CN110498664B - Preparation method of high-strength injectable multiphase calcium phosphate-based bone cement - Google Patents
Preparation method of high-strength injectable multiphase calcium phosphate-based bone cement Download PDFInfo
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- CN110498664B CN110498664B CN201910874656.9A CN201910874656A CN110498664B CN 110498664 B CN110498664 B CN 110498664B CN 201910874656 A CN201910874656 A CN 201910874656A CN 110498664 B CN110498664 B CN 110498664B
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- 239000002639 bone cement Substances 0.000 title claims abstract description 92
- 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 67
- 229910000389 calcium phosphate Inorganic materials 0.000 title claims abstract description 53
- 239000001506 calcium phosphate Substances 0.000 title claims abstract description 53
- 235000011010 calcium phosphates Nutrition 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000000843 powder Substances 0.000 claims abstract description 67
- 239000007788 liquid Substances 0.000 claims abstract description 28
- 239000000463 material Substances 0.000 claims abstract description 28
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims abstract description 17
- 229960003194 meglumine Drugs 0.000 claims abstract description 17
- 238000002156 mixing Methods 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims description 32
- 108010020346 Polyglutamic Acid Proteins 0.000 claims description 22
- 238000000498 ball milling Methods 0.000 claims description 22
- 229920002643 polyglutamic acid Polymers 0.000 claims description 22
- 239000002002 slurry Substances 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 239000005313 bioactive glass Substances 0.000 claims description 17
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- ZOMBKNNSYQHRCA-UHFFFAOYSA-J calcium sulfate hemihydrate Chemical compound O.[Ca+2].[Ca+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O ZOMBKNNSYQHRCA-UHFFFAOYSA-J 0.000 claims description 11
- 238000000465 moulding Methods 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000007791 liquid phase Substances 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims 4
- 239000012530 fluid Substances 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 abstract description 19
- 230000008439 repair process Effects 0.000 abstract description 11
- 238000006731 degradation reaction Methods 0.000 abstract description 4
- 150000002500 ions Chemical class 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 239000011575 calcium Substances 0.000 abstract description 2
- 239000000945 filler Substances 0.000 abstract description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 239000012567 medical material Substances 0.000 abstract description 2
- 238000002324 minimally invasive surgery Methods 0.000 abstract description 2
- 150000001413 amino acids Chemical class 0.000 abstract 1
- 230000004819 osteoinduction Effects 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 12
- 239000004568 cement Substances 0.000 description 10
- 238000006703 hydration reaction Methods 0.000 description 8
- 230000036571 hydration Effects 0.000 description 6
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 6
- 239000004926 polymethyl methacrylate Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 230000007547 defect Effects 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
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- 239000000203 mixture Substances 0.000 description 2
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- 239000000178 monomer Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- ZHJGWYRLJUCMRT-UHFFFAOYSA-N 5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide Chemical compound C=1C=CC=C(C(F)(F)F)C=1C(C)OC(=C(S1)C(N)=O)C=C1N(C1=C2)C=NC1=CC=C2CN1CCN(C)CC1 ZHJGWYRLJUCMRT-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000010478 bone regeneration Effects 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000000278 osteoconductive effect Effects 0.000 description 1
- 230000002138 osteoinductive effect Effects 0.000 description 1
- 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 description 1
- 238000011056 performance test Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 206010041569 spinal fracture Diseases 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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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
- A61L27/02—Inorganic materials
- A61L27/10—Ceramics or glasses
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- 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
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61L27/58—Materials at least partially resorbable by the body
