CN111422842A - Amorphous calcium phosphate with excellent compression resistance and preparation method and application thereof - Google Patents
Amorphous calcium phosphate with excellent compression resistance and preparation method and application thereof Download PDFInfo
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- CN111422842A CN111422842A CN202010307140.9A CN202010307140A CN111422842A CN 111422842 A CN111422842 A CN 111422842A CN 202010307140 A CN202010307140 A CN 202010307140A CN 111422842 A CN111422842 A CN 111422842A
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- compression resistance
- phosphate
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- 239000001506 calcium phosphate Substances 0.000 title claims abstract description 35
- 229910000389 calcium phosphate Inorganic materials 0.000 title claims abstract description 35
- 235000011010 calcium phosphates Nutrition 0.000 title claims abstract description 35
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 title claims abstract description 35
- 230000006835 compression Effects 0.000 title claims abstract description 20
- 238000007906 compression Methods 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title abstract description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 63
- 229910052761 rare earth metal Inorganic materials 0.000 claims abstract description 28
- 239000000126 substance Substances 0.000 claims abstract description 28
- 239000000463 material Substances 0.000 claims abstract description 22
- 238000010146 3D printing Methods 0.000 claims abstract description 17
- 159000000003 magnesium salts Chemical class 0.000 claims abstract description 17
- 150000002910 rare earth metals Chemical class 0.000 claims abstract description 17
- 238000001027 hydrothermal synthesis Methods 0.000 claims abstract description 15
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 14
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 12
- 239000011858 nanopowder Substances 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 11
- 239000010452 phosphate Substances 0.000 claims abstract description 11
- 238000001035 drying Methods 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 8
- 238000005406 washing Methods 0.000 claims abstract description 8
- 238000007599 discharging Methods 0.000 claims abstract description 7
- 238000000227 grinding Methods 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 16
- 239000011777 magnesium Substances 0.000 claims description 15
- 239000011575 calcium Substances 0.000 claims description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical group [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 9
- 239000012065 filter cake Substances 0.000 claims description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 7
- 239000001110 calcium chloride Substances 0.000 claims description 6
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 6
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 6
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 6
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 6
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 6
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 5
- 229910004664 Cerium(III) chloride Inorganic materials 0.000 claims description 4
- 238000004321 preservation Methods 0.000 claims description 4
- 229910000333 cerium(III) sulfate Inorganic materials 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 235000021317 phosphate Nutrition 0.000 claims 5
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 abstract description 18
- 239000013078 crystal Substances 0.000 abstract description 3
- 230000001089 mineralizing effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 19
- 239000002245 particle Substances 0.000 description 11
- -1 rare earth ion modified magnesium hydroxide Chemical class 0.000 description 11
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000012535 impurity Substances 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 238000006703 hydration reaction Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 229910014472 Ca—O Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910052586 apatite Inorganic materials 0.000 description 2
- 230000033558 biomineral tissue development Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 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 2
- 230000008439 repair process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- HSJPMRKMPBAUAU-UHFFFAOYSA-N cerium nitrate Inorganic materials [Ce+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O HSJPMRKMPBAUAU-UHFFFAOYSA-N 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000005548 dental material Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000192 extended X-ray absorption fine structure spectroscopy Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001153 fluoro group Chemical class F* 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000011164 primary particle Substances 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000002054 transplantation Methods 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
-
- A—HUMAN NECESSITIES
- 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
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- A—HUMAN NECESSITIES
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B12/00—Cements not provided for in groups C04B7/00 - C04B11/00
