Three-in-One Multifunctional Metal-Organic Gel-Encapsulated Microneedles for Programmed Treatment of Infected Wounds.

Abstract

Refractory wounds caused by multidrug-resistant (MDR) bacterial infections are characterized by biofilm formation, persistent inflammation, and impaired angiogenesis, requiring stage-specific therapeutic strategies. Herein, we propose a three-in-one multifunctional metal-organic gel-encapsulated microneedle (Cu-MOG MN) with integrated antibacterial, anti-inflammatory, and pro-angiogenic capabilities for the programmed treatment of infected wound. Cu-MOG is constructed via facile coordination and self-assembly between naturally antioxidant phytic acid (PA) and essential trace element copper, and exhibits well-defined pH-responsive multienzyme activities. During the early stage of bacterial infection, Cu-MOG activates superoxide dismutase-peroxidase (SOD-POD) cascade to generate localized reactive oxygen species (ROS), enabling efficient bacterial eradication and biofilm disruption. As the wound microenvironment transitions to neutral inflammatory conditions, the catalytic profile shifts to SOD-glutathione peroxidase (GPx) activity, scavenging excess ROS and alleviating oxidative stress. In addition, Cu-MOG exerts potent immunomodulatory effects by promoting macrophage polarization toward the pro-regenerative M2 phenotype, while simultaneously enhancing collagen deposition, angiogenesis, and cell migration to accelerate wound healing. Collectively, the Cu-MOG MN system achieves a comprehensive therapeutic cascade through synergistic deep tissue penetration, pH-responsive antibacterial/anti-inflammatory actions, and pro-regenerative stimulation of collagen deposition/angiogenesis, showing great potential for precise, dynamic and adaptive treatment of refractory wounds.