Biosciences Research Seminar - Micro engineered systems for advanced 3D in vitro models

Recently developed three-dimensional (3D) stem cell-based in vitro models, such as organoids, have raised hopes to further close the gap between in vitro and in vivo experiments. Self-sustaining and functional micro tissues, reminiscent of the structure and function of the corresponding organ, help us to shed further light on fundamental biological processes and allow us to study and manipulate developmental, physiological and pathophysiological mechanisms on a tissue level. However, the development of one-pot protocols, where assemblies of multiple cells are exposed to seemingly equal conditions and the formation of higher order architectures is solely based on self-organization, has led to in vitro models with a high heterogeneity, variability and an overall still highly stochastic organization. The lack of systemic guidance and coordination, which is an essential part in living organisms, hinders the formation of long-range orders since uncoordinated self-organization of cells only works efficiently on very small scales.

Micro engineered cell culture platforms and microfluidic systems provide new opportunities to mimic and control the biochemical and biophysical microenvironment of 3D in vitro models. These tools allow us not only to form and instruct complex micro tissues but also help us to analyze and dissect the intricate interactions between cells in multicellular biological systems. However, these roles are often at odds; systems that allow a precise control of micro environmental cues are becoming so complex that they can only be operated in specialized labs and are no longer amenable to high-throughput applications.

Our research group is interested in simplified and user-friendly modular systems, which combine open microwell arrays with tailored microfluidic systems. In the last two decades, we have developed a unique technology platform, which holds great benefits for 3D cell culture applications. The technology is based on solid-state forming of potentially pre-patterned, thin and highly transparent polymer films. It facilitates the integration of biophysical and –chemical cues at lithographic/sub-cellular resolution, e.g. cell adhesion patterns or nano topographies, on the inner curvilinear surfaces of thermoformed microstructures. This technology is complemented by our in-house developed modular micro bioreactors and microfluidic flow cells to realize dynamic culture conditions in order to continuously replenish medium, create dynamic concentration profiles of bioactive molecules or apply shear forces. Always taking standardized interfaces of automated screening platforms into consideration while designing our platforms, our systems grant continuous access to our in vitro models not only for manipulation but also for visualization, including high-content and high-throughput screening. Here, we are presenting a few selected projects showcasing the potential of our technology platform and describe how our micro engineered systems can be used to improve stem cell-based in vitro models.