Electrical stimulation alters protein adsorption and nerve cell interactions with electrically conducting biomaterials

Electrical charges have been shown to enhance nerve regeneration; however, the mechanisms for this effect are unclear. One hypothesis is that an electrical stimulus alters the local electrical fields of extracellular matrix molecules, changing protein adsorption. We have investigated this hypothesis — that electrical stimulation increases the adsorption of serum proteins, specifically fibronectin (FN), to the electrically conducting polymer polypyrrole (PP), thereby, increasing neurite extension. PP was used because electrical stimulation of PP has been shown to significantly enhance neurite outgrowth, and more importantly, PP can be formed into conduits to guide nerve regeneration in vivo. Here, we looked at the effects of electrical stimulation on protein adsorption when an electrical current was applied to PP (1) during protein adsorption (immediate stimulation) and (2) several hours after protein adsorption (delayed stimulation). We found that immediate stimulation of PP increases FN adsorption from purified FN and serum-containing solutions. Correspondingly, PC-12 cells grown on PP films that had been previously adsorbed with FN during immediate stimulation expressed longer neurites. However, for delayed stimulation, no significant differences in adsorption or neurite outgrowth were observed. These studies suggest that increased FN adsorption with immediate electrical stimulation may explain enhanced neurite extension on electrically stimulated PP.