Injectable calcium sulphate and calcium phosphate bone substitutes

Detta är en avhandling från Department of Orthopedics, University Hospital, SE-22185 Lund

Sammanfattning: Two formulations of biphasic injectable bone substitutes have been developed for the treatment of bone defects and stabilisation of fragility fractures. The first formulation consists of a calcium sulphate matrix with embedded hydroxyapatite (HA) particles to provide osteoconductivity. The mechanical properties of this formulation were investigated by focussing on the factors affecting the compressive strength of the bone substitute. It was found that the relation between liquid and powder in the formulation was the key factor. By adding less liquid the strength increased. However, a lower amount of liquid makes the paste difficult to inject. Other factors that affected the strength were the amount of HA particles, their size and morphology. Increased strength was obtained for a lower content of HA particles with smaller size and smaller specific surface area. It was possible to obtain a strength comparable to trabecular bone. Vitamin E was added to facilitate the injection. This bone substitute showed a favourable tissue response in both rat muscles and rabbit bone. New ingrowing bone was in direct contact with the material, without fibrous tissue interposition or inflammatory reaction. After 4 weeks, most of the calcium sulphate was resorbed and new bone tissue surrounded the HA particles. The second biphasic injectable bone substitute formulation consists of a calcium deficient HA matrix with embedded calcium sulphate crystals. Apatitic bone substitutes have shown excellent biocompatibility but slow resorption in the human body. By incorporation of calcium sulphate, macroporosity may be obtained to allow bone ingrowth. The strength of this second formulation was correlated to the weight proportions of the phases. Porosity was gradually obtained both at the surface and in the bulk of the material during aging in simulated body fluid. The rheology was investigated by observing the creep response as a function of the shear stress, the L/P ratio, the temperature and the addition of citric acid. It was shown that the shear stress applied on the paste did not affect the setting, but that both increased L/P ratio and decreased temperature retarded the setting. Citric acid enhances the injectability and works, at the same time, as a water-reducing agent, providing the possibility to reduce the L/P ratio while retaining desired workability, or to improve the workability for a given L/P ratio in order to make the bone substitute injectable. Due to the lack of satisfying standards, a new technique, based on pulse-echo ultrasound, for monitoring the entire setting process of injectable bone substitutes was also developed. The technique provides objective and non-destructive testing. The two formulations of biphasic injectable bone substitutes that are presented in this thesis have a large potential to provide new possibilities in bone defect treatment and fragility fracture stabilisation. Since they are injectable and partly resorbable they may be applied using minimal invasive surgery and also act as drug delivery systems.

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