Objective:To construct a new injectable bone cement material,we use alpha calcium sulphate hemihydrate as the base material,modified its surface by metal-phenolic network and mixed it with natural polymer hyaluronic acid.The new bone cement has good antibacterial,anti-inflammatory and osteogenic effects,and suits the clinical application situation better.We evaluated its potential application in the treatment of orthopaedic diseases.Methods:1.In this study,α-calcium sulphate hemihydrate(α-CSH)was prepared as a base material using an atmospheric salt solution method.We obtained MPN@CSH by modifying tannic acid(TA)and metallic elements(Cu,Fe,Ce)on the surface of α-CSH via metal phenolic network(MPN)in hot water system and ambient anhydrous ethanol system.The MPN@CSH powders prepared under different systems were characterised by SEM,XRD,XPS,FTIR,TGA,ICP,and the better modification route was clarified by comparison.2.In this study,Cu-TA@CSH was used as the solid phase and 1%hyaluronic acid(HA)solution was used as the liquid phase,and they were mixed in proportion to obtain Cu-TA@CS/HA bone cement scaffolds.The Cu-TA@CS/HA cement scaffold was characterised by SEM and XRD.The basic physical properties of the Cu-TA@CS/HA cement scaffold were examined,including setting time,injectability and degradation properties.3.In this study,the antimicrobial properties of Cu-TA@CS/HA cement scaffolds were examined by in vitro microbiological assays,including agar plate diffusion assay and in vitro antibacterial assay;the osteogenic properties of Cu-TA@CS/HA cement scaffolds were examined by in vitro biological assays,including leachate toxicity and proliferation assay(CCK-8 method),ALP staining,alizarin red staining,and RT-PCR for osteogenic genes.4.In this study,the antibacterial and bone repair effects of CuTA@CS/HA cement scaffold were examined in vivo by constructing a rat tibial infection bone defect model.The in vivo antimicrobial performance was measured by tissue culture-agar plate coating,while the bone repair effect was assessed by Micro CT and histological staining of sections.Results1.In this study,α-CSH was prepared by an atmospheric salt solution method and the Cu-TA layer was innovatively modified on its surface by a one-step method using anhydrous ethanol as the solvent,which is a convenient and rapid process.SEM,XPS,FT-IR,results verified that the surface modified layer was continuous and consistent without defects and the metal elements were uniformly distributed,and TGA and ICP confirmed that the TGA and ICP confirmed that the modification efficiency of the Cu-TA film layer was 2.1% after 2 min of reaction,and the Cu content was 2000 ppm.2.In this study,Cu-TA@CSH was combined with HA to construct Cu-TA@CS/HA bone cement.Compared with CS bone cement,the setting time of Cu-TA@CSH/HA bone cement was increased by 3 times and the injectability was increased by 4 times,while the Cu-TA@CS/HA had sufficient mechanical strength.3.Degradation experiments confirmed that the resulting Cu-TA@CSH/HA bone cement has significant bacterial environmental response properties;in vitro microbiological experiments confirmed that the CuTA@CS/HA cement scaffold has good bactericidal properties against Staphylococcus aureus.In vitro cytological experiments demonstrated that the Cu-TA@CS/HA cement scaffold could better promote the growth of MC3T3-E1 cells and promote the expression of their osteogenic genes.4.By constructing a rat tibial infected bone defect model,this study demonstrated that the Cu-TA@CS/HA cement scaffold could play an antibacterial and osteogenic role and repair infected bone defects more effectively compared to the control group.Conclusion:In this study,Cu-TA@CSH was prepared by a one-step process,which was simple and rapid.The Cu-TA@CS/HA cement scaffold obtained by mixing Cu-TA@CSH and 1% HA showed good antibacterial and bone-enhancing properties in both in vitro and in vivo animal experiments,and has great potential for clinical treatment of infected bone defects. |