Preparation Of Two-Dimensional Metal Organic Frameworks Composites And Application For Infected Wound

Persistent bacterial infection of wounds can result in chronic wounds that are difficult to heal.Antibiotics in combination with various dressings are the mainstay of clinical treatment for chronically infected wounds,but antibiotic abuse has led to the emergence of pathogenic bacteria resistance and superbugs,posing a more serious threat to human health.Therefore,the construction of multifunctional dressing materials with good antimicrobial properties and the ability to promote wound healing is essential to meet the needs of wound care.Two-dimensional metal-organic frameworks（2D MOFs）are emerging nano-functional materials with multiple enzymatic activities,tunable compositions,easily modified surfaces,and remarkable antibacterial effects,making them excellent antibacterial material and drug carrier platforms.However,the harsh synthesis conditions and low yield of 2D MOFs greatly limit their practical applications.Based on this,this paper focuses on the preparation of 2D MOFs and their biomedical applications,designs and simplifies the synthesis on a large scale of 2D MOFs pure materials with a high-quality catalytic system,and constructs2D MOFs composites with antibacterial,anti-inflammatory,and antioxidant"one stone three birds"composite system for improving the healing effect of infected wounds.We investigated the possibility and clinical application of 2D MOFs composites as a new antimicrobial dressing for infected wounds.The research content and results are as follows.1.Preparation of two-dimensional metal-organic framework pure materials and their enzymatic catalysis for antibacterial propertiesTo solve the problems caused by"superbugs",the improvement of antimicrobial properties for clinical wound dressing materials is urgent.We used a biomimetic strategy to enhance the peroxide-like catalytic activity of 2D MOFs to enhance the bactericidal effect of MOFs.In this work,we investigated:a simple one-pot solution phase method and the production of a series of novel 2D MOFs（Ni₂Co₁）_1-xCu_x（x=0,0.1,0.25,0.5）by varying the molar ratio of raw materials in yield;the application of multivariate characterization to determine the sheet-like characteristics of nanomaterials;the application of UV and fluorescence analysis to analyze The peroxidase-like（POD-like）activity of（Ni₂Co₁）_1-xCu_x catalyzed the production of·OH from H₂O₂.Differences in the POD-like activity of the synthesized 2D MOFs with different molar ratios were found,while（Ni₂Co₁）_0.5Cu_0.5 exhibited more prominent POD-like activity.In vitro antibacterial experiments were conducted by constructing Escherichia coli and methicillin-resistant Staphylococcus aureus（MRSA）pathogen models.Due to the better POD-like activity of（Ni₂Co₁）_0.5Cu_0.5,they can catalyze exogenous H₂O₂ to produce·OH to achieve efficient and sustained bacterial killing in the presence of exogenous H₂O₂.In this study,we designed 2D MOFs pure materials with a high-quality catalytic system for simple large-scale synthesis and screened（Ni₂Co₁）_0.5Cu_0.5 with high-quality POD-like activity for practical antibacterial applications.This provides a basis for further application of the antimicrobial properties of 2D MOFs’pure materials in infectious wound healing.2.Preparation of multifunctional two-dimensional metal-organic framework composites and application in infected wound healingBased on the previous chapter,（Ni₂Co₁）_0.5Cu_0.5 can catalyze exogenous H₂O₂ to generate·OH and has a higher antibacterial ability.But the（Ni₂Co₁）_0.5Cu_0.5 pure material has a single enzymatic activity and requires the participation of exogenous H₂O₂ for sterilization,which leads to cumbersome operation.The design of metal-organic framework materials with safe and efficient H₂O₂ self-supply capacity remains a huge challenge.Inspired by the dynamic balance between H₂O₂ production and clearance in infected wound cells,we designed a multifunctional hybrid nanocomposite to supply endogenous H₂O₂.In our design,the hybrid composite was prepared by physically adsorbing superoxide dismutase（SOD）after in-situ reduction of Au by（Ni₂Co₁）_0.5Cu_0.5 and covalently binding G-quadruplex/hemim DNAzyme.On the one hand,the composites with SOD activity can convert superoxide anions into oxygen and H₂O₂,promoting antioxidant and H₂O₂production.Meanwhile,the covalent binding of G-quadruplex/hemin DNAzyme leads to the enhanced POD-like catalytic activity of the composite,and the glutathione-like activity of the composite can deplete glutathione,weakening the conversion of·OH to downstream.The intracellular H₂O₂ level is increased by promoting the production of H₂O₂,which ultimately enhances the POD-like mediated·OH bactericidal effect.MRSA and P.aeruginosa as model strains were used as model strains to verify that the hybrid composite had the excellent continuous bactericidal ability.On the other hand,an in vitro inflammatory model of macrophages induced by lipopolysaccharide（LPS）was established.The results showed the content of inflammatory factors in the cell supernatant treated with LPS and composites was significantly reduced,proving the excellent anti-inflammatory ability for the 2D MOF composites.The ability of SOD of the composites to scavenge superoxide anion provides sufficient oxygen and endogenous H₂O₂ for wound healing,which avoids the use of exogenous H₂O₂.The enzyme-linked level reaction demonstrates the ability of efficient antimicrobial,anti-inflammatory,and antioxidant"one stone three birds"and good biosafety in infected wound treatment.The work in this chapter not only designs metal-organic framework composites with H₂O₂ supply capacity,but also provides a new strategy for the"one stone three birds"of antimicrobial,anti-inflammatory,and antioxidant in nursing dressings to promote wound healing.