Silk-inspired fiber implant with multi-cues enhanced bionic microenvironment for promoting peripheral nerve repair

Successful repair and desirable functional recovery of large-gap nerve injuries using artificial nerve implants remains a significant clinical challenge. The beneficial bionic microenvironment within scaffolds can significantly promote the outgrowth of newborn nerve tissues after implantation. Herein, we developed an aligned silk-inspired fiber scaffold (RGD@ASFFs) with a synergistic effect of an extracellular matrix mimicking physical cues and RGD (Arg-Gly-Asp) signals to provide an enhanced cell-friendly microenvironment for repairing large-gap peripheral nerve injuries. The topographic alignment of the methacrylated silk fibroin electrospun fibers effectively facilitated axonal guidance and oriented Schwann cell growth. Importantly, the mechanical cue combined with cell adhesion signals provided by RGD peptides further triggered enriched myelination of Schwann cells by nuclear translocation of Yes-associated protein 1 (YAP) to secrete neurotrophins to support axonal growth. Moreover, benefiting from improved neuronal extension and re-myelination, promising motor function recovery in vivo was achieved by RGD@ASFFs, which is comparable to that of autografts. Thus, the design of this engineered bionic scaffold is a powerful strategy for peripheral nerve defect repair.