CN113666349B - Selenium-doped hydroxyapatite with bone-like structure and preparation method thereof - Google Patents
Selenium-doped hydroxyapatite with bone-like structure and preparation method thereof Download PDFInfo
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- 229910052588 hydroxylapatite Inorganic materials 0.000 title claims abstract description 86
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 title claims abstract description 83
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 29
- 238000003756 stirring Methods 0.000 claims abstract description 18
- 239000002159 nanocrystal Substances 0.000 claims abstract description 15
- 229940082569 selenite Drugs 0.000 claims abstract description 12
- 150000004668 long chain fatty acids Chemical class 0.000 claims abstract description 11
- MCAHWIHFGHIESP-UHFFFAOYSA-L selenite(2-) Chemical compound [O-][Se]([O-])=O MCAHWIHFGHIESP-UHFFFAOYSA-L 0.000 claims abstract description 11
- 150000001412 amines Chemical class 0.000 claims abstract description 9
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 9
- 239000010452 phosphate Substances 0.000 claims abstract description 9
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims abstract description 7
- 238000001027 hydrothermal synthesis Methods 0.000 claims abstract description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 6
- 239000012266 salt solution Substances 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 239000011669 selenium Substances 0.000 claims description 23
- 229910052711 selenium Inorganic materials 0.000 claims description 20
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 19
- 229940091258 selenium supplement Drugs 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical group [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 claims description 8
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical group [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 claims description 8
- 235000020778 linoleic acid Nutrition 0.000 claims description 8
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 claims description 8
- 229910052698 phosphorus Inorganic materials 0.000 claims description 8
- 239000001488 sodium phosphate Substances 0.000 claims description 8
- 229960001471 sodium selenite Drugs 0.000 claims description 8
- 235000015921 sodium selenite Nutrition 0.000 claims description 8
- 239000011781 sodium selenite Substances 0.000 claims description 8
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical group [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 8
- 229910000406 trisodium phosphate Inorganic materials 0.000 claims description 8
- 235000019801 trisodium phosphate Nutrition 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 7
- 239000011574 phosphorus Substances 0.000 claims description 7
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 6
- 229910001424 calcium ion Inorganic materials 0.000 claims description 5
- 150000003017 phosphorus Chemical class 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 4
- 239000002243 precursor Substances 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 239000008367 deionised water Substances 0.000 claims description 2
- 229910021641 deionized water Inorganic materials 0.000 claims description 2
- 239000012535 impurity Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 13
- 239000011664 nicotinic acid Substances 0.000 abstract description 9
- 210000001519 tissue Anatomy 0.000 abstract description 5
- 206010028980 Neoplasm Diseases 0.000 abstract description 4
- 230000007547 defect Effects 0.000 abstract description 3
- 206010052428 Wound Diseases 0.000 abstract description 2
- 208000027418 Wounds and injury Diseases 0.000 abstract description 2
- 239000007864 aqueous solution Substances 0.000 description 13
- 230000005540 biological transmission Effects 0.000 description 13
- 238000001000 micrograph Methods 0.000 description 13
- 229910052586 apatite Inorganic materials 0.000 description 7
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 7
- 239000012295 chemical reaction liquid Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000007789 sealing Methods 0.000 description 6
- 208000018084 Bone neoplasm Diseases 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- -1 phosphorus ions Chemical class 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 230000008827 biological function Effects 0.000 description 3
- 239000011573 trace mineral Substances 0.000 description 3
- 235000013619 trace mineral Nutrition 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- 230000033558 biomineral tissue development Effects 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000009388 chemical precipitation Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000005501 phase interface Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 238000002524 electron diffraction data Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000004098 selected area electron diffraction Methods 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B25/00—Phosphorus; Compounds thereof
- C01B25/16—Oxyacids of phosphorus; Salts thereof
- C01B25/26—Phosphates
- C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
- C01B25/325—Preparation by double decomposition
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/12—Phosphorus-containing materials, e.g. apatite
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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- C01P2004/50—Agglomerated particles
Abstract
The invention relates to selenium-doped hydroxyapatite with a bone-like structure and a preparation method thereof. The selenium-doped hydroxyapatite with the bone-like structure provided by the invention simulates the micro-level structure of natural bone and is obtained by uniaxially orienting and co-assembling rod-shaped selenium-doped hydroxyapatite nanocrystals with primary structures. The preparation method comprises the following steps: and (3) dropwise adding the calcium salt solution into a mixed system containing long-chain fatty acid and equal-length chain fatty amine, dropwise adding a phosphate solution and a selenite solution into the mixed system, stirring, and performing hydrothermal reaction at 105-150 ℃ for 4-16h to obtain the orderly assembled bionic selenium-doped hydroxyapatite. Compared with non-bionic selenium-doped hydroxyapatite, the selenium-doped hydroxyapatite with the simulated bone structure has better bioactivity and higher effective bioavailability, and has wide application prospect in the field of repairing bones and other hard tissue defects caused by tumors and wounds as a novel multifunctional bionic material.
