CN114538914A - Zinc-doped calcium phosphate ceramic microsphere with antibacterial function and preparation method thereof - Google Patents
Zinc-doped calcium phosphate ceramic microsphere with antibacterial function and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a zinc-doped calcium phosphate ceramic microsphere with an antibacterial function and a preparation method thereof, belongs to the technical field of biomedical materials, and solves the problem that calcium phosphate ceramic in the prior art has no long-acting antibacterial capacity. The method of the invention mixes zinc into calcium phosphate to form composite microspheres, and obtains the zinc-doped calcium phosphate ceramic particles after high-temperature sintering. The method of the invention realizes the uniform doping of zinc ions in the phosphate ceramic matrix, the zinc ions are gradually released along with the degradation of the phosphate ceramic, and the long-acting antibacterial activity of the calcium phosphate ceramic particles is endowed. The invention unexpectedly discovers that the zinc-doped calcium phosphate ceramic microspheres prepared by the method have better osteoinduction effect.
Description
Technical Field
The invention belongs to the technical field of biomedical materials, and particularly relates to a zinc-doped calcium phosphate ceramic microsphere with an antibacterial function and a preparation method thereof.
Background
Calcium phosphate ceramics are widely applied to clinical bone defect regeneration and repair due to excellent biological characteristics of good biocompatibility, osteoinductivity, osteoconductivity, biodegradability and the like. It has been shown that osteomyelitis caused by clinical trauma, diabetes, etc. can form large bone defects locally after clinical debridement, and is often accompanied by secondary infection. The conventional treatment mode of carrying antibiotics by the bone repair material has the defects of no long-acting antibacterial ability, bacterial resistance, biotoxicity and the like, and often leads to the failure of the postoperative treatment of the osteomyelitis. Therefore, clinical treatment of infectious bone defects requires higher requirements for the antibacterial performance of bone repair materials.
The design of a drug-loaded structure or the doping of an antibacterial agent is a common means for endowing calcium phosphate ceramics with long-acting antibacterial capability, for example, Chinese patent, CN112891622A discloses a porous calcium-magnesium dual-phase ceramic microsphere and a preparation method thereof, and the method can load antibacterial, anti-tumor, anti-osteoporosis or osteogenesis promoting medicines to achieve the slow release effect. However, the defects of bacterial spectrum, drug-resistant bacteria and the like exist in drug treatment, so that the late period of drug treatment fails, and infection or inflammation relapse may be caused. In recent years, zinc has been widely studied and applied as an inorganic antibacterial agent in biomaterials, because it has both high antibacterial activity and excellent cell activity. Current research shows that zinc and its oxides have multiple killing effects on bacterial infection, such as active oxygen mechanism, and reduce the possibility of drug resistance of bacteria (Nano-Micro Letters, (2015)7(3): 219) 242). In addition, zinc can play an important role in bone formation and mineralization by increasing bone mass through The inhibition of osteoclastic bone resorption and promotion of osteoblastic bone formation (The Journal of Nutrition,2000,130(5S supply), 1437S-1446S). However, zinc-doped bioactive materials are currently of less interest for use in anti-infectious bone defect regenerative repair. Therefore, the technical problem to be solved by the calcium phosphate ceramic at present is how to realize effective and uniform doping of zinc ions while ensuring excellent osteoinductive activity of the calcium phosphate ceramic, endow the calcium phosphate ceramic with long-acting antibacterial performance, and meet the clinical requirement on infectious bone defect.
Disclosure of Invention
One of the purposes of the invention is to provide a preparation method of zinc-doped calcium phosphate ceramic microspheres with an antibacterial function, and solve the problem that calcium phosphate ceramic in the prior art has no long-acting antibacterial capability.
The second purpose of the invention is to provide the zinc-doped calcium phosphate ceramic microspheres with antibacterial function prepared by the preparation method.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
according to the preparation method of the zinc-doped calcium phosphate ceramic microspheres with the antibacterial function, zinc is doped into calcium phosphate to form composite microspheres, and the composite microspheres are sintered at high temperature to obtain the zinc-doped calcium phosphate ceramic particles.
