CN107281554B - Method for preparing calcium phosphate-based composite material suitable for 3D printing through mechanical activation - Google Patents
Method for preparing calcium phosphate-based composite material suitable for 3D printing through mechanical activation Download PDFInfo
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- CN107281554B CN107281554B CN201710321270.6A CN201710321270A CN107281554B CN 107281554 B CN107281554 B CN 107281554B CN 201710321270 A CN201710321270 A CN 201710321270A CN 107281554 B CN107281554 B CN 107281554B
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- 239000001506 calcium phosphate Substances 0.000 title claims abstract description 174
- 229910000389 calcium phosphate Inorganic materials 0.000 title claims abstract description 170
- 239000002131 composite material Substances 0.000 title claims abstract description 66
- 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 63
- 235000011010 calcium phosphates Nutrition 0.000 title claims abstract description 52
- 238000010146 3D printing Methods 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 25
- 238000004137 mechanical activation Methods 0.000 title claims abstract description 22
- 239000000843 powder Substances 0.000 claims abstract description 175
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 135
- 239000000243 solution Substances 0.000 claims abstract description 93
- 239000007788 liquid Substances 0.000 claims abstract description 32
- 238000002156 mixing Methods 0.000 claims abstract description 30
- 239000011259 mixed solution Substances 0.000 claims abstract description 28
- 238000003756 stirring Methods 0.000 claims abstract description 27
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 24
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 22
- 229920005615 natural polymer Polymers 0.000 claims abstract description 18
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 15
- 239000010452 phosphate Substances 0.000 claims abstract description 15
- 238000000498 ball milling Methods 0.000 claims abstract description 14
- 238000001035 drying Methods 0.000 claims abstract description 14
- 238000000227 grinding Methods 0.000 claims abstract description 14
- 238000005406 washing Methods 0.000 claims abstract description 14
- 239000012266 salt solution Substances 0.000 claims abstract description 11
- 235000019441 ethanol Nutrition 0.000 claims description 39
- ZHJGWYRLJUCMRT-UHFFFAOYSA-N 5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide Chemical group 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 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- 238000002360 preparation method Methods 0.000 claims description 28
- 239000008367 deionised water Substances 0.000 claims description 26
- 229910021641 deionized water Inorganic materials 0.000 claims description 26
- 239000011575 calcium Substances 0.000 claims description 24
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 22
- 229910052791 calcium Inorganic materials 0.000 claims description 22
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical group [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 claims description 22
- 229910000388 diammonium phosphate Inorganic materials 0.000 claims description 22
- 235000019838 diammonium phosphate Nutrition 0.000 claims description 22
- 238000004108 freeze drying Methods 0.000 claims description 22
- 102000008186 Collagen Human genes 0.000 claims description 20
- 108010035532 Collagen Proteins 0.000 claims description 20
- 229920001436 collagen Polymers 0.000 claims description 20
- 230000015572 biosynthetic process Effects 0.000 claims description 16
- 238000003786 synthesis reaction Methods 0.000 claims description 16
- 241000283690 Bos taurus Species 0.000 claims description 15
- 239000001110 calcium chloride Substances 0.000 claims description 14
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 14
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 12
- 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 claims description 12
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 10
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 9
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 8
- 229910000387 ammonium dihydrogen phosphate Inorganic materials 0.000 claims description 6
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 6
- 235000019837 monoammonium phosphate Nutrition 0.000 claims description 6
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 6
- 235000019796 monopotassium phosphate Nutrition 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
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 5
- 229920001817 Agar Polymers 0.000 claims description 5
- 229920001661 Chitosan Polymers 0.000 claims description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 108010010803 Gelatin Proteins 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- 108010058846 Ovalbumin Proteins 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 5
- 239000008272 agar Substances 0.000 claims description 5
- 235000010419 agar Nutrition 0.000 claims description 5
- 239000008273 gelatin Substances 0.000 claims description 5
- 229920000159 gelatin Polymers 0.000 claims description 5
- 235000019322 gelatine Nutrition 0.000 claims description 5
- 235000011852 gelatine desserts Nutrition 0.000 claims description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 5
- 239000000787 lecithin Substances 0.000 claims description 5
- 235000010445 lecithin Nutrition 0.000 claims description 5
- 229940067606 lecithin Drugs 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229940092253 ovalbumin Drugs 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- 229920001221 xylan Polymers 0.000 claims description 5
- 150000004823 xylans Chemical class 0.000 claims description 5
- 229920002678 cellulose Polymers 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 229910000392 octacalcium phosphate Inorganic materials 0.000 claims description 4
- YIGWVOWKHUSYER-UHFFFAOYSA-F tetracalcium;hydrogen phosphate;diphosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].OP([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O YIGWVOWKHUSYER-UHFFFAOYSA-F 0.000 claims description 4
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 4
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 4
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 4
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 239000002002 slurry Substances 0.000 abstract description 19
- 238000007639 printing Methods 0.000 abstract description 14
