Functional Self-Assembling Peptide Nanofiber Hydrogels Designed for Nerve Degeneration

TLDR: A strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH to provide a more permissive environment for nerve regeneration than the RADA 16-I hydrogel is presented and a new mechanism that might be beneficial for the synthesis of SAPs for in vitro 3D cell culture and nerve regeneration is reported.

Abstract: Self-assembling peptide (SAP) RADA16-I (Ac-(RADA)4-CONH2) has been suffering from a main drawback associated with low pH, which damages cells and host tissues upon direct exposure. In this study, we presented a strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH. RADA16-I was appended with functional motifs containing cell adhesion peptide RGD and neurite outgrowth peptide IKVAV. The two SAPs were specially designed to have opposite net charges at neutral pH, the combination of which created a nanofiber hydrogel (-IKVAV/-RGD) characterized by significantly higher G′ than G″ in a viscoelasticity examination. Circular dichroism, Fourier transform infrared spectroscopy, and Raman measurements were performed to investigate the secondary structure of the designer SAPs, indicating that both the hydrophobic/hydrophilic properties and electrostatic interactions of the functional motifs play an important role in the self-assembling behavior of the designer SAPs. The neural progenitor cells...