Polyurethane based bone adhesive formulations

Millions of people are in need of bone injury treatment for many reasons such as traffic accidents, daily injuries, sports injuries. For the stabilization of bone fractures in the health field; plastering, external stabilization, the use of plates and screws. However, these methods are not suitable for all types of bone fractures. Hard tissue adhesives are needed when the fractures are on an irregular surface, in thin bones or in broken bones proximity to sensitive tissues. For this purpose, it is planned to develop polyurethane based bone adhesive to adhere bone tissues to each other and composite tissue scaffolds consisting of polyurethane and ceramic to support bone tissue formation in damaged area. In this way, it is aimed to develop osteoconductive and osteoinductive bone adhesives and graft formulations which can be shaped according to the shape of the defect area. For this purpose, in the first step of the thesis, polyurethane bone adhesive and tissue scaffold including different size (0,5-1 mm, 1-2 mm and 2-4 mm) and different percentages (20%, 30% and 40% by weight) beta-tricalcium phosphate were prepared. In the second step of the thesis, Fourier Transform Infrared Spectroscopy (FTIR) and Hydrogen-Nuclear Magnetic Resonance (1H-NMR) analyzes were performed to determine the functional groups present in the tissue scaffold and the synthesis of the desired polyurethane structure was verified. The thermal behavior of the material is characterized by differential scanning calorimetry (DSC) analysis. By using scanning electron microscopy (SEM) and micro-computerized tomography (μ-CT), it is observed that the tissue scaffolds have porosity above 90%, the organic and inorganic phases are well integrated with each other and the homogeneous distribution of β-TCP particles in the structure. It was also found that average pore size of the groups are about 267 ± 25 μm. In the compression tests, performed to determine the mechanical strength of the tissue scaffold candidates, the highest compressive strength was found in the group including 1-2 mm particle size with 40% β-TCP. Also it has been observed that increasing the TCP ratio increases the compression strength. In order to determine the adhesion strength of the polyurethane based bone adhesive, the fractured bovine rib bones were glued and subjected to mechanical tensile test, and the adhesive strength of the material was determined to be 1,34 MPa. In the final stage of the thesis, in order to investigate in vitro performance of the polyurethane/β-TCP scaffolds, MG63 human osteosarcoma cells were seeded onto polyurethane/β-TCP tissue scaffolds. To investigate the cell viability and the proliferation Alamar Blue assay was performed. Among the groups, the highest cell viability values were observed in the group containing 40% (w/w) β-TCP with 1-2 mm particle size and this group was found to be more successful than the other groups due to supporting cell proliferation. Cytotoxicity analysis performed by means of the elution method according to ISO 10993-2 showed 85.75% cell viability. This result indicates that the materials are not toxic. Keywords: bone adhesive, polyurethane, ceramic, beta-tricalcium phosphate, bone graft, bone defects