Cascaded, self-decomposing messenger in MXene@Cu-MOF heterostructures for on-demand infection control and pro-angiogenic wound repair

Infected diabetic wounds are sustained by excessive reactive oxygen species (ROS), persistent bacteria, and poor angiogenesis. We present a hydrogel-encapsulated MXene@Cu-MOF platform made by in-situ growth of copper metal-organic framework (Cu-MOF) nanocrystals on Ti₃C₂T_x MXene sheets, forming a unified 2D/3D heterostructure. MXene provides ROS modulation and efficient photothermal conversion; the Cu-MOF acts as a degradable "functional backpack" that releases a self-decomposing messenger (Cu²⁺) in response to acidic microenvironments and near-infrared (NIR) irradiation. The interface suppresses MXene restacking, ensures uniform MOF dispersion, and converts photothermal input into gated ionic output. The platform scavenged multiple radicals, lowered intracellular ROS in macrophages, and showed robust, cyclable photothermal heating with NIR-amplified Cu²⁺ release in dispersion and GelMA hydrogels. Under NIR, it achieved broad antibacterial activity against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> and promoted endothelial proliferation, migration, tube formation, and up-regulation of VEGF, eNOS, HIF-1α, and FGF2. In a bacteria-infected diabetic wound model, MXene@Cu-MOF/GelMA accelerated closure, enhanced re-epithelialization, increased collagen deposition with maturation from collagen III to I, reduced tissue oxidative stress, shifted macrophages toward a CD206-positive reparative phenotype, and increased CD31-positive microvessels. Day-14 RNA-seq revealed enrichment of antibacterial defense, tightly regulated inflammatory programs, angiogenesis, and antioxidant pathways. This interface-engineered dressing delivers cascaded, on-demand therapy in which photothermal energy actively gates therapeutic ion generation, unifying infection control and vascularized regeneration in a single platform.