Electroresponsive Hydrogel for Wound Healing with Real-Time Monitoring of Bacterial NADH To Prevent Infection

Stimuli-responsive hydrogels represent an important class of materials for biomedical applications. Electroresponsive hyaluronic acid (HA) hydrogels synthesized via a click-reaction between thiol-functionalized HA and semi-interpenetrated with poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-MeOH), which are denoted as clickHA/PEDOT-MeOH, were found to promote cell migration upon electrostimulation and to exhibit very promising wound healing activity. In this work, we focus on the electrochemical response of clickHA/PEDOT-MeOH hydrogels by analyzing the electrochemical stability, the internal structure of the semi-interpenetrated material, and the capacity to act as electrochemical sensors. After demonstrating the remarkable electrochemical stability of clickHA/PEDOT-MeOH using cyclic voltammetry, the influence of the semi-interpenetrated PEDOT-MeOH chains on the structure of the hydrogel matrix and the interactions connecting both components are studied using molecular dynamics (MD) simulations. The results reveal that the accommodation of PEDOT-MeOH chains after the polymerization of the EDOT-MeOH monomers caused only minor modifications in the pore architecture. Finally, the selective electrochemical detection of nicotinamide adenine dinucleotide (NADH), a biomarker used to identify bacterial infection, was demonstrated both in laboratory-prepared solutions and in vitro using bacterial culture media. Overall, our findings indicate that the semi-interpenetrated clickHA/PEDOT-MeOH hydrogel behaves as a bifunctional platform capable of simultaneously promoting tissue repair and selectively detecting NADH, thereby enabling the prevention of bacterial infections during the healing process.