Remote-Activated Electrical Stimulation via Piezoelectric Scaffold System for Functional Peripheral and Central Nerve Regeneration
A lack of therapeutic technologies that enable electrically stimulating nervous tissues in a facile and clinically relevant manner has partly hindered the advancement in treating nerve injuries for full functional recovery. Currently, the gold standard for nerve repair is autologous nerve grafting. However, this method has several disadvantages, such as necessity for multiple surgeries, creation of functionally impaired region where graft was taken from, disproportion of graft to nerve tissue in size and structure, and most substantially, high risk of neuroma formation. Therefore, there is an increasing need for the development of alternative strategies to enhance nerve regeneration. To address these limitations, the development of a piezoelectric neuroconduit that can self-generate optimized levels of electrical stimulation can be utilized to wrap a damaged nerve and remotely activated by acoustically-driven piezoelectricity. Unlike biochemical-embedded conduit in which the release of neurotrophic factors is limited by loading or electro-conductive conduit in which only passive electrical stimulation by autologous cells is possible without intrusive electrodes, the piezoelectric conduit provides unlimited opportunity to properly stimulate the neuronal cells in vivo. In this regard, a piezoelectric scaffold was developed using electrospinning technology and its piezoelectric performance was optimized by controlling the fiber diameter and scaffold thickness. Various types of neural cells including PC12 cells, Schwann cells, and neural stem cells (NSCs), were subjected to mechanical/electrical stimulation to examine their behavioral changes. When PC12 cells, a model system for neurons, were subjected to multi-day application of mechanical/electrical stimulation, enhancements in neurite formation and elongation were observed. Alternatively, mechanical/electrical stimulation induced Schwan cells, the glial cell of the peripheral nervous system, to differentiate into its myelinating phenotype and induced the enhanced production of the neurotrophic protein, nerve growth factor. Aside from enhancing the functionality of neuronal and glial cells, mechanical/electrical stimulation also induced the differentiation of NSCs towards the functional cell types of the central nervous system, neurons, oligodendrocytes, and astrocytes. Therefore, this project develops a novel method for enhancing nerve regeneration by modulating neuron and glial cell functionality for the repair of nerve injuries.