Description
Technical Field
The invention relates to selenium-doped hydroxyapatite with a bone-like structure and a preparation method thereof, belonging to the technical field of biological materials.
Background
Hydroxyapatite is a main inorganic component of human bones and other hard tissues, and has good biocompatibility and bioactivity, so that the hydroxyapatite has a wide and deep research and application foundation in the field of filling and repairing bone defects. In natural bone, the void region and the overlapping region in the collagen fiber repeatedly appeared with calcium and phosphorus ions are mineralized and grown along the direction of the long axis of the collagen to form nano hydroxyapatite with low crystallinity, trace element doping and highly ordered hierarchical assembly. It follows that the uniaxially assembled hierarchical structure and the trace element doping are two major features of hydroxyapatite in natural bone.
Selenium, a trace element essential to the human body, plays an important role in bone formation and development. In addition, selenium also has various biological functions of inhibiting tumor, regulating immunity, resisting bacteria, etc. In recent years, therefore, selenium-doped hydroxyapatite has attracted attention from researchers. The first time in 2011 we disclose a selenium-doped nano-hydroxyapatite synthesized by chemical precipitation (chinese patent CN 102249206A), then Hui Junfeng et al disclose a monodisperse selenium-doped nano-hydroxyapatite and a preparation method (chinese patent CN 106063947A), and in 2017 we also apply for a preparation method of micron-sized monocrystal selenium-containing hydroxyapatite (chinese patent CN 107902636A). However, no report of selenium doped hydroxyapatite simulating the microstructure of natural bones is currently available.
Bionic materials often have better biocompatibility and special biological functions because of the high similarity to natural tissues. The preparation of the hierarchical structure simulating the natural bone is expected to promote the biological efficacy of selenium-doped hydroxyapatite and expand the application range of the selenium-doped hydroxyapatite in the biomedical field.
Disclosure of Invention
Aiming at the technical blank, the invention provides selenium-doped hydroxyapatite with a bone-like structure and a preparation method thereof. The method is simple and convenient to operate, and can realize mass production, and the provided selenium-doped hydroxyapatite has a microstructure similar to that of natural bones.
The invention is realized by adopting the following technical scheme:
the selenium-doped hydroxyapatite with the bone-like structure is provided, simulates the micro-level structure of natural bone and is obtained by uniaxially orienting and co-assembling rod-shaped selenium-doped hydroxyapatite nanocrystals with primary structures.
Further, the bone-like structure selenium-doped hydroxyapatite has a rod-like primary structure selenium-doped hydroxyapatite nanocrystal with a diameter of 5nm-10nm and a length of 40nm-200nm.
Further, the selenium-doped hydroxyapatite with the bone-like structure is formed by uniaxially orienting and assembling selenium-doped hydroxyapatite nanocrystals with a primary structure rod-like shape along the long axis direction of nanocrystal growth, wherein the width is 100nm-700nm, and the length is 500nm-2 mu m.
Furthermore, the bone-like structure selenium-doped hydroxyapatite is of a polycrystalline structure, and the molar substitution degree of selenium to phosphorus is 1-10%.
