Development of peptide nanomaterials for neural regeneration

Abstract

Nervous system consists of a dense network of cells and their connections and exhibits a high level of complexity. This complexity arises from the high variety of cell types with very specific functions, the high number of cells along with the abundance of connections between these cells. When combined with the nonproliferative nature of neural cells and inhibitory nature of the pathological extracellular matrix (ECM), this complexity leads to a very limited regenerative potential. Thus neurodegenerative disorders and traumatic injuries of neural tissues lead to lifelong disabilities due to the poor success of current therapies. Novel therapeutic approaches which can overcome barriers that impede neural regeneration are therefore required to be developed. Smartly designed nanomaterials that can direct cells towards desired functions can improve the regeneration of neural tissues. Herein, I have described my work on development of peptide nanofibers for neuroregeneration and biological applications of these nanomaterials. To achieve the regeneration of the nervous system, the composition of the neural ECM under healthy conditions and during early development was mimicked through structural resemblance and bioactive epitope presentation using nanofibers. Laminin derived IKVAV peptide sequence and glycosaminoglycan mimicking, growth factor-binding sulfonated peptide sequence were presented on peptide nanofiber scaffolds. Differentiation of PC-12 cells, a model cell system for neuroregenerative studies, was found to be improved on these nanofiber scaffolds when compared to the cells on epitope free control scaffolds. Cells could even extend neurites on these scaffolds in the presence of inhibitory chondroitin sulfate proteoglycans. These nanofibers also proved to be efficient in sciatic nerve regeneration after injury. When injected into the lumen of polymeric nerve guidance channels, this bioactive nanofiber system provided guidance to the elongating axons and resulted in better axonal regeneration that was evident both from histological analysis and electromyography results. Results of in vitro and in vivo experiments were correlated and indicated the neuroregenerative potential of these peptide nanofibers. In addition, semiconductive oligothiophene was encapsulated in peptide nanofibers without compromising the biocompatibility. These hybrid nanofiber scaffolds can potentially be used for electrical stimulation of neurons that can further boost regeneration.