Hydrothermal conversion of porous Ca carbonate biominerals into antibiotic and antiosteoporotic Ca phosphate bone implant materials containing Mg, Sr, Zn and Ag ions

• Applicant: Professor Dr. Hans-Joachim Kleebe
• Subject Area: Biomaterials
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261597544

Millions of bone graft procedures are performed annually to repair bone defects caused by trauma or tumor resection. Synthetic calcium phosphate-based (CaP) materials (mostly ceramics) are commonly used as bone graft substitutes. Their chemical similarity to bone guarantees biocompatibility while macroporosity enables firm integration of CaP materials into the bone by ingrowth of natural bone tissue into the pores. Since the mechanical performance of the synthetic materials is generally inferior to natural bone, gradual resorption of synthetic CaP implants and simultaneous replacement by natural bone is often desirable. In the human body, the thermodynamically most stable mineral phase of CaP, hydroxyapatite, is almost non-resorbable. Therefore, many CaP implants represent biphasic calcium phosphates (BCP) as a composite of hydroxyapatite and the more soluble tricalcium phosphate (similar to the mineral whitlockite). In the presence of Mg ions the formation of whitlockite is favoured over hydroxyapatite. Mg ions incorporated into whitlockite are released during degradation of the synthetic implant and stimulate the formation of natural bone. Similarly, Sr and Zn ions are known to stimulate bone formation and retard bone resorption. Hence, these ions play an important role in the treatment of bone loss and fracture related to osteoporosis. The antibacterial effect of Ag ions can potentially be employed to avoid wound infection during surgical graft procedures.This project aims at the development of novel antimicrobial and antiosteoporotic BCP bone implant materials via a single-step hydrothermal process, avoiding high-temperature sintering. Macroporous calcium carbonate biominerals (coral skeletons and sea urchin spines) will be replaced pseudomorphically by BCP while the natural porosity is preserved. A method suitable for simultaneously incorporating a number of functional ions (Mg, Sr, Zn and Ag) into the BCP scaffolds during the hydrothermal mineral replacement process will be developed. Resulting materials will be analyzed in detail for their dopant concentration and distribution. Additionally, ion concentrations released by the BCP materials upon degradation in simulated body fluid will be analyzed. These concentrations will be optimized for stimulating bone formation (according to published values) by adjusting the ion contents of the materials through modification of the production parameters. Antibacterial properties of the Ag-modified materials will be investigated by bacterial culture experiments (inhibition of bacterial growth and biofilm formation) and optimized as well. This research project is expected to provide an effective new method of producing BCP-based multifunctional bone replacement materials that may represent valuable alternatives to conventional CaP bone grafts substitutes.

• DFG Programme: Research Grants
• Participating Persons: Dr. Sabrina Fröls; Professorin Dr. Felicitas Pfeifer