A preparation method of selenium-doped hydroxyapatite with a bone-like structure comprises the following steps: and (3) dropwise adding the calcium salt solution into a mixed system containing long-chain fatty acid and equal-length chain fatty amine, dropwise adding a phosphate solution and a selenite solution into the mixed system, stirring, and performing hydrothermal reaction at 105-150 ℃ for 4-16h to obtain the orderly assembled bionic selenium-doped hydroxyapatite. In the mineralization system, calcium ions and phosphate radical/selenite ions in an aqueous solution phase are respectively combined with carboxyl and amino at the tail ends of long-chain fatty acid and long-chain fatty amine carbon chains in an oil phase, and then the bone-like selenium-doped hydroxyapatite crystals which are orderly arranged are formed by growing and assembling at the oil-water phase interface of the mixed system.
According to the scheme, the carbon chain length of the long-chain fatty acid and the long-chain fatty amine is more than 12. Linoleic acid and octadecylamine are preferred, respectively.
According to the scheme, the preparation method comprises the following specific steps:
(1) Dropwise adding a calcium salt solution into a mixed solution of long-chain fatty acid, equal-length chain fatty amine and absolute ethyl alcohol while stirring at the reaction temperature of 10-40 ℃, dropwise adding a phosphorus salt and selenite solution into the mixed solution after uniform mixing, and stirring for 2-10min to obtain an amorphous precursor suspension;
(2) Transferring the amorphous precursor suspension into a reaction kettle, and reacting for 4-16 hours at the constant temperature of 105-150 ℃;
(3) Alternately washing and centrifuging with absolute ethyl alcohol and deionized water to remove impurities and obtain the selenium-doped hydroxyapatite with the simulated bone structure.
In the method, the molar ratio of the calcium element to the phosphorus element is 10: (5.454-5.96), the molar ratio of selenium element to phosphorus element is (1-15): 100.
according to the scheme, the long-chain fatty acid is in excess relative to the calcium ion substances in the calcium salt; the equivalent chain fatty amine is in excess relative to the total mass of phosphate and selenite in the phosphate and selenite salts.
Preferably, the calcium salt is calcium nitrate.
Preferably, the phosphorus salt is trisodium phosphate.
Preferably, the selenite is sodium selenite.
In the mineralization system containing long-chain fatty acid and long-chain fatty amine, calcium ions and phosphate radical/selenite ions are respectively combined with carboxyl and amino at the tail ends of long-chain fatty acid and long-chain fatty amine carbon chains, and through the growth regulation and control of the calcium ions and the phosphate radical/selenite ions at the oil-water phase interface of the mixed system and the selection of hydrothermal reaction conditions (certain hydrothermal temperature and hydrothermal time), the selenium-doped hydroxyapatite crystal with the bone-like structure can be finally prepared. The hydrothermal reaction temperature is too low, the reaction time is too short, and the materials are not enough to form an orderly assembled structure; the hydrothermal reaction temperature is too high, the reaction time is too long, and the orderly assembled structure can be damaged, so that the selenium-doped hydroxyapatite product with the bone-like structure can not be obtained.
The invention has the advantages that:
the invention provides a novel selenium-doped hydroxyapatite material imitating a natural bone microcosmic hierarchical structure, which is formed by assembling rod-shaped selenium-doped hydroxyapatite nanocrystals along the long axis direction of nanocrystal growth in a uniaxial orientation way. Preferably, the primary structure is a rod-shaped selenium-doped hydroxyapatite nanocrystal with the diameter of 5nm-10nm and the length of 40nm-200nm, and the secondary structure size is near micron.
Compared with selenium-doped hydroxyapatite without a bionic hierarchical structure, the selenium-doped hydroxyapatite with the simulated bone structure has better bioactivity and higher efficient bioavailability, and has wide application prospect in the field of repairing bones and other hard tissue defects caused by tumors and wounds as a novel multifunctional bionic material.
The preparation process provided by the invention is simple and feasible, the cost of raw materials is controllable, and the quantitative production is convenient.
Drawings
FIG. 1 is a transmission electron microscope image of selenium-doped hydroxyapatite of the bone structure simulated in example 1.
