Peptide nanostructures on nanofibers for peripheral nerve regeneration.

Abstract

Self-assembled peptide nanofibrous scaffolds with designer sequences, similar to neurite growth promoting molecules enhance the differentiation of neural stem cells. However, self-assembled peptide nanofibrous scaffolds lack the required mechanical strength to suffice to bridge long critical-sized peripheral nerve defects. Hence, there is a demand for a potential neural substrate, which could be biomimetic coupled with bioactive nanostructures to regrow the denuded axons towards the distal end. In the present study, we developed designer self-assembling peptide-based aligned poly(lactic-co-glycolic acid) (PLGA) nanofibrous scaffolds by simple surface coating of peptides or coelectrospinning. Retention of secondary structures of peptides in peptide-coated and cospun fibers was confirmed by circular dichroism spectroscopy. The rod-like peptide nanostructures enhance the typical bipolar morphology of Schwann cells. Although the peptide-coated PLGA scaffolds exhibited significant increase in Schwann cell proliferation than pristine PLGA and PLGA-peptide cospun scaffolds (p<.05), peptide cospun scaffolds demonstrated better cellular infiltration and significantly higher gene expression of neural cell adhesion molecule, glial fibrillary acidic protein, and peripheral myelin protein22 compared to the pristine PLGA and PLGA-peptide-coated scaffolds. Our results demonstrate the positive effects of aligned peptide coelectrospun scaffolds with biomimetic cell recognition motifs towards functional proliferation of Schwann cells. These scaffolds could subsequently repair peripheral nerve defects by augmenting axonal regeneration and functional nerve recovery.