Introduction: Due to lack of replacement of lost cells and neural factors in the affected area, regeneration and repair in the nervous system is complicated and has been of interest to researchers in recent years. Extensive studies in this field, such as cell therapy and tissue engineering methods, have provided novel approaches for nerve regeneration. The use of neural stem cells and scaffolds with sub-micron and nano-sized fiber structure similar to the natural extracellular matrix are the perfect choice for nervous tissue engineering. To this end two-dimensional (2D) and three-dimensional (3D) cultures have been used. 2D cell culture has been performed in hundreds of laboratories during the last two decades. This method of culture is elementary and does not reproduce the anatomy or physiology of a tissue for useful study. Therefore, a new method is needed to mimics the cell function and tissue architecture. Although design of 3D cell culture systems is more relevant, there are still several hurdles that must be overcome. When to be mentioned the 3D, investigators require for consider the design of matrix for supporting and proliferation of the cells. In general, scaffolds have been categorized in three groups, including natural, synthetic, and hybrid (natural & synthetic). Scaffolds combined with any chemical or physical properties are suitable for tissue engineering of the central nervous system if they are non-toxic, with size fiber of 200-600 nm, with the gradual degradation of the scaffold after implantation in the body, and with capability of cell growth and proliferation. Conclusion: Recent investigations demonstrated that 3D culture is more mature and relevant to human and animal physiology than 2D cell culture. The hybrid scaffolds are best choice for fiber diameter size and high capacity of cell proliferation. The purpose of this review is to provide a general overview of scaffold design by natural and synthetic polymers and their effects on regeneration of the central nervous system