Conductive and Biofunctional Hydrogels for Regenerative Living Interfaces in the Nervous System

Neurological disorders affect more than 60 million people every year and constitute a major clinical challenge. Due to the limited cellular turnover and the significant degeneration triggered by neural injury and disease, regenerative therapies constitute a promising strategy to ameliorate the symptoms. Living bioelectronics offer the potential to create living interactions between implants and the endogenous neural system. By providing a tissue engineered scaffolds containing neuroprogenitor (or stem) cells at the neural interface, this approach can grow connections, creating an intimate and regenerative cell-level interface. The major challenge in this technology is the need to support the cells and encourage their development into mature neurons, while creating functional synapses with target tissue. Hydrogels with conductive elements have been designed with degradation kinetics that are matched to neuronal differentiation and wound healing, while also being electrically addressable. Critically, these hydrogels provide biological and topographical cues that promote the survival of cells and ability to produce neurite processes. A system based on PVA and gelatin has been shown to support the differentiation of neuroprogenitor cells into functional neural networks at the interface of bionic devices. The incorporation of gelatin into poly(vinyl alcohol) - norbornene hydrogels (PVA-Gel-NB) was shown to provide biochemical cues that were able to be modified by the encapsulated progenitors, which ulitmately integrated into brain tissue. In an alternate injectable system, self assembly peptides (SAPs) were modified to form fibers with conductive cores that supported cells in producing directional growth. The use of electrical stimulation that mimicked the pattern of brain activity experienced <i>in utero</i> by the developing mammalian CNS, was subsequently demonstrated to increase the number of mature differentiated neurons. Action potentials have been observed within both of the cell populations, showing their development into appropriate cells types. Ultimately, this work demonstrates the ability to bring bioelectronics and tissue engineering concepts together to produce regenerative neural tissue constructs.