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- 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
- C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
- C04B28/34—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders
- C04B28/344—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders the phosphate binder being present in the starting composition solely as one or more phosphates
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- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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- C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
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- 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
- C04B2201/00—Mortars, concrete or artificial stone characterised by specific physical values
- C04B2201/50—Mortars, concrete or artificial stone characterised by specific physical values for the mechanical strength
- C04B2201/52—High compression strength concretes, i.e. with a compression strength higher than about 55 N/mm2, e.g. reactive powder concrete [RPC]
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Abstract
本发明公开了骨修复医用材料领域内的一种高强度可注射的多相磷酸钙基骨水泥的制备方法，其由α‑磷酸三钙粉末、半水硫酸钙粉末、生物活性玻璃及聚谷氨酸按一定比例混合均匀后获得的骨水泥粉末与含有甲葡胺的固化液调和均匀固化后得到高强度的骨水泥材料。该发明制备的骨水泥材料具有良好的可注射性、抗溃散性能、37℃条件下固化7天后力学压缩强度达到113.68±7.11Mpa，在降解过程中除了有Ca2+和PO4 3‑还可释放促进骨诱导的Si离子，适用于PVP/PKP微创手术中椎体填充剂。此外，本发明提供的制备方法工艺简单，产品综合性能佳，可大规模生产应用。
The invention discloses a preparation method of a high-strength injectable multiphase calcium phosphate-based bone cement in the field of bone repair medical materials. A high-strength bone cement material is obtained after uniformly solidifying the bone cement powder obtained by mixing the amino acid in a certain proportion with the solidifying liquid containing meglumine. The bone cement material prepared by the invention has good injectability and anti-collapse performance, and the mechanical compressive strength reaches 113.68±7.11Mpa after curing at 37°C for 7 days. In the degradation process, in addition to Ca 2+ and PO 4 3‑ Releases Si ions that promote osteoinduction, and is suitable for vertebral body fillers in PVP/PKP minimally invasive surgery. In addition, the preparation method provided by the present invention has simple process, good product comprehensive performance, and can be applied in large-scale production.
Description
Technical Field
The invention relates to the technical field of bone repair medical materials, in particular to a preparation method of high-strength injectable multiphase calcium phosphate-based bone cement.
Background
With the gradual improvement and improvement of living conditions and living quality, the life of human beings is generally prolonged, the proportion of aging population is larger and larger, the incidence rate of a plurality of diseases is increased, vertebral fracture or bone defect caused by osteoporosis is the most common disease of the aging population, although human skeleton has certain self-repairing and regenerating functions, the bone defect cannot be healed by only depending on the bone self-repairing function. Therefore, there is a need to implant bone repair materials to heal and repair bone defects. Among them, the most commonly used bone repair material is Polymethyl methacrylate (PMMA), which has good biocompatibility, high mechanical properties and strong operability, and is widely used in Balloon-expanded kyphoplasty (BKP) and Vertebroplasty (VP), but the further clinical application of PMMA is limited due to the defects of poor bioactivity, large amount of heat release after monomer polymerization, thermal necrosis of tissues in an operation area, toxicity of unpolymerized monomers, and the like. Compared with PMMA, Calcium Phosphate Cement (CPC) does not have the phenomenon of large amount of heat release after reaction similar to PMMA, and has good biocompatibility, bioactivity and bone conduction activity so as to become a hot bone repair material, however, CPC has no osteoinductive activity like PMMA. In addition, the mechanical properties of CPCs are poor, which limits the use of CPCs in load bearing areas. Therefore, there is an urgent need for a bone repair material integrating good biocompatibility, bioactivity, biodegradability, osteoconductive activity, excellent mechanical properties, etc.
Disclosure of Invention
The invention aims to provide a preparation method of high-strength injectable multiphase calcium phosphate-based bone cement, which not only has good injectability and anti-collapsibility, but also has excellent mechanical properties and can provide enough mechanical support for damaged parts.
