Targeted Synergistic Antibacterial Based On Silver-based Nanocomposite Biomaterials For Bone Infection Treatment

Bacterial infection is the most common complication after orthopaedic surgery.Antibiotics are currently the most important clinical means of treating bacterial infections.However,the frequent abuse of antibiotics has led to serious bacterial resistance problems and even led to the emergence of"super bacteria".Left unchecked,it can lead to bacterial infections with no medicine available.Therefore,it is of great significance to develop new nanomaterial composite antibacterial agents to supplement or replace the treatment of bacterial infections.Ag NPs have great advantages in the field of antibacterial due to their high specific surface area and chemical activity,as well as broad-spectrum antibacterial and persistent antibacterial properties.The construction of nanocomposite antibacterial materials based on Ag NPs,synergistic immunomodulators,chemodynamic therapy and photothermal therapy and other novel therapeutic methods has good theoretical guidance for the treatment of bacterial infections in vivo.In addition,in order to enhance the enrichment ability of the material on the surface of bacteria,the surface of the material is modified by the bacterial target head to obtain the targeting ability and improve the antibacterial properties of the nanomaterial.Based on this,two antibacterial nanocomposite biomaterials with bacterial targeting synergy were designed for the treatment of bacterial infection in bone tissue.The main contents are as follows:(1)Ag NPs around 50 nm were synthesized by a solvothermal method,and further coated with mesoporous Si O₂ by a sol-gel method.After surface modification,the bacterial target head(UBI_29-41)was grafted,and the immunomodulatory drug oligomycin-A(Oli)was loaded into the mesoporous pores to achieve the targeted synergy between Ag NPs and Oli.The material is denoted as Oli@Ag@m Si O₂-U.Experiments show that Ag@m Si O₂-U(specific surface area of 221.86 m~2/g and pore volume of 0.58 cm~3/g)has a large load space.The Oli loading rate was about 2.67%,and the release rate reached 34%within 2 h,showing a good release effect.In vitro biological experiments show that Oli@Ag@m Si O₂-U nanocomposites have good biocompatibility,can be targeted to the surface of Staphylococcus aureus,and exhibit great in vitro antibacterial properties(minimum inhibitory concentration of 60?g/m L).(2)Fe₃O₄ nanoparticles with a size of about 150 nm were synthesized by a solvothermal method,and then coated with a polydopamine layer and loaded with Ag NPs in an alkaline Tris buffer system.Finally,after grafting the bacterial target head(UBI_29-41),Fe₃O₄@PDA-Ag/U(Ag content about 32.54 wt%)was obtained.The Fe₃O₄@PDA-Ag/U has a great photothermal conversion effect(Under 1 w/cm~2 808 nm near-infrared light,the temperature can reach 51.7°C)and can significantly release ROS.Also,the Ag⁺release rate reaches 9.4%within 7 days,showing the multi-mode synergistic antibacterial ability of chemodynamic-photothermal-Ag.In vitro biological experiments show that low concentration Fe₃O₄@PDA-Ag/U has great biocompatibility and low cytotoxicity,and can effectively target the bacterial surface.In addition,Fe₃O₄@PDA-Ag/U has excellent antibacterial properties in the bone tissue microenvironment(minimum inhibitory concentration of 8?g/m L),and at the same time,it can significantly destroy the biofilm structure and inhibits the reproduction of resistant bacteria within 12 h.bacterial growth.Therefore,Fe₃O₄@PDA-Ag/U as a multi-modal targeted synergistic nano-antibacterial material,can avoid the abuse of antibiotics and the reproduction of drug-resistant bacteria,and has broad application prospects in the field of bacterial infection of bone tissue.