Tenascin-C derived signaling induces neuronal differentiation in a three-dimensional peptide nanofiber gel

The development of new biomaterials mimicking the neuronal extracellular matrix (ECM) requires signals for the induction of neuronal differentiation and regeneration. In addition to the biological and chemical cues, the physical properties of the ECM should also be considered while designing regenerative materials for nervous tissue. In this study, we investigated the influence of the microenvironment on tenascin-C signaling using 2D surfaces and 3D scaffolds generated by a peptide amphiphile nanofiber gel with a tenascin-C derived peptide epitope (VFDNFVLK). While tenascin-C mimetic PA nanofibers significantly increased the length and number of neurites produced by PC12 cells on 2D cell culture, more extensive neurite outgrowth was observed in the 3D gel environment. PC12 cells encapsulated within the 3D tenascin-C mimetic peptide nanofiber gel also exhibited significantly increased expression of neural markers compared to the cells on 2D surfaces. Our results emphasize the synergistic effects of the 3D conformation of peptide nanofibers along with the tenascin-C signaling and growth factors on the neuronal differentiation of PC12 cells, which may further provide more tissue-like morphology for therapeutic applications.