Additive manufacturing of a novel class of implants with heterogeneous structures, combining different biomaterials and printing methods

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The additive method of micro-extrusion can be operated at room temperature and a multitude of biodegradable biomaterials is available in the meanwhile for this method. Here, we aim at creating new types of implants and tissue constructs that support full regeneration of common defects that occur at tissue interfaces like the osteochondral unit (bone and articular cartilage) or the tendon-bone interface (enthesis). Novel solutions will be developed by combining biomaterials that are specifically adapted to the respective tissues by means of multi-channel extrusion printing. Operation at room temperature will enable integration of tissue-specific, sensitive bioactive factors directly in the printing process. A major innovation of this project is the development and utilization of new printing patterns. Influence of the printing design is still a mostly unexplored topic in micro-extrusion printing, where so far commonly basic wood pile geometries are printed. Focus for the development is the generation of a maximum of concave surfaces as those have been proven to support cell adhesion and migration better than planar and convex surfaces. In addition, size and accessibility of the pores will be taken into account that are crucial for O2 and nutrient supply, both during cell culture and after implantation into the tissue defects. The mechanical properties of the scaffold resulting from the designed pattern will be included in the optimization processes, supported by computational modelling. Besides micro-extrusion, the AM technology of Melt Electrowriting (MEW) of thermoplastic polymers will be integrated in the scaffold design. As shown in preliminary experiments by the applicants, micro-extrusion (strand diameter >= 200 Mikrometer) and MEW (fiber diameter ca. 0.5-20 micromters) can be combined within one printing process. As with MEW highly defined microfiber meshes can be produced, the combination of both AM technologies allows the fabrication of scaffolds with hierarchical structures that provide suitable surfaces for cell attachment and development - but also microfiber networks that mimic the extracellular matrices of mammalian tissues. Integration of MEW meshes can enhance the mechanical stability of calcium phosphate scaffolds, improve the connection of different, extrusion-printed biomaterials and provide guiding structures for alignment of cells. Overall, a new generation of scaffolds and tissue constructs will be developed that consists of several biodegradable biomaterials and are fabricated by innovative combination of two AM technologies in one printing process. The resulting constructs will be thoroughly investigated concerning their structural, mechanical and biological properties, utilizing microscopy, mechanical testing, and state-of-the-art in vitro tests with primary human cells and human mesenchymal stem cells. All this data will be deeply analyzed to conclude about structure-property relation.