Piezoelectric Stimulation of Neural Cells: Exploring the Synergistic Potential of Hybrid Scaffolds for Enhanced Regeneration

Abstract While the peripheral nervous system (PNS) possesses regenerative capabilities, injuries to the central nervous system (CNS) can often result in debilitating and irreversible damage, leading to significant clinical challenges. Neural stem cell (NSC) transplantation is an emerging research area that is being explored for tissue regeneration; however, the potential of this approach relies on a suitable microenvironment to provide the necessary support to allow cells to grow and proliferate. Hybrid piezoelectric scaffolds are attractive, since they integrate structural and bioelectric cues to create a suitable microenvironment for NSC transplantation and neural regeneration, providing both structural support and electrical stimulation. Current research in the development of these piezoelectric materials focuses on pure scaffolds, based on a single type of material, for CNS injury. Here, a range of porous hybrid scaffolds are reviewed and compared, highlighting their application potential for CNS neural regeneration, through the combination of material, electrical, and biological properties. Key material properties are identified that influence neural cell adhesion, proliferation, and differentiation, highlighting the potential of hybrid scaffolds to promote neural regeneration. Recognizing the current limitation in directly comparing scaffolds, due to inconsistent analysis and methods, a standardized analytical framework for analyzing piezoelectric material‐driven CNS neural regeneration is proposed.