The design of new bioactive materials, provided with "instructive properties" and able to regulate stem cell behavior, is the goal for several research groups involved in tissue engineering. This new function, commonly reserved for growth factors, can lead to the development of a new class of implantable scaffolds, useful for accelerating tissue regeneration in a controlled manner. In this scenario, the likely most versatile and effective tools for the realization of such scaffolds are based on nano- and microtechnology. Here, we show how exploiting the electrostatic spinning (ES) technique for producing a nanofibrillar composite structure, by mimicking topographically the extracellular matrix environment, can influence the fate of human bone marrow mesenchymal stem cells, inducing osteogenic differentiation in the absence of chemical treatments or cellular reprogramming. Basic cues on the choice of the materials and useful experimental instructions for realizing composite nanofibrous scaffolds will be given as well as fundamental tips.