- C04B12/02—Phosphate cements
- C04B12/025—Phosphates of ammonium or of the alkali or alkaline earth metals
-
- A—HUMAN NECESSITIES
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
-
- A—HUMAN NECESSITIES
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/60—Particles characterised by their size
- C01P2004/61—Micrometer sized, i.e. from 1-100 micrometer
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2006/00—Physical properties of inorganic compounds
- C01P2006/80—Compositional purity
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Ceramic Engineering (AREA)
- Materials Engineering (AREA)
- Structural Engineering (AREA)
- Materials For Medical Uses (AREA)
Abstract
The modified amorphous calcium phosphate with excellent compression resistance comprises 0.1-0.5 part of rare earth, 0.1-0.5 part of magnesium salt, 1-5 parts of sodium hydroxide solution, 100-300 parts of calcium salt and 100-300 parts of phosphate. The preparation method of the modified amorphous calcium phosphate with excellent compression resistance comprises the following steps of S1, respectively adding a rare earth substance and a soluble magnesium salt into pure water, and dripping a sodium hydroxide solution into the pure water; s2, stirring, and carrying out hydrothermal reaction; and S3, discharging, filtering, washing, drying to constant weight, and grinding to obtain the nano powder. The invention is used for biomedical 3D printing materials. The invention not only recovers the capability of mineralizing and phase changing, but also obviously enhances the internal bonding force of the hydrated product crystal, thereby preparing the printed bone finished product with excellent mechanical strength, especially compressive strength, and thoroughly overcoming the technical bottleneck that the printed bone finished product can not be used for treating and repairing organism bearing bone. In addition, the invention has the characteristics of high stability and high purity.
Description
Technical Field
The invention relates to the technical field of printing materials, in particular to amorphous calcium phosphate with excellent compression resistance and a preparation method and application thereof.
Background
Amorphous Calcium Phosphate (ACP) is a type of long-range disordered, short-range ordered glassy material. The chemical composition range of the short-range structure of the ACP is wide (the ratio of calcium to phosphorus generally fluctuates between 1.0 and 2.0). Since ACP is isotropic and there is no selective growth of crystalline substances, ACP has a typical spherical morphology of amorphous substances (spherical primary particles of ACP, which are observed by SEM to have diameters of about several tens of nanometers, are susceptible to secondary agglomeration resulting in diameters as large as several tens of microns). Due to the unique properties of ACP, ACP has a position which cannot be replaced by other calcium phosphate materials in the aspect of biomedicine and has very important significance in the aspect of biomineralization.
In the field of biomedical materials, particularly with the maturity of 3D printing technology in recent years, preparing an organism bone implant material in a required shape by an ACP through a 3D printer is one of clinical technologies with the best development prospect. The ACP/3D printing bone finished product has been clinically used to a certain extent in developed countries such as the United states, Japan, Germany, the Netherlands and the like (particularly, the ACP/3D printing bone finished product has been rapidly applied and developed in industries such as CPC bone cement, tissue engineering scaffolds, dental materials, drug controlled release carriers and the like), but is still in a blank state in China.
The ACP preparation method at present mainly can be divided into two main categories, namely a wet method and a dry method; however, both wet process and dry process, the prepared ACP contains many impurities (especially, the ACP prepared by the dry process has high impurity content and poor controllability of the chemical structure of the ACP), so that the ACP cannot be widely applied in the biomedical industry at present. Meanwhile, even if pure ACP is obtained, since ACP is a thermodynamically unstable calcium phosphate phase, it spontaneously changes phase to a more stable apatite phase in about one month even when stored under vacuum, and rapidly changes phase in several days in a humid environment; ACP can only maintain an amorphous phase for a short period of time, even if certain specific ions or biomacromolecules are added for structural modification.
In order to obtain high-purity and high-stability ACP, the invention patent of China with the application number of 201910172278.X adopts rare earth substances, silica sol, soluble magnesium salts, soluble aluminum salts, fluorine salts and the like as raw materials, prepares a zero-charge magnesium aluminum silicate auxiliary agent through high-temperature hydrothermal reaction, and participates in high-temperature water phase reaction of a calcium source and a phosphorus source to prepare the amorphous calcium phosphate nano powder material. The technical scheme improves the stability of the traditional ACP and simultaneously obtains a finished product with high purity.
