Final Activity Report Summary - HS RESORB BONE CEM (High Strengh Resorbable Ceramic Bone Cement) The project was a multidisciplinary project with aspects relating to medicine (development of a clinical bone substitute), physics (material characterisation), chemistry (understanding the setting mechanisms of calcium phosphates) and biomaterials engineering (development of a resorbable bioactive bone cement with controlled properties). The project led to the development and characterisation of an injectable (to allow minimally invasive surgery) and resorbable (ultimately replaced by natural bone) cement system with an adjustable setting time of up to 10minutes (enabling a suitable working time for the surgeon) while still providing the highest strength ever achieved for such a system. Calcium phosphate cements (CPC) are in clinical use for filling non-load bearing bone defects in cranial- and maxillofacial surgery(surgery replacing bone loss in the skull and face). These cements rely on acid base reactions between several calcium phosphate combinations to set inside the body in the presence of water. Two types of CPCs are distinguishable, those forming hydroxyapatite (the major component of bone and teeth) and brushite. HA cements are non-resorbable due to the stability of HA within the body. In contrast, brushite cements are resorbable, because brushite has a much higher solubility inside the body compared with HA. Several HA-forming cements have been successfully introduced for clinical application in Europe recently (BoneSource, Norian SRS, α-BSM), but to date only one commercial brushite forming bone cement (chronoOS Inject) is available for clinical use. This material has a comparatively low mechanical strength due to the high growth rate of brushite crystal that causes a rapid setting of the cement paste. Typical compressive strengths of brushite cements reported previously are around 17MPa with setting times of only 3-5 minutes even in the presence of retardants, neither of which represent ideal properties of a cement designed for clinical use. The first phase of this project dealt with the production and conditioning of calcium phosphate powder components, namely tricalcium phosphate (b-TCP) and monocalcium phosphate (MCP), and the evaluation of suitable setting reaction retardants and cement paste liquefiers. A suitable particle size distribution of the reactant powders to provide high strength, prolonged setting and low viscosity of the cement paste was identified. Citric acid was identified as the best setting retardant which also acted as a liquefier for the cement paste and generated brushite almost entirely by the end of the setting reaction. In the second phase of the project novel methods for monitoring of the setting reaction were developed. For the first time isothermal calorimetry (micro-DSC) was used to monitor the fast exothermic setting of a calcium phosphate cement as it actually happened. The chemical changes within the setting paste, i.e. the transformation of the reactants to brushite, were real time monitored for the first time by infrared spectroscopy (ATR-FTIR). These two methods allowed observation of the setting in real time and therefore new insights into the effect of setting retardants and the course of calcium phosphate bone cement setting. In the third phase the degradability of the cement system was characterised and the cement system optimised with regard to strength, injectability and setting time leading to the final cement system. This novel high strength resorbable ceramic bone cement system is now ready for animal testing that could ultimately lead to its clinical use. The scientific findings during this research project have already been highlighted in 6 scientific journal articles and 8 presentations at international scientific conferences.
