**4.4 Neural tissue engineering**

Injuries affecting peripheral or central nervous systems can cause long-lasting loss of neurological functions due to the severity of the injuries. The usual path of an injury is the inhibition of nerve regeneration, which triggers the formation of compact scar tissue at the defect site. The scar tissue inhibits the connection of the axons across the gap, which will result in disruption of the native tissue and signaling pathways. Short nerve injuries, which have less than 20 mm transaction gap between nerves, are usually repaired surgically; however, long-distance nerve defects require nerve healing/regeneration. For long-distance nerve defects, allografts are usually the gold standard, but there are some disadvantages such as limited donor source, nerve size mismatch, neuroma, etc. To overcome these

#### **Figure 21.**

*In vitro release profiles of BSA and NGF. (A) Release curve of BSA from (R/A)-PCL-BSA scaffolds, (B) release properties of NGF from (R/A)-PCL-NGF scaffolds, (C) NGF release from (R/A)-PCL-NGF&BSA scaffolds. Fluorescent images of PC12 cells cultured for 8 days on the surface of different samples with labeling of cytoplasm (red) and nuclei (blue). (D) R-PCL, (E) R-PCL-BSA, (F) R-PCL-NGF, (G) R-PCL-NGF&BSA, (H) A-PCL, (I) A-PCL-BSA, (J) A-PCL-NGF, (K) A-PCL-NGF&BSA, (L) CS-positive, (M) CS-blank for immunofluorescent staining, (N) CS-negative. (yellow arrow indicates the alignment direction for the underlying nanofibers, and blue arrow shows the neurite-bearing PC12 cells.) (Figure was reproduced with the permission from Hu et al. [92]).*

#### *Nanofibers: Production, Characterization, and Tissue Engineering Applications DOI: http://dx.doi.org/10.5772/intechopen.102787*

challenges, design and fabrication of nerve grafts composed of synthetic or natural polymers are a promising approach for neural tissue engineering.

Nanoporous scaffolds for neural tissue engineering purposes should provide enough surface area for Schwann cells growth and migration, which will direct axons to elongate. Since the orientation structure of axons is axial, some researchers recommended the use of aligned scaffolds, which can provide better contact guidance for cells. Hu et al. fabricated aligned and random PCL scaffolds via ES, and PC-12 (pheochromocytoma of the rat adrenal medulla) neural-like cells were seeded (**Figure 21**).

The results showed that aligned scaffold increased the length of the neurites and directed the extension parallely to the fiber axis. The study also showed that NGF and bovine serum albumin (BSA) incorporated PCL core-shell nanofibrous scaffolds provide sustained release of NGF and neuronal marker expressions and differentiation of PC-12 cells, which indicates that cells were responded to released NGF [92]. Zhang et al. fabricated a conductive scaffold composed of polyaniline (PAN) and poly (L-lactic-co-Ɛ-caprolactone)/silk fibroin nanofibers with incorporation of nerve growth factor (NGF) by using coaxial ES method. The scaffolds successfully support the neurite outgrowth of PC-12 cells, and under electrical stimulation, the amount of neurite-bearing cells and median neurite length were increased [93]. Oxidative stress has a negative impact on nerve cells, so novel approaches, which include antioxidant agents, were investigated. Wang et.al fabricated an antioxidant scaffold composed of lignin/PCL copolymer, and results showed increased mechanical properties of the scaffold and antioxidant activity on cells.