In some embodiments of the invention, the method comprises the steps of:
step 1, preparing a zinc salt solution;
step 3, heating the mixed slurry for a certain time, then dropwise adding the heated mixed slurry into the zinc salt solution in the step 1 to form composite microspheres, and standing to form gel until the gel is completely cured;
and 4, taking out the completely solidified composite microspheres, cleaning, drying and sintering at high temperature to obtain the zinc-doped calcium phosphate ceramic microspheres.
In some embodiments of the invention, the zinc salt solution is one of a zinc chloride solution and a zinc nitrate solution;
preferably, the mass concentration of the zinc salt solution is 1-10%.
In some embodiments of the present invention, the zinc salt solution is used in an amount at least to completely submerge the composite microsphere.
In some embodiments of the present invention, the calcium phosphate powder is at least one selected from hydroxyapatite and β -tricalcium phosphate, and the molar ratio of Ca/P is 1.50 to 1.67.
In some embodiments of the present invention, the binder is selected from at least one of polyvinyl alcohol, methyl cellulose and hydroxypropyl methyl cellulose, and preferably, the mass concentration of the binder solution is 1 to 10%.
In some embodiments of the invention, the foaming agent is at least one selected from hydrogen peroxide, sodium dodecyl sulfate and fatty alcohol-polyoxyethylene ether sodium sulfate, and preferably, the mass concentration of the foaming agent solution is 1-30%.
In some embodiments of the present invention, in step 2, the amount of each raw material is: 1 part by mass of calcium phosphate powder, 0.5-5 parts by volume of sodium alginate solution, 0.1-1 part by volume of binder solution, 0.5-5 parts by volume of water and 0.1-1 part by volume of foaming agent solution, wherein when the unit of the part by mass is g, the unit of the part by volume is mL.
In some embodiments of the invention, in the step 4, the composite microspheres are sintered at 900-1200 ℃;
preferably, when the muffle furnace is adopted for sintering, the heating rate is 1-20 ℃/min, and the heat preservation time is 1-5 h;
preferably, when microwave sintering is adopted, the heating rate is 25-400 ℃/min, and the heat preservation time is 1-20 min.
In some embodiments of the invention, in step 3, the mixed slurry is heated at 40-80 ℃ for 5-30min to form a foamed slurry with uniform size and rich bubbles, and then the foamed slurry is added dropwise into the zinc salt solution in step 1.
The zinc-doped calcium phosphate ceramic microspheres with the antibacterial function prepared by the preparation method provided by the invention;
preferably, the zinc-doped calcium phosphate ceramic microspheres have a three-dimensional through porous structure and a regular spherical shape, the porosity is 50% -90%, the particle size is 0.1-5mm, and zinc ions are uniformly distributed, and the mass content is 1-10%.
Compared with the prior art, the invention has the following beneficial effects:
the method has the advantages of scientific design, simple method and simple and convenient operation, realizes the uniform doping of zinc ions in the phosphate ceramic matrix, gradually releases the zinc ions along with the degradation of the phosphate ceramic, endows the calcium phosphate ceramic particles with long-acting antibacterial activity, and meets the dual requirements of clinical infectious bone defects on the bone repair capability and the long-acting antibacterial function of bone materials.
The ceramic particles prepared by the foaming method and the solution-gel method endow the ceramic particles with regular spherical morphology and a penetrating porous structure, and are beneficial to the regeneration and repair of materials induced bones and tissues. The invention belongs to the technical field of biomedical materials, and particularly relates to a zinc-doped calcium phosphate ceramic microsphere with an antibacterial function and a preparation method thereof.
Provides a preparation method of zinc-doped calcium phosphate ceramic microspheres with an antibacterial function, and solves the problem that calcium phosphate ceramic in the prior art has no long-acting antibacterial ability.
The method comprises the steps of doping zinc into calcium phosphate to form composite microspheres, and sintering at high temperature to obtain the zinc-doped calcium phosphate ceramic particles.
By adopting the method, the zinc ions are uniformly doped in the phosphate ceramic matrix, and the zinc ions are gradually released along with the degradation of the phosphate ceramic, so that the long-acting antibacterial activity of the calcium phosphate ceramic particles is endowed, and the dual requirements of clinical infectious bone defect on the bone repair capability and the long-acting antibacterial function of the bone material are met.
