Interaction mechanisms of medical agents with calcium phosphate cements for the application as pharmacologically active bone substitutes

• Applicants: Professor Dr. Uwe Gbureck; Dr. Katrin Hurle
• Subject Area: Biomaterials
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 327924663

Due to their excellent biocompatibility, calcium phosphate cements (CPCs) are applied for the repair of bone defects. Further therapeutic effects can be achieved by the addition of medical agents. Antibiotics are helpful to contain bacterial infections. After biopsies to remove tumour tissue, the addition of cytostatics can reduce the risk of cancerrecurrence. Antiosteoporotic agents like bisphosphonates can impair further bone resorption in case of bone fracture. By direct addition of those agents to the cements, they can be efficient at the place there are needed. Furthermore, systemic adverse effects can be reduced. Since the approval of such composites as a medical device is practically impossible for regulatory reasons, clinical applicants should be given the opportunity to individually combine approved CPCs and medical agents. Medical agents can have an influence on applicationrelevant properties of the cements, like the hydration performance, rheological properties and the achieved hardness after setting. Conversely, the cements can affect the efficacy of the medical agents,for example via their pH. Hence, for a successful application of such formulations it is essential to understand the interactions in detail. Therefore, in the proposed study different model cements resembling clinically available CPCs will be characterized with the addition of selected antibiotics, antiosteoporotics and cytostatics. The first evaluation of the agent´s influence on cement hydration will be performed by isothermal calorimetry. The development of the quantitative phase composition in the modified cements will be analysed by in-situ X-ray diffraction. For this purpose, an external standard method will be applied, which besides the quantification of crystalline phases also allows quantification of the amorphous fraction. Initial and final setting times will be determined by an Imeter equipped with Gillmore Needle apparatus. Furthermore, rheological properties and injectability of the cement pastes will be investigated. Assays with bacterial cultures will be applied to check the efficacy of antibiotics in the selected cement systems, while the efficacy of antiosteoporotics and cytostatics will be assessed via appropriate cell cultures. The release kinetics of the agents will be quantitatively measured. Since release kinetics is expected to correlate with porosity, porosity measurements will also be performed. Additionally, mechanical properties of set cements will be investigated. At the end of the study, medical applicants should be provided reliable information about the suitability and efficacy as local drug delivery system, based on the cement composition and the kind of medical agent planned for application.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Friedlinde Götz-Neunhoeffer