3D-fabrication of cell-type selective scaffolds

Modern methods for solid freeform fabrication (e.g. rapid prototyping - RP) allow the fabrication of arbitrarily complex structures with high feature resolution. Using these methods, it is possible to fabricate cellular materials, whose geometry offers the ideal environment for the cultivation of cells which can form bone-like tissue. Besides geometric constraints, the scaffolds with open porosity have to fulfill a number of requirements regarding the utilized bulk material. The material should exhibit no cytotoxicity. Additionally it should be biodegradable in such a way that over time the scaffold can be replaced by natural tissue. The biodegradability will be achieved by using modified gelatine. By appropriate chemical modifications the gelatine can be made soluble in the photopolymerizable formulation, which is required for the following lithographic shaping process. Additional modifications make the gelatine photopolymerizable. In this project, new photopolymers are developed which can be shaped by RP-methods like stereolithography. It is therefore possible to fabricate scaffolds with defined internal and external geometry. The pore size can be tailored in such a way that the fabricated part offers a similar geometric environment as trabecular bone. The scaffolds are then seeded with mesenchymal stem cells. In the given environment these cells differentiate into osteoblasts which are able to generate bone tissue. By modifying the surface of the scaffolds with collagen I and IV the adhesion of detrimental haematopoietic cells can be prevented, thus leading to an improved tissue generation.

Modern Additive Manufacturing Technologies (AMT) are capable of producing arbitrarily complex objects with high spatial resolution. This way cellular materials with geometries providing an ideal environment for the adhesion of bone tissue progenitor cells can be fabricated by AMT. Apart from geometrical parameters, highly porous scaffolds also have to fulfill some requirements concerning the used material. It should be not be toxic to seeded cells and in addition it has to be biodegradable, so that the scaffolds can be replaced by natural tissue with time. In this project a new class of biophotopolymers with biocompatibility improved by factor of 10 to 100 in comparison to conventional photopolymers, was successfully developed. The photopolymers are based on vinyl esters and vinyl carbonates, and they are structurable with AMTs (i.e. stereolithography). By this means scaffolds with defined inner and outer geometry could be produced. The pore size can be set such that the geometrical relations of the bone spongiosa are preserved. The produced scaffolds were seeded with osteoblasts and mesenchymal stem cells. Selective control over cells adhesion was achieved by surface modification of polymer structures. Their biodegradation behaviour of the developed materials can be adjusted by appropriate choice of photopolymer composition. Produced structures degrade under physiological conditions within the time span from few weeks to a few years, depending on the polymer formulation and geometry of the part. In several publications the project team has demonstrated that scaffolds with spatial resolution of few hundreds of nanometers can be produced using photopolymerization. Compared to conventional methods, the use of photopolymers allows easier functionalization of material properties. In order to further investigate the suitability of developed polymer classes for medical use, two international Patent applications were submitted.