Drawings
FIG. 1 is a sectional microscope of the zinc-doped calcium phosphate ceramic microspheres prepared in example 1 of the present invention.
FIG. 2 is an SEM image of zinc-doped calcium phosphate ceramic microspheres prepared in example 2 of the present invention. Three-dimensionally through-going pore structure (2A) and grain size (2B).
Fig. 3 is an EDS spectrum of the zinc-doped calcium phosphate ceramic microspheres prepared in example 4 of the present invention.
FIG. 4 is a schematic diagram showing the result of co-culturing 5D CCK-8 with bone marrow mesenchymal stem cells (BMSCs) using the zinc-doped calcium phosphate ceramic microspheres prepared in example 6 of the present invention.
FIG. 5 is a long-acting antibacterial experiment in vitro of the zinc-doped calcium phosphate ceramic microspheres prepared in example 8 of the present invention
Fig. 6 shows the growth of bacteria in the zinc-doped calcium phosphate ceramic microspheres prepared in example 9 of the present invention after 8 weeks of implantation in animals.
Fig. 7 is a photograph of H & E section staining after 8 weeks of implantation of the zinc-doped calcium phosphate ceramic microspheres prepared in example 9 of the present invention into animals.
Detailed Description
The present invention will be described in further detail with reference to the following examples. It should not be understood that the scope of the above-described subject matter of the present invention is limited to the following examples.
Example 1
The preparation process of the zinc-doped calcium phosphate ceramic microspheres in the embodiment is as follows:
(1) 10g of biphase calcium phosphate powder, 25mL of sodium alginate aqueous solution with the mass concentration of 6%, 2mL of methylcellulose solution with the mass concentration of 6%, 30mL of deionized water and 5mL of hydrogen peroxide with the mass concentration of 25% are uniformly mixed to obtain the calcium phosphate mixed slurry. The biphase calcium phosphate powder is compounded by hydroxyapatite and calcium phosphate, and the Ca/P molar ratio is 1.58;
(2) heating the obtained calcium phosphate mixed slurry at 60 ℃ for 5min to obtain foamed slurry with uniform and rich bubbles;
(3) dripping the obtained foaming slurry into a zinc chloride solution with the mass concentration of 5% to form composite microspheres, and soaking the composite microspheres in the zinc chloride solution until the composite microspheres are completely cured;
(4) taking out the completely cured composite microspheres, cleaning, drying, and sintering by adopting a muffle furnace, wherein the specific sintering conditions are as follows: the sintering temperature is 1100 ℃, the heating rate is 5 ℃/min, the heat preservation time is 2h, and the zinc-doped calcium phosphate ceramic microspheres are obtained by sintering.
The spherical morphology of the zinc-doped calcium phosphate ceramic microspheres prepared in this example is shown in fig. 1.
Example 2
The preparation process of the zinc-doped calcium phosphate ceramic microspheres in the embodiment is as follows:
(1) uniformly mixing 10g of hydroxyapatite powder, 25mL of sodium alginate aqueous solution with the mass concentration of 6%, 2mL of methylcellulose solution with the mass concentration of 6%, 30mL of deionized water and 5mL of hydrogen peroxide with the mass concentration of 20% to obtain the calcium phosphate mixed slurry. The Ca/P molar ratio of the hydroxyapatite powder is 1.61.
(2) And heating the obtained calcium phosphate mixed slurry at 40 ℃ for 20min to form uniform and abundant bubbles in the slurry, thereby obtaining the foaming slurry.
(3) And dripping the obtained foaming slurry into a zinc chloride solution with the mass concentration of 3% to form composite microspheres, and soaking the composite microspheres in the zinc chloride solution until the composite microspheres are completely cured.
(4) Taking out the completely cured composite microspheres, cleaning, drying, and sintering by using microwave, wherein the specific sintering conditions are as follows: sintering at 1050 deg.C, heating at 200 deg.C/min for 10min, and sintering to obtain the final product.
