A Strategy for the Construction of Controlled, Three-Dimensional, Multilayered, Tissue-Like Structures

Differentiated cells make up tissues and organs, and communicate within a complex, three dimensional (3D) environment. The spatial arrangement of cellular interactions is difficult to recapitulate in vitro. Here, a simple and rapid method for stepwise formation of 2D multicellular structures through the biotin-streptavidin (SA) interaction and further construction of controlled, 3D, multilayered, tissue-like structures by using the stress-induced rolling membrane (SIRM) technique is reported. The biotinylated cells connect with the SA-coated adherent cells to form a bilayer. The bilayer of two types of cells on the SIRM is transformed into 3D tubes, in which two types of cells can directly interact and communicate with each other, mimicking the in vivo conditions of tubular structures such as blood vessel. This method has the potential to recapitulate functional tubular structures for tissue engineering.