| Hdroxyapatite(HA),similar to the inorganic components of natural hard tissues,with good biocompatibility and strong bone conduction ability has been widely used as hard tissue damage repair materials.However,there are some problems in the application of HA materials,such as,HA has a certain degree of solubility in body fluids,thus HA coating will be partially dissolved in the body after a period of implantation,resulting in the failure of bone integration;moreover the antibacterial activity of HA is poor,which may cause infection,implants loose and other issues.In order to prepare a hard tissue implant material having both biological activity and antibacterial property,we have investigated the effect of trace elements in natural hard tissues on their crystal structure,biological activity and antibacterial activity to better understand the effects of trace elements on the multi-ordered structure and superior biological properties of hard tissues.The main results achieved in this research are summarized as follows:1.The effect of trace fluorine on the phase transition of fluorine-substituted hydroxyapatite(FHA)from the precursor during the formation process.Pure FHA nanocrystal aggregates with hierarchical structure were synthesized by a simple onepot hydrothermal method.The role of F in FHA phase transition was analyzed by observing the structural and topographical changes during the formation of FHA.Compared with the formation of HA,fluorine caused remarkable differences in the crystallographic orientation from DCPA to FHA.Combine with the HRTEM results and the crystal structure model of DCPA and FHA,the crystallographic relationship was found to be FHA[010]∥DCPA[001]and FHA(001)∥DCPA(010),and the relationship between the c-axis of DCPA vertical to that of FHA,rather than parallel to the c-axis of HA,which might cause the c-axis oriented hierarchical FHA was formed.This fluorine induced crystal growth mechanism of the c-axis oriented FHA nanocrystals provides us a new perspective into the influence of fluorine on the crystal growth and formation mechanism of FHA.It also provides new insights into the important role of trace fluorine in tooth enamel.2.Trace amounts of fluorine caused active centers such as Ca-defects in FHA crystals and also changed the mophology and surface properties of FHA,giving them good osteoblast activity and antibacterial activity.Trace F-substitued HA(F0.02)was calcium-deficient HA,and the number of defects in its crystal structure was significantly higher than HA and the FHAs with large amount of F.The trace fluorine induced Ca(II)vacancy and lattice defects resulted in the formation of net dipole moments,changes of potential energy levels,and stronger acid sites for the necessary bioactive centers.F0.02 also had a similar aspect ratio to that of natural apatite,as well as a large specific surface area.Therefore,the trace F-doped HA sample F0.02 had better protein adsorption capacity than HA and the samples with higher fluorine content(F1 and F2),and thus significantly promoted the adhesion,proliferation and differentiation activity and the osteogenesis-related gene expressions of osteoblasts on the surface of the material.In addition,trace F increases the lattice energy of HA,lowered the solubility,and reduced the hydrophilicity of the material.Together with the reactive sites formed by Ca defects,the trace F-doped HA showed significant Escherichia coli antibacterial activity.Trace fluorine substituted hydroxyapatite had both excellent osteogenic activity and antibacterial activity,meanwhile no cytotoxicity,making it potentially useful in hard tissue replacement materials.3.Studies on the biological effects of trace F-Sr and trace F-Zn codoped HA.Srdoped HA,Zn-doped HA,F-Sr co-doped HA and F-Zn co-doped HA were prepared by hydrothermal method.It was found that Sr-doped HA not only promoted the adhesion and proliferation of osteoblasts,but also inhibited the growth of tumor cells,which is of great significance to the study of the repairment of bone defects from bone tumors.F-Zn co-doping could increase the doping content of Zn,and thus significantly improved the stability of Zn in the HA crystal lattice.Both the trace F-Sr co-doped HA and the trace F-Zn co-doped HA samples had better protein adsorption and cell vability of osteoblasts than the large amount of elements co-doped HA,and the increase in the doping amount significantly reduced the biological activity of the materials.In addition,trace F-Sr co-doped HA and trace F-Zn co-doped HA had better promotion on the osteoblast adhesion,proliferation and differentiation than single element doped HA.At the same time,the co-doping of trace elements had good antibacterial properties,especially F-Zn co-doped HA,which has significant antibacterial effect on Escherichia coli and Staphylococcus aureus.Therefore,the co-doping of trace elements plays an important role in improving the crystal structure stability,biological activity and antibacterial properties of HA and co-doping with trace elements may help improve the long-term stability of HA implants.4.In vitro and in vivo osteogenic and antibacterial properties of trace F-substituted HA and trace F-Zn co-doped HA vacuum plasma spray coatings.The trace F-substituted and F-Zn co-doped HA coatings all retained the crystal structure after subjecting the high temperature of plasma spraying process.They had more stable structure and higher coating bond strength than HA coating.In addition,the trace element-doped HA coating had better in vitro osteoblasts activity and no hemolysis,which is suitable for further animal experiments.Animal in vivo experiments showed that the trace element-doped HA coating extracts had no organ toxicity to rats and did not affect the normal life activities of rats.At the same time,the trace element doped HA coating implants had good osteogenicity in New Zealand rabbits.And it was found that both coated implants were well-integrated with bone tissue in the presence of S.aureus from the bacterial infection experiments.Moreother the new bone tissue formed on the surface of trace element-doped HA implants were all significantly more than HA,thus the materials had a good antibacterial and osteogenic.Therefore,the trace F-doped HA coating and the trace F-Zn co-doped HA coating would have broad application prospects as bone replacement materials. |
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