Study On Preparation And Properties Of Antibacterial PMMA Bone Cement Based On Methacrylate Monomers Containing Aromatic Heterocycles

PMMA bone cement is one kind of room-temperature self-cured material that plays an important role in orthopedic surgery such as total hip arthroplasty(THA).Surgical infection usually leads to failure of the surgery in such an open surgery,and antibiotic-loaded PMMA bone cement is used for preventing and treating post-surgical infection in clinic.However,antibiotic-loaded PMMA bone cement has some disadvantages such as“burst effect”and long-term release of low concentration of antibiotics.Therefore,there is an urgent need for the development of non-antibiotic-loaded acrylic PMMA bone cement.Amid antibacterial agents,reactive antibacterial agents could covalently graft antibacterial groups into polymeric backbone of PMMA bone cement and have been expected as an ideal antibacterial agent to avoid the drawbacks of antibiotics and other kinds of antibacterial agents.In this thesis,two types of novel methacrylate monomers containing structure of imidazolium salts and benzothiazole were synthesized according to design,and incorporated into PMMA bone cement to prepare PMMA bone cement with long-term antibacterial effect,the results were listed as follows:(1)Seven N-alkyl imidazolium containing mono-methacrylates named MEIM-x(x=6-18)weresynthesizedviathereactionsbetween1-(2-hydroxyethyl)imidazole,2-isocyanatoethylmethacrylate(IEMA),1-bromohexane,1-bromooctane,1-bromodecane,1-bromododecane,1-bromotetradecane,1-bromohexadecane and 1-bromooctadecane.The structures of MEIM-x were confirmed by ~1H-NMR and FT-IR spectra.Antibacterial effect of MEIM-x increased with increasing of N-alkyl chain length at first,after reaching a certain length,the antibacterial effect started to decrease with further increasing of chain length.In all of MEIM-x,MEIM-14 showed the strongest antibacterial effect,whose minimum inhibitory concentrations(MIC)were 8μg/m L and 2μg/m L against E.coli and S.aureus,respectively.Hemolytic effect of MEIM-x increased with the increasing of its N-alkyl chain length,and the MEIM-x with N-alkyl chain length shorter or equal to decane showed relative lower hemolysis(HC50>250μg/m L).(2)A mono-methacrylate with benzothiazole structure named BTTMA was synthesized via the reaction between 2-(2-benzothiazolylthio)ethanol and IEMA.The structure of BTTMA was confirmed by ~1H-NMR and FT-IR spectra.The BTTMA was non-water-soluble and its suspension of 8192μg/m L showed no antibacterial effect.Hemolytic effect of BTTMA suspension of 1000μg/m L was not significantly different from the negative control,which suggested that BTTMA has no hemolysis.(3)With the increasing of alkyl chain length in MEIM-x’s structure,PMMA bone cements containing MEIM-x’doughing time increase initially,then decreased,and slight increased finally.All of the PMMA bone cements contained MEIM-x with alkyl chain longer than decane had less doughing time than control,and the doughing time decreased with the increase of MEIM-x’s content.MEIM-x had a delay effect on curing process of PMMA bone cement,which resulted in longer setting time of PMMA bone cements containing MEIM-x as compared with the plain cement,but the extent of delay effect reduced with the increasing of alkyl chain length in MEIM-x’s structure.PMMA bone cements containing MEIM-x had lower maximum temperature than the plain cement,but the temperature increased with the increasing of alkyl chain length in MEIM-x’s structure.PMMA bone cements containing MEIM-x had higher water solubility and water sorption,and the water solubility decreased with the increasing of alkyl chain length in MEIM-x’s structure.With increasing of MEIM-x content,the mechanical properties of PMMA bone cements containing MEIM-x were impaired.When content of MEIM-x reached 5%,the mechanical properties of PMMA bone cements became significant lower than control,but roughly enhanced with increasing of the length of alkyl chain in MEIM-x’s structure.When content of MEIM-x was 2%,the mechanical properties of PMMA bone cements had little difference from the plain cement,which had no impact on its application.(4)The MEIM-x could endow PMMA bone cement with excellent antibacterial effect.Antibacterial efficiency of PMMA bone cements contained MEIM-x increased as the content of MEIM-x increased.With 2%of MEIM-x,antibacterial efficiency of PMMA bone cements increased initially with the increasing of alkyl chain length,and then stablized with further increasing of alkyl chain length in MEIM-x’s structure.PMMA bone cements contained 5%of MEIM-10 and MEIM-12 had antibacterial efficiency over 99.9%against E.coli.PMMA bone cements contained 5%of MEIM-x showed antibacterial efficiency over 95%against S.aureus even after 12 days of water extraction,showing an excellent long-term antibacterial effect.PMMA bone cements containing MEIM-x’hemolysis rised with the increasing of MEIM-x’s content.The PMMA bone cements with 2%of MEIM-x had hemolysis rate lower than 5%,fullfilling the requirement of related standard.PMMA bone cements containing MEIM-x showed no obvious cytotoxicity to rat bone marrow mesenchymal stem cells(BMSC).(5)With the increasing of BTTMA content,BTTMA-containing PMMA bone cements’doughing time increased initially and then slightly decreased,and the setting time,maximum temperature,water solubility and water sorption were all reduced.The BTTMA-containing PMMA bone cements’compressive strength and flexural modulus enhanced drastically when BTTMA content rised,but flexural strength decreased dramaticlly after an initial increase,exhibiting the characteristics of brittle materials.(6)BTTMA-containing PMMA bone cements showed antibacterial effect against S.aureus,and antibacterial efficiency of PMMA bone cement contained 15%of BTTMA was 54%,but no antibacterial effect against E.coli could be observed.BTTMA-containing PMMA bone cements showed no hemolysis and no cytotoxicity to BMSC,which suggested that they had excellent biocompatibility.