Preparation And Fluoride Release Research Of Hydroxyapatite Carrier Microspheres

Hydroxyapatite(Ca₁₀（PO₄）₆（OH）₂,HA)is the main inorganic component of verte-brate bones and teeth.Due to its excellent biocompatibility,bioactivity,bone conductivity,osteoinductivity and bone formation,it was widely used as an important alternative material in the field of orthopedics and dentistry.Mover,doping HA to improve its structure and function has became a research hotspot in the field of human repair materials because of the different functional requirements and structural peculiarities.It is generally believed that regular 3D porous HA microspheres have large specific surface area,pore volume,uniform pore size and high active adsorption sites,which easily absorbed the organism and released drug molecules in all directions.A lot of researches had been done.Sr was one of the most important trace elements in the human body.It could promote the proliferation of osteoblasts and inhibit the differentiation of osteoclasts.Therefore,it has been widely used in the treatment of osteoporosis.F also has an irreplaceable role in trace elements in the human body.It could increase alkaline phosphatase activity,promote bone formation and inhibit bacterial growth,so it was also widely used in the treatment of osteoporosis in humans.However,doping HA with a single Sr or F is difficult to release through the in situ element to meet the treatment requirements.Although there were reports about Sr and F co-doped HA,its research was not perfect,and it was less concerned with the study of morphology and element release by co-doping.Therefore,this article will focus on Sr and F co-doped HA,without any surfactant and organic template,using hydrothermal combination of ion replacement method to regulate the self-assembly process of apatite.Through the control of hydrothermal conditions and homogeneous precipitant,the introduction of strontium substitution ions with structural adjustment function can affect the self-assembly of the crystal to induce the formation of a spherical structure,which can control the long-term and stable release of F element to meet the treatment requirements.It is of great significance to promote the research and development of HA biomaterials.In this paper,Sr-FHA with 3D microsphere structure was successfully prepared using urea to adjust the p H of the reaction systems and provide CO₃^2-.Through the discussion and research of different urea contentes,different reaction temperatures,times and reactant concentrations,and using XRD,SEM,FTIR,BET and TEM to characterize the sample phase composition,crystal structure and micro-morphology.The results showed that when the urea was 0.75 mol/ L,the crystal grows obviously in the direction of（002）,a large number of long flakes were scattered and the balling effect was poor.when the contentes of urea was increased,the size of the crystal increased in the direction of（002）and decreased in the direction of（300）,the amount of spheres also increased in the samples and the microsphere structure was uniform and dense.However,when the urea contentes increases to 1.50 mol/L,the size of the microspheres was uneven and the uniformity was poor.Because the urea would decompose during the reaction to produce CO₃^2- which doped into the HA lattice,it would significantly reduce the crystallinity and structural stability of HA,so that Fcould be slowly released from the 3D microsphere structure and meet the requirement to long-term and stable release for 30 days in the range of 95-190 μg/L.Moreover,the effect of different reactant concentrations on the microspheres was more obvious.When the reaction concentration was low,the reaction rate decreased and the generated grains tended to grow into long flakes,so that it was difficult to self-assemble to form complete microspheres.As the concentration increased,the amount of microspheres increased and the self-assembly effect was significantly improved.However,when the concentration of the reactants was too high,the reactants could not be completely dissolved and the effective concentration and the amount of microspheres would decreased.Therefore,maintaining an appropriate concentration of reactants was necessary for the formation of microspheres and self-assembly.The effects of different contents of Sr and F on the microscopic morphology of HA were also obvious.The amount of porous microspheres formed by a single fluorine doping was small and a large number of long lamellae were scattered.when the Sr2+ /(Sr²⁺+Ca²⁺)molar ratio was 0.01,Sr was doped into FHA and the contentes of microsphere will increased and the sizes of long flake would decrease.When the Sr²⁺/(Sr²⁺+Ca²⁺)molar ratio increased to 0.09,the effect of sphere formation was good and the distribution of microspheres was more uniform.As the Sr content increased,the lattice parameters a and c,the crystallinity,unit cell volume and microscopic strain would increased,but the crystal density and grain size would decreased.On the side,the main crystal phase peak shifted toward a low angle.The refining results showed that with the increase of Sr contents,the occupation rate of Sr to CaⅠ gradually increased and the position of CaⅡ decreases first and then increased.The overall results showed that Sr tend to occupy CaⅡ.When F^-/(Sr²⁺+Ca²⁺)molar ratio was 0.02,it would lead to the generation of CaF₂ heterophase in Sr-FHA,affecting the morphology and structure of the crystal.when the F^-/(Sr²⁺+Ca²⁺)molar ratio increases to 0.07,it would not cause the formation of miscellaneous phases and the ball formation effect was good and it met the requirements of fluoride release well.when the molar ratio of F^-/(Sr²⁺+Ca²⁺)was continued to 0.12,the crystal grew in the（002）direction and the size increased and the effect of ball formation became worse.In addition to this,a large number of long flakes were produced and the phenomenon of agglomeration was serious and the amount of fluorine release was large,which was not suitable as a slow-release material for fluorine in the human body.