FIG. 2 is a high-power field emission transmission electron microscope image of the selenium-doped hydroxyapatite of the bone-like structure in example 1.
FIG. 3 is an X-ray diffraction pattern of selenium-doped hydroxyapatite of the bone structure simulated in example 1.
FIG. 4 is an infrared spectrum of selenium-doped hydroxyapatite of the bone structure simulated in example 1.
FIG. 5 is a selective electron diffraction pattern of selenium-doped hydroxyapatite of the bone-like structure of example 1.
FIG. 6 is a transmission electron microscope image of selenium-doped hydroxyapatite of the bone structure simulated in example 3.
FIG. 7 is a field emission transmission electron microscope image of selenium doped hydroxyapatite of the bone structure simulated in example 4.
FIG. 8 is a field emission transmission electron microscope image of selenium doped hydroxyapatite of non-simulated bone structure for control in example 5.
FIG. 9 shows the cell viability of bone tumor cells treated with two selenium doped hydroxylapatite at different concentrations for CCK-8 as tested in example 5 for 24h and 48 h.
FIG. 10 is a transmission electron microscope image of selenium-doped hydroxyapatite of comparative example 1.
FIG. 11 is a transmission electron microscope image of selenium-doped hydroxyapatite of comparative example 2.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited to the following.
Example 1
(1) 0.3g of octadecylamine was dissolved in 2.4mL of linoleic acid and 9.6mL of absolute ethanol, 5mL of a 200mM calcium nitrate aqueous solution was added dropwise thereto with stirring, and then 4mL of a mixed aqueous solution of 14.06mM sodium selenite and 140.6mM trisodium phosphate was added dropwise thereto with stirring for 5 minutes at room temperature;
(2) Transferring the reaction liquid into a reaction kettle, sealing, and reacting for 10 hours at 120 ℃;
(3) And (3) cooling the reaction kettle to room temperature, opening, alternately using absolute ethyl alcohol, and washing reaction and precipitation for a plurality of times by water to obtain the selenium-doped hydroxyapatite with the bone-like structure.
Fig. 1 is a transmission electron microscope image of the selenium-doped hydroxyapatite, and fig. 2 is a high-power field emission transmission electron microscope image of the selenium-doped hydroxyapatite, and it can be seen from the image that the prepared material has a hierarchical assembly structure similar to bone apatite: the primary structure of the selenium-doped hydroxyapatite with the bone-like structure is a rod-shaped selenium-doped hydroxyapatite nanocrystal, the diameter is about 5nm to 10nm, and the length is about 100nm to 200nm; the secondary structure of the selenium-doped hydroxyapatite with the bone-like structure is formed by uniaxially orienting and assembling the primary structure along the long axis direction of the growth of the nanocrystals, the width is about 200-400nm, and the length is about 500nm-1 mu m. FIG. 3 is an X-ray diffraction pattern of the selenium doped hydroxyapatite, from which it can be seen that the reaction product shows typical characteristic peaks of hydroxyapatite, indicating that the phase of the reaction product prepared by the invention is hydroxyapatite. FIG. 4 is an infrared spectrogram of the selenium-doped hydroxyapatite, which shows obvious selenium oxygen bonds, hydroxyl groups and phosphate groups, and shows that the selenium element doping exists in the material, and the combination of X-ray diffraction results can fully prove that the product obtained by the invention is the selenium-doped hydroxyapatite. Table 1 shows the atomic percentage of Ca, P and Se elements and the molar percentage of Se to P substitution in the product detected by the X-ray fluorescent probe, and the substitution degree of Se to P in the product is slightly lower than the Se to P ratio of the reaction raw materials. FIG. 5 is a selected area electron diffraction pattern of the product, from which it can be seen that the resulting product is polycrystalline, similar to apatite in natural bone.