Therefore, the invention is realized by the following technical scheme: a preparation method of high-strength injectable multiphase calcium phosphate-based bone cement comprises the following steps:
1) mixing alpha-tricalcium phosphate powder, semi-hydrated calcium sulfate powder and bioactive glass powder as raw materials;
2) putting the mixed raw materials, agate medium balls and absolute ethyl alcohol into a ball mill for ball milling;
3) taking out the wet materials subjected to ball milling, and placing the wet materials in a drying oven at the temperature of 60-100 ℃ for drying for 5-10 hours to obtain bone cement powder;
4) and uniformly mixing the bone cement powder and the polyglutamic acid powder to obtain multiphase calcium phosphate-based bone cement powder, uniformly mixing the multiphase calcium phosphate-based bone cement powder with a meglumine curing liquid, and curing and molding the slurry to obtain the high-strength multiphase calcium phosphate-based bone cement material.
Compared with the prior art, the invention has the beneficial effects that:
(1) the polyglutamic acid not only has the performances of water solubility, biodegradability, high viscosity and the like, but also contains a large number of carboxyl groups on molecular chains, and can effectively combine free calcium ions released in the hydration reaction process of calcium phosphate cement so as to form a forming nuclear site, induce the generation of hydroxyapatite and improve the mechanical property of the cement.
(2) The introduction of the bioactive glass can improve the bioactivity of the bone cement material, and Si ions released by the degradation of the bioactive glass are beneficial to promoting the bone induction capability of the material, so that the bone regeneration and repair are accelerated.
(3) The meglumine serving as the curing liquid of the bone cement can reduce the liquid phase used by the hydration reaction of the bone cement, and improve the density of the bone cement so as to improve the mechanical property of the bone cement. In addition, the pH value of the meglumine aqueous solution is alkaline, so that the acidity caused by degradation of polyglutamic acid can be relieved.
The high-strength multiphase calcium phosphate-based bone cement prepared by the invention can be used as a bone repair scaffold, has excellent mechanical properties, good biocompatibility, bioactivity and bone conduction activity, and can be used as a bone tissue repair material. In the degradation process, Ca is removed2+And PO4 3-Can also release Si ions for promoting bone induction, is suitable for being used as a vertebral body filler in PVP/PKP minimally invasive surgery, and has great application potential in the field of bone tissue repair. The preparation method provided by the invention has the advantages of simple process and good product comprehensive performance, and can be used for large-scale production and application.
The calcium sulfate hemihydrate is obtained by heating calcium sulfate dihydrate at the temperature of 100-150 ℃ for 12-24 hours.
The molecular weight of the polyglutamic acid is preferably 150-200 KDa.
The mass fractions of alpha-tricalcium phosphate, calcium sulfate hemihydrate and bioactive glass in the raw material are preferably 76wt%, 19wt% and 5 wt%.
The mass percentage of the polyglutamic acid in the multiphase calcium phosphate-based bone cement powder is preferably 5-40 wt%.
The further improvement of the invention is that the raw materials, the agate medium balls and the absolute ethyl alcohol are ball-milled for 8-12 hours at the rotating speed of 400-900 rpm according to the mass ratio of 1 (28-32) to (10-14).
The curing liquid is an aqueous solution of meglumine, wherein the mass fraction of the meglumine is 3-10 wt%. In the slurry in the step (4), the liquid-solid ratio of the multiphase calcium phosphate-based bone cement powder to the curing liquid is (0.30-0.60) ml/g.
The further improvement of the invention is that the slurry obtained in the step (4) is injected into a mold for molding, then is taken out, is put into an environment with the temperature of 37 +/-0.5 ℃ and the relative humidity of 100 percent for hydration for 6 to 8 days, and then the high-strength multiphase calcium phosphate-based bone cement is obtained. After curing, the mechanical compression strength reaches 113.68 +/-7.11 MPa, and the invention has injectability and can meet the filling requirements of different vertebral bodies.
Drawings
Fig. 1 is a graph illustrating the compressive strength of bone repair scaffolds P1, P2, P3, P4 and P5 prepared in example 1, example 2, example 3, comparative example 1 and comparative example 2.
