Electrospun Membranes Loaded With Liraglutide And Zinc Oxide As A Dressing For Bacterially Infected Wound

As the largest organ in the human body,the skin can usually effectively protect the body from external damage.When the skin is damaged to varying degrees,a wound will be formed and its protective effect on the body will be lost.At the same time,when the wound is serious and infected by pathogens and bacteria,an infected wound will be formed.After the infected wound is infected by bacteria,it is difficult for the body to achieve self-healing function,making healing difficult and even leaving scars.Therefore,it is particularly important to prepare a dressing that can reduce bacterial infection and rapidly repair wounds.The nanofibers membrane prepared by electrospinning technology has high permeability and high moisturizing rate,and the structure of the biomimetic extracellular matrix（ECM）formed by the randomly staggered distribution of nanofibers in the fiber is conducive to promoting the adhesion of cells,accelerate cell proliferation and wound repair.In addition,by loading active substances in nanofibers,it can also play a sustained release effect,avoiding the sudden release effect.Therefore,electrospinning technology was chosen to prepare nanofiber membrane dressings for the repair of infected skin wounds.In this paper,the Poly（L-lactide-co-glycolide）（PLGA）and the denaturation product gelatin（Gel）of collagen,which are safe and approved by the U.S.Food and Drug Administration（FDA）,were selected to prepare nanofiber membranes.Zinc oxide（ZnO）and the protein drug Liraglutide（Lira）were loaded into the nanofiber membrane to prepare a composite nanofiber membrane containing ZnO and Lira,which was named PGZL.Then,the morphology and physicochemical properties of the nanofiber membranes were characterized by scanning electron microscopy,surface element analysis,fourier transform infrared spectroscopy,thermal weight loss,hydrophilicity and hydrophobicity,mechanical properties,and pore size distribution analyzer.Porosity,degradation properties and biocompatibility of each group nanofibrous membranes were also measured.SEM and EDS showed that each group of nanofibers had a smooth surface,no beaded structure,and uniform distribution of Znelements;FTIR results showed that there was no new chemical reaction between the components in the nanofiber membranes,and they could coexist stably;TGA results showed that the addition of nano-ZnO had no significant effect on the thermal stability of the nanofiber membranes;the hydrophilicity experiment showed that the addition of nano-ZnO and Lira can increase the hydrophilicity of the nanofiber membranes;the mechanical properties test showed that the addition of nano-ZnO could reduce the mechanical properties of the nanofiber membranes;pore size test and porosity results showed that the addition of nano-ZnO and Lira has no significant effect on the pore size and porosity of the nanofiber membranes,and the pore size and porosity of each group meet the application requirements of wound dressings.The experimental results of in vitro degradation showed that nano-ZnO would slow down the degradation rate of the nanofiber membranes,while the addition of Lira would accelerate its degradation rate.Human umbilical vein endothelial cells（HUVECs）were co-cultured on the nanofiber membranes,and the cells were observed by microscope.The results showed that the nanofibrous membranes loaded with nano-ZnO and Lira could significantly promote the proliferation of cells,and the cells showed good viability and spindle shape,indicating that the nanofibrous membranes had good biocompatibility.In addition,the antioxidative activity,antibacterial activity,hemocompatibility,coagulation activity,in vitro angiogenesis ability,cell migration ability and infection wound repair ability of the nanofibrous membranes were further evaluated.The antioxidant activity of each group of nanofibrous membranes was evaluated by DPPH method,and the results showed that both nano-ZnO and Lira could significantly improve the antioxidant activity of nanofibrous membranes,and there was a synergistic effect between them,showing superior antioxidant performance;bacterial tests showed that the nanofiber membrane loaded with nano-ZnO and Lira could significantly inhibit the growth of Escherichia coli（E.coli）and Staphylococcus aureus（S.aureus）;by measuring thromboplastin time,prothrombin time and blood coagulation index to evaluate the coagulation ability of the nanofibrous membranes in each group,and the results showed that nano-ZnO and Lira could significantly accelerate the coagulation process of the wound,both showed good blood compatibility.The results of cell scratch experiments showed that the nanofiber membrane loaded with nano-ZnO and Lira could significantly improve the cell migration rate,which was beneficial to cell migration and tissue reconstruction during wound repair.In addition,the nanofibrous membranes loaded with nanoZnO and Lira could significantly promote the tube formation of cells,which is beneficial to the regeneration of wound blood vessels;the bacterial infection wound model showed that the nanofibrous membranes loaded with nano-ZnO and Lira could significantly accelerate the wound healing process.In summary,the composite nanofiber membranes dressing loaded with nano-ZnO and Lira was successfully prepared in this paper.Under the synergistic effect of Lira and ZnO,the nanofibrous membranes could significantly promote the growth and proliferation of HUVECs,showing good cytocompatibility.In addition,the nanofibrous membrane has significant antibacterial properties and hemostatic ability,which could significantly promote the tube formation and migration of cells,and effectively improve the wound healing speed and effect of the infection model in rats.In conclusion,as a new type of dressing,the PLGA/Gel nanofiber membranes dressing loaded with nano-ZnO and Lira has certain application value in the field of wound healing and tissue engineering.