The SEM image of the zinc-doped calcium phosphate ceramic microspheres prepared in this example is shown in figure 2. Three-dimensionally through-going pore structure (2A) and grain size (2B).
Example 3
The preparation process of the zinc-doped calcium phosphate ceramic microspheres in the embodiment is as follows:
(1) uniformly mixing 10g of beta-tricalcium phosphate powder, 25mL of sodium alginate aqueous solution with the mass concentration of 6%, 2mL of polyvinyl alcohol solution with the mass concentration of 3%, 15mL of deionized water and 5mL of hydrogen peroxide with the mass concentration of 20% to obtain the calcium phosphate mixed slurry. The Ca/P molar ratio of the beta-tricalcium phosphate powder is 1.55.
(2) Heating the obtained calcium phosphate mixed slurry at 80 ℃ for 8min to obtain the foaming slurry with uniform size and rich bubbles.
(5) Dripping the obtained foaming slurry into a zinc chloride solution with the mass concentration of 5% to form composite microspheres, and soaking the composite microspheres in the zinc chloride solution until the composite microspheres are completely cured;
(3) taking out the completely cured composite microspheres, cleaning, drying, and sintering by adopting a muffle furnace, wherein the specific sintering conditions are as follows: the sintering temperature is 1100 ℃, the heating rate is 5 ℃/min, the heat preservation time is 2h, and the zinc-doped calcium phosphate ceramic microspheres are obtained by sintering.
Example 4
The preparation process of the zinc-doped calcium phosphate ceramic microspheres in the embodiment is as follows:
(1) 10g of biphase calcium phosphate powder, 25mL of sodium alginate aqueous solution with the mass concentration of 6%, 2mL of methylcellulose solution with the mass concentration of 6%, 30mL of deionized water and 5mL of sodium dodecyl sulfate with the mass concentration of 4% are uniformly mixed to obtain the calcium phosphate mixed slurry. The biphase calcium phosphate powder is compounded by hydroxyapatite and calcium phosphate, and the Ca/P molar ratio is 1.58.
(2) Heating the obtained calcium phosphate mixed slurry at 50 ℃ for 15min to obtain the foaming slurry with uniform size and rich bubbles.
(3) Dripping the obtained foaming slurry into a zinc nitrate solution with the mass concentration of 5% to form composite microspheres, and soaking the composite microspheres in the zinc nitrate solution until the composite microspheres are completely cured;
(4) taking out the completely cured composite microspheres, cleaning, drying, and sintering by adopting a muffle furnace, wherein the specific sintering conditions are as follows: the sintering temperature is 1100 ℃, the heating rate is 10 ℃/min, the heat preservation time is 1h, and the zinc-doped calcium phosphate ceramic microspheres are obtained by sintering.
The EDS spectrum of the zinc-doped calcium phosphate ceramic microspheres prepared in this example is shown in fig. 3.
Example 5
The preparation process of the zinc-doped calcium phosphate ceramic microspheres in the embodiment is as follows:
(1) 10g of biphase calcium phosphate powder, 25mL of 8% sodium alginate aqueous solution, 2mL of 3% hydroxypropyl methyl cellulose solution, 20mL of deionized water and 5mL of 6% sodium dodecyl sulfate solution are uniformly mixed to obtain the calcium phosphate mixed slurry. The biphase calcium phosphate powder is compounded by hydroxyapatite and calcium phosphate, and the Ca/P molar ratio is 1.60.
(2) Heating the obtained calcium phosphate mixed slurry at 80 ℃ for 5min to obtain the foaming slurry with uniform size and rich bubbles.
(3) Dripping the obtained foaming slurry into a zinc nitrate solution with the mass concentration of 3% to form composite microspheres, and soaking the composite microspheres in the zinc nitrate solution until the composite microspheres are completely cured;
(4) taking out the completely cured composite microspheres, cleaning, drying, and sintering by adopting a muffle furnace, wherein the specific sintering conditions are as follows: sintering at 1050 deg.C, heating rate of 10 deg.C/min, and holding for 1h to obtain the final product.
