Design and Application of Piezoelectric Conductive Smart Scaffold for Noninvasive Neural Tissue Regeneration via Custom-Made In Vitro Mechano-Stimulator

Peripheral nerve injuries frequently result in long-term functional disability and sensory loss due to the lack of appropriate treatment options. Autologous nerve transplantation is currently the gold standard for repairing damaged nerves, but the increased risk of neuroma formation is the most significant issue with this approach. Moreover, the lack of effective treatment methods that allow for simple and clinically significant neural-tissue electrical stimulation has also restricted full functional nerve recovery. To circumvent these limitations, this study devises an electrospun nanofiber-based piezoelectric and conductive nerve conduit (PCNC) that can self-generate electrical stimulations analogous to neural tissues. This work also focuses on designing a low-cost, customizable 3D printed bioreactor to deliver controlled dynamic compressive loading on cell-cultured piezoelectric nanocomposite constructs. By using a custom-designed mechano-stimulator in conjunction with PCNC, the invitro biocompatibility and neuronal differentiation of the PC12 cells are investigated. The results evidence the expression of increased neurogenic differentiation markers from the stimulated PCNC group compared to the unstimulated PCNC control group. When wrapped around a damaged nerve and remotely activated by dynamic mechanical stimulation, this PCNC can give in situ topographical and electrical cues for optimal nerve regeneration due to its unique structure, composition, piezoelectric, and conducting capabilities.