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

磷酸镁矿物在骨替代材料领域是一个相对较新的领域，因此对这些化合物中的大多数关于它们在原位植入部位的降解和骨再生能力的了解有限。此外，缺乏将大多数矿物质转化为临床适用形式(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，以合成不同的磷酸镁矿物，如鸟粪石、钾鸟粪石、镁镁铁矿、镁镁铁矿或钙镁矿，并确定粒度和物相组成。这些化合物在生理条件下的溶解度乘积和溶解速度，以及它们与胞外液接触时相组成的变化，都是人们非常感兴趣的。在第二部分中，将矿物转化为适合骨替代的应用形式，包括颗粒和水泥浆体。后者将根据水泥浆体的化学计量比和pH值形成上述矿物。这些材料将被彻底表征，包括破骨细胞介导的吸收，因此活跃的细胞吸收将根据释放的镁离子和磷酸根离子来确定。基于这些结果，项目的最后部分包括在活体绵羊模型中以水泥浆体和颗粒的形式对四种不同材料的研究。在这里，颗粒将被植入到股骨髁内的钻孔缺损处，骨水泥糊剂将被用于研究胫骨近端的部分承重缺损处。2个月和4个月后，处死动物，进行组织学和生物力学检查。材料的降解将通过X射线衍射进行分析和量化，镁离子进入新形成的骨中将通过EDX分析来确定。

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.