Mulberry-inspired tri-act hydrogel for visual monitoring and enhanced diabetic wound repair

Imbalanced inflammatory response and impaired angiogenesis are significant factors contributing to the non-healing of diabetic wounds. The susceptibility to bacterial infection further complicates the management of diabetic wounds. Here, an innovative “Tri-Act” bilayer hydrogel dressing (AlgHA-MFE/sHA-sEVs^miR) has been developed, which integrates visual monitoring of wound infection, immune regulation, and angiogenesis promotion, aiming to address the complex challenges posed by diabetic infected wounds. Utilizing the pH-responsive color-changing properties of anthocyanin-rich mulberry fruit extract (MFE), the upper layer of the hydrogel is endowed with the capability to visually monitor infections. Additionally, miR-210-3p-engineered small extracellular vesicles (sEVs^miR) are constructed and encapsulated in the lower layer hydrogel composed of Schiff base crosslinked hyaluronic acid (sHA). Regarding the therapeutic aspect, sEVs^miR is released from the hydrogel in a pH-responsive manner, thereby improving its utilization. In diabetic infected wounds, AlgHA-MFE/sHA-sEVs^miR hydrogel exhibits effective hemostasis and antibacterial effects, while alleviating oxidative stress and endoplasmic reticulum stress in the wound area. By enhancing macrophage M2 polarization and angiogenesis, the hydrogel achieves therapeutic efficacy superior to traditional treatments. These results highlight the potential of this “Tri-Act” hydrogel to improve diabetic wound management, providing new insights into the development of novel wound dressings.