Fig. 2 to 6 are physical diagrams of the bone cement slurries prepared in example 1, example 2, example 3, comparative example 1 and comparative example 2, respectively, after being directly injected into PBS for 6 hours.
Detailed Description
Example 1
A preparation method of high-strength injectable multiphase calcium phosphate-based bone cement comprises the following steps:
1) mixing alpha-tricalcium phosphate powder, semi-hydrated calcium sulfate powder and bioactive glass powder as raw materials; wherein the calcium sulfate hemihydrate is obtained by heating calcium sulfate dihydrate at 100-150 ℃ for 12-24 hours;
the preparation method of the bioactive glass comprises the following steps: firstly, 1.8g of calcium nitrate tetrahydrate is added into 5ml of ethyl orthosilicate, then 16 ml of a mixed solution of deionized water and absolute ethyl alcohol with a molar ratio of 1:1 is added into the mixture, and finally 6g of glacial acetic acid is added into the mixture. The sol is obtained by reaction with stirring, and the obtained sol is dried in an oven at 60 ℃ for 12 to 24 hours to obtain xerogel. And (3) placing the xerogel in a muffle furnace, heating to 550-750 ℃ at the heating rate of 5-10 ℃/min, preserving the heat for 2 hours, and naturally cooling to obtain the bioactive glass.
In the raw materials, the mass fractions of the alpha-tricalcium phosphate, the calcium sulfate hemihydrate and the bioactive glass are 76wt%, 19wt% and 5wt%, respectively.
2) Putting the mixed raw materials, agate medium balls and absolute ethyl alcohol into a ball mill for ball milling; the raw materials are fully and uniformly mixed, and the particle size of the raw materials is uniform through ball milling; during ball milling, the raw materials, the agate medium balls and the absolute ethyl alcohol are ball milled for 8-12 hours at the rotating speed of 400-900 r/min according to the mass ratio of 1:30: 12.
3) Taking out the wet material which is ball-milled and contains absolute ethyl alcohol, and placing the wet material in a drying oven at the temperature of 60-100 ℃ for drying for 5-10 hours to obtain bone cement powder;
4) uniformly mixing bone cement powder and polyglutamic acid powder to obtain multiphase calcium phosphate-based bone cement powder, and adding the multiphase calcium phosphate-based bone cement powder into a curing liquid, wherein the curing liquid is a meglumine solution with the mass fraction of 6wt% (1.2 g of meglumine is added into 18.8ml of deionized water to prepare the meglumine curing liquid with the mass fraction of 6 wt%); the molecular weight of the polyglutamic acid is 150-200KDa, and the mass content of the polyglutamic acid powder in the multiphase calcium phosphate-based bone cement powder is 20 wt%; and (3) uniformly mixing the multiphase calcium phosphate-based bone cement powder and the curing liquid in a solid-liquid ratio of 1g to 0.6ml to obtain slurry, namely the injectable multiphase calcium phosphate-based bone cement material.
The slurry is injected into a cavity for molding and then taken out, the molded cement is placed in an environment with the temperature of 37 ℃ and the relative humidity of 100% for hydration for 7 days, and then the hydrated cement is taken out to obtain the high-strength multiphase calcium phosphate-based bone cement, which is marked as P1, and the compressive strength of the cement can reach 113.68 +/-7.11 MPa after 7 days.
Example 2
A preparation method of high-strength injectable multiphase calcium phosphate-based bone cement comprises the following steps:
1) premixing alpha-tricalcium phosphate powder, semi-hydrated calcium sulfate powder and bioactive glass powder serving as raw materials; in the raw materials, the mass fractions of the alpha-tricalcium phosphate, the calcium sulfate hemihydrate and the bioactive glass are 76wt%, 19wt% and 5wt%, respectively;
2) putting the premixed raw materials, agate medium balls and absolute ethyl alcohol into a ball mill for ball milling; the raw materials are fully and uniformly mixed, and the particle size of the raw materials is uniform through ball milling; during ball milling, the raw materials, the agate medium balls and the absolute ethyl alcohol are ball milled for 8-12 hours at the rotating speed of 400-900 r/min according to the mass ratio of 1:30: 12.