Although the technical scheme is improved in stability and purity, for a key technical bottleneck, the mechanical strength, especially the compressive strength, of an organism skeleton implantation solid finished product (ACP/3D printing bone finished product) prepared by ACP is low, the compressive strength of the finished product in the technical scheme is about 11.5PMa, the finished product is difficult to be used for bone transplantation and repair of a human body bearing part, the current ACP/3D printing bone finished product is directly caused to obtain a fundamental reason of less clinical application, and further technical development and market application of the finished product are severely restricted.
Disclosure of Invention
The primary object of the present invention is to provide a modified amorphous calcium phosphate which has improved compression resistance in addition to high stability and high purity, in view of the above-mentioned drawbacks and disadvantages.
Another object of the present invention is to provide a method for preparing a modified amorphous calcium phosphate having excellent compressibility.
It is still another object of the present invention to provide a modified amorphous calcium phosphate having excellent compressibility.
In order to achieve the purpose, the invention adopts the following specific technical scheme:
the modified amorphous calcium phosphate with excellent compression resistance comprises a rare earth substance, a soluble magnesium salt, sodium hydroxide, a calcium salt and a phosphate; the weight ratio of the components is as follows: 0.1-0.5 part of rare earth substance, 0.1-0.5 part of soluble magnesium salt, 1-5 parts of sodium hydroxide solution with the mass fraction of 1-5%, 100-300 parts of calcium salt and 100-300 parts of phosphate.
As a further technical scheme of the invention, the components are prepared from the following components in parts by weight: 0.2-0.4 part of rare earth substance, 0.2-0.4 part of soluble magnesium salt, 2-4 parts of 1-5% sodium hydroxide solution by mass, 200-250 parts of calcium salt and 200-250 parts of phosphate.
As a further technical scheme of the invention, the modified amorphous calcium phosphate with excellent compression resistance further comprises 800-1200 parts of pure water.
As a further aspect of the inventionThe rare earth substance is Ce (NO)3)3、Ce2(SO4)3、CeCl3、Dy(NO3)3、Dy2(SO4)3Or DyCl3One or more of the above components can be combined randomly.
As a further technical scheme of the invention, the soluble magnesium salt is MgSO4、MgCl2Or Mg (NO)3)2One or more combinations thereof.
As a further technical solution of the present invention, the calcium salt is Ca (NO)3)2Or CaCl2One or a combination of both.
As a further technical scheme, the phosphate is one or a combination of two of sodium dihydrogen phosphate and disodium hydrogen phosphate.
The preparation method of the modified amorphous calcium phosphate with excellent compression resistance comprises the following steps:
s1, respectively adding rare earth substances and soluble magnesium salts into pure water, and then slowly dripping sodium hydroxide solution for 10-30 min;
s2, adding calcium salt and phosphate after dropwise adding, stirring, transferring all the materials into a hydrothermal reaction kettle, heating to 120-140 ℃, and carrying out heat preservation stirring reaction for 3-5 hours;
and S3, stopping the reaction, cooling to room temperature, discharging, filtering and washing the reaction solution, drying a filter cake at the temperature of not higher than 80 ℃ to constant weight, and finally grinding until the granularity is not larger than 200 meshes to obtain the chemically-structured modified amorphous calcium phosphate nano powder.
In the technical scheme of the invention, the research of various analytical instruments such as XRD, FT-IR, AFM, TEM, SEM, EXAFS and the like and other characterization means proves and finds that:
Ce(NO3)3equal rare earth substance and MgSO4And mixing the soluble magnesium salts, adding 1-5 parts of sodium hydroxide solution with the mass fraction of 1-5% for coprecipitation to obtain the rare earth ion modified magnesium hydroxide colloidal particles. Rare earth ion/Mg (OH)2The colloidal particles areThe method is one of the core innovative technologies, calcium salt and phosphate are guided to form a precursor structure by taking the precursor as a template under the high-temperature hydrothermal condition, and then the precursor is converted into ACP at the high-temperature roasting stage. Rare earth ions/Mg (OH) if the concentration of the sodium hydroxide solution is less than 1% or the amount is less than 1 part2The colloidal particles are not mature enough and cannot play a role in guiding the template; and if the concentration of the sodium hydroxide solution is higher than 5% or the amount is more than 5 parts, rare earth ion/Mg (OH)2The colloidal particles are over aged and the template directing effect is rapidly reduced. Meanwhile, rare earth substances or soluble magnesium salts are added independently or not added, so that the template guiding effect is completely disappeared, and an ACP structure cannot be generated at all.
