Mechanobiology in Epithelial
3D Tissue Constructs

Methods already established within the MEƎT consortium are expanded to include novel material platforms, technologies and devices. Our aim is to establish new methodologies in close cooperation with the other project areas to answer mechanobiological questions, which cannot be addressed by current systems. In order to recreate 3D biological systems in a controlled manner, the microenvironment must be experimentally characterized and furthermore mimicked artificially. Despite some progress, it remains challenging to build biomaterial constructs with a native-like ECM structure and 3D architecture, including spatiotemporal control over biofunctional domains and mechanical gradients. To overcome these limitations, section D develops 3D hierarchical and interactive biomaterial systems. Synthetic biocompatible, polymeric building blocks are combined with biological peptides and domains, and novel technologies, such as magnetic assembly (D1), bioprinting (D2), and magnetic micro-manipulation (D3), are applied. This offers more control of biochemical, mechanical and structural properties and methods to locally analyze the effect of these properties on cell behavior inside a 3D matrix. The close collaboration between the engineers and the life science groups of the other project areas enables the development and use of these novel tools so that viable and functional multicomponent tissue models can be constructed in order to study mechanobiology at the epithelial cell-ECM, nerve-keratinocyte and air-epithelium interface (D1-D2). The magnetic micromanipulation devices engineered in D3 are applied to measure local cellular rheological properties with high precision.

Impact: The expected results of work area D will help to design novel and biocompatible materials with spatially defined and controlled mechanical properties for the assembly of multicomponent tissue constructs (D1). The findings will also support the establishment of 3D bioprinting in tissue engineering and address potential constraints of this emerging technology (D2). Assessment of local mechanical properties of living tissues and their surrounding matrix will be enabled by D3. Together, they represent several key technologies that are crucial for advancements in the field of mechanobiology.