Unraveling the semi-interpenetration with conducting polymer of electroresponsive click-hydrogels made of hyaluronic acid via molecular dynamics simulations

Electroresponsive hydrogels have been prepared by semi-interpenetrating a hyaluronic acid-based click-hydrogel (clickHA) with different concentrations of poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-MeOH). The morphology of the resulting hydrogels, which showed excellent electrochemical response, consisted in a homogeneous distribution of PEDOT-MeOH nanoparticles decorating the pore well of the honeycomb-like clickHA hydrogel. In order to investigate this particular organization, atomistic molecular dynamics simulations have been conducted on clickHA hydrogels with and without hydroxymethyl-3,4-ethylenedioxythiophene (EDOT-MeOH) monomers. Results have shown that, while EDOT-MeOH molecules do not affect the physical and structural characteristics of clickHA, infiltrated monomers rapidly tend to aggregate inside the hydrogel, forming small clusters stabilized by π-π stacking interactions. These clusters probably act as polymerization nuclei for the formation of PEDOT-MeOH nanoparticles, which explains not only the morphology observed but also the remarkable electrochemical response of clickHA/PEDOT-MeOH hydrogels.