Development of Novel Formulations of Bioactive Glass based Calcium Phosphate Cement for Bone Grafting
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The aim of this study was to develop a novel injectable bioactive glass (BG) based calcium phosphate cement (CPC) that would address some of the limitations of current bone grafting materials. The cement was prepared by mixing a glass powder and a calcium phosphate salt with a 2.5% solution of Na2HPO4. In the first part of the thesis, the effects of substituting strontium for calcium in the glass composition are investigated. Setting time and compressive strength of the resultant cement increased proportionally with strontium substitution in the glass up to 25%, whereas for higher substitutions they decreased. The presence of strontium influenced the rate and morphology of the crystal phases formed. Octacalcium Phosphate was the main phase present at 1 h and 1 d of immersion in either Tris buffer or SBF, whereas by 28 d it had completely transformed to strontium-containing hydroxyapatite (HA). Cements were not cytotoxic and osteoblast proliferation increased when cells were cultured with cement dissolution products compared with the control (non-conditioned) media. The second part of the thesis investigates the optimization and characterization of a strontium free formulation which was chosen with the aim of developing a product for potential CE mark approval. While having strontium proved to be beneficial in vitro, from a regulatory point of view, its addition in the cement shifts the category from a medical device to a drug, making the process for approval more challenging and costly. Raw materials were fully evaluated for risk assessment and quality assurance purposes. The cement produced, using a mixing and delivery device, was characterized by in vitro methods to ensure properties of the material were reproducible and in line with set specifications. In the third part, the in vivo performance, and local effects, of the new formulation in a minipig alveolar bone model demonstrated that the material was a moderate irritant at 3 and 6 weeks, but a slight irritant at 12 weeks. Low levels of new bone were present at early time points, but extensive new bone formation was seen by 12 weeks. A safe, novel injectable in situ setting BG based CPC has been developed and used in vivo. Further investigations are needed to elucidate the variability of the local effects.
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