In the high-temperature hydrothermal synthesis process (sealing, heating to 120-140 ℃ and stirring and reacting for 30-60 min under heat preservation), adding rare earth ions/Mg (OH)2Ca (NO) under the guidance of colloidal particles3)2、CaCl2Gradually form Ca-O trioctahedral structure, PO4 3-In a trioctahedral arrangement with a calcium to phosphorus ratio of 1.5. After the reaction is finished, filtering and washing to remove soluble salt which does not participate in the reaction system and salt substances generated in the hydrothermal reaction process, and then drying the filter cake in vacuum at the temperature of not higher than 80 ℃ to constant weight.
In the high-temperature hydrothermal synthesis stage, if the hydrothermal reaction temperature is lower than 120 ℃ or higher than 140 ℃ and if the reaction time is less than 3 hours or more than 5 hours, more byproduct impurities are generated in the final product. Meanwhile, the research finds that K exists in the hydrothermal system if K exists+Or NH4 +Then ACP cannot be generated.
According to the chemical characteristics and the radial distribution of X-ray attenuation, the ACP prepared by the technology is similar to the classical Posner cluster in structural morphology, but has a brand-new chemical structure: each PO4 3-The interior of the Ca-O trioctahedron contains a certain amount of rare earth ions/Mg (OH)2Colloidal particles; then 5-8 trioctahedral bodies are combined by Van der Waals force and randomly stacked to form a sphere with the diameter of about 2-5 nm. The Posner cluster of the classical ACP is formed by stacking about 3-4 calcium phosphate amorphous particles, and the diameter of the calcium phosphate amorphous particles is less than 1 nm.
The special brand-new ACP chemical structure is the second core innovation of the invention because of the rare earth ions/Mg (OH) in the trioctahedron2The colloidal particles prevent the cluster from dissociating and collapsing, and fundamentally destroy the spontaneous phase transition process of the ACP, so that the ACP is in a thermodynamic stable state. Only with this completely new chemical structure, ACP assumes a thermodynamically stable state.
In the 3D printing and forming process, when ACP with a brand-new chemical structure meets bonding solution (such as dilute phosphoric acid, dilute citric acid and other dilute acid solution), rare earth ions/Mg (OH)2Colloidal particle is subjected to H+Attack to generate rare earth ions/Mg with complex structure2+Which guides ACP and water molecules or H in the bonding solution+The rapid hydration reaction can lead Posner clusters to be dissociated and collapsed at a higher speed, and the ACP hydration products to be rapidly crystallized and aged and lead the bonding force between crystal grains to be stronger, namely the ACP/3D printing bone finished product has very high mechanical strength (far beyond ACP or imported ACP nano powder prepared by the prior art).
As a further technical scheme of the invention, the dripping time in the step S1 is 15-25 min.
As a further technical scheme of the invention, in the step S2, the temperature is raised to 125-135 ℃ in a sealed manner, and the reaction is carried out for 3.5-4.5 h.
As a further technical solution of the present invention, in the step S3, vacuum drying is adopted.
The application of the modified amorphous calcium phosphate with excellent compression resistance is used for biomedical 3D printing materials.
Compared with the prior art, the invention has the following beneficial effects:
the invention adopts the prepared modified ACP as a powder material to be applied to a 3D printer, and dilute acid is used as a matched bonding solution, namely rare earth ion/Mg2+Under the guiding action of the ACP, the modified ACP not only restores the mineralization phase change capability, but also obviously enhances the internal bonding force of the hydration product crystals, thereby preparing the printed bone finished product with excellent mechanical strength and thoroughly overcoming the defect of printingThe bone finished product cannot be used as the biggest key technical bottleneck of treatment and repair of organism load-bearing bones.
