Electroresponsive hyaluronic acid click hydrogels for combined antibacterial delivery and wound healing applications

The versatility of electroresponsive hyaluronic acid (HA)-based hydrogels, a promising platforms for wound healing, can be further extended to controlled drug delivery, enabling on-demand release of therapeutic agents. This work reports the development of advanced HA-based electroresponsive hydrogels incorporating electrospun poly(lactic acid) (PLA) fiber mats functionalized with conducting polymers (CPs), such as poly(hydroxymethyl-3,4-ethylenedioxythiophene) and polypyrrole, and loaded with chloramphenicol (CAM). The systems were fabricated through a multi-step approach involving plasma treatment, in situ polymerization of CPs on the fiber mats, and then semi-interpenetration with CP within a click-chemistry crosslinked HA network. The resulting hybrid hydrogels exhibited suitable mechanical properties, swelling behavior, and electrochemical activity, enabling CAM release under both passive and controlled electrically stimulated conditions while maintaining biocompatibility. Electrical stimulation significantly enhanced the initial burst release, while the subsequent release phase showed a sustained profile over an extended period (11 days). The antibacterial activity of the released CAM was confirmed against E. coli and S. aureus using an agar diffusion assay. Although both CPs exhibited comparable CAM release behavior, the polypyrrole-based hydrogel demonstrated superior wound healing performance. Overall, these findings highlight the potential of electroresponsive HA-based composite hydrogels as smart wound dressings capable of controlled and sustained antibiotic delivery.