Inflammation-responsive DNA hydrogel integrating probiotic outer membrane vesicles for infection monitoring and precision therapy of diabetic wounds
Abstract
Chronic diabetic wounds remain a formidable clinical challenge, largely attributed to persistent inflammation, excessive oxidative stress, and impaired angiogenesis. Current therapeutic approaches rarely integrate real-time infection monitoring with immunomodulation and tissue repair. Herein, we report an inflammation-responsive DNA hydrogel engineered with Lactobacillus reuteri-derived outer membrane vesicles (OMVs) and a self-reporting probe, enabling autonomous infection surveillance and on-demand therapeutic intervention. The hydrogel was constructed by crosslinking Y-shaped DNA motifs with disulfide-bridged linker strands conjugated to indocyanine green (ICG) and black hole quencher 3 (BHQ3), affording reactive oxygen species (ROS)-triggered signal activation and controlled OMV release. Benefiting from the intrinsic antioxidant and anti-apoptotic activities of OMVs, the hydrogel not only promoted keratinocyte migration, angiogenesis, and M2 macrophage polarization in vitro, but also delivered potent antibacterial activity under NIR light through fluorescence-guided photothermal therapy. In diabetic wound models, the system markedly accelerated closure by enhancing collagen deposition, neovascularization, and immune resolution while suppressing pro-inflammatory cytokine expression. Transcriptomic profiling further confirmed activation of regenerative pathways coupled with suppression of inflammatory cascades. Collectively, this multifunctional platform offer a paradigm…
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