Ultrasound-Responsive Iron-Barium Titanate Schottky Heterojunction-Embedded Hydrogel Accelerates Burn Wound Healing through Bidirectional Hydrogen-Piezocatalytic Redox Modulation.

Abstract

Burn wound healing is regulated by a spatiotemporal redox hierarchy, where early reactive oxygen species (ROS) overload drives inflammation, while late ROS deficiency hinders regeneration. Programming this bidirectional sequence requires time-phased, counter-directional ROS control. Herein, we report a nanocomposite hydrogel that integrates hydrogen therapy with piezocatalytic therapy, enabling on-demand redox programming across the entire healing cascade. The system constructs a metal-semiconductor Schottky heterojunction derived from the in situ reduction of Fe2+ within the mesopores of barium titanate. The mesoporous confinement and interfacial coupling program the hydrolysis of nanoscale zero-valent iron for sustained, early-stage hydrogen delivery to scavenge toxic ROS, while the established Schottky barrier efficiently suppresses charge recombination, thereby executing ultrasound-triggered piezoelectric polarization and charge separation for on-demand ROS generation in later-stage pro-regenerative signaling. Embedded within a polyacrylamide/carboxymethyl chitosan double-network hydrogel with inherent antibacterial activity, the resulting system exhibits superior antioxidant capacity and piezocatalytic responsivity, as well as promotion of fibroblast migration, angiogenesis, and M2 macrophage polarization. In a mouse burn model, this redox-programmable platform orchestrates phased healing, attenuating early inflammation, sustaining neovascularization, and suppressing late fibrosis, achieving accelerated wound closure. Collectively, this work establishes a redox programming paradigm via heterojunction catalysis, coupling spatiotemporal ROS scavenging and generation for dynamic tissue regeneration.

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