Biomimetic Silk Fibroin Hydrogel for Enhanced Peripheral Nerve Regeneration: Synergistic Effects of Graphene Oxide and Fibroblast Exosome

Peripheral nerve injury represents a critical clinical challenge. Employing tissue engineering, biomimetic scaffolds mimicking the biophysical and biochemical cues of the native extracellular matrix have shown promise. Specifically, conductive matrices, mirroring neural tissue's electrical properties, hold potential for neural tissue repair. However, the synergistic impact of conductivity and biomolecules on injured peripheral nerves remains unexplored. In this study, conductive hydrogels via a three-step click chemical reaction method, incorporating silk fibroin, graphene oxide, and Polyethylene Glycol Diacrylate is crafted. The inclusion of fibroblast exosomes yielded a synergistic effect, enhancing recovery from peripheral nerve injuries. Graphene oxide heightened the electron transmission capacity of the hydrogels, while fibroblast exosomes endowed them with the ability to modulate cellular behaviors. This resulted in enhanced axon and myelin regeneration. Furthermore, the hydrogel facilitated vascular regeneration during peripheral nerve recovery through the VEGF/NOTCH signaling pathway. Transplanting conductive hydrogel conduits laden with fibroblast exosomes led to substantial functional recovery in a rat sciatic nerve transection model. Consequently, a novel strategy to expedite the intricate repair of peripheral nerve injuries is proposed. The biomimetic silk fibroin hydrogel is endowed with bioactivity and biophysical cues by incorporating fibroblast-derived exosomes and graphene oxide. The hydrogel shows excellent biological effects both in vivo and in vitro. The hydrogel conduit promotes peripheral nerve regeneration in situ through mechanisms such as enhancing Schwann cell myelination, promoting neuronal axon growth, and facilitating endothelial cell vascularization.image