiation factors MCSF and RANK-L, of which the differentiation is quantitatively evaluated via the activity of the osteoclast-specific enzymes TRAP (tartrate-resistant acid phosphatase) and carbonic anhydrase II. The angiogenic potency of cements modified with metal ions is exam-ined by means of human endothelial cells cultivated in collagen/fibrin gels, whereby their ad-hesion, proliferation and formation of tubular structures are studied by fluorescence micros-copy. To obtain a better understanding of the effects of metal ions on endothelial cells respectively the angiogenesis, additional examinations of the expression of different genes and proteins involved in the angiogenic process will be carried out. Finally, the osteoclastic re-sorption and vascularization of the materials will be evaluated in vivo in a small animal model, whereby the resorption studies occur orthotopically in rat tibia, while the angiogenesis is quantified in subcutaneous tissue of rats.

• DFG Programme: Research Grants