| In bone repair surgery,the two main factors leading to the failure of the operation are:poor osteogenic activity of the materials and bacterial infection.Poor bone-promoting of the material leads to prolonged treatment cycle,which will not only increase the mental and economic burden of patients,but also increase the risk of bacterial infection.Bone repair surgery itself is prone to bacterial infection,and during surgery,the spread of bacteria into the bloodstream can cause inflammation or more serious conditions.In order to reduce the risk of failure of bone repair surgery,a kind of bifunctional bone repair material is needed,which not only can promote bone well,but also has the ability to inhibit bacteria during surgery.Hydroxyapatite(HA)occupies an important position in the research field of bone repair materials due to its excellent biocompatibility,bone conductivity and non-toxic effect in vivo,and has a good application prospect in the research field of bone filling materials,bone replacement materials and drug carriers.In this study,the functional element strontium(Sr)was added into mesoporous HA microspheres by hydrothermal method with HA as the base material with good bioactivity and bone inductivity,in order to obtain HA microspheres with good osteogenic activity.Then,strontium-doped HA microspheres with good osteogenic activity were used as the carrier of antibacterial drugs,and berberine hydrochloride,a traditional Chinese medicine antibacterial agent,was loaded into the microspheres to construct bone repair materials with both osteogenic activity and antibacterial effect.In order to provide theoretical basis for the construction of bifunctional materials,osteogenesis and antibacterial experiments were combined in vitro.The main contents of this study are as follows:(1)HA microspheres and Strontium-doped HA microspheres with Sr doping concentrations of 1%,3%,5%and 7%were prepared by hydrothermal method.X-ray diffraction(XRD)and Fourier transform infrared spectroscopy(FT-IR)showed that the incorporation of Sr ions did not produce new phases and functional groups.Scanning electron microscopy(SEM)and transmission electron microscopy(TEM)images showed that the incorporation of Sr ions had no significant effect on the microstructure and particle size of microspheres in a certain doping concentration range.Scanning electron microscope energy dispersive spectroscopy(EDS)showed that the elements of microspheres prepared by hydrothermal method were complete and evenly distributed.Nitrogen adsorption and desorption tests verified that the microspheres had a mesoporous structure and a high specific surface area between 49 m~2/g and 55 m~2/g.Ion dissolution experiments showed a positive correlation between Sr ion doping concentration and Sr release rate.The higher Sr doping concentration increased Sr release rate of Sr doped HA microspheres.(2)Mouse bone marrow mesenchymal stem cells(r BMSCs)were used as seed cells,and cell proliferation experiments were conducted to explore the cytotoxicity of the materials by co-culture with each group of microspheres.Combined with in vitro osteogenic experiments(including alkaline phosphatase(ALP)activity test and calcified nodule staining),the doping group with the best osteogenic activity was selected,and the experimental group with 3%doping amount(HA-3Sr)showed the best osteogenic activity.(3)The drug loading model was constructed by loading berberine hydrochloride with HA-3Sr microspheres with the best osteogenic activity.The successful construction of drug loaded microspheres and the drug loading capacity of the microspheres were verified by a series of characterization,and the sustained-release capacity and antibacterial capacity of the model were further explored by sustained-release and antibacterial experiments.The results showed that HA-3Sr+BBH had good sustained-release effect and excellent antibacterial performance. |
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