- 238000001125 extrusion Methods 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 230000003213 activating effect Effects 0.000 abstract 1
- 210000000988 bone and bone Anatomy 0.000 description 16
- 239000005696 Diammonium phosphate Substances 0.000 description 15
- -1 hydroxypropyl methyl Chemical group 0.000 description 13
- 239000000463 material Substances 0.000 description 10
- 235000021317 phosphate Nutrition 0.000 description 10
- 230000007547 defect Effects 0.000 description 5
- 239000011148 porous material Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000000465 moulding Methods 0.000 description 4
- 238000003828 vacuum filtration Methods 0.000 description 4
- 238000009777 vacuum freeze-drying Methods 0.000 description 4
- 239000012620 biological material Substances 0.000 description 3
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 3
- 235000019797 dipotassium phosphate Nutrition 0.000 description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
- 238000000110 selective laser sintering Methods 0.000 description 3
- 238000007711 solidification Methods 0.000 description 3
- 230000008023 solidification Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 238000005470 impregnation Methods 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 241001391944 Commicarpus scandens Species 0.000 description 1
- 208000032984 Intraoperative Complications Diseases 0.000 description 1
- 206010057765 Procedural complication Diseases 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 239000004068 calcium phosphate ceramic Substances 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
-
- 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y70/00—Materials specially adapted for additive manufacturing
Abstract
A method for preparing a calcium phosphate-based composite material suitable for 3D printing by mechanical activation comprises the following steps: A. synthesizing natural polymer-calcium hydrogen phosphate powder, preparing calcium salt solution and phosphate solution, adding natural polymer into the calcium salt solution to obtain mixed solution, adding phosphate into the mixed solution, stirring for 1-4h, centrifuging, washing, and drying; B. preparing natural polymer-calcium phosphate powder; C. mechanically activating natural polymer-calcium phosphate powder, adding anhydrous ethanol into the natural polymer-calcium phosphate powder to obtain ethanol solution of the powder, pouring the ethanol solution into a grinding tank, and ball-milling; D. preparing a curing liquid; E. mixing mechanically activated natural polymer-calcium phosphate powder and solidifying solution uniformly. The calcium phosphate-based composite material prepared by the method is suitable for 3D printing of calcium phosphate-based supports, and the calcium phosphate-based supports prepared by extrusion forming 3D printing methods are used as raw materials and are good in mechanical property, high in reliability, high in printing efficiency and high in utilization rate of slurry.
Description
Technical Field
The invention relates to a preparation method of a calcium phosphate-based composite material suitable for 3D printing.
Background
Bone repair materials are one of the most clinically needed biomaterials (Filingham Y, Jacobs J. Bone graft and the patient sustitutes. the Bone and Joint Journal,2016,98-B (1 Suppl A): 6-9). The inorganic component of bone is mainly Calcium phosphate (CaP), and Calcium phosphate-based biomaterials have excellent biocompatibility. Meanwhile, the porous calcium phosphate-based three-dimensional scaffold can ensure the ingrowth of cells and tissues and the transport of nutrients and metabolites (Bouler JM, Pilet P, et al., Biphasic calcium phosphate technologies for bone recovery: A review of biological response, actaBiomaterialia, 2017). Therefore, the calcium phosphate-based porous scaffold is widely applied to clinical bone defect filling.
The traditional preparation methods of the calcium phosphate-based porous scaffold include a particle leaching method, a gas foaming method, an organic foam impregnation method and the like (Zhang J, Zhou HJ, et. al. RhBMP-2-loaded calcium silicate/calcium phosphate technical scaffold with a modified bone tissue generation. biomaterials.2013,34(37):9381 and 9392.). The pore diameter of the porous bracket prepared by the particle leaching method is adjustable, but the pore connectivity is poor; the gas foaming method is simple and does not introduce impurities, but the size, shape and distribution of pores are difficult to control; the porous scaffold prepared by the organic foam impregnation method has adjustable pore structure and high pore connectivity, but the mechanical strength of the prepared scaffold is lower. In addition, these methods produce scaffolds whose shape and size are difficult to precisely match the bone defect of the patient; thereby increasing the incidence of intraoperative complications such as bone non-healing or delayed healing.
3D printing (Three dimensional printing), also called rapid prototyping, is a technology which appears in the 90 s of the 20 th century and designs a Three-dimensional model on the basis of a digital model file, adopts the principle of layered manufacturing and layer-by-layer superposition to construct an entity, and has the characteristics of individuation, complexity, refinement, diversification and the like in manufacturing (Tang D, Tare RS, et al. The prosthesis with similar structure formed by natural tissues and organs obtained by 3D printing is applied in the medical field in an attempt mode and becomes one of hot spots in the current manufacturing industry. Based on the personalized shape of the bone defect of the patient and the medical image design model of the porous structure of the bone tissue, the computer precisely controls the integrated manufacture of the complex shape and the internal fine structure, so that the irregular macroscopic shape of the complex shape can be precisely matched with the bone defect, the bone integration can be promoted by simulating the fine microstructure of the bone, and the personalized customization aiming at the specific requirements of different patients can be realized, so as to meet the bone defect shapes of different patients (Trombeta R, Inzana J, et. al., 3D printing of calcium phosphate ceramics for bone tissue engineering and drug delivery. Annals of biomedical engineering.2017,45(1): 23-44.).
The main methods for 3D printing calcium phosphate base include Stereolithography (SLA), Fused Deposition Modeling (FDM), Selective Laser Sintering (SLS), Three-Dimensional printing, bonding and blending (3 DP), and extrusion molding.
