万古霉素阳离子脂质体复合n-hacskgm支架对金黄色葡萄球菌生物膜体外抑制作用研究-inhibitory effect of vancomycin cationic liposome combined with n - hacskgm scaffold on staphylococcus aureus biofilm in vitro.docx

第三军医大学博士学位论文 第三军医大学博士学位论文 PAGE PAGE 3 Nano-hydroxyapatite/chitosan/konjac glucomannan scaffolds loaded with cationic liposomal vancomycin: activity against Staphylococcus aureus biofilms Abstract Osteomyelitis is a persistent type of biofilm infection known to be refractory to surgical interventions and antibiotic therapy. Antibiotic-loaded scaffolds have been effective in the treatment of osteomyelitis. However, in some infections caused by gram-positive cocci biofilms, the effectiveness of antibiotic-loaded scaffolds is limited. Furthermore, high concentrations of some antibiotics at infection sites can delay the healing of fractures by interfering with the proliferation of human osteoblasts and endothelial cells. Therefore, the development of a new strategy for targeting antimicrobial agents for the treatment of bacterial biofilms is necessary. Antibiotic-impregnated liposomes have been shown to reduce the congregation of microorganisms. Furthermore, antibiotic-impregnated liposomes have a strong affinity for biofilms and increase the concentration of antibiotics at the surface of biofilms. Cationic liposomal vancomycin inhibits the formation of Staphylococcus aureus (S. aureus) biofilms more effectively than vancomycin alone at equivalent concentrations. However, the rapid removal of liposomal antibiotics by the reticuloendothelial system of liver Kupffer cells and spleen macrophages limits the use of intravenously injected liposomal drugs. Therefore, incorporating liposomal antibiotics into a suitable scaffold may allow for the selective increase of liposomal antibiotic concentrations at the site of bone infections, allowing more effective treatment of bone infections. A number of studies have focused on the use of scaffolds such as beads, ceramics or bone cement as most of these can carry antibiotics. However, a high temperature and pressure are needed for the preparation of beads or ceramics and organic solvents are used in the preparation of acrylic bon