Ultrasound-activated piezoionic hydrogel with intrinsic antibacterial activity accelerates infected wound healing via biomimetic electrical signaling

Infected wounds are characterized by a cycle of bacterial colonization and chronic inflammation that severely impairs tissue regeneration. Exogenous electrical stimulation can mimic endogenous bioelectric fields to promote healing, but current approaches rely on bulky power sources or cytotoxic inorganic materials. Here, we engineer an all-organic piezoionic hydrogel utilizing the cationic antimicrobial peptide ε-poly- L -lysine (ε-PLL) as both a bactericidal agent and a mobile ionic charge carrier within a photo-crosslinked Pluronic F127 diacrylate (F127DA) matrix. Upon ultrasound stimulation, this hydrogel generates biomimetic electrical signals of approximately 33 mV and 3 μA, while exhibiting potent broad-spectrum antibacterial activity. In infected full-thickness wounds, ultrasound-activated piezoionic therapy eliminates bacterial burden, accelerates wound closure, and restores skin architecture. Reference based cell-type deconvolution of bulk RNA sequencing data reveals a transition from a neutrophil-dominated inflammatory state to a regenerative progenitor enriched state, with the NF-κB network suppressed through Il1b and Il6 downregulation and angiogenic programs activated through Vegfa and Pecam1 upregulation. This system provides a programmable platform for precision bioelectronic therapy and infectious wound management.