3) Taking out the wet material which is ball-milled and contains absolute ethyl alcohol, and placing the wet material in a drying oven at the temperature of 60-100 ℃ for drying for 5-10 hours to obtain bone cement powder;
4) uniformly mixing bone cement powder and polyglutamic acid powder to obtain multiphase calcium phosphate-based bone cement powder, and putting the multiphase calcium phosphate-based bone cement powder into a curing liquid, wherein the curing liquid is meglumine solution with the mass fraction of 6 wt%; the molecular weight of the polyglutamic acid is 150-200KDa, and the mass content of the polyglutamic acid powder in the multiphase calcium phosphate-based bone cement powder is 15 wt%; the multiphase calcium phosphate-based bone cement and the curing liquid are mixed uniformly in a solid-liquid ratio of 1g to 0.60ml to obtain slurry, namely the injectable multiphase calcium phosphate-based bone cement material.
After the slurry is injected into a cavity for molding, the slurry is placed in an environment with the temperature of 37 ℃ and the relative humidity of 100% for hydration for 7 days, and then the slurry is taken out to obtain the high-strength multiphase calcium phosphate-based bone cement, which is marked as P2, and the compressive strength of the cement can reach 73.67 +/-5.35 MPa after 7 days.
Example 3
A preparation method of high-strength injectable multiphase calcium phosphate-based bone cement comprises the following steps:
1) premixing alpha-tricalcium phosphate powder, semi-hydrated calcium sulfate powder and bioactive glass powder serving as raw materials; in the raw materials, the mass fractions of the alpha-tricalcium phosphate, the calcium sulfate hemihydrate and the bioactive glass are 76wt%, 19wt% and 5wt%, respectively;
2) putting the mixed raw materials, agate medium balls and absolute ethyl alcohol into a ball mill for ball milling; the raw materials are fully and uniformly mixed, and the particle size of the raw materials is uniform through ball milling; during ball milling, the raw materials, the agate medium balls and the absolute ethyl alcohol are ball milled for 8-12 hours at the rotating speed of 400-600 revolutions per minute in the mass ratio of 1:30: 12.
3) Taking out the wet material which is ball-milled and contains absolute ethyl alcohol, and placing the wet material in a drying oven at the temperature of 60-100 ℃ for drying for 5-10 hours to obtain bone cement powder;
4) uniformly mixing bone cement powder and polyglutamic acid powder to obtain the multiphase calcium phosphate-based bone cement powder, and putting the multiphase calcium phosphate-based bone cement powder into a curing liquid, wherein the curing liquid is meglumine solution with the mass fraction of 6 wt%; the molecular weight of the polyglutamic acid is 150-200KDa, and the mass content of the polyglutamic acid powder in the multiphase calcium phosphate-based bone cement powder is 10 wt%; the multiphase calcium phosphate-based bone cement and the curing liquid are mixed uniformly in a solid-liquid ratio of 1g to 0.60ml to obtain slurry, namely the injectable multiphase calcium phosphate-based bone cement material.
After the slurry is injected into a cavity for molding, the slurry is placed in an environment with the temperature of 37 ℃ and the relative humidity of 100% for hydration for 7 days, and then the slurry is taken out to obtain the high-strength multiphase calcium phosphate-based bone cement, which is marked as P3, and the compression strength of the cement can reach 35.62 +/-3.92 MPa after 7 days.
Comparative example 1
The preparation method of the stent of the comparative example comprises the following specific steps:
(1) placing alpha-tricalcium phosphate and calcium sulfate hemihydrate into a planetary ball mill for ball milling according to the mass ratio of 1: 0.20-0.40. And after the ball milling is finished, drying the wet material subjected to the ball milling to obtain the required bone cement powder.
