Stage-aligned electro-ionic biobattery hydrogel for enhanced wound closure and scar reduction

Abstract

Coupling electrical stimulation (ES) with biochemical signaling is attractive for coordinating multi-stage wound healing, yet existing biobatteries rarely deliver stable microcurrents with stage-aligned chemical therapy in a scalable format. Here, we report a 3D-printed zinc-iron biobattery hydrogel (ZFBH) with a button-cell-inspired architecture, enabling integrated electro-chemo-bio regulation via sustained microcurrents and biodegradation-controlled sequential release of Zn 2+ and Fe 3+ within a self-adhesive hydrogel. The ZFBH amplifies endogenous electrical cues, promoting cell proliferation and migration accompanied by increased TGF-β/Smad3 expression. Concurrently, the sequential ion release modulates the wound microenvironment: Zn 2+ predominates early to attenuate inflammation and promote M2 macrophage polarization during the inflammatory stage, followed by Fe 3+ -associated angiogenesis during the subsequent proliferative stage. This combined biophysical and biochemical stimulation accelerates full-thickness skin wound closure in rats, achieving rapid healing with reduced scarring within 16 days and outperforming a clinically used silicone dressing. Mechanistically, the ZFBH orchestrates stage-aligned repair through integrated electro-chemo-bio cues, offering a compelling strategy for advanced wound care.