The fused deposition molding and the selective laser sintering printing are carried out by adding high polymer with low melting point to assist the molding of calcium phosphate-based powder; however, the calcium phosphate-based material has high melting point and is difficult to melt and solidify, so that the requirement on the temperature of a 3D printer is high, the printing cost is high, and the product yield is low. The stereolithography realizes 3D printing and forming by adding photosensitive polymers, but the biocompatibility of photosensitive materials is low, so that the biocompatibility of the stent is low. The three-dimensional printing, bonding and forming method has the advantages that due to the limitation of the surface tension and the spraying state of the binder and the wettability between the calcium phosphate-based powder, the precision of a printed part is low, the loss phenomenon of the calcium phosphate-based powder is serious, and the product percent of pass is low.
Extrusion printing of calcium phosphate based materials is currently the most used method. The paste-like calcium phosphate-based material, namely 'ink', is extruded to a preset position from a pipeline and then solidified, so that 3D printing of the calcium phosphate-based support is realized. However, the existing slurry calcium phosphate-based material is a slurry formed by mixing calcium phosphate powder and phosphate buffer solution in situ. Calcium phosphate in the slurry is high in solidification speed, and the slurry is diluted and then concentrated when being extruded, so that the slurry is not extruded in a pipeline, namely is solidified. The printer is stopped during printing, all the residual slurry needs to be discharged, the blocked pipeline needs to be dredged, and the new slurry is refilled and then printed again. The injection rate of the existing slurry calcium phosphate-based material is only up to (73 ± 5)%, that is, only 73 ± 5 parts by weight of slurry in 100 parts by weight of slurry can be extruded out of a pipeline for smooth molding (document 1:O'Neill R,McCarthy HOthe journal of Materials Science-Materials in medicine.2016,27(2): 29). This results in, on the one hand, a low utilization of the paste and, on the other hand, frequent shutdowns which also reduce the printing efficiency(ii) a And the joint is formed on the bracket when the bracket is restarted after the shutdown, so that the bracket is easy to break from the joint, and the reliability of the bracket is reduced.
Disclosure of Invention
The invention aims to provide a method for preparing a calcium phosphate-based composite material suitable for 3D printing by mechanical activation, the calcium phosphate-based composite material prepared by the method is suitable for 3D printing of a calcium phosphate-based support, and the calcium phosphate-based support obtained by an extrusion forming 3D printing method by taking the calcium phosphate-based composite material as a raw material has the advantages of good mechanical property, high reliability, high printing efficiency, high utilization rate of slurry and low printing cost.
The technical scheme adopted by the invention for realizing the aim is that the method for preparing the calcium phosphate-based composite material suitable for 3D printing by mechanical activation comprises the following steps:
A. synthesizing natural polymer-calcium hydrophosphate composite powder:
dissolving soluble calcium salt in deionized water to obtain a calcium salt solution; dissolving soluble phosphate in deionized water to obtain a phosphate solution; the molar ratio of the calcium salt in the calcium salt solution to the phosphate in the phosphate solution is 0.5-1.67: 1;
adding natural polymer into the calcium salt solution to obtain a mixed solution, wherein the mol number of the added natural polymer is 0.1-2 times of that of the calcium salt in the calcium salt solution;
then, adding the phosphate into the mixed solution under stirring, continuing stirring for 1-4h, standing for 20-24h, then centrifugally washing, vacuum filtering, and freeze-drying to obtain natural polymer-calcium hydrophosphate composite powder;
B. preparation of natural high molecular calcium phosphate powder
Uniformly mixing 1 part by weight of the natural polymer-calcium hydrophosphate composite powder obtained in the step A with 0.5-5 parts by weight of calcium phosphate salt to obtain natural polymer-calcium hydrophosphate powder;
C. mechanical activation of natural polymer-calcium phosphate powder
Adding 5-7 parts by weight of the natural polymer-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethyl alcohol to obtain an ethanol solution of the natural polymer-calcium phosphate powder, and pouring the ethanol solution of the natural polymer-calcium phosphate powder into a grinding tank of a ball mill; starting the ball mill, and carrying out ball milling for 4-10h at the rotating speed of 300-700 r/min; then drying or freeze-drying the ethanol solution of the natural polymer-calcium phosphate powder at 37-80 ℃ to obtain mechanically activated natural polymer-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 1-5 wt.% of natural polymer aqueous solution, and storing for later use;
E. and D, uniformly mixing 65-80 parts by weight of the mechanically activated natural polymer calcium phosphate powder obtained in the step C and 100 parts by weight of the curing liquid obtained in the step D to obtain the composite material.
When in use, the calcium phosphate-based composite material prepared by the invention is placed in an injector in a 3D printer; and (3) curing the support printed by the 3D printer in a constant-temperature water bath with the temperature of 37 ℃ and the humidity of 100% for 24 hours to obtain the calcium phosphate-based composite material support. In addition, it should be noted that the calcium phosphate-based composite material prepared by the present invention has a short setting time and needs to be prepared at the present time (i.e., the powder obtained in step C and the solidification solution prepared in step D can be stored for a long time respectively, but the slurry prepared by mixing the powder obtained in step C and the solidification solution prepared in step D must be used immediately).
Compared with the prior art, the invention has the beneficial effects that:
firstly, in the mechanical activation treatment process in the step C, the ball mill is matched with the mechanical energy of balls, so that impact, collision, friction and the like occur among solid powder, one part of the mechanical energy is firstly converted into heat energy and then converted into internal energy inside the powder, the other part of the mechanical energy is directly converted into the internal energy of the solid powder, so that the calcium phosphate powder can crack until the calcium phosphate powder is broken, the average size of the powder is reduced, the setting time of the calcium phosphate slurry is reduced, and the injectability of the calcium phosphate slurry is improved.
