Mineral bone adhesives with isocyanate modified prepolymers as adhesion mediators

以异氰酸酯改性预聚物作为粘合介质的矿物骨粘合剂

• 批准号: 448975488
• 负责人: Professor Dr. Uwe Gbureck
• 金额: --
• 依托单位: Klinik für Mund-, Kiefer- und Plastische Gesichtschirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/448975488?language=en
• 关键词: Mineral; bone; adhesives; isocyanate; modified

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.

该项目的目的是开发矿物骨粘合剂，​​添加异氰酸酯官能化预聚物以增加对湿骨的粘合力。此类粘合剂对于颅颌面外科或创伤外科等外科学科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对骨有足够的粘附力、各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，通过调整粒径和反应性以及植酸浓度，对相关材料特性（例如粘合强度、凝固时间和降解行为）进行系统优化。异氰酸酯官能化预聚物的添加导致在粘合剂中形成聚氨酯网络，并且被认为通过异氰酸酯部分与骨表面的反应进一步增强粘合力。预聚物将进一步用用于水解降解的丙交酯间隔基和用于光化学交联的末端甲基丙烯酸基团进行改性。在开发阶段，将在标准化羟基磷灰石基材以及皮质或松质牛骨样品上研究粘合强度。其他方面涉及材料的临床处理，例如它们的灭菌能力、外科医生的处理或流变特性。此外，还研究了粘合剂中临床相关抗生素的释放情况。除了针对成骨细胞的体外细胞相容性之外，细胞降解还通过破骨细胞模型在体外测定。最后，将具有最佳粘附和加工性能的组合物植入新西兰白兔体内。在这里，将研究股骨钻孔缺损的植入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，并评估骨缺损中的骨再生情况。