On-demand sIPN microneedles promote infected burn wound healing via microenvironment remodeling and activation of the Wnt–KLF5 regenerative axis

Rationale: The healing of severe infected burn wounds is impeded by a vicious cycle of bacterial biofilms, oxidative stress, immune dysregulation, and hypoxia. Existing microneedle (MN) platforms often fail to address these multifactorial barriers due to insufficient mechanical robustness, lengthy fabrication times, and limited therapeutic scope. Our goal was to develop a multifunctional, on-demand MN platform that can simultaneously overcome these challenges by systematically dismantling pathological barriers and activating endogenous regenerative pathways. Methods: , nanoceria (CeO₂) for reactive oxygen species (ROS) scavenging and in-situ oxygen generation, and anthocyanin (An) as an antioxidant and anti-inflammatory agent. The therapeutic efficacy of the MN platform was evaluated in a rat model of MRSA-infected full-thickness burns. Healing was assessed through macroscopic observation, histological analysis, and immunofluorescence staining. The underlying molecular mechanisms were investigated using transcriptomic and protein analyses of wound tissues. Results: The fabricated sIPN MNs exhibited exceptional mechanical strength, rapid fabrication time, and strong tissue adhesion. In the rat model, the MNs effectively dismantled biofilms, reduced oxidative stress, alleviated hypoxia, and shifted the immune balance towards M2 macrophage polarization. This comprehensive microenvironment remodeling led to accelerated wound closure, promoted angiogenesis, and encouraged ordered collagen deposition, resulting in higher-quality tissue regeneration compared to control groups. Transcriptomic and protein analyses revealed that this enhanced healing was driven by the significant activation of the epidermal Wnt/KLF5 signaling axis. Conclusions: Our study presents a mechanistically elucidated, multimodal sIPN MN platform that effectively promotes the healing of infected burn wounds. By remodeling the pathological microenvironment and activating the Wnt/KLF5 regenerative axis, this on-demand platform demonstrates significant potential for clinical translation in the management of complex wounds.