Experiments prove that when the calcium phosphate-based composite material prepared by the invention is used as a raw material and the calcium phosphate-based support is printed by an extrusion forming 3D printing method, the material injection rate reaches 90 +/-2%, and the slurry utilization rate is high; the printing stop frequency is reduced, the printing efficiency is high, and the printing cost is low. The printing stop frequency is reduced, meanwhile, the seam formed on the support by twice printing is reduced, and the integrity and the reliability of the support are improved.
And secondly, natural polymers in the curing liquid have excellent viscosity, so that the friction force between the calcium phosphate-based powder and the curing liquid is increased in the printing process, and the solid-liquid phase separation phenomenon is reduced. The same natural polymer exists in the solid phase and the liquid phase at the same time, molecular chains of the natural polymer are easy to tangle, and the mechanical strength of the 3D printing support is improved.
Further, the soluble calcium salt added in the calcium salt solution of step A of the present invention is calcium nitrate tetrahydrate (Ca (NO)3)2·4H2O) or calcium chloride (CaCl)2)。
The two calcium salts are common calcium salts in the synthesis of calcium phosphate salts, have good solubility, wide sources and low price, and the anions of the calcium salts have no influence on the synthesis product.
Further, the soluble phosphate added in the phosphate solution in the step A is diammonium hydrogen phosphate ((NH)4)2HPO4) Ammonium dihydrogen phosphate (NH)4H2PO4) Dipotassium hydrogen phosphate (K)2HPO4) Potassium dihydrogen phosphate (KH)2PO4) Disodium hydrogen phosphate (Na)2HPO4) Or sodium dihydrogen phosphate (NaH)2PO4)。
The phosphates are common phosphates in the synthesis of calcium phosphate salts, have good solubility, wide sources and low price, and cations of the phosphates have no influence on the synthesis product.
Further, the natural polymer in steps A and D of the present invention is gelatin, collagen, bovine collagen cellulose, chitosan, agar, starch, hydroxypropyl methylcellulose, ovalbumin, mannitol, xylan or lecithin.
The natural polymer has good biocompatibility, wide source, low price and wide application.
Further, the calcium phosphate salt in step B of the present invention is one or a mixture of more than one of tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, octacalcium phosphate, and hydroxyapatite.
The calcium phosphate salt has rich resource, high biocompatibility, stable performance and wide application.
Detailed Description
The technical solution of the present invention will be described in further detail with reference to the following embodiments.
Example 1
A. Synthesis of gelatin-calcium hydrogen phosphate composite powder
Dissolving calcium nitrate tetrahydrate in deionized water to obtain a calcium nitrate tetrahydrate solution; dissolving diammonium phosphate in deionized water to obtain a diammonium phosphate solution; the molar ratio of the calcium nitrate tetrahydrate to the diammonium phosphate is 0.5: 1;
adding gelatin into the calcium nitrate tetrahydrate solution to obtain a mixed solution, wherein the mole number of the added gelatin is 0.1 time of that of the calcium nitrate tetrahydrate solution;
then, adding a diammonium hydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 1h, standing for 20h, then centrifugally washing, vacuum-filtering, and freeze-drying to obtain gelatin-calcium hydrogen phosphate composite powder;
B. preparation of gelatin-calcium phosphate powder
Respectively and uniformly mixing 1 part by weight of the gelatin-calcium hydrogen phosphate composite powder obtained in the step A with 0.5 part by weight of tricalcium phosphate and 0.5 part by weight of hydroxyapatite to obtain gelatin-calcium phosphate powder;
C. mechanical activation of gelatin-calcium phosphate powders
Adding 5 parts by weight of the gelatin-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethanol to obtain an ethanol solution of the gelatin-calcium phosphate powder, and pouring the ethanol solution of the gelatin-calcium phosphate powder into a grinding tank of a ball mill; starting a ball mill, and carrying out ball milling for 4 hours at the rotating speed of 300 r/min; then drying or freeze-drying the ethanol solution of the gelatin-calcium phosphate powder at 37 ℃ to obtain mechanically activated gelatin-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 1 wt.% gelatin water solution, and storing for later use;
E. and D, uniformly mixing 65 parts by weight of the mechanically activated natural polymer-calcium phosphate powder obtained in the step C and 100 parts by weight of the curing liquid obtained in the step D to obtain the curing liquid.
Tests show that the injection rate of the calcium phosphate-based composite material suitable for 3D printing can reach (92 +/-3)%, namely, in 100 parts by weight of slurry, 92 +/-3 parts by weight of slurry can be extruded out of a pipeline for smooth molding. The injection rate of the conventional calcium phosphate-based slurry is only 73. + -. 5 at the maximum (document 1). .
