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

Abstract

Electroconductive biomaterials (ECBs) recreate the bioelectrical microenvironment of nerve tissue, facilitating action potential propagation and enhancing regeneration via electrical stimulation (ES). We report a pseudocapacitive ECB with high conductivity, charge density, and low impedance, combining mixed electronic-ionic transport with reversible redox activity to deliver stable ES without electrode degradation. The scaffold comprises aligned microfibrous polypyrrole (PPy) and Bombyx mori silk fibroin (BmSF), functionalized with Antheraea assamensis silk fibroin (AaSF) rich in RGD motifs. Anionic AaSF acts as a secondary dopant for PPy, improving electrical conductivity (∼9.18 mS cm−1) and charge-transfer efficiency (∼24 Ω), while increasing charge injection at low potentials (∼0.5 µC cm−2 at 50 mV) beyond conventional bioelectrodes. Under pulsed ES at 50 mV cm−1, primary dorsal root ganglion neurons extended neurites up to 830 µm in 7 days. Excessive current or voltage reduced outgrowth, underscoring the importance of ES optimization. Biocompatibility tests showed AaSF functionalization enhanced cell adhesion, reduced pro-inflammatory responses, and promoted neuronal and glial differentiation of primary adipose-derived mesenchymal stem cells via improved intercellular communication. This work links scaffold electrochemical properties to neuronal outcomes, providing a framework for selecting ES parameters in excitable tissues. The developed biohybrid scaffold offers a promising platform for next-generation nerve guidance conduits in regenerative therapies.