Example 6
The preparation process of the zinc-doped calcium phosphate ceramic microspheres in the embodiment is as follows:
(1) 10g of biphase calcium phosphate powder, 25mL of sodium alginate aqueous solution with the mass concentration of 6%, 2mL of methylcellulose solution with the mass concentration of 6%, 20mL of deionized water and 8mL of hydrogen peroxide solution with the mass concentration of 30% are uniformly mixed to obtain the calcium phosphate mixed slurry. The biphase calcium phosphate powder is compounded by hydroxyapatite and calcium phosphate, and the Ca/P molar ratio is 1.58.
(2) And heating the obtained calcium phosphate mixed slurry at 50 ℃ for 5min to obtain the foaming slurry with uniform size and rich bubbles.
(3) Dripping the obtained foaming slurry into a zinc chloride solution with the mass concentration of 5% to form composite microspheres, and soaking the composite microspheres in the zinc chloride solution until the composite microspheres are completely cured;
(4) taking out the completely cured composite microspheres, cleaning, drying, and sintering by adopting a muffle furnace, wherein the specific sintering conditions are as follows: sintering at 1050 deg.C, heating rate of 3 deg.C/min, and holding for 1h to obtain the final product.
The result of co-culturing 5D CCK-8 by using the prepared zinc-doped calcium phosphate ceramic microspheres and bone marrow mesenchymal stem cells (BMSCs) in this example is shown in the attached FIG. 4.
Example 7
The preparation process of the zinc-doped calcium phosphate ceramic microspheres in the embodiment is as follows:
(1) uniformly mixing 10g of hydroxyapatite powder, 25mL of sodium alginate aqueous solution with the mass concentration of 6%, 2mL of hydroxypropyl methyl cellulose solution with the mass concentration of 3%, 30mL of deionized water and 5mL of sodium dodecyl sulfate solution with the mass concentration of 6% to obtain the calcium phosphate mixed slurry. The Ca/P molar ratio of the hydroxyapatite powder is 1.55.
(2) And heating the obtained calcium phosphate mixed slurry at 70 ℃ for 15min to obtain the foaming slurry with uniform size and rich bubbles.
(3) Dripping the obtained foaming slurry into a zinc chloride solution with the mass concentration of 7% to form composite microspheres, and soaking the composite microspheres in the zinc chloride solution until the composite microspheres are completely cured;
(4) taking out the completely solidified composite microspheres, cleaning, drying, and sintering by adopting a muffle furnace, wherein the specific sintering conditions are as follows: the sintering temperature is 1100 ℃, the heating rate is 5 ℃/min, the heat preservation time is 2h, and the zinc-doped calcium phosphate ceramic microspheres are obtained by sintering.
Example 8
The preparation process of the zinc-doped calcium phosphate ceramic microspheres in the embodiment is as follows:
(1) uniformly mixing 10g of biphase calcium phosphate powder, 25mL of 6% sodium alginate aqueous solution, 2mL of 3% methyl cellulose solution, 30mL of deionized water and 5mL of 30% hydrogen peroxide solution to obtain the calcium phosphate mixed slurry. The biphase calcium phosphate powder is compounded by hydroxyapatite and calcium phosphate, and the Ca/P molar ratio is 1.62.
(2) And heating the calcium phosphate mixed slurry at 60 ℃ for 6min to obtain the foaming slurry with uniform size and rich bubbles.
(3) Dripping the obtained foaming slurry into a zinc chloride solution with the mass concentration of 5% to form composite microspheres, and soaking the composite microspheres in the zinc chloride solution until the composite microspheres are completely cured;
(4) taking out the completely cured composite microspheres, cleaning, drying, and sintering by adopting a muffle furnace, wherein the specific sintering conditions are as follows: sintering at 1050 deg.C, heating rate of 3 deg.C/min, and holding for 2h to obtain the final product.
The long-acting antibacterial result of the zinc-doped calcium phosphate ceramic microspheres prepared in this example is shown in fig. 5.
