Ion-Immobilizing Low-Conductivity Hydrogel Reservoirs for Electrically Gated Anti-Inflammatory Drug Delivery in Diabetic Wounds

Diabetic wounds often remain trapped in a chronic inflammatory state, preventing the transition from inflammation to the proliferative phase of tissue repair. Dexamethasone sodium phosphate (DSP) is a potent anti-inflammatory drug, but its ionic and highly water-soluble nature can lead to rapid passive leakage and increased electrical conductivity when directly incorporated into hydrogel dressings. Here, we propose an ion-immobilizing, low-conductivity hydrogel reservoir for electrically gated anti-inflammatory drug delivery. DSP was sequestered within polyelectrolyte complex domains formed by positively charged HTCC and negatively charged hyaluronic acid (HA), reducing the fraction of mobile drug ions in the hydrogel matrix. These DSP-loaded domains were incorporated into a PVA hydrogel, and perfluorodecalin (PFD) emulsion droplets were introduced to disrupt continuous aqueous pathways for ion transport. This design enables the hydrogel to retain ionic anti-inflammatory drugs while suppressing baseline conductivity and passive diffusion. Under an applied AC electric field, DSP transport can be selectively enhanced, enabling on-demand modulation of inflammatory responses for diabetic wound healing.