As a conductive nanomaterial, graphene has huge potentials in nerve function restoration by promoting electrical signal transduction and metabolic activities with unique topological properties. Polydopamine (PDA) and arginylglycylaspartic acid (RGD) can improve cell adhesion in tissue engineering. Here we report an integrated 3D printing and layer-by-layer casting (LBLC) method in multi-layered porous scaffold fabrication. The scaffold is composed of single-layered graphene (SG) or multi-layered graphene (MG) and polycaprolactone (PCL). The electrically conductive 3D graphene scaffold can significantly improve neural expression both in vitro and in vivo. It promotes successful axonal regrowth and remyelination after peripheral nerve injury. These findings implicate that graphene-based nanotechnology have great potentials in peripheral nerve restoration in preclinical and clinical application.

Treating peripheral nerve injury faces major challenges and may benefit from bioactive scaffolds due to the limited autograft resources. Graphene oxide (GO) has emerged as a promising nanomaterial with excellent physical and chemical properties. GO has functional groups that confer biocompatibility that is better than that of graphene. Here, GO/polycaprolactone (PCL) nanoscaffolds are fabricated using an integration molding method. The nanoscaffolds exhibit many merits, including even GO nanoparticle distribution, macroporous structure, and strong mechanical support. Additionally, the process enables excellent quality control. In vitro studies confirm the advantages of the GO/PCL nanoscaffolds in terms of Schwann cell proliferation, viability, and attachment, as well as neural characteristics maintenance. This is the first study to evaluate the in vivo performance of GO‐based nanoscaffolds in this context. GO release and PCL biodegradation is analyzed after long‐term in vivo study. It is also found that the GO/PCL nerve guidance conduit could successfully repair a 15 mm sciatic nerve defect. The pro‐angiogenic characteristic of GO is evaluated in vivo using immunohistochemistry. In addition, the AKT‐endothelial nitric oxide synthase (eNOS)‐vascular endothelial growth factor (VEGF) signaling pathway might play a major role in the angiogenic process. These findings demonstrate that the GO/PCL nanoscaffold efficiently promotes functional and morphological recovery in peripheral nerve regeneration, indicating its promise for tissue engineering applications.

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