(2) Adding 1.2g of meglumine into 18.8ml of deionized water to prepare a meglumine curing liquid with the mass fraction of 6%; and uniformly mixing the bone cement powder and the curing liquid according to the solid-liquid ratio of 1g to 0.45ml to obtain bone cement paste.
(3) And (3) after the bone cement paste is formed, placing the bone cement paste in an oven with the temperature of 37 ℃ and the relative humidity of 100% for hydration for 7 days, and taking out the bone cement paste to obtain the bone cement bracket, wherein the bone cement bracket is marked as P4, and the compressive strength of the bone cement bracket can reach 7.67 +/-1 MPa after 7 days.
Comparative example 2
The preparation method of the stent of the comparative example comprises the following specific steps:
(1) placing beta-tricalcium phosphate and bioactive glass into a planetary ball mill for ball milling according to the mass ratio of 1: 0.10-0.40. And after the ball milling is finished, drying the wet material subjected to the ball milling to obtain the required bone cement powder.
(2) Adding 2.0g of polyglutamic acid into 18.0 ml of deionized water to prepare polyglutamic acid curing liquid with the mass fraction of 10 wt%; and uniformly mixing the bone cement powder and the curing liquid according to the solid-liquid ratio of 1g to 0.60ml to obtain bone cement paste.
(3) And (3) after the bone cement paste is formed, placing the bone cement paste in an oven with the temperature of 37 ℃ and the relative humidity of 100% for hydration for 7 days, and taking out the bone cement paste to obtain the bone cement bracket, wherein the bone cement bracket is marked as P5, and the compressive strength of the bone cement bracket can reach 21.15 +/-3.14 MPa after 7 days.
The bone repair scaffolds prepared in examples 1-3 and comparative examples 1-2 were subjected to the following performance tests.
Compressive strength
Fig. 1 is a graph showing the compressive strength of the bone cement scaffolds P1, P2, P3, P4 and P5 prepared in example 1, example 2, example 3, comparative example 1 and comparative example 2. The height of the bracket is 9.0 plus or minus 1.0mm, the diameter is 4.5 plus or minus 0.5mm, and the loading rate is 1.0 mm/min.
Resistance to collapsibility
Fig. 2, 3, 4, 5 and 6 are physical diagrams of the bone cement slurries prepared in example 1, 2, 3, comparative example 1 and 2, respectively, after being directly injected into PBS for 6 hours. The cement bars in fig. 2, 3, 4 and 6 remained intact in PBS without collapse; the cement strip in fig. 5 is fully collapsed.
The present invention is not limited to the above-mentioned embodiments, and based on the technical solutions disclosed in the present invention, those skilled in the art can make some substitutions and modifications to some technical features without creative efforts according to the disclosed technical contents, and these substitutions and modifications are all within the protection scope of the present invention. The method is within the protection scope of the invention as long as the following steps and value ranges are included, and the method comprises the following steps:
1) mixing alpha-tricalcium phosphate powder, semi-hydrated calcium sulfate powder and bioactive glass powder as raw materials; wherein the calcium sulfate hemihydrate is obtained by heating calcium sulfate dihydrate at the temperature of 100-150 ℃ for 12-24 hours; in the raw materials, the mass fractions of the alpha-tricalcium phosphate, the calcium sulfate hemihydrate and the bioactive glass are 76wt%, 19wt% and 5wt%, respectively.
2) Putting the mixed raw materials, agate medium balls and absolute ethyl alcohol into a ball mill for ball milling; the raw materials are fully and uniformly mixed, and the particle size of the raw materials is uniform through ball milling; during ball milling, the raw materials, the agate medium balls and the absolute ethyl alcohol are ball milled for 8 to 12 hours at the rotating speed of 400-900 revolutions per minute according to the mass ratio of 1 (28 to 32) to (10 to 14).
