Phosphorylated amino acids as complex-forming agents in mineral bone adhesives and fillers

• Applicants: Professor Dr. Uwe Gbureck; Professorin Dr. Stefanie Hölscher-Doht; Professorin Dr. Anita Ignatius
• Subject Area: Biomaterials
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 551249353

Subject of the project are mineral bone adhesives, which have a high clinical application potential for surgical disciplines such as oral and maxillofacial surgery or trauma surgery. The application builds on the recent experience that phosphoserine-containing adhesives with magnesium phosphates have a four times higher adhesion strength to bone compared to adhesives made from calcium phosphates and phosphoserine. The reason for this has not yet been finally clarified and could lie in the complexation tendency of the phosphate group depending on the pH value and the counter ion (Mg2+ or Ca2+). The complex formation will be characterised by a detailed mechanistic analysis by XRD and FT-IR spectroscopy as a function of the pH value and the type of the counterion. The qualification of the adhesives is further based on measuring the bond strength to cortical bone substrates and synthetic test specimens, the intrinsic strength under compressive or bending load and the viscosity as a as a function of the composition. In addition, the adhesives are biomechanically tested using different fracture models on the tibial plateau (split and split compression fractures) for their initial adhesive properties and their biomechanical properties in combination with clinical stabilisation techniques (screws, plates), whereby the unscrewing strength is determined as a measure of quality. The biological in vitro investigation aims at the osteogenic differentiation potential of the adhesives in contact with mesenchymal stromal cells (MSC), which is determined by the expression of relevant makers such as osteocalcin and alkaline phosphatase. The influence of adhesives on the proliferation and viability of chondrocytes will be assessed using MTT and resazurin assays. In addition, the expected degradation behavior is simulated in vitro by aging in physiological model solutions (passive degradation) and by culturing an osteoclast cell line (RAW 264.7, active degradation) and quantified by measuring the ion concentration in serum by ICP-MS. In vivo, the adhesives are assessed in a sheep model with regard to their degradation and tissue regeneration capacity in a partially loaded bone defect model on the proximal sheep tibia. In the same animals, screws implanted in the distal femoral condyle will be augmented with the bone adhesives in order to investigate whether the bony integration of the screws can be improved by the new materials. If the results of the project are positive, areas of application for the augmentation of dental or orthopaedic implants would also arise in osteoporotic bone.

• DFG Programme: Research Grants