The invention thoroughly solves the key technical problem that ACP is easy to spontaneously change phase. The prepared modified ACP has a special and brand-new chemical structure, so that the modified ACP is in a thermodynamic stable state, and the purity of the modified ACP can be kept above 95% for a long time. The purity of the ACP prepared by the existing dry method or wet method is generally lower than 90 percent, and the ACP can be rapidly transformed into apatite substances even if stored under the vacuum condition. At the same time, rare earth ion/Mg (OH)2The colloidal particles can smoothly guide the synthesis of the ACP, thereby preparing the high-purity ACP.
Detailed Description
The present invention is further explained and illustrated by the following embodiments, which should be understood to make the technical solution of the present invention clearer and easier to understand, and not to limit the scope of the claims.
Example 1
In the high mechanical strength modified amorphous calcium phosphate for 3D printing and the preparation method thereof in this example 1, first, 0.1 part of Ce (NO) is added3)3And 0.1 part of MgSO4Respectively adding the mixture into 1000 parts of pure water, and then slowly dripping 1 part of sodium hydroxide solution with the mass fraction of 1% for 10 min; after the addition, 100 parts of Ca (NO) are added3)2And 100 parts of sodium dihydrogen phosphate are fully and uniformly stirred, then the materials are completely transferred into a hydrothermal reaction kettle, and then the temperature is raised to 120 ℃ in a closed manner, and the materials are stirred and reacted for 3 hours under the condition of heat preservation; and then stopping the reaction, cooling to room temperature, discharging, filtering and fully washing the reaction solution, drying a filter cake at the temperature of not higher than 80 ℃ in vacuum to constant weight, and finally grinding until the granularity is not more than 200 meshes to obtain the modified ACP nano powder No. 1.
Example 2
In this embodiment 2, 0.2 part of Ce is first added to the modified amorphous calcium phosphate with high mechanical strength for 3D printing and the preparation method thereof2(SO4)30.3 parts of DyCl30.3 part of MgCl20.2 part of Mg (NO)3)2Respectively adding into 1000 parts of pure water, and slowly dripping5 parts of sodium hydroxide solution with the mass fraction of 5 percent, and controlling the dripping time to be 30 min; after the addition, 150 parts of Ca (NO) are added3)2150 parts of CaCl2100 parts of sodium dihydrogen phosphate and 200 parts of disodium hydrogen phosphate are fully and uniformly stirred, then the materials are completely transferred into a hydrothermal reaction kettle, and then the temperature is raised to 140 ℃ in a sealed way, and the materials are kept warm and stirred for reaction for 5 hours; and then stopping the reaction, cooling to room temperature, discharging, filtering and fully washing the reaction solution, drying a filter cake at the temperature of not higher than 80 ℃ in vacuum to constant weight, and finally grinding until the granularity is not more than 200 meshes to obtain the modified ACP nano powder No. 2.
Example 3
In this example 3, 0.1 part of CeCl is first added to prepare the modified amorphous calcium phosphate with high mechanical strength for 3D printing and the preparation method thereof30.1 part of Dy (NO)3)30.1 part of Dy2(SO4)30.1 part of MgSO40.1 part of MgCl20.1 part of Mg (NO)3)2Respectively adding into 1000 parts of pure water, and slowly dripping into sodium hydroxide solution (prepared by mixing 1 part of sodium hydroxide solution with mass fraction of 2% and 2 parts of sodium hydroxide solution with mass fraction of 3%), wherein the dripping time is controlled to be 20 min; after the addition, 100 parts of Ca (NO) are added3)250 parts of CaCl250 parts of sodium dihydrogen phosphate and 100 parts of disodium hydrogen phosphate are fully and uniformly stirred, then the materials are completely transferred into a hydrothermal reaction kettle, and then the temperature is raised to 130 ℃ in a sealed way, and the materials are kept warm and stirred for reaction for 3.5 hours; and then stopping the reaction, cooling to room temperature, discharging, filtering and fully washing the reaction solution, drying a filter cake at the temperature of not higher than 80 ℃ in vacuum to constant weight, and finally grinding until the granularity is not more than 200 meshes to obtain the modified ACP nano powder No. 3.
