Additive Fertigung in der Biotechnologie und Pharmaindustrie

Abstract

The additive manufacturing (3D printing) as a new tool for creating high quality products was established in the early 1980s and emerged to a relevant production strategy since then. Crucial improvements of both 3D printing methods and material development in the past decade allow its application in highly regulated areas in biotechnology and chemical industry. This thesis relies on this trend and aims to evaluate different fields of applications, possibilities and borders of 3D printing technology. In the first section, a functional and additively manufactured shake flask lid for continuous and minimal-invasive (fed-) batch processes in shake flask scale is presented. The design and manufacturing process are described and a proof-of-concept is given. Furthermore, the additive manufacturing strategies used are scope of this part discussing their overall applicability for inhouse labware production. The second part describes with the testing and the characterization of additively manufactured biopolymer structures for implant development. Implants are highly personalized objects and additive manufacturing strategies are an interesting and efficient way to realize fast production yielding both high quality and individual products. Based on high resolution imaging methods (MRT, CT) the needed 3D information about the objects dimensions are often available already and can serve as digital blueprints for the 3D printing of implants. This part evaluates different resorbable materials in sight of their applicability as commodity material for additively manufactured implants. The cell behavior of different cell types is assessed including cell viability, proliferation, adherence and differentiation when in contact with respective material. Furthermore, the in-vitro degradation properties of the materials were evaluated under in-vivo mimicking conditions. The third part addresses 3D-bioprinting. With this technique, 3D cell cluster can be designed and manufactured. By providing the cells with an adequate extracellular matrix, this approach enhances the validity of cell assays and improves their transferability to in-vivo conditions. Here, a novel method for extrusion-based bioprinting was developed, allowing to gelate the hydrogel with a nebulized CaCl2 solution, instead of a CaCl2 solution. With this new approach, the incubation time and the concentration of the possibly cell-toxic CaCl2 to the generated object can be reduced. In addition to the research presented in the single chapters, this thesis shows the possibilities of different additive manufacturing methods in biotechnology.