Procedural Promotion of Wound Healing by Graphene-Barium Titanate Nanosystem with White Light Irradiation

BACKGROUND: Wound healing is a continuous and complex process that comprises multiple phases including hemostasis, inflammation, multiplication (proliferation) and remodeling. Although a variety of nanomaterials have been developed to control infection and accelerate wound healing, most of them can only promote one phase but not multiple phases, resulting in lower efficient healing. Although various formulations such as nitric oxide releasing wound dressings were developed for dual action, the nanostructure synthesis and the encapsulation process were complex. MATERIALS AND METHODS: Here, we report on the design of graphene-barium titanate nanosystem to procedural promote the wound healing process. The antibacterial effect was assessed in Gram-negative Escherichia coli bacteria (E. coli) and Gram-positive Staphylococcus aureus bacteria (S. aureus), the cell proliferation and migration experiment was investigated in mouse embryonic fibroblast (NIH-3T3) cells, and the wound healing effect was analyzed in female BALB/c mice with infected skin wound on the back. RESULTS: Results showed that graphene-barium titanate nanosystem could generate abundant ROS to kill both E. coli and S. aureus. The growth curves, bacterial viability, colony number formation and scanning electron microscopy (SEM) images of E. coli and S. aureus all confirmed the antibacterial effect. Cell Counting Kit-8 (CCK-8) assay displayed that GBT possesses great biocompatibility. EdU assay showed that GBT plus white light irradiation significantly promoted the proliferation and migration of NIH-3T3 cells. Scratch assay found that GBT could achieve a fast scratch closure compared to the control. In vivo wound healing effect indicates that GBT can accelerate wound repair procedure. CONCLUSION: GBT nanocomposite is capable of programmatically accelerating wound healing through multiple stages, including production of a large amount of ROS after white light exposure to effectively kill E. coli and S. aureus to prevent wound infection and as a scaffold to accelerate fibroblast proliferation and migration to the wound to accelerate wound healing.