TABLE 1
Example 2
(1) 0.3g of octadecylamine was dissolved in 2.4mL of linoleic acid and 9.6mL of absolute ethanol, 5mL of a 200mM calcium nitrate aqueous solution was added dropwise thereto with stirring, and then 4mL of a mixed aqueous solution of 11.39mM sodium selenite and 142.41mM trisodium phosphate was added dropwise thereto with stirring for 8 minutes at room temperature;
(2) Transferring the reaction liquid into a reaction kettle, sealing, and reacting for 12 hours at 110 ℃;
(3) And (3) cooling the reaction kettle to room temperature, opening, alternately using absolute ethyl alcohol, and washing reaction and precipitation for a plurality of times by water to obtain the selenium-doped hydroxyapatite with the bone-like structure.
Example 3
(1) 0.3g of octadecylamine was dissolved in 2.4mL of linoleic acid and 9.6mL of absolute ethanol, 5mL of a 200mM calcium nitrate aqueous solution was added dropwise thereto with stirring, and then 4mL of a mixed aqueous solution of 7.26mM sodium selenite and 145.16mM trisodium phosphate was added dropwise thereto with stirring for 4 minutes at room temperature;
(2) Transferring the reaction liquid into a reaction kettle, sealing, and reacting for 5 hours at 120 ℃;
(3) And (3) cooling the reaction kettle to room temperature, opening, alternately using absolute ethyl alcohol, and washing reaction and precipitation for a plurality of times by water to obtain the selenium-doped hydroxyapatite with the bone-like structure.
Fig. 6 is a transmission electron microscope image of the selenium-doped hydroxyapatite, and it can be seen from the image that the prepared material has a hierarchical assembly structure similar to bone apatite.
Example 4
(1) 0.5g of octadecylamine was dissolved in 3.0mL of linoleic acid and 9.6mL of absolute ethanol, 5mL of a 200mM calcium nitrate aqueous solution was added dropwise thereto with stirring, and then 4mL of a mixed aqueous solution of 14.06mM sodium selenite and 140.6mM trisodium phosphate was added dropwise thereto with stirring for 4 minutes at room temperature;
(2) Transferring the reaction liquid into a reaction kettle, sealing, and reacting for 5 hours at 140 ℃;
(3) And (3) cooling the reaction kettle to room temperature, opening, alternately using absolute ethyl alcohol, and washing reaction and precipitation for a plurality of times by water to obtain the selenium-doped hydroxyapatite with the bone-like structure.
Fig. 7 is a field emission transmission electron microscope image of the selenium-doped hydroxyapatite, and it can be seen from the image that the prepared material has a hierarchical assembly structure similar to bone apatite.
EXAMPLE 5 functional analysis of biological Activity
The bionic material has more excellent biological functions because of the high similarity with natural tissues, and has better bioavailability and anti-tumor functions for proving the selenium-doped hydroxyapatite with the bone-like structure. In the experiment, selenium doped hydroxyapatite without a bone-like apatite hierarchical structure is used as a control, and bone tumor cells HOS/MNNG are cultured under in vitro conditions. Fig. 8 is a typical selenium doped nano-hydroxyapatite without a bone-like apatite hierarchical structure prepared by a common chemical precipitation method. FIG. 9 shows the cell viability of bone tumor cells treated with two selenium doped hydroxylapatite at different concentrations for CCK-8 after 24h and 48 h. The inhibition effect of the selenium doped hydroxyapatite with the bone-like structure on bone tumor cells is obviously higher than that of a control group, and the selenium doped hydroxyapatite with the bone-like structure is notable in that the tumor inhibition effect is still higher than that of the control group with higher concentration (50 mug/mL) at lower concentration (20 mug/mL), so that the bionic material has higher efficient bioavailability.
Comparative example 1
(1) 0.3g of octadecylamine was dissolved in 2.4mL of linoleic acid and 9.6mL of absolute ethanol, 5mL of a 200mM calcium nitrate aqueous solution was added dropwise thereto with stirring, and then 4mL of a mixed aqueous solution of 14.06mM sodium selenite and 140.6mM trisodium phosphate was added dropwise thereto with stirring for 5 minutes at room temperature;
(2) Transferring the reaction liquid into a reaction kettle, sealing, and reacting for 5 hours at 95 ℃;
(3) And (3) cooling the reaction kettle to room temperature, opening, alternately using absolute ethyl alcohol, and washing reaction precipitation for a plurality of times by water to obtain the selenium-doped hydroxyapatite.