3) Taking out the wet material which is ball-milled and contains absolute ethyl alcohol, and placing the wet material in a drying oven at 60-100 ℃ for drying for 5-10 hours to obtain bone cement powder.
4) Uniformly mixing bone cement powder and polyglutamic acid powder to obtain multiphase calcium phosphate-based bone cement powder, and adding the multiphase calcium phosphate-based bone cement powder into a curing liquid, wherein the curing liquid is meglumine solution with the mass fraction of 3-10 wt%; the molecular weight of the polyglutamic acid is 150-200KDa, and the mass content of the polyglutamic acid powder in the multiphase calcium phosphate-based bone cement powder is 5-40 wt%; and (3) uniformly mixing the multiphase calcium phosphate-based bone cement powder and the curing liquid in a liquid-solid ratio of (0.30-0.60) ml/g, injecting the obtained slurry into a cavity for molding, placing the molded slurry in an environment with the temperature of 37 +/-0.5 ℃ and the relative humidity of 100% for hydrating for 6-8 days, and taking out the hydrated slurry to obtain the high-strength multiphase calcium phosphate bone cement.
Claims (6)
1. A preparation method of high-strength injectable multiphase calcium phosphate-based bone cement is characterized by comprising the following steps:
1) mixing alpha-tricalcium phosphate powder, semi-hydrated calcium sulfate powder and bioactive glass powder as raw materials; in the raw materials, the mass fractions of the alpha-tricalcium phosphate, the calcium sulfate hemihydrate and the bioactive glass are 76wt%, 19wt% and 5 wt%;
2) putting the mixed raw materials, agate medium balls and absolute ethyl alcohol into a ball mill for ball milling;
3) taking out the wet materials subjected to ball milling, and placing the wet materials in a drying oven at the temperature of 60-100 ℃ for drying for 5-10 hours to obtain bone cement powder;
4) uniformly mixing the bone cement powder and the polyglutamic acid powder to obtain multiphase calcium phosphate-based bone cement powder, uniformly mixing the multiphase calcium phosphate-based bone cement powder with a meglumine curing liquid phase to obtain slurry, and curing and molding to obtain a high-strength multiphase calcium phosphate-based bone cement material; the mass percent of the polyglutamic acid in the multiphase calcium phosphate-based bone cement powder is 5-40 wt%; the curing liquid is aqueous solution of meglumine, wherein the mass fraction of the meglumine is 3-10 wt%.
2. The method for preparing a high strength injectable multi-phase calcium phosphate based bone cement as claimed in claim 1, wherein the calcium sulfate hemihydrate is calcium sulfate dihydrate obtained by heating at 100-150 ℃ for 12-24 hours.
3. The method for preparing a high-strength injectable multi-phasic calcium phosphate-based bone cement as set forth in claim 1, wherein the molecular weight of the polyglutamic acid is 150-200 KDa.
4. The method for preparing the high-strength injectable multi-phase calcium phosphate-based bone cement as claimed in claim 1, wherein the raw materials, the agate medium balls and the absolute ethyl alcohol are ball-milled at a mass ratio of 1 (28-32) to (10-14) at a rotation speed of 400-900 rpm for 8-12 hours.
5. The method for preparing a high-strength injectable multi-phase calcium phosphate-based bone cement according to claim 1, wherein the slurry of step (4) has a liquid-to-solid ratio of multi-phase calcium phosphate-based bone cement powder to setting fluid of (0.30-0.60) ml/g.
6. The method for preparing a high-strength injectable heterogeneous calcium phosphate-based bone cement according to any one of claims 1 to 5, wherein the slurry obtained in step (4) is injected into a mold, molded, taken out, and hydrated in an environment of 37 ± 0.5 ℃ and a relative humidity of 100% for 6 to 8 days to obtain the high-strength heterogeneous calcium phosphate-based bone cement.
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