Mineral bone adhesives with isocyanate modified prepolymers as adhesion mediators

该项目的目标是开发添加异氰酸酯官能化预聚体的矿物骨粘合剂，以增加对湿骨的粘附力。这种粘合剂在颅颌面外科或创伤外科等外科学科中具有很高的临床应用潜力。对材料的要求是在潮湿的生理环境中与骨有足够的粘附性，单个成分及其降解产物的细胞相容性，以及临床上足够的处理性能。材料基础是磷酸镁或硅酸钙镁粉末，它们与稀释的植酸溶液作为液相反应。首先，将通过调整颗粒大小和反应活性以及植酸浓度来对系统进行相关材料性能的优化，如粘结强度、凝结时间和降解行为。异氰酸酯功能化预聚体的加入在粘结剂中形成了一层聚氨酯网络，并被认为通过异氰酸酯部分与骨表面的反应进一步增强了粘合力。预聚体将进一步用丙交酯间隔物进行水解降解，并用末端甲基丙烯酸基进行光化学交联。在开发阶段，将在标准化的羟基磷灰石衬底以及皮质骨或松质骨样本上研究粘合强度。其他方面涉及材料的临床处理，例如它们的杀菌能力、外科医生的处理或流变性。此外，还研究了粘合剂中临床相关抗生素的释放情况。除了体外对成骨细胞的细胞相容性外，细胞的降解是通过破骨细胞模型来确定的。最后，将粘附性和加工性最好的组合物植入新西兰大白兔体内。在这里，将研究植入股骨钻孔缺损处以及通过粘合剂固定的股骨中完全分离的骨柱的愈合。将对外植体进行组织学检查，并对骨缺损处的骨再生进行评估。

The aim of the project is the development of mineral bone adhesives with the addition of isocyanate functionalized prepolymers to increase adhesion to wet bone. Such adhesives have a high clinical application potential for surgical disciplines such as craniomaxillofacial surgery or trauma surgery. Requirements for the materials are a sufficient adhesion to bone in the moist physiological environment, a cytocompatibility of the individual components and their degradation products as well as clinically adequate handling properties. Material basis are magnesium phosphate or calcium magnesium silicate powders, which are reacted with a diluted phytic acid solution as liquid phase. Initially, an optimization of the system will be performed with regard to relevant material properties such as adhesive strength, setting time and degradation behavior by adjusting particle sizes and reactivity as well as the phytic acid concentration. The addition of isocyanate functionalized prepolymers results in the formation of a polyurethane network in the adhesive and is thought to further enhance the adhesion by a reaction of the isocyanate moieties with the bone surface. The prepolymers will be further modified with lactide spacers for hydrolytic degradation and terminal methacrylic groups for photochemical cross-linking. The adhesive strength will be investigated during the development phase on standardized hydroxyapatite substrates as well as on cortical or cancellous bovine bone samples. Further aspects concern the clinical handling of the materials, such as their sterilization ability, handling by the surgeon or the rheological properties. In addition, the release of clinically relevant antibiotics from the adhesives is investigated. In addition to the in vitro cytocompatibility against osteoblastic cells, the cellular degradation is determined in vitro by an osteoclast model. Finally, the compositions with the best properties for adhesion and processing are implanted in vivo into New Zealand White Rabbits. Here, both an implantation into a femoral drill-hole defect as well as the healing of completely separated bone cylinder in the femur fixed by means of the adhesives will be investigated. The explants will be histologically examined and the bone regeneration in the bone defect will be assessed.