Natural silk nanofibrils enabled nerve repair grafts

Spinal cord injury repair remains a major challenge in regenerative medicine. However, most existing artificial nerve scaffolds fail to replicate the native nanofibrous architecture and soft mechanics of the spinal extracellular matrix, resulting in limited endogenous neural tissue regeneration. In this paper, natural silk nanofibrils (SNFs) are used as the core building block to preserve silk's intrinsic hierarchical crystalline structure and high specific surface area. Biomimetic porous scaffolds are fabricated via directional freeze-drying, incorporated with hyaluronic acid (HA) and conductive polypyrrole (PPy). The scaffold achieves a specific surface area over 124 m²/g and an elastic modulus of ~4.1 kPa, matching that of native neural tissue, and retains 82% of its initial modulus after 200 compression cycles. In vitro evaluation confirms favorable cytocompatibility, supporting steady adhesion and proliferation of PC12 cells over 7 days of culture. In vivo, the SNF/HA group recovers 20% body weight at day 14 and reaches BBB scores of 8-9 from weeks 3 to 7, significantly promoting axonal regeneration and motor recovery, while PPy-induced inflammation attenuates the conductive benefit. This natural silk-based scaffold offers a new design paradigm for spinal cord injury repair materials and holds promising potential in neural tissue engineering.