Example 4
In the high mechanical strength modified amorphous calcium phosphate for 3D printing and the preparation method thereof in this embodiment 4, first, 0.1 part of Ce (NO) is added3)30.1 part of CeCl30.1 part of Dy2(SO4)30.1 part of DyCl30.1 part of MgSO40.15 part of MgCl20.15 part of Mg (NO)3)2Adding into 1000 parts of pure water, and slowly dropping hydrogen and oxygenSodium dissolving solution (prepared by mixing 1.5 parts of sodium hydroxide solution with the mass fraction of 2.5%, 1.5 parts of sodium hydroxide solution with the mass fraction of 3% and 1 part of sodium hydroxide solution with the mass fraction of 3.5%), and controlling the dropping time to be 25 min; after the addition, 75 parts of Ca (NO) was added3)2175 parts of CaCl2125 parts of sodium dihydrogen phosphate and 135 parts of disodium hydrogen phosphate are fully and uniformly stirred, then the materials are completely transferred into a hydrothermal reaction kettle, and then the temperature is raised to 135 ℃ in a sealed way, and the materials are kept warm and stirred for reaction for 4.5 hours; and then stopping the reaction, cooling to room temperature, discharging, filtering and fully washing the reaction solution, drying a filter cake at the temperature of not higher than 80 ℃ in vacuum to constant weight, and finally grinding until the granularity is not more than 200 meshes to obtain the modified ACP nano powder No. 4.
Comparative example 1
Adding only 0.1 part of Ce2(SO4)30.1 part of CeCl30.1 part of Dy (NO)3)3And 0.1 part of DyCl3The same procedure as in example 4 was repeated except that no soluble magnesium salt was added, and the powder thus obtained was designated as No. 5.
Comparative example 2
Adding only 0.1 part of MgSO40.15 part of MgCl20.15 part of Mg (NO)3)2No.6 was assigned to the powder prepared in the same manner as in example 3 except that no rare earth substance was added.
Comparative example 3
The hydrothermal reaction temperature was set at 110 ℃ and the whole was in accordance with example 2, and the powder thus prepared was designated as No. 7.
Comparative example 4
The hydrothermal reaction temperature was set at 150 ℃ and the whole was in accordance with example 2, and the powder thus obtained was designated as No. 8.
The nano-powders Nos. 1 to 8 and imported ACP nano-powders (model: Objet-CP1, produced by 3D systems, USA) prepared in the above examples and comparative examples were used as powder materials, and 0.1mo L. L-13D printing dilute citric acid solution (bonding solution) to prepare a finished artificial bone entity product with the thickness of 10mm × 10mm, 10mm × 10mm, and performing related tests, wherein the results are shown in Table 1, and the experimental conditions of 3D printing are Z3Model 10 3D printer (ZCorporation, usa), a total of 128 holes (diameter about 0.05mm) for piezoelectric batch print head, layer thickness set to 0.175mm, and saturation set to 0.7.
Table 1 comparative test data
As can be seen from Nos. 5 to 8 in Table 1, the addition of rare earth substances or soluble magnesium salts alone not only failed to produce ACP (purity less than 10%) but also resulted in poor mechanical strength of the 3D-printed bone product; meanwhile, the hydrothermal reaction temperature is lower than 150 ℃ or higher than 200 ℃, a plurality of by-product impurities exist in the prepared ACP, and the mechanical strength of the 3D printed bone finished product is extremely poor and completely has no practicability. From No.1 to No.4, the ACP nano powder prepared by the technology of the invention has the purity of 95 percent or more, and the stability is excellent, and the purity is basically not changed after long-term standing, which means that the ACP chemical structure is in a thermodynamic stable state (while the purity of imported like commodities is reduced from 81 percent to 80 percent after standing for one month). Meanwhile, the most critical is that: the 3D printing bone finished product prepared from the ink has extremely excellent mechanical strength (especially, the compressive strength is not less than 40.1MPa, and the compressive modulus is not less than 569MPa), and is far better than imported ACP similar products, so that the bone medical clinical application prospect is quite bright.