Example 2
A. Synthesis of collagen-calcium hydrogen phosphate composite powder
Dissolving calcium nitrate tetrahydrate in deionized water to obtain a calcium nitrate tetrahydrate solution; dissolving diammonium phosphate in deionized water to obtain a diammonium phosphate solution; the molar ratio of the calcium nitrate tetrahydrate to the diammonium phosphate is 1.67: 1;
adding collagen into the calcium nitrate tetrahydrate solution to obtain a mixed solution, wherein the addition mole number of the collagen is 1 time of that of the calcium nitrate tetrahydrate;
then, adding a diammonium hydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 4 hours, standing for 24 hours, and then carrying out centrifugal washing, vacuum filtration and freeze drying to obtain collagen-calcium hydrogen phosphate composite powder;
B. preparation of collagen-calcium phosphate powder
Uniformly mixing 1 part by weight of collagen-calcium hydrogen phosphate composite powder obtained in the step A with 5 parts by weight of hydroxyapatite to obtain collagen-calcium phosphate powder;
C. mechanical activation of collagen-calcium phosphate powders
Adding 7 parts by weight of the collagen-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethanol to obtain an ethanol solution of the collagen-calcium phosphate powder, and pouring the ethanol solution of the collagen-calcium phosphate powder into a grinding tank of a ball mill; starting the ball mill, and carrying out ball milling for 10 hours at the rotating speed of 700 r/min; then drying or freeze-drying the ethanol solution of the collagen-calcium phosphate powder at 80 ℃ to obtain mechanically activated collagen-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 5 wt.% of collagen water solution, and storing for later use;
E. and D, uniformly mixing 80 parts by weight of the mechanically activated collagen-calcium phosphate powder obtained in the step C with 100 parts by weight of the curing liquid obtained in the step D to obtain the collagen-calcium phosphate composite material.
Example 3
A. Synthesis of chitosan-calcium hydrophosphate composite powder
Dissolving calcium chloride in deionized water to obtain a calcium chloride solution; dissolving disodium hydrogen phosphate in deionized water to obtain a disodium hydrogen phosphate solution; the molar ratio of calcium chloride to disodium hydrogen phosphate is 0.85: 1;
adding chitosan into the calcium chloride solution to obtain a mixed solution, wherein the adding mole number of the chitosan is 0.4 times of that of the calcium chloride;
then, adding the disodium hydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 4 hours, standing for 24 hours, and then centrifugally washing, vacuum-filtering, and freeze-drying to obtain chitosan-calcium hydrophosphate composite powder;
B. preparation of chitosan-calcium phosphate powder
Uniformly mixing 1 part by weight of chitosan-calcium hydrophosphate composite powder obtained in the step A with 1 part by weight of octacalcium phosphate to obtain chitosan-calcium phosphate powder;
C. mechanical activation of chitosan-calcium phosphate powders
Adding 6 parts by weight of chitosan-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethyl alcohol to obtain an ethanol solution of chitosan-calcium phosphate powder, and pouring the ethanol solution of chitosan-calcium phosphate powder into a grinding tank of a ball mill; starting a ball mill, and carrying out ball milling for 6 hours at the rotating speed of 500 r/min; then drying or freeze-drying the ethanol solution of the chitosan-calcium phosphate powder at 60 ℃ to obtain mechanically activated chitosan-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 2 wt.% of chitosan aqueous solution, and storing for later use;
E. and D, uniformly mixing 70 parts by weight of the mechanically activated chitosan-calcium phosphate powder obtained in the step C with 100 parts by weight of the curing liquid obtained in the step D to obtain the chitosan-calcium phosphate composite material.
Example 4
A. Synthesis of bovine collagen fiber-calcium hydrogen phosphate composite powder
Dissolving calcium chloride in deionized water to obtain a calcium chloride solution; dissolving disodium hydrogen phosphate in deionized water to obtain a disodium hydrogen phosphate solution; the molar ratio of calcium chloride to disodium hydrogen phosphate is 0.85: 1;
adding bovine collagen cellulose into the calcium chloride solution to obtain a mixed solution, wherein the mole number of the bovine collagen cellulose is 0.4 times of that of the calcium chloride;
then, adding the disodium hydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 2 hours, standing for 22 hours, and then centrifugally washing, vacuum-filtering, and freeze-drying to obtain bovine collagen cellulose-calcium hydrogen phosphate composite powder;
B. preparation of bovine collagen cellulose-calcium phosphate powder
Uniformly mixing 1 part by weight of bovine collagen cellulose-calcium hydrogen phosphate composite powder obtained in the step A with 3 parts by weight of octacalcium phosphate to obtain bovine collagen cellulose-calcium phosphate powder;
C. mechanical activation of bovine collagen cellulose-calcium phosphate powder
Adding 6.5 parts by weight of the bovine collagen cellulose-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethanol to obtain an ethanol solution of alginate-calcium phosphate powder, and pouring the ethanol solution of the bovine collagen cellulose-calcium phosphate powder into a grinding tank of a ball mill; starting a ball mill, and carrying out ball milling for 8 hours at the rotating speed of 600 r/min; then drying or freeze-drying the ethanol solution of the bovine collagen cellulose-calcium phosphate powder at 37 ℃ to obtain mechanically activated bovine collagen cellulose-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 2 wt.% of alginate aqueous solution, and storing for later use;
E. and D, uniformly mixing 80 parts by weight of the mechanically activated bovine collagen cellulose-calcium phosphate powder obtained in the step C with 100 parts by weight of the curing liquid obtained in the step D to obtain the composite material.
