Emerging approaches of neural regeneration using physical stimulations solely or coupled with smart piezoelectric nano-biomaterials

Neural regeneration is a challenging venture as it is limited by various intrinsic physiological parameters such as the presence of biomolecules like Nogo-A, Ephrin-B3 and Neurocan, that inhibit Central nervous system (CNS) regeneration, and the absence of conducive factors such as ATF3, Sox2 and GAP-43, that promote the neuronal differentiation and regeneration. The design of an effective strategy for neuronal repair or regeneration is a daunting task as neural cells are responsive to a very narrow window of the conductive cellular microenvironment. It requires specific inductive signals and chemical cues from neighbouring cells that can trigger the process of regeneration or repair. It is this complexity that adds to the plight in the scenarios of patients confronted with trauma resulting in spinal cord injury (SCI) or traumatic brain injury (TBI). SCI or TBI may cause temporary or permanent locomotory disorders in patients, affecting the quality of their lives. The regenerative potential of neural cells in the CNS is comparatively lesser than that of peripheral nervous system (PNS). Also, the activation and migration of astrocytes to the injury site causes glial scar, thus hindering further repair process, especially in CNS injuries. Therefore, an effective strategy for stimulating neuritic branching and growth can be a solution to the problem. This review discusses the various facets of strategies that have been adopted to understand and improve the progress of neural tissue engineering for treating the conditions like SCI and TBI. This review also provides an insight regarding the influence of various nano-topographical cues on neuronal cell behavior, the importance of inherent piezoelectric properties in biological systems, various forms of physical stimulation methods that can drive the process of neuritic outgrowth, and finally concludes with the elucidations of advances in development of various biomaterials that have been found effective in achieving enhancement in neuronal physiological properties. It also shares some opinions as perspectives that may help in the further advancement of this field.