Inflammation-responsive DNA hydrogel integrating probiotic outer membrane vesicles for infection monitoring and precision therapy of diabetic wounds.

The DNA hydrogel was constructed by crosslinking Y-shaped DNA motifs with disulfide-bridged linker strands conjugated to ICG and BHQ3, enabling ROS-triggered fluorescence signal activation and controlled OMV release.

• Disulfide bonds in the linker strands serve as the ROS-responsive element, cleaved by elevated reactive oxygen species in the wound microenvironment
• ICG and BHQ3 are co-conjugated to the linker strands, maintaining fluorescence quenching under normal conditions and activating signal upon ROS-mediated strand cleavage
• The system enables autonomous infection surveillance through self-reporting fluorescence activation
• Controlled release of Lactobacillus reuteri-derived outer membrane vesicles (OMVs) is triggered by the same ROS-responsive mechanism

Lactobacillus reuteri-derived OMVs exhibited intrinsic antioxidant and anti-apoptotic activities that promoted keratinocyte migration and angiogenesis in vitro.

• OMVs were derived from Lactobacillus reuteri, a probiotic organism
• In vitro assays demonstrated promotion of keratinocyte migration
• OMV treatment promoted angiogenesis in vitro
• Anti-apoptotic activity of OMVs was demonstrated in cellular experiments

The hydrogel platform promoted M2 macrophage polarization in vitro, indicating immunomodulatory capability.

• M2 macrophage polarization is associated with anti-inflammatory and pro-healing phenotypes
• This effect was attributed at least in part to the bioactive properties of the Lactobacillus reuteri-derived OMVs
• Macrophage polarization toward M2 was demonstrated in in vitro experimental conditions

The hydrogel system delivered potent antibacterial activity through fluorescence-guided photothermal therapy under NIR light irradiation.

• ICG serves as both the fluorescence reporter and the photothermal agent for NIR-activated antibacterial therapy
• Fluorescence signal activation upon ROS-triggered ICG release from BHQ3 quenching guides photothermal treatment
• Near-infrared (NIR) light was used to activate the photothermal effect for infection control
• The integration of real-time infection monitoring with on-demand photothermal therapy constitutes the precision intervention aspect of the platform

In diabetic wound models, the hydrogel system markedly accelerated wound closure by enhancing collagen deposition, neovascularization, and immune resolution while suppressing pro-inflammatory cytokine expression.

• The study used in vivo diabetic wound models
• Accelerated wound closure was observed compared to controls
• Histological outcomes included enhanced collagen deposition and neovascularization
• Pro-inflammatory cytokine expression was suppressed in treated wounds
• Immune resolution was enhanced, consistent with the M2 macrophage polarization observed in vitro

Transcriptomic profiling confirmed activation of regenerative pathways coupled with suppression of inflammatory cascades in treated diabetic wounds.

• RNA-sequencing or equivalent transcriptomic analysis was performed on wound tissue samples
• Results confirmed upregulation of pathways associated with tissue regeneration
• Simultaneous suppression of inflammatory signaling cascades was confirmed at the transcriptomic level
• Transcriptomic data provided mechanistic support for the observed therapeutic outcomes

Current therapeutic approaches for chronic diabetic wounds rarely integrate real-time infection monitoring with immunomodulation and tissue repair, representing the clinical gap this platform addresses.

• Chronic diabetic wounds are attributed to persistent inflammation, excessive oxidative stress, and impaired angiogenesis
• The authors identified the lack of integrated monitoring and therapy as a key limitation of existing approaches
• The proposed platform combines infection surveillance, immunomodulation, antioxidant activity, and photothermal antibacterial therapy in a single system