Mineral bone adhesives with isocyanate modified prepolymers as adhesion mediators

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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.