Example 5
A. Synthesis of agar-calcium hydrogen phosphate composite powder
Dissolving calcium chloride in deionized water to obtain a calcium chloride solution; dissolving dipotassium phosphate into deionized water to obtain dipotassium phosphate solution; the molar ratio of calcium chloride to dipotassium hydrogen phosphate is 0.7: 1;
adding agar into the calcium chloride solution to obtain a mixed solution, wherein the addition mole number of the agar is 0.4 times of that of the calcium chloride;
then, adding the dipotassium phosphate solution into the mixed solution under stirring, continuing stirring for 4 hours, standing for 22 hours, then centrifugally washing, vacuum-filtering, and freeze-drying to obtain agar-calcium hydrophosphate composite powder;
B. preparation of agar-calcium phosphate powder
Uniformly mixing 1 part by weight of the agar-calcium hydrophosphate composite powder obtained in the step A with 5 parts by weight of hydroxyapatite to obtain agar-calcium hydrophosphate powder;
C. mechanical activation of agar-calcium phosphate powders
Adding 7 parts by weight of the agar-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethanol to obtain an ethanol solution of the agar-calcium phosphate powder, and pouring the ethanol solution of the agar-calcium phosphate powder into a grinding tank of a ball mill; starting the ball mill, and carrying out ball milling for 10 hours at the rotating speed of 500 r/min; drying or freeze-drying the ethanol solution of the agar-calcium phosphate powder at 37 ℃ to obtain mechanically activated agar-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 5 wt.% of agar aqueous solution, and storing for later use;
E. and D, uniformly mixing 70 parts by weight of the mechanically activated agar-calcium phosphate powder obtained in the step C and 100 parts by weight of the curing liquid obtained in the step D to obtain the agar-calcium phosphate curing liquid.
Example 6
A. Synthesis of starch-calcium hydrogen phosphate composite powder
Dissolving calcium nitrate tetrahydrate in deionized water to obtain a calcium nitrate tetrahydrate solution; dissolving potassium dihydrogen phosphate in deionized water to obtain potassium dihydrogen phosphate solution; the molar ratio of the calcium nitrate tetrahydrate to the potassium dihydrogen phosphate is 1: 1;
adding starch into the calcium nitrate tetrahydrate solution to obtain a mixed solution, wherein the mole number of the added starch is 0.6 times of that of the calcium nitrate tetrahydrate;
then, adding the potassium dihydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 4 hours, standing for 24 hours, then centrifugally washing, vacuum-filtering, and freeze-drying to obtain starch-calcium hydrogen phosphate composite powder;
B. preparation of starch-calcium phosphate powder
Uniformly mixing 1 part by weight of the starch-calcium hydrophosphate composite powder obtained in the step A with 5 parts by weight of hydroxyapatite to obtain starch-calcium hydrophosphate powder;
C. mechanical activation of starch-calcium phosphate powders
Adding 7 parts by weight of the starch-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethanol to obtain an ethanol solution of the starch-calcium phosphate powder, and pouring the ethanol solution of the starch-calcium phosphate powder into a grinding tank of a ball mill; starting a ball mill, and carrying out ball milling for 8 hours at the rotating speed of 600 r/min; then drying or freeze-drying the ethanol solution of the starch-calcium phosphate powder at 60 ℃ to obtain mechanically activated starch-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 4 wt.% starch water solution, and storing for later use;
E. and D, uniformly mixing 70 parts by weight of the mechanically activated starch-calcium phosphate powder obtained in the step C and 100 parts by weight of the curing liquid obtained in the step D to obtain the starch-calcium phosphate composite material.
Example 7
A. Synthesis of hydroxypropyl methyl cellulose-calcium hydrogen phosphate composite powder
Dissolving calcium nitrate tetrahydrate in deionized water to obtain a calcium nitrate tetrahydrate solution; dissolving ammonium dihydrogen phosphate in deionized water to obtain an ammonium dihydrogen phosphate solution; the molar ratio of the calcium nitrate tetrahydrate to the ammonium dihydrogen phosphate is 1: 1;
adding hydroxypropyl methyl cellulose into the calcium nitrate tetrahydrate solution to obtain a mixed solution, wherein the addition mole number of the hydroxypropyl methyl cellulose is 1.5 times of the mole number of the calcium nitrate tetrahydrate;
then, adding the ammonium dihydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 4h, standing for 24h, then centrifugally washing, vacuum-filtering, and freeze-drying to obtain hydroxypropyl methyl cellulose-calcium hydrophosphate composite powder;
B. preparation of hydroxypropyl methylcellulose-calcium phosphate powder
Uniformly mixing 1 part by weight of hydroxypropyl methyl cellulose-calcium hydrogen phosphate composite powder obtained in the step A with 5 parts by weight of tricalcium phosphate and hydroxyapatite to obtain hydroxypropyl methyl cellulose-calcium phosphate powder;
C. mechanical activation of hydroxypropyl methylcellulose-calcium phosphate powders
Adding 7 parts by weight of hydroxypropyl methylcellulose-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethyl alcohol to obtain an ethanol solution of hydroxypropyl methylcellulose-calcium phosphate powder, and pouring the ethanol solution of hydroxypropyl methylcellulose-calcium phosphate powder into a grinding tank of a ball mill; starting a ball mill, and carrying out ball milling for 6 hours at the rotating speed of 600 r/min; then drying or freeze-drying the ethanol solution of the hydroxypropyl methyl cellulose-calcium phosphate powder at 37 ℃ to obtain the mechanically activated hydroxypropyl methyl cellulose-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 2 wt.% hydroxypropyl methyl cellulose aqueous solution, and storing for later use;
E. and D, uniformly mixing 65 parts by weight of the mechanically activated hydroxypropyl methyl cellulose-calcium phosphate powder obtained in the step C and 100 parts by weight of the curing liquid obtained in the step D to obtain the hydroxypropyl methyl cellulose-calcium phosphate curing liquid.
