Biomimetic tussah silk conduit containing porous matrix with aligned macrochannels for peripheral nerve repair

Peripheral nerve injuries requiring long-gap repair remain a critical challenge due to the limited efficacy of current nerve guidance conduits (NGCs) in providing directional axon guidance and sustained regenerative support. To address this, we developed a 3D biomimetic NGC utilizing tussah silk nanofibers (TSn) with oriented macrochannels (40.19 ± 7.24 μm and 35.68 ± 8.34 μm in width) and tunable mechanical properties (Young's modulus: 12.74 ± 3.95 kPa to 58.44 ± 3.95 kPa), mimicking native nerve architecture. In vitro studies showed that such biomimetic scaffolds support the adhesion, proliferation, and directional distribution of Schwann cells and PC12 cells along the oriented structure. Furthermore, we evaluated the regenerative potential of TSn-integrated NGCs featuring aligned macrochannels in a rat model of 10 mm sciatic nerve defects. The NGC achieved comparable efficacy to autologous nerve grafts in functional recovery (SFI: -51.76 ± 11.34 vs. -54.99 ± 4.76), attributable to the macrochannels' role in providing contact guidance and support for directional axonal elongation. This newly developed biomimetic TSn-based NGC is a promising candidate for treating peripheral nerve injuries.