## 2 Tissue-Engineered Scaffolds with GBM and Neural Tissues
### Electrospun Fibers for Manufacturing 3D Scaffold
By applying ES, the cell membrane is subjected to a degree of depolarization, and significant depolarization can induce cell migration, proliferation, and axonal growth by modulating the distributions of ion channels (Figure 5) [6; 45; 51]. It is evident that increasing G concentration increases the scaffold's conductivity. Additionally, increasing the voltage up to 100 mv/cm results in more axons of PC12 cells sprout [7]. [PERSON] et al. demonstrated that the presence of 100 mv/cm causes not only perfect in vitro analyzes (Schwann cell migration, proliferation, myelin gene expression, neurotrophin secretion, and induced PC12 cell differentiation) but also promotes peripheral nerve repair in vivo at a similar level to the gold standard autograft [49]. Although most studies applied an intensity of 100 mv/cm [7; 49; 52], less intensity also leads to acceptable results. For instance, applying ES with an intensity of 50 mv/cm for one h/day through sodium dodecyl benzenesulfonate (DBS)/GO/polypyrrole-poly-l-lactic acid (PLLA) nanofiber can significantly promote neurite elongation and alignment [53]. Another study represents that significant intensity of ES may damage the neural cells and tissue, thus fabricating electrical responsive scaffolds that can deliver electrical signals to neuron cells and modulate cellular behavior for developing functional connection is highly recommended [32; 54; 52]. Applying a nominal ES intensity of 10 mv (1 h/day) alongside a superior conductive scaffold (4% G/thermoplastic polyurethane) with conductivity of 33.45 \(\pm\) 0.78 S/m would be an ideal candidate for guiding neural cell growth [32]. However, applying negligible intensity of ES demonstrated a positive effect on cell proliferation and differentiation; some researchers believe in fabricating self-electroactive nanofibrous scaffolds without requiring ES [45; 55]. A number of studies have demonstrated that aligned nano and micro-electrospun fibers can facilitate cell spreading, avoiding aggregation, and lead to improved cell migration and proliferation [56; 44; 57]. Furthermore, the anisotropic characteristic of the aligned fibrous scaffold can significantly increase the mechanical properties along with cell-scaffold integration, compared with random fibrous orientation [58]. Studies revealed that aligned electrospun fibers can conduct neonatal nerve capillary growth as well as fiber orientation to support functional nerve regeneration [46]. This environment is an ideal candidate for peripheral nerve regeneration due to its morphological resemblance to axons [44]. Various studies have demonstrated the importance of the similarity of nanofibers orientation to the ECM [7; 7; 47; 48; 59; 60; 61; 62; 63]. A minority of researchers neglect this parameter referring to orientation, which is possibly secondary to a lack of equipment for the electrospinning of aligned nanofibers. Cell type is a significant parameter for electrospun mats and is often controversial with selection. In addition to the mentioned stem cells in the introduction  
Figure 5: The schematic illustration of ES effect on neural injury regeneration (**A**) Injured neuron without the conductive platform and electrical stimulation, (**B**) Injured neuron exposed conductive platform and electrical stimulation. Reused with permission from [6]. section, in some nanofibrous mats research, cellular analyzes were repeated with different cell lines to validate their results. The most frequently used cells are PC12 and Schwann cells [7; 49; 52; 61]. Subsequently, their results can prove more reliable for future or even clinical studies. Like the electrospun fibers or mats, membranes (films) can be helpful in particular NTE applications. The membranes are usually produced by the solvent casting method, and the G, GO, or rGO concentration selected is typically between 0.1% and 1.5% wt to achieve the best results in electrical conductivity, membrane flux, mechanical characteristics, and cellular behavior [64; 65; 66].