Example 8
A. Synthesis of ovalbumin-calcium hydrogen phosphate composite powder
Dissolving calcium nitrate tetrahydrate in deionized water to obtain a calcium nitrate tetrahydrate solution; dissolving diammonium phosphate in deionized water to obtain a diammonium phosphate solution; the molar ratio of the calcium nitrate tetrahydrate to the diammonium phosphate is 1: 1;
adding ovalbumin into a calcium nitrate tetrahydrate solution to obtain a mixed solution, wherein the mole number of the added ovalbumin is 1 time of that of the calcium nitrate tetrahydrate;
then, adding a diammonium hydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 4 hours, standing for 24 hours, and then carrying out centrifugal washing, vacuum filtration and freeze drying to obtain ovalbumin-calcium hydrogen phosphate composite powder;
B. preparation of ovalbumin-calcium phosphate powder
Uniformly mixing 1 part by weight of the ovalbumin-calcium hydrophosphate composite powder obtained in the step A with 0.5 part by weight of hydroxyapatite to obtain ovalbumin-calcium hydrophosphate powder;
C. mechanical activation of ovalbumin-calcium phosphate powders
Adding 7 parts by weight of the ovalbumin-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethyl alcohol to obtain an ethanol solution of the ovalbumin-calcium phosphate powder, and pouring the ethanol solution of the ovalbumin-calcium phosphate powder into a grinding tank of a ball mill; starting a ball mill, and carrying out ball milling for 8 hours at the rotating speed of 600 r/min; then drying or freeze-drying the ethanol solution of the ovalbumin-calcium phosphate powder at 37 ℃ to obtain the mechanically activated ovalbumin-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 2 wt.% of ovalbumin aqueous solution, and storing for later use;
E. and D, uniformly mixing 80 parts by weight of the mechanically activated ovalbumin-calcium phosphate powder obtained in the step C with 100 parts by weight of the curing liquid obtained in the step D to obtain the composite material.
Example 9
A. Synthesis of xylan-calcium hydrogen phosphate composite powder
Dissolving calcium nitrate tetrahydrate in deionized water to obtain a calcium nitrate tetrahydrate solution; dissolving diammonium phosphate in deionized water to obtain a diammonium phosphate solution; the molar ratio of the calcium nitrate tetrahydrate to the diammonium phosphate is 1: 1;
adding xylan into the calcium nitrate tetrahydrate solution to obtain a mixed solution, wherein the addition mole number of the xylan is 2 times of that of the calcium nitrate tetrahydrate;
then, adding a diammonium hydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 4 hours, standing for 24 hours, and then carrying out centrifugal washing, vacuum filtration and freeze drying to obtain xylan-calcium hydrogen phosphate composite powder;
B. preparation of xylan-calcium phosphate powder
Uniformly mixing 1 part by weight of xylan-calcium hydrogen phosphate composite powder obtained in the step A with 0.5 part by weight of hydroxyapatite to obtain xylan-calcium phosphate powder;
C. mechanical activation of xylan-calcium phosphate powders
Adding 7 parts by weight of xylan-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethanol to obtain an ethanol solution of the xylan-calcium phosphate powder, and pouring the ethanol solution of the xylan-calcium phosphate powder into a grinding tank of a ball mill; starting a ball mill, and carrying out ball milling for 8 hours at the rotating speed of 600 r/min; then drying or freeze-drying the ethanol solution of the ovalbumin-calcium phosphate powder at 37 ℃ to obtain xylan-calcium phosphate powder after mechanical activation, and storing for later use;
D. preparation of curing liquid
Preparing 2 wt.% of xylan aqueous solution, and storing for later use;
E. and D, uniformly mixing 80 parts by weight of the mechanically activated xylan-calcium phosphate powder obtained in the step C with 100 parts by weight of the curing liquid obtained in the step D to obtain the chitosan-calcium phosphate composite material.
Example 10
A. Synthesis of lecithin-calcium hydrophosphate composite powder
Dissolving calcium nitrate tetrahydrate in deionized water to obtain a calcium nitrate tetrahydrate solution; dissolving diammonium phosphate in deionized water to obtain a diammonium phosphate solution; the molar ratio of the calcium nitrate tetrahydrate to the diammonium phosphate is 1: 1;
adding lecithin into the calcium nitrate tetrahydrate solution to obtain a mixed solution, wherein the addition mole number of the lecithin is 1 time of that of the calcium nitrate tetrahydrate;
then, adding a diammonium hydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 4 hours, standing for 24 hours, and then carrying out centrifugal washing, vacuum filtration and freeze drying to obtain lecithin-calcium hydrogen phosphate composite powder;
B. preparation of lecithin-calcium phosphate powder
Uniformly mixing 1 part by weight of the lecithin-calcium hydrophosphate composite powder obtained in the step A with 5 parts by weight of hydroxyapatite to obtain lecithin-calcium hydrophosphate powder;
C. mechanical activation of lecithin-calcium phosphate powders
Adding 7 parts by weight of lecithin-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethanol to obtain an ethanol solution of the lecithin-calcium phosphate powder, and pouring the ethanol solution of the lecithin-calcium phosphate powder into a grinding tank of a ball mill; starting a ball mill, and carrying out ball milling for 8 hours at the rotating speed of 600 r/min; then drying or freeze-drying the ethanol solution of lecithin-calcium phosphate powder at 37 ℃ to obtain the mechanically activated lecithin-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 2 wt.% lecithin water solution, and storing for later use;
E. and D, uniformly mixing 80 parts by weight of the mechanically activated lecithin-calcium phosphate powder obtained in the step C with 100 parts by weight of the curing liquid obtained in the step D to obtain the lecithin-calcium phosphate composite material.
