Regenerating injured nerves is difficult because they have little spontaneous regeneration potential. Advances in tissue engineering and regenerative medicine have emphasized the possibility of biomaterial-based methods for nerve healing. Natural protein-based biomaterials have benefits over synthetic ones, such as biocompatibility, non-immunogenicity, and biodegradability. Silk fibroin, generated from mulberry and non-mulberry silkworms, is especially promising because of its abundance, simplicity of processing into nerve-like structures, adjustable biodegradability, and mechanical robustness. Furthermore, non-mulberry silk fibroin contains the cell-affinitive RGD tripeptide, which enhances its ability to repair nerves. Studies using silk fibroin (SF)--based nerve conduits have demonstrated nerve regeneration rates of up to 80–90% compared to autografts, which remain the clinical gold standard. SF conduits exhibit outstanding mechanical properties, with tensile strengths up to 300 MPa and elastic moduli adjustable between kPa-MPa range, which closely mimic the native tissue and ensure durability in dynamic environments. This review explores the diverse types of silkworm silk fibroin (SSF) and their applications in biomaterial-based Peripheral Nerve Repair (PNR). It discusses the integration of SSF with other biopolymers and synthetic polymers, highlighting advancements in nerve guidance channels incorporating electro-conductive materials to enhance regeneration rates. The literature search was primarily conducted using the Web of Science database, employing relevant keyword combinations such as “silk fibroin + nerve repair,” “silk fibroin + peripheral nerve repair,” “silk + nerve repair,” and “silk + nerve repair + electrical stimulation.” As this review focuses on silkworm silk-based biomaterials, studies involving spider silk or recombinant silk-based biomaterials were excluded. The period considered began with the earliest relevant studies, with an emphasis on more recent advancements up to November 2024 to capture the latest developments in the field. Identified studies were categorized based on the biomaterial composition, including pure silk biomaterials, silk biopolymer binary composites, silk synthetic binary composites, and silk-hybrid composites. Key findings were synthesized to highlight the progress, challenges, and future directions in applying silk fibroin-based scaffolds and electrical stimulation technologies for nerve repair. The findings provide insights into the potential of SSF-based biomaterials and propose future directions for developing advanced nerve repair strategies.
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