Conclusions and Future Directions

The most promising techniques to address neural tissue regeneration combine multiple stimuli in a single scaffold. NGCs have exhibited positive results in a number of in vivo studies and have been translated to clinical use. However, there is room for improvement in providing stimulatory cues and enhancing the interface between the NGC and the healthy tissue. Advanced properties of dynamic NGCs will deliver additional stimuli to further enhance tissue regeneration. The complexity of regeneration and the balance of minimizing inhibitory cues while providing and maximizing stimulatory cues requires multifaceted solutions. Due to the degree to which surface area can be increased and surface roughness and energy can be tailored, nanomaterials offer a promising avenue for biomaterial design. A further understanding of how even brief, low-intensity electrical stimulation can enhance axon outgrowth and neural tissue regeneration, makes the development of practical applications of electrically active materials even more appealing. Nanoscale conductive and piezoelectric materials have the potential to offer permissive environments for neural and beneficial glial cells, a reduction in the astroglial response, and critical stimulatory cues that could provide extended periods of enhanced regeneration after brief periods of treatment. Select biomaterials, including a ZnO and polymer composite with piezoelectric properties, have been shown to reduce astroglial cell activity, a critical step in the regeneration of functional neural tissue in the CNS. The piezoelectric effect of the material may provide a neural cell activity enhancing both CNS and PNS regeneration. The nanoscale dimensions of a piezoelectric material may further enhance the piezoelectric response due to the increased surface to volume ratio of the particles and the creation of a substrate that mimics the natural nanoroughness of neural tissue. Ultimately, this composite material, among other electrically active nanomaterials, when fabricated into a NGC and implanted into the body, could reduce inhibitory cues which prevent healthy tissue regeneration and provide critical stimulatory cues to promote neural cell activity and axon growth.

Acknowledgments The authors would like to thank the National Science Foundation for fellowship support (Brown University GK-12) and the Hermann Foundation for funding part of the work presented here. The authors thank Geoffrey Williams of the Leduc Bioimaging Facility at Brown University for SEM assistance for some of the work presented here.

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