Multicellular Biohybrid Materials: Probing the Interplay of Cells of Different Types Precisely Positioned and Constrained on 3D Wireframe-Like Microstructures.

Driven by the unbroken miniaturization trend in microtechnology, the development of smaller, yet reliable and efficient, highly integrated microsystems can benefit from inherent capabilities of biological cells. In particular, by featuring multiple types of cells, biohybrid systems exhibiting self-contained sensing and actuation capabilities can be conceived. To ensure the proper functioning of such multicellular biohybrid systems, the intended cell arrangement needs to be maintained over time. Microscaffolds designed for this purpose should therefore selectively guide or hinder cell migration. However, the basic cell-structure interactions governing the cell migration and extension processes are not yet fully understood. This paper explores these interactions and proposes a method for the fabrication of advanced multicellular biohybrid materials. The method is based on wireframe-like 3D microstructures onto which several types of cells are successfully positioned and arranged by optical manipulation. Experiments exploring cell dynamics reveal geometry-dependent maximal migration and extension distances. Microscaffolds designed on the basis of these characteristics can guide cell migration, trigger structure-contained cell growth, and maintain a predetermined cell arrangement. The methods reported herein therefore provide insight into cell assembly and migration on 3D microscaffolds, which is an essential early step towards advanced multicellular biohybrid materials.