The aim of this chapter is to expound on the methods for the development of a synthetic analog of the extracellular matrix (ECM) that, because of a careful choice of its characteristics, can regulate cell behavior and tissue progression for applications in neural regenerative medicine. Neural cells—neurons—are the smallest building blocks of the central and peripheral nervous systems. The function of neurons is to elaborate the information that a man receives from the environment, share it with other neurons, and use it to activate complex functions such as language, behavior and surviving, reasoning, and self-correction. In the body, neurons are linked to other neurons and are supported by the ECM. The scaffolds are an artificial analog of the ECM: they are designed and fabricated using a combination of chemical, physical, and engineering techniques. Thus the scope of tissue engineering and neural regenerative medicine is to optimize the characteristics of the scaffold to assure the best performance of the neurons cultivated in them. Performance is another word for efficiency: depending on the variables that one want to maximize, one can have different definitions of efficiency. Thus as for some examples, scaffolds can be designed to optimize cell adhesion, growth, proliferation, clustering, or activity. In this chapter, we will explain how one can use micro- and nanofabrication techniques to produce scaffolds with a tight control over its characteristics, including the physical, chemical, geometrical, and mechanical characteristics. Then, we will see how a combination of characteristics can influence cell behavior, and to what extent.@en

Understanding the mechanisms underlying cell-surface interaction is of fundamental importance for the rational design of scaffolds aiming at tissue engineering, tissue repair and neural regeneration applications. Here, we examined patterns of neuroblastoma cells cultured in three-dimensional polymeric scaffolds obtained by two-photon lithography. Because of the intrinsic resolution of the technique, the micrometric cylinders composing the scaffold have a lateral step size of ~200 nm, a surface roughness of around 20 nm, and large values of fractal dimension approaching 2.7. We found that cells in the scaffold assemble into separate groups with many elements per group. After cell wiring, we found that resulting networks exhibit high clustering, small path lengths, and small-world characteristics. These values of the topological characteristics of the network can potentially enhance the quality, quantity and density of information transported in the network compared to equivalent random graphs of the same size. This is one of the first direct observations of cells developing into 3D small-world networks in an artificial matrix.@en