Sprayable thermosensitive in-situ gels loaded with apoptotic body-integrated nanozymes for improved diabetic wound healing

Serious vascular dysfunction and recurrent bacterial infection are critical obstacles in diabetic wound healing. Developing novel therapeutic strategies is crucial to address these challenges. Endothelial cell-derived apoptotic bodies (H-Abs), a novel type of extracellular vesicles with anti-inflammation and pro-angiogenesis properties, show great potential for diabetic wound treatment. Herein, a sprayable and thermosensitive in-situ forming composite gel based on poloxamer 407 (P407) was fabricated for the delivery of H-Abs camouflaged manganese dioxide nanozymes (BM), termed BM@H-Abs/TSCG-P407. In vitro and in vivo studies demonstrated that BM@H-Abs/TSCG-P407 undergoes a rapid sol-to-gel transformation in response to wound temperature during spraying treatment, thereby effectively covering irregularly shaped wounds. The incorporated H-Abs-camouflaged BM (BM@H-Abs) can effectively accelerate endothelial cell proliferation and migration, normalize oxygen supply, scavenge reactive oxygen species (ROS) accumulation, inhibit bacterial growth, and eventually enhance the healing of infected wounds in diabetic mice. These results indicate that BM@H-Abs/TSCG-P407 is a promising candidate for the treatment of diabetic wounds.