A photothermally addressable Tomato extracellular vesicle-integrated polypyrrole/gellan gum hydrogel for microenvironmental reprogramming of diabetic wounds.

Chronic diabetic wounds remain difficult to treat because they are characterized by persistent oxidative stress, prolonged inflammation, impaired angiogenesis, and delayed tissue regeneration. Here, we report a smart TEV/PVA-PEI-PPY@GG hydrogel that integrates tomato-derived extracellular vesicles (TEV), a polypyrrole (PPY)-based near-infrared (NIR)-responsive photothermal component, and a gellan gum (GG) matrix for diabetic wound treatment. The engineered platform exhibited favorable colloidal stability, a porous and structurally integrated architecture, tunable mild photothermal responsiveness under 808 nm irradiation, and retained antioxidant activity associated with the vesicular fraction. In vivo, TEV/PVA-PEI-PPY@GG significantly accelerated wound closure, improved epidermal continuity, and enhanced dermal remodeling in streptozotocin-induced diabetic wounds, while showing no obvious histopathological toxicity in major organs. Immunohistochemical and histological analyses revealed altered expression patterns of AHR, TNF-α, CD31, and CD34 in treated tissues, which may contribute to tissue repair, modulation of inflammatory responses, and angiogenic remodeling during wound healing. These changes were associated with improved wound regeneration and restoration of tissue architecture. Overall, this work demonstrates the potential of a plant EV-integrated photothermally responsive hydrogel as a therapeutic strategy for diabetic wound repair and supports the possibility that local microenvironment modulation may contribute to its beneficial effects.