Fig. 10 is a transmission electron microscope image of the selenium-doped hydroxyapatite, and it can be seen that the assembled structure of the material is disordered, unlike the ordered hierarchical structure of the natural bone apatite.
Comparative example 2
(1) 0.3g of octadecylamine was dissolved in 2.4mL of linoleic acid and 9.6mL of absolute ethanol, 5mL of a 200mM calcium nitrate aqueous solution was added dropwise thereto with stirring, and then 4mL of a mixed aqueous solution of 7.26mM sodium selenite and 145.16mM trisodium phosphate was added dropwise thereto with stirring for 5 minutes at room temperature;
(2) Transferring the reaction liquid into a reaction kettle, sealing, and reacting for 24 hours at 180 ℃;
(3) And (3) cooling the reaction kettle to room temperature, opening, alternately using absolute ethyl alcohol, and washing reaction precipitation for a plurality of times by water to obtain the selenium-doped hydroxyapatite.
Fig. 11 is a transmission electron microscope image of the selenium-doped hydroxyapatite, and it can be seen that the material has no significant ordered hierarchical structure.
Claims (6)
1. The selenium-doped hydroxyapatite with the bone-like structure is characterized in that: the selenium-doped hydroxyapatite nano crystal is simulated to be of a micro-level structure of natural bone, is formed by uniaxially orienting and co-assembling a rod-shaped selenium-doped hydroxyapatite nano crystal with a primary structure along the long axis direction of the rod-shaped selenium-doped hydroxyapatite nano crystal with the primary structure, wherein the width of a secondary structure formed by assembling the primary structure is 100nm-700nm, the length of the secondary structure is 500nm-2 mu m, the secondary structure is of a polycrystalline structure, the diameter of the rod-shaped selenium-doped hydroxyapatite nano crystal with the primary structure is 5nm-10nm, the length of the rod-shaped selenium-doped hydroxyapatite nano crystal is 40nm-200nm, and the molar substitution degree of selenium to phosphorus is 1% -10%.
2. The method for preparing the selenium-doped hydroxyapatite with the simulated bone structure according to claim 1, wherein the method is characterized in that: the calcium salt solution is dripped into a mixed system containing long-chain fatty acid linoleic acid and equilong-chain fatty amine octadecylamine, then the phosphorus salt and selenite solution are dripped into the mixed system, and the mixed system is stirred, and then the selenium doped hydroxyapatite with the bone-like structure is obtained after the hydrothermal reaction for 4 to 16 hours at the temperature of 105 to 150 ℃.
3. The preparation method according to claim 2, characterized in that: the method comprises the following specific steps:
(1) Dropwise adding a calcium salt solution into a mixed solution of long-chain fatty acid linoleic acid, equal-length chain fatty amine octadecylamine and absolute ethyl alcohol while stirring at the reaction temperature of 10-40 ℃, dropwise adding a phosphorus salt and selenite solution into the mixed solution after uniform mixing, and stirring for 2-10min to obtain an amorphous precursor suspension;
(2) Transferring the amorphous precursor suspension into a reaction kettle, and reacting for 4-16 hours at the constant temperature of 105-150 ℃;
(3) Alternately washing and centrifuging with absolute ethyl alcohol and deionized water to remove impurities and obtain the selenium-doped hydroxyapatite with the simulated bone structure.
4. A method of preparation according to claim 2 or 3, characterized in that: the molar ratio of the calcium element to the phosphorus element is 10: (5.454-5.96), the molar ratio of selenium element to phosphorus element is (1-15): 100.
5. a method of preparation according to claim 2 or 3, characterized in that: the long chain fatty acid is in excess relative to the calcium ion substances in the calcium salt; the equivalent chain fatty amine is in excess relative to the total mass of phosphate and selenite in the phosphate and selenite salts.
6. A method of preparation according to claim 2 or 3, characterized in that: the calcium salt is calcium nitrate; the phosphorus salt is trisodium phosphate; the selenite is sodium selenite.
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