Nonmulberry Silk Fibroin Doping Boosts Charge Transfer and Charge Injection in Aligned Polypyrrole-Silk Scaffolds for Low-Voltage Neurostimulation

This study developed aligned microfibrous electroconductive scaffolds for peripheral nerve repair by coating aligned Bombyx mori silk fibroin (BmSF) fiber mats with polypyrrole nanoparticles (PPy) and then functionalizing the surface with Antheraea assamensis silk fibroin (AaSF), a nonmulberry silk rich in RGD motifs. AaSF acted as a bioactive interface and a secondary anionic dopant that increased scaffold conductivity (reported ~9.18 mS cm−1), reduced charge-transfer resistance (reported as low as ~24 Ω in PBS), and increased charge storage capacity and charge/current injection under charge-balanced pulsing. In vitro, AaSF functionalization improved cytocompatibility and reduced macrophage inflammatory responses, enhanced neuronal/glial differentiation of porcine adipose-derived MSCs, and supported robust neurite extension from primary porcine dorsal root ganglion neurons under pulsed electrical stimulation—showing maximal neurite outgrowth at low stimulation amplitude (50 mV cm−1) with longest neurites reported near ~830 µm, while higher amplitudes reduced neurite outgrowth, underscoring the need for safe stimulation windows.