Example 9
The preparation process of the zinc-doped calcium phosphate ceramic microspheres in the embodiment is as follows:
(1) uniformly mixing 10g of hydroxyapatite powder, 25mL of sodium alginate aqueous solution with the mass concentration of 6%, 2mL of hydroxypropyl methyl cellulose solution with the mass concentration of 3%, 30mL of deionized water and 8mL of hydrogen peroxide solution with the mass concentration of 30% to obtain the calcium phosphate mixed slurry. The Ca/P molar ratio of the hydroxyapatite powder is 1.58.
(2) Heating the obtained calcium phosphate mixed slurry at 60 ℃ for 10min to obtain the foaming slurry with uniform size and rich bubbles.
(3) And dropwise adding the obtained foaming slurry into a zinc chloride solution with the mass concentration of 5% to form composite microspheres, and soaking the composite microspheres in the zinc chloride solution until the composite microspheres are completely cured.
(4) Taking out the completely cured composite microspheres, cleaning, drying, and sintering by adopting a muffle furnace, wherein the specific sintering conditions are as follows: the sintering temperature is 1100 ℃, the heating rate is 5 ℃/min, the heat preservation time is 2h, and the zinc-doped calcium phosphate ceramic microspheres are obtained by sintering.
The infection condition of the material taken out after the zinc-doped calcium phosphate ceramic microspheres prepared in the embodiment are implanted into the animal body for 8 weeks is shown in the attached figure 5.
Test example I, cell compatibility test
1. Test subjects: bone marrow mesenchymal stem cells were selected as experimental cells (BMSCs) and provided by the cell bank of the Committee for culture and preservation of the Chinese academy of sciences, Shanghai, China.
2. Test materials: zinc doped calcium phosphate ceramic microspheres prepared in example 6.
3. The test method comprises the following steps:
bone marrow mesenchymal stem cells (BMSCs) are recovered, passed through passages and proliferated. And (3) inoculating BMSCs with good growth vigor in a pore plate, after the cells adhere to the wall, sequentially taking the ceramic microspheres and soaking the ceramic microspheres in the culture medium for 1, 3 and 5 days to culture the cells, observing the growth conditions of the cells after 1, 3 and 5 days, and measuring the activity of the cells by adopting CCK-8.
4. The test results are shown in fig. 4:
CCK-8 panel results show that BMSCs have no significant dead cells after this immersion in media. Test results show that the zinc-doped calcium phosphate ceramic microspheres provided by the invention have no toxic or side effect on normal cells and have an obvious proliferation effect in 3 d.
Test example two, antibacterial test
1. Test subjects: staphylococcus aureus and Escherichia coli are selected as experimental bacteria and provided by China general microbiological culture Collection center.
2. Test materials: zinc doped calcium phosphate ceramic microspheres prepared in example 8.
3. The test method comprises the following steps:
sucking about 10ml of culture medium into each of two 15ml centrifuge tubes, then picking out a bacterial colony from a staphylococcus aureus and escherichia coli culture dish, blowing and beating the bacterial colony into the corresponding culture medium, slightly and uniformly shaking, culturing in a shaking table for 3-4 hours, taking out the cultured bacterial liquid, diluting the bacterial liquid, adding the diluted bacterial liquid into a pore plate, putting the bacterial liquid into a material, and then placing the material in an incubator to culture for 1, 3, 5, 7, 9 and 15 days respectively; after the incubation was completed, 100. mu.L of each of the corresponding bacterial solutions was added to a 96-well plate, and the results were measured with a microplate reader.
The results are shown in fig. 5, which shows that the zinc-doped calcium phosphate ceramic microspheres of the present invention have long-lasting antibacterial effect.
Test example three evaluation of anti-infection and bone regeneration inducing effects of materials implanted in animals
1. Test materials: zinc doped calcium phosphate ceramic microspheres prepared in example 9.
2. Subject: the rats were 8, provided by the western laboratory animals center of Sichuan university.
3. The test method comprises the following steps: a defect of a certain size was constructed in the femoral head of 8 rats, after adding bacteria, the sample was implanted and the muscle, fascia and skin were sutured layer by layer. Taking materials after operation, 1) stripping the materials from femoral head, placing the materials in sterile PBS solution for 5-10min by ultrasonic treatment, taking ten times of the solution for dilution, uniformly coating the solution on a solid agar plate, and observing the result after 24 h; 2) the sample is prepared into a paraffin section after 5um through the steps of fixing, dehydrating, transparentizing, paraffin embedding and the like, and H & E staining is adopted to investigate the induced bone regeneration effect of the material.
