A pH-responsive metal-lignin nanozyme microneedle system for stage-adapted therapy of infected skin wounds.

Infected wounds feature a dynamic microenvironment characterized by persistent bacterial infection and excessive reactive oxygen species (ROS), yet existing therapies often lack the ability to dynamically adapt to the evolving wound microenvironment. We developed a microenvironment-responsive microneedle delivery system (RuCe@D-P MNs) integrating a bimetallic lignin nanozyme for spatiotemporally adaptive wound therapy. The optimal RuCe@D-P nanozyme was synthesized by screening lignin-metal assemblies based on assembly yield, particle size, and enzyme-like activities (peroxidase/superoxide dismutase/catalase). This nanozyme was incorporated into a sodium alginate/polyvinylpyrrolidone microneedle array, where spontaneous metal-carboxylate coordination cross-linking significantly enhanced the mechanical strength and puncture integrity of the microneedles. Crucially, the RuCe@D-P MN system exhibited coordinated pH-responsive release and catalytic behaviors: under acidic infection-associated conditions, accelerated release of RuCe@D-P nanozymes, together with their POD-like activity promoted bacterial suppression; as the wound microenvironment evolved toward less acidic, near-neutral, or weakly alkaline conditions during healing, RuCe@D-P release became more sustained, and the dominant enzyme-like activity shifted toward SOD/CAT-like activity, thereby scavenging ROS and modulating the immune microenvironment to support tissue regeneration. This scalable, self-cross-linking microneedle platform provides an adaptive spatiotemporal strategy for managing complex infected wounds.