3D printed microdevices for advanced tissue culture

Physiologically accurate tissue models are of great interest for preclinical drug safety screening or efficacy studies, as they can bridge the gap between simplified 2D cell culture and animal studies, which are not always translatable to humans. To that end, high throughput devices for advanced tissue culture are required. Stereolithography (SLA) as a high-resolution 3D printing method can create such micro-devices with complex and adaptable designs in a single processing step. However, as available materials for SLA are limited, it can become challenging to accurately mimic key factors of the modelled tissue microenvironment. Presently, we aim to explore new resins for SLA to attain a more diverse material catalogue for the fabrication of devices used in microphysiological systems.
A dual material SLA resin is developed, which can structure a tough, diffusion-closed network as well as a compliant, diffusion open hydrogel material from a single resin bath by selection of illumination wavelength. We retain fast printing speeds of 2.25 mm h^-1 and resolution down to 60 μm with 150 μm patent channels printable in both materials. In proof of concept devices, we achieve a stable chemical gradient by selective dye diffusion through hydrogel structures and a negative Poisson ratio structure by the interplay of compliant hinges and stiff rotators. Furthermore, cytocompatibility by culturing of a human liver cell line is demonstrated.
In an attempt to include a conductive polymer into the dual material resin, polymerization of pyrrole as well as 3,4-ethylenedioxythiophene (EDOT) by initiation through photocleavage of onium salts is investigated, unfortunately without success.
As water-free compliant materials enable easier handling and storage of printed devices, a further material is developed in the current thesis. Tunable mechanical properties are achieved by modulation of cross-linker content in the more hydrophobic macromolecular precursors. Thus, shear moduli of 0.4 – 8.3 MPa are achieved, and due to the high printing resolution, pillars with physiological stiffness in the order of 0.17 N m^-1 could be printed. These structures are used as passive resistance to contraction of engineered cardiac tissues, with the aim of attaining superior maturity of the cardiac constructs. Initial drug tests were successfully performed on these constructs. Nevertheless, further optimization is needed to attain reproducible tissues for long-term culture.
Finally, inclusion of magnetic particles into the resin for the creation of soft non-contact actuators was envisioned. While printing of these magnetic resins was possible in large structures and actuation could be shown, the smaller dimensions required for actuation of the previously  developed cardiac constructs were not achieved.
Thus, the exploration of the parameter space of SLA resins within this thesis yielded some vital insights as well as promising candidates for the application in advanced tissue culture devices.