4. The test results are shown in fig. 6 and 7.
The result shows that compared with the traditional ceramics, the zinc-doped calcium phosphate ceramic microsphere has obvious anti-infection effect in vivo and better bone regeneration induction effect, and has good application prospect in the treatment of infectious bone defect.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (10)
1. A preparation method of zinc-doped calcium phosphate ceramic microspheres with an antibacterial function is characterized in that zinc is doped into calcium phosphate to form composite microspheres, and the composite microspheres are sintered at high temperature to obtain zinc-doped calcium phosphate ceramic particles.
2. The preparation method of the zinc-doped calcium phosphate ceramic microspheres with antibacterial function according to claim 1, characterized by comprising the following steps:
step 1, preparing a zinc salt solution;
step 2, uniformly mixing the calcium phosphate powder, the sodium alginate solution, the binder solution, the deionized water and the foaming agent to obtain mixed slurry;
step 3, heating the mixed slurry for a certain time, then dropwise adding the heated mixed slurry into the zinc salt solution in the step 1 to form composite microspheres, and standing to form gel until the gel is completely cured;
and 4, taking out the completely solidified composite microspheres, cleaning, drying and sintering at high temperature to obtain the zinc-doped calcium phosphate ceramic microspheres.
3. The method for preparing zinc-doped calcium phosphate ceramic microspheres with antibacterial function according to claim 2, wherein the zinc salt solution is one of a zinc chloride solution and a zinc nitrate solution;
preferably, the mass concentration of the zinc salt solution is 1-10%.
4. The preparation method of the zinc-doped calcium phosphate ceramic microspheres with the antibacterial function according to claim 2, wherein the calcium phosphate powder is at least one selected from hydroxyapatite and beta-tricalcium phosphate, and the molar ratio of Ca to P is 1.50-1.67.
5. The preparation method of the zinc-doped calcium phosphate ceramic microspheres with the antibacterial function according to claim 2, wherein the binder is at least one selected from polyvinyl alcohol, methyl cellulose and hydroxypropyl methyl cellulose, and preferably, the mass concentration of the binder solution is 1-10%.
6. The preparation method of the zinc-doped calcium phosphate ceramic microspheres with the antibacterial function according to claim 2, wherein the foaming agent is at least one selected from hydrogen peroxide, sodium dodecyl sulfate and sodium fatty alcohol-polyoxyethylene ether sulfate, and preferably, the mass concentration of the foaming agent solution is 1-30%.
7. The method for preparing zinc-doped calcium phosphate ceramic microspheres with antibacterial function according to any one of claims 2 to 6, wherein in the step 2, the dosage of each raw material is as follows: 1 part by mass of calcium phosphate powder, 0.5-5 parts by volume of sodium alginate solution, 0.1-1 part by volume of binder solution, 0.5-5 parts by volume of water and 0.1-1 part by volume of foaming agent solution, wherein when the unit of the part by mass is g, the unit of the part by volume is mL.
8. The method as claimed in claim 2, wherein the slurry is heated at a certain temperature for 1-30min in step 3.
9. The preparation method of the zinc-doped calcium phosphate ceramic microspheres with the antibacterial function according to claim 2, wherein in the step 4, the composite microspheres are sintered at 900-1200 ℃;
preferably, when the muffle furnace is adopted for sintering, the heating rate is 1-20 ℃/min, and the heat preservation time is 1-5 h;
preferably, when microwave sintering is adopted, the heating rate is 25-400 ℃/min, and the heat preservation time is 1-20 min.
10. Zinc-doped calcium phosphate ceramic microspheres having an antibacterial function prepared by the preparation method of any one of claims 1 to 9;
preferably, the zinc-doped calcium phosphate ceramic microspheres have a three-dimensional through porous structure and a regular spherical shape, the porosity is 50% -90%, the particle size is 0.1-5mm, and zinc ions are uniformly distributed, and the mass content is 1-10%.
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