ApoEVs@FeSe2-RGD nanorods accelerate full-thickness wound healing by suppressing NF-κB and promoting angiogenesis.

Acute wound healing faces significant challenges, including excessive oxidative stress, persistent inflammation, and disrupted angiogenesis, often leading to delayed healing and scarring. Current treatments frequently fall short in simultaneously addressing these complex issues. This study explores a novel biomimetic platform combining the robust reactive oxygen species (ROS)-scavenging capacity of FeSe2 nanorods with the biocompatibility and targeted delivery of mesenchymal stem cell-derived apoptotic extracellular vesicles (ApoEVs) functionalized with cyclic RGD (cRGD) peptides, aiming for a synergistic redox-immune regulation.

Researchers developed a biomimetic hybrid platform, ApoEVs@FeSe2-RGD, by anchoring redox-active FeSe2 nanorods onto ApoEVs, then functionalizing the surface with cRGD peptides. In vitro, they assessed the platform's ability to clear abnormally produced ROS, inhibit pro-inflammatory activation, and drive macrophage polarization. They also evaluated the impact of reprogrammed macrophage-derived cytokines on endothelial cell migration, proliferation, and angiogenic capacity. In vivo, a full-thickness wound healing model was used to demonstrate enhanced wound closure, re-epithelialization, collagen deposition, and neovascularization. Mechanistic insights were gained through transcriptomic profiling and protein validation.

The ApoEVs@FeSe2-RGD platform effectively cleared abnormally produced ROS in vitro, recalibrating the oxidative microenvironment. This led to inhibited pro-inflammatory activation and successfully drove macrophage polarization toward an anti-inflammatory phenotype. The reparative cytokines from these reprogrammed macrophages significantly enhanced the migration, proliferation, and angiogenic capacity of endothelial cells. In a full-thickness wound healing model, the vesicle-scaffolded regulator enhanced the wound closure rate and promoted re-epithelialization, collagen deposition, and neovascularization, demonstrating good biosafety. Mechanistically, transcriptomic profiling combined with protein validation confirmed that these therapeutic effects were mediated by the suppression of the NF-κB signaling pathway. This multi-pronged approach suggests a powerful strategy for tissue regeneration.

The platform synergistically restored redox homeostasis and orchestrated immune-vascularization coupling, leading to high-quality tissue regeneration.