Abstract

Along with hypoxia, severe bacterial infection, and abnormal pH, continuous inflammatory response hinders diabetic wounds from healing. It leads to the accumulation of large amounts of reactive oxygen species (ROS) and therefore prevents the transition of diabetic wounds from the inflammatory phase to the proliferative phase. In this work, a nanohybrid double network hydrogel with injectable, self-healing, and tissue adhesion properties based on a platinum nanozyme composite (PFOB@PLGA@Pt) was constructed to manage diabetic wound healing. PFOB@PLGA@Pt exhibited oxygen supply capacity and enzyme catalytic performance accompanied by pH self-regulation in the entire phases of wound healing. In the first stage, the oxygen carried by perfluorooctyl bromide (PFOB) can ameliorate the hypoxia and boost the glucose oxidase-like catalyzed reaction of Pt NPs, leading to a lowered pH environment with gluconic acid. As a result, the NADH oxidase-like, peroxidase-like, and oxidase-like multiple enzyme activities were activated successively, leading to synergistic antibacterial effects through the production of ROS. After the bacterial infection had cleared, the catalase-like and superoxide dismutase-like activities of Pt NPs reshaped the redox microenvironment by scavenging the excess ROS, which transitioned the wound from the inflammatory phase to the proliferative phase. The microenvironmentally adaptive hydrogel treatment can cover all phases of wound healing, showing the significant promoting effect in the repair of diabetic infected wounds.

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