Example 11
A. Synthesis of mannitol-calcium hydrogen phosphate composite powder
Dissolving calcium chloride in deionized water to obtain a calcium chloride solution; dissolving sodium dihydrogen phosphate in deionized water to obtain sodium dihydrogen phosphate solution; the molar ratio of calcium chloride to sodium dihydrogen phosphate is 0.85: 1;
adding mannitol into the calcium chloride solution to obtain a mixed solution, wherein the mol number of the added mannitol is 0.4 time of that of the calcium chloride;
then, adding the sodium dihydrogen phosphate solution into the mixed solution under stirring, continuing stirring for 4h, standing for 24h, then centrifugally washing, vacuum-filtering, and freeze-drying to obtain mannitol-calcium hydrogen phosphate composite powder;
B. preparation of mannitol-calcium phosphate powder
Uniformly mixing 1 part by weight of mannitol-calcium hydrogen phosphate composite powder obtained in the step A and 1 part by weight of tetracalcium phosphate to obtain mannitol-calcium phosphate powder;
C. mechanical activation of mannitol-calcium phosphate powders
Adding 6 parts by weight of the mannitol-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethyl alcohol to obtain an ethanol solution of the mannitol-calcium phosphate powder, and pouring the ethanol solution of the mannitol-calcium phosphate powder into a grinding tank of a ball mill; starting a ball mill, and carrying out ball milling for 6 hours at the rotating speed of 500 r/min; then drying or freeze-drying the ethanol solution of the mannitol-calcium phosphate powder at 60 ℃ to obtain mechanically activated mannitol-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 2 wt.% of mannitol aqueous solution, and storing for later use;
E. and D, uniformly mixing 70 parts by weight of mechanically activated mannitol-calcium phosphate powder obtained in the step C and 100 parts by weight of curing liquid obtained in the step D to obtain the composite material.
Claims (3)
1. A method for preparing a calcium phosphate-based composite material suitable for 3D printing by mechanical activation, comprising the steps of:
A. synthesis of natural polymer-calcium hydrogen phosphate composite powder
Dissolving soluble calcium salt in deionized water to obtain a calcium salt solution; dissolving soluble phosphate in deionized water to obtain a phosphate solution; the molar ratio of the calcium salt in the calcium salt solution to the phosphate in the phosphate solution is 0.5-1.67: 1;
adding natural polymer into the calcium salt solution to obtain a mixed solution, wherein the mol number of the added natural polymer is 0.1-2 times of that of the calcium salt in the calcium salt solution; the calcium phosphate salt is a mixture of more than one of tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, octacalcium phosphate and hydroxyapatite; the natural polymer is gelatin, collagen, bovine collagen cellulose, chitosan, agar, starch, hydroxypropyl methyl cellulose, ovalbumin, mannitol, xylan or lecithin;
then, adding the dissolved phosphate solution into the mixed solution under stirring, continuing stirring for 1-4h, standing for 20-24h, then centrifugally washing, vacuum filtering, and freeze-drying to obtain natural polymer-calcium hydrophosphate composite powder;
B. preparation of natural high molecular calcium phosphate powder
Uniformly mixing 1 part by weight of the natural polymer-calcium hydrophosphate composite powder obtained in the step A with 0.5-5 parts by weight of calcium phosphate salt to obtain natural polymer-calcium hydrophosphate powder;
C. mechanical activation of natural polymer-calcium phosphate powder
Adding 5-7 parts by weight of the natural polymer-calcium phosphate powder obtained in the step B into 10 parts by weight of absolute ethyl alcohol to obtain an ethanol solution of the natural polymer-calcium phosphate powder, and pouring the ethanol solution of the natural polymer-calcium phosphate powder into a grinding tank of a ball mill; starting the ball mill, and carrying out ball milling for 4-10h at the rotating speed of 300-700 r/min; then drying or freeze-drying the ethanol solution of the natural polymer-calcium phosphate powder at 37-80 ℃ to obtain mechanically activated natural polymer-calcium phosphate powder, and storing for later use;
D. preparation of curing liquid
Preparing 1-5 wt.% of natural polymer aqueous solution, and storing for later use; the natural polymer used by the natural polymer aqueous solution is consistent with the natural polymer used in the step A;
E. and D, uniformly mixing 65-80 parts by weight of the mechanically activated natural polymer calcium phosphate powder obtained in the step C and 100 parts by weight of the curing liquid obtained in the step D to obtain the calcium phosphate-based composite material.
2. The method for preparing calcium phosphate-based composite material suitable for 3D printing according to claim 1, wherein the soluble calcium salt is calcium nitrate tetrahydrate (Ca (NO)3)2·4H2O) or calcium chloride (CaCl)2)。
3. The method for preparing phosphoric acid suitable for 3D printing by mechanical activation according to claim 1A method for producing a calcium-based composite material, characterized in that said soluble phosphate is diammonium hydrogen phosphate ((NH)4)2HPO4) Ammonium dihydrogen phosphate (NH)4H2PO4) Dipotassium hydrogen phosphate (K)2HPO4) Potassium dihydrogen phosphate (KH)2PO4) Disodium hydrogen phosphate (Na)2HPO4) Or sodium dihydrogen phosphate (NaH)2PO4)。
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