Anisotropic Single-layer Graphene/Nanodiamond Loaded PCL Conduits Provide Biophysical Cues to Manipulate Nerve Biomechanics and Bioelectric Function in the Restoration of Nerve Microenvironment

Impaired peripheral nerves are characterized by a disturbed nerve microenvironment where nerve mechanics and physiology are disrupted. Adequate biophysical cues on nerve scaffolds that resemble the mechanical and bioelectrical microenvironments represent an advanced technique for the realization of desirable neural interfaces. Considering that Schwann cells and axons are surrounded by a unique mechanical microenvironment and the electrically sensitive nature of peripheral nerve, a novel neural device is designed by incorporating single-layer graphene (SLG) and nanodiamond (ND) into nanogrooved polycaprolactone (PCL) fibers. The combination of these nanomaterials with the anisotropic topography (formed by the nanogrooves on surfaces of PCL fiber and the micrometer gaps between neighboring fibers) from fibrous conduit shows extraordinary synergy in enhancing the nerve regeneration process. The SLG/ND/PCL nerve guidance conduit (NGC) successfully triggers the myelinating capacity of Schwann cells via Piezo1 signaling and further enables the concurrent activation of NFAT and Krox-20 molecule. Cells on the scaffold also present higher mechano-sensitivity, with the simultaneous suppression of fibrotic activity and the collagen production of fibroblasts. Taken together, the concept of combining nanomaterials with anisotropic topography can enable the myelinating capacity of Schwann cells, thus offering a platform strategy toward the fabrication of a desirable microenvironment for peripheral nerve regeneration.