Mimicking the biological world: Methods for the 3D structuring of artificial cellular environments

Combining modern methods in microsystem technology with the latest advancements in the life sciences, namely those in tissue engineering and advanced cell culturing, is promoting the development of a promising toolbox for modeling biological systems. The core problem to solve using this toolbox is the design of 3D artificial cellular environments, both in fluidic systems and on solid substrates. The construction of 3D biological fluidic environments involves the use of microfluidic devices where fluid direction and behavior can be tightly regulated in a geometrically constrained environment for advanced cell cultivation. This is used in modern cultivation devices, such as bioreactors and multicompartment systems, including systems with integrated multielectrode arrays in both 2D and 3D. The construction of 3D cell cultures on substrates involves various fabrication techniques that use different polymers and biopolymers processed by micromachining, chemical pattern guided cell cultivation, photopolymerization, and organ printing methods. These methods together have the potential to create an artificial system with the complete hierarchical, geometrical, and functional organization found in an actual biological system. In this review, we describe representative developments in this research area and the fusion of formerly unrelated disciplines that are generating new beneficial applications in life sciences.