Multifunctional microneedle patch synergized with electrical stimulation to regulate microenvironment for enhanced healing of infected diabetic wounds

Currently, treatments for infected diabetic wounds remain a significant clinical challenge due to the complex wound microenvironment. Combination therapies, capable of synergizing multiple functions, have demonstrated promise in accelerating infected diabetic wound repair. Here, a novel self-powered multifunctional microneedle patch (termed GDZ@mMNP-PENG) was developed to regulate the microenvironment of infected diabetic wounds. The GDZ@mMNP-PENG combines a self-powered piezoelectric nanogenerator (PENG) with a multifunctional microneedle patch loaded with GA@DFO@ZIF-8 nanoparticles (GDZ@mMNP). The PENG in the system collects and converts biomechanical motion to electrical stimulation (ES) in order to promote neovascularization and collagen deposition in infected diabetic wounds. The GDZ@mMNP continuously releases deferoxamine in response to acidic microenvironment and ES. The incorporation of GA@DFO@ZIF-8 nanoparticles impart the GDZ@mMNP with excellent antibacterial (antibacterial rate exceeded 96 %) and antibiofilm capabilities. Moreover, the GDZ@mMNP with abundant phenolic hydroxyl groups also exhibits excellent tissue adhesion, antioxidant, anti-inflammation, and hemostatic properties. In vitro experiments demonstrate that the GDZ@mMNP-PENG effectively enhances cell proliferation and migration. In vivo assay and proteomic analysis demonstrate that the GDZ@mMNP-PENG can down-regulate Staphylococcus aureus infection and neutrophil extracellular trap formation, as well as up-regulate HIF-1 signaling pathway to synergistically regulate the inflammatory microenvironment and neovascularization in infected wounds, thereby accelerating infected diabetic wound healing. Overall, this study offers a new combination strategy for infected diabetic wound healing.