Chitosan Fiberbased Threedimensional Hybrid Scaffolds for Bone Tissue Engineering

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Novel NSN-Hybrid-Scaffolds made of chitosan micro- and nanofibres which are constructed in hierarchically simple scaffold structures with defined porosity, were successfully developed in the first stage of funding. Their suitability as a 3D-scaffold structure for bone TE was tested in vitro. Based on the extensive and promising results of the first stage of funding novel, complexly structured and functionalized NSN-Hybrid-Scaffolds with local adjustable porosities are to be developed in the proposed second stage of funding, in order to generate a scaffold, which has the same structure and material composition as the bone tissue. Therefore, the main objective is the development of textile technological solutions for the realization of such complex collagen-coated NSN-Hybrid-Scaffolds with local adjustable pore gradients and both numerically definable and reproducible properties. For this purpose, the properties of the complex NSN structures shall be modelled by means of computer systems in order to predict the relationships between the applied fibre types, fabrication parameters and coatings and the thus resulting structure and porosity as well as to drive the design guidelines for NSN-Hybrid-Scaffolds. A continuous process chain that uses the algorithms developed in the material model must be established, allowing the defined and pre-set fabrication of complexly structured NSN-Hybridscaffolds and thus minimizing trial & error attempts. A new quantitative method must be developed to analyse the pore size gradients in a statistically valid way. The application of collagen coating for the generation of pore gradients, which is also advantageous for cell response, requires a further study of the influential parameters in the coating of NSN-Hybridscaffolds. A further improvement in cell adhesion, proliferation and differentiation is intended by the targeted mineralization of NSN-Hybrid-Scaffolds and functionalization with growth factors (BMP-2, or VEGF) on the nanofibre-scale. The absorption kinetics of the NSN-Scaffolds will be investigated by varying the fibre types and sterilization methods. By means of fluorescence labelling of the chitosan fibres within the NSN-Hybrid-Scaffolds the bioresorption will be studied in the presence of bone resorbing osteoclasts to obtain conclusions regarding the in vivo degradation behaviour. The most suitable scaffold functionalization for bone cells will be determined by cell culture experiments in mono- and co-cultures. In preparation for in vivo studies the influence of the NSN-Scaffolds on the formation of blood vessels will be examined. As a result of this research work a NSN model scaffold shall be provided, which seems promising for future in vivo experiments.