Effect of Electrical and Electromechanical Stimulation on PC12 Cell Proliferation and Axon Outgrowth

This study developed stretchable, biocompatible AgNWs/PDMS electrodes to evaluate how electrical stimulation and combined electromechanical stimulation regulate PC12 neuron-like cell proliferation and axon outgrowth relevant to peripheral nerve regeneration. AgNWs were encapsulated within PDMS to maintain conductivity while minimizing direct Ag exposure, and electrode resistance stability was characterized during repeated stretch–relax cycles. Under electrical stimulation alone (square wave, 20 Hz; 60–240 mV; 4 h/day), PC12 proliferation increased with voltage intensity and axon length increased versus unstimulated controls. Under electromechanical stimulation (electrical stimulation combined with cyclic tensile stretch), proliferation and axon outgrowth remained enhanced versus controls but were reduced relative to higher-intensity electrical-only conditions, consistent with stretch-induced resistance changes. Notably, electromechanical stimulation introduced strong directional guidance: axons preferentially aligned perpendicular to the stretch direction, indicating that mechanical cues can dominate neurite orientation even in the presence of an applied electric field.