Application of additive manufacturing technologies for the realization of clinically relevant cocultures of mammalian cells and microalgae

The regeneration of lost tissue functions by transplantation of cells, often in combination with biomaterials as artificial matrix, is a promising approach for the treatment of various diseases and tissue defects. However, the success of cell-based therapies strongly depends on the supply of the cells, especially with oxygen, immediately after implantation. For most tissue engineering approaches, strategies for a fast revascularization are subject of research. On the other side, there are treatment approaches which intend to circumvent contact of the implanted cells with immunological components in blood in order to avoid rejection and therefore need alternative strategies for efficient oxygen supply. One example of high clinical relevance is the transplantation of allogenic (potentially xenogenic) pancreatic islets of Langerhans in case of patients suffering from diabetes type 1. First short-term experiments demonstrated the great potential of the utilization of photosynthetically active microalgae for coverage of the high oxygen demand of pancreatic islets.

In the proposed project, cocultures of photosynthetically active microalgae and mammalian cells will be realized by means of bioprinting. Both cell types will be encapsulated (separated from each other) in hydrogels; by applying the additive manufacturing technology of 3D plotting for shaping, the advantages of a spatially defined arrangement of the different cell types in a structured hydrogel matrix with defined geometry will be used (Fig. 1). Beyond that, a bioreactor system with light coupling and integrated oxygen sensors will be developed that allows a demand-oriented control of the photosynthesis activity depending on the actual oxygen concentration. With the coculture/bioreactor system the fundamentals will be developed for a systematic investigation of the interaction between the different cell types, the influence of the oxygen concentration on the cells as well as the oxygen transport between the different compartments. Moreover, an efficient and long-lasting supply of the mammalian cells with photosynthetically generated oxygen should be achieved as prerequisite for the translation of the coculture/bioreactor system towards clinical application for islet transplantation. For the establishment of the coculture, a suitable microalgae strain should be identified which is able to growth at 37°C and is characterized by a high rate of photosynthesis. Coculture conditions will be worked out which meet the demands of both cell types. The influence of organic carbon sources on the photoautotrophic microalgae as well as the influence of light on the heterotrophic mammalian cells will be investigated in detail. Finally, it is expected that results of the project concerning the bioprinting with microalgae will provide valuable insights for biotechnological applications.