While the present invention has been described by way of examples, and not by way of limitation, other variations of the disclosed embodiments, as would be readily apparent to one of skill in the art, are intended to be within the scope of the present invention, as defined by the claims.
Claims (10)
1. A modified amorphous calcium phosphate with excellent compression resistance is characterized in that: including rare earth materials, soluble magnesium salts, sodium hydroxide, calcium salts, and phosphates; the weight ratio of the components is as follows: 0.1-0.5 part of rare earth substance, 0.1-0.5 part of soluble magnesium salt, 1-5 parts of sodium hydroxide solution with the mass fraction of 1-5%, 100-300 parts of calcium salt and 100-300 parts of phosphate.
2. The modified amorphous calcium phosphate excellent in compression resistance according to claim 1, characterized in that: the weight ratio of the components is as follows: 0.2-0.4 part of rare earth substance, 0.2-0.4 part of soluble magnesium salt, 2-4 parts of 1-5% sodium hydroxide solution by mass, 200-250 parts of calcium salt and 200-250 parts of phosphate.
3. The modified amorphous calcium phosphate excellent in compression resistance according to claim 1 or 2, characterized in that: the modified amorphous calcium phosphate with excellent compression resistance further comprises 800-1200 parts of pure water.
4. The modified amorphous calcium phosphate excellent in compression resistance according to claim 1, characterized in that: the rare earth substance is Ce (NO)3)3、Ce2(SO4)3、CeCl3、Dy(NO3)3、Dy2(SO4)3Or DyCl3One or more of the above components can be combined randomly.
5. The modified amorphous calcium phosphate excellent in compression resistance according to claim 1, characterized in that: the soluble magnesium salt is MgSO4、MgCl2Or Mg (NO)3)2One or more combinations thereof.
6. The modified amorphous calcium phosphate excellent in compression resistance according to claim 1, characterized in that: the calcium salt is Ca (NO)3)2Or CaCl2One or a combination of both.
7. The modified amorphous calcium phosphate excellent in compression resistance according to claim 1, characterized in that: the phosphate is one or the combination of two of sodium dihydrogen phosphate and disodium hydrogen phosphate.
8. A method for preparing the modified amorphous calcium phosphate excellent in compression resistance according to any one of claims 1 to 7, characterized in that: the method comprises the following steps:
s1, respectively adding rare earth substances and soluble magnesium salts into pure water, and then slowly dripping sodium hydroxide solution for 10-30 min;
s2, adding calcium salt and phosphate after dropwise adding, stirring, transferring all the materials into a hydrothermal reaction kettle, heating to 120-140 ℃, and carrying out heat preservation stirring reaction for 3-5 hours;
and S3, stopping the reaction, cooling to room temperature, discharging, filtering and washing the reaction solution, drying a filter cake at the temperature of not higher than 80 ℃ to constant weight, and finally grinding until the granularity is not larger than 200 meshes to obtain the chemically-structured modified amorphous calcium phosphate nano powder.
9. The method for preparing a modified amorphous calcium phosphate excellent in compression resistance according to claim 7, characterized in that: the dripping time in the step S1 is 15-25 min; in the step S2, the temperature is raised to 125-135 ℃ in a sealed manner, and the reaction lasts for 3.5-4.5 h; vacuum drying is adopted in the step S3.
10. Use of the modified amorphous calcium phosphate according to any one of claims 1 to 6, characterized in that: the method is used for biomedical 3D printing materials.
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