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  • Microenvironment responsive...
    Zhu, Shuangli; Zhao, Bangjiao; Li, Maocai; Wang, Hao; Zhu, Jiayi; Li, Qingtao; Gao, Huichang; Feng, Qi; Cao, Xiaodong

    Bioactive materials, 08/2023, Letnik: 26
    Journal Article

    Bacterial infection, excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer. At present, most of wound repair materials are passive and can't response to the wound microenvironment, resulting in a low utilization of bioactive substances and hence a poor therapeutic effect. Therefore, it's essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality. In this work, metformin-laden CuPDA NPs composite hydrogel (Met@ CuPDA NPs/HG) was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine (Gel-DA), Cu-loaded polydopamine nanoparticles (CuPDA NPs) with hyaluronic acid modified by phenyl boronate acid (HA-PBA), which possessed good injectability, self-healing, adhesive and DPPH scavenging performance. The slow release of metformin was achieved by the interaction with CuPDA NPs, boric groups (B–N coordination) and the constraint of hydrogel network. Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently. Moreover, CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of >95% within 10 min and also the slow release of Cu2+ to protect wound from infection for a long time. Met@ CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu2+. More importantly, Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway. Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria, inhibiting inflammation, improving angiogenesis and accelerating the deposition of ECM and collagen. Therefore, Met@CuPDA NPs/HG had a great application potential for diabetic wound healing. Display omitted •A metformin-laden CuPDA NPs composite hydrogel (Met@ CuPDA NPs/HG) was fabricated.•The hydrogel had a microenvironment response to release metformin intelligently.•The hydrogel eradicated bacteria by photothermal responsiveness and the slow release of Cu2+.•The hydrogel promoted vascularization and decreased the inflammation.•Met@ CuPDA NPs/HG had a significant promotion on diabetic infected wound healing.