Synthesis, processing and in vivo degradation behaviour of magnesium phosphate minerals for bone replacement

磷酸镁矿物质在骨替代材料领域中是相对较新的，因此关于这些化合物中的大多数化合物在原位植入部位的降解和骨再生能力的知识有限。此外，缺乏将大多数矿物质转化为临床适用形式（例如水泥、颗粒、固体）的加工制度。该项目旨在填补这一空白，首先评估不同的工艺技术，用于合成不同的磷酸镁矿物，如鸟粪石，钾鸟粪石，bobierrite，dittmarite或cattiite，具有确定的粒度和相组成。这些化合物在生理条件下的溶度积和溶解速率，以及当与细胞外液接触时它们的相组成的变化都是至关重要的。在第二部分中，矿物质将被转化为合适的骨替代应用形式，包括颗粒和水泥浆。后者将根据水泥浆化学计量和pH值形成上述矿物。将对材料进行全面表征，包括破骨细胞介导的吸收，从而根据释放的Mg2+和磷酸根离子确定活性细胞吸收。基于这些结果，该项目的最后一部分包括在绵羊体内模型中以水泥浆和颗粒形式研究四种不同材料。在此，将颗粒植入股骨髁的钻孔缺损中，并在部分承重胫骨近端缺损中研究骨水泥浆。2个月和4个月后，处死动物，从组织学和生物力学角度评估再生骨的质量。将通过XRD分析和量化材料降解，并通过EDX分析确定镁离子掺入新形成的骨中。

Magnesium phosphate minerals are relatively new within the field of bone replacement materials, whereby the knowledge about most of those compounds is limited regarding their degradation and bone regeneration capacity at orthotopic implantation sites. In addition, there is a lack of processing regimes to transfer most of the minerals into clinically applicable forms (e.g. cements, granules, solid bodies). The project aims to fill this gap by firstly evaluating diverse process techniques for the synthesis of different magnesium phosphate minerals such as struvite, K-struvite, bobierrite, dittmarite or cattiite with defined particles sizes and phase composition. Both the solubility product and rate of dissolution of those compounds under physiological conditions, as well as changes of their phase composition when in contact with the extracellular liquid, are of crucial interest. In the second part, the minerals will be transferred into suitable application forms for bone replacement, including granules and cement pastes. The latter will form the aforementioned minerals depending on cement paste stoichiometry and pH value. The materials will be thoroughly characterized inclusive of the osteoclast-mediated resorption, whereby the active cellular resorption will be determined from released Mg2+ and phosphate ions. Based on these results, the last part of the project comprises the investigation of four different materials in form of cement pastes and granules in a sheep model in vivo. Here, granules will be implanted into a drill hole defect into the femoral condyle and the cement pastes will be investigated in a partial load-bearing proximal tibial defect. After 2 and 4 months, the animals will be sacrificed to assess the quality of the regenerated bone histologically and biomechanically. The material degradation will be analysed and quantified by XRD and the incorporation of magnesium ions into the newly formed bone will be determined by EDX analysis.