CN116392632A - Calcium-magnesium mineralized collagen material, preparation method and application - Google Patents
Calcium-magnesium mineralized collagen material, preparation method and application Download PDFInfo
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- CN116392632A CN116392632A CN202310295717.2A CN202310295717A CN116392632A CN 116392632 A CN116392632 A CN 116392632A CN 202310295717 A CN202310295717 A CN 202310295717A CN 116392632 A CN116392632 A CN 116392632A
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- magnesium
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- 102000008186 Collagen Human genes 0.000 title claims abstract description 120
- 108010035532 Collagen Proteins 0.000 title claims abstract description 120
- 229920001436 collagen Polymers 0.000 title claims abstract description 120
- ZFXVRMSLJDYJCH-UHFFFAOYSA-N calcium magnesium Chemical compound [Mg].[Ca] ZFXVRMSLJDYJCH-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 239000000463 material Substances 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 158
- 238000000034 method Methods 0.000 claims abstract description 34
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910001425 magnesium ion Inorganic materials 0.000 claims abstract description 20
- 235000011187 glycerol Nutrition 0.000 claims description 61
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 48
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 36
- 239000011777 magnesium Substances 0.000 claims description 36
- 229910052749 magnesium Inorganic materials 0.000 claims description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 33
- 238000003756 stirring Methods 0.000 claims description 33
- 210000000988 bone and bone Anatomy 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 26
- 102000012422 Collagen Type I Human genes 0.000 claims description 24
- 108010022452 Collagen Type I Proteins 0.000 claims description 24
- 239000011575 calcium Substances 0.000 claims description 23
- 238000002156 mixing Methods 0.000 claims description 23
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 23
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 22
- 229910052791 calcium Inorganic materials 0.000 claims description 22
- 239000001488 sodium phosphate Substances 0.000 claims description 19
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 19
- 239000008367 deionised water Substances 0.000 claims description 17
- 229910021641 deionized water Inorganic materials 0.000 claims description 17
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 16
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 16
- 229910001424 calcium ion Inorganic materials 0.000 claims description 16
- 229910000406 trisodium phosphate Inorganic materials 0.000 claims description 16
- 235000019801 trisodium phosphate Nutrition 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 13
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- 238000004108 freeze drying Methods 0.000 claims description 12
- 239000000512 collagen gel Substances 0.000 claims description 10
- 230000007547 defect Effects 0.000 claims description 10
- 238000002791 soaking Methods 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 8
- 239000001110 calcium chloride Substances 0.000 claims description 8
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 8
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 8
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 8
- YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Chemical compound [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 claims description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 7
- 239000011574 phosphorus Substances 0.000 claims description 7
- 229910052698 phosphorus Inorganic materials 0.000 claims description 7
- 241000283690 Bos taurus Species 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 229910000147 aluminium phosphate Inorganic materials 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 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 4
- 241001529936 Murinae Species 0.000 claims description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 4
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 4
- 239000001639 calcium acetate Substances 0.000 claims description 4
- 235000011092 calcium acetate Nutrition 0.000 claims description 4
- 229960005147 calcium acetate Drugs 0.000 claims description 4
- 239000012535 impurity Substances 0.000 claims description 4
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 4
- 239000011654 magnesium acetate Substances 0.000 claims description 4
- 229940069446 magnesium acetate Drugs 0.000 claims description 4
- 235000011285 magnesium acetate Nutrition 0.000 claims description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 claims description 3
- 229910000020 calcium bicarbonate Inorganic materials 0.000 claims description 3
- JXRVKYBCWUJJBP-UHFFFAOYSA-L calcium;hydrogen sulfate Chemical compound [Ca+2].OS([O-])(=O)=O.OS([O-])(=O)=O JXRVKYBCWUJJBP-UHFFFAOYSA-L 0.000 claims description 3
- QWDJLDTYWNBUKE-UHFFFAOYSA-L magnesium bicarbonate Chemical compound [Mg+2].OC([O-])=O.OC([O-])=O QWDJLDTYWNBUKE-UHFFFAOYSA-L 0.000 claims description 3
- 239000002370 magnesium bicarbonate Substances 0.000 claims description 3
- 229910000022 magnesium bicarbonate Inorganic materials 0.000 claims description 3
- 235000014824 magnesium bicarbonate Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 3
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- 235000011008 sodium phosphates Nutrition 0.000 claims description 3
- 238000000527 sonication Methods 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 1
- 229910000397 disodium phosphate Inorganic materials 0.000 claims 1
- 235000019800 disodium phosphate Nutrition 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- -1 phosphate radical ions Chemical class 0.000 claims 1
- 235000011007 phosphoric acid Nutrition 0.000 claims 1
- 230000011164 ossification Effects 0.000 abstract description 12
- 230000033558 biomineral tissue development Effects 0.000 abstract description 11
- 238000006243 chemical reaction Methods 0.000 abstract description 8
- 230000008569 process Effects 0.000 abstract description 8
- 239000001506 calcium phosphate Substances 0.000 abstract description 6
- 229910000389 calcium phosphate Inorganic materials 0.000 abstract description 6
- 235000011010 calcium phosphates Nutrition 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 6
- 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 abstract description 6
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- 230000035876 healing Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
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- 238000010382 chemical cross-linking Methods 0.000 description 2
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- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 2
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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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- 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
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
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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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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- Oral & Maxillofacial Surgery (AREA)
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Abstract
The invention relates to a calcium-magnesium mineralized collagen material, a preparation method and application thereof. The method has the advantages that a certain amount of magnesium ions are introduced into the reaction system, so that the mineralization process can be controlled, and the osteogenesis activity of the mineralized collagen material can be greatly improved; a certain amount of glycerol or glycerol aqueous solution is introduced into the reaction system, and the speed and the assembly structure of collagen and the nucleation condition of mineral substances in fibers are controlled by controlling the precipitation speed of the glycerol, so that the collagen can be mineralized deeply at the same time; the calcium-magnesium mineralized collagen material can be in a gel state, has good compression resistance and good plasticity, and can be made into different shapes to meet different medical requirements; the preparation method has the characteristics of simplicity, convenience, high efficiency and controllability, and utilizes the characteristic that the glycerol can control the formation of calcium phosphate and simultaneously assemble collagen into a large-size continuous space structure to form a deeply and uniformly mineralized product.
Description
Technical Field
The invention relates to the technical field of material synthesis, in particular to a calcium-magnesium mineralized collagen material, a preparation method and application.
Background
Bone grafting is a surgical procedure that promotes bone healing by implanting new bone or alternative materials at the fracture or bone defect. The existing clinic used autogenous bone, allogeneic bone, xenogeneic bone and synthetic bone can not meet the increasing clinic demand for effective bone grafting, and the problems of infection of donor areas, immune rejection reaction, spread of diseases of the autogenous bone and the xenogeneic bone, high price and slow bone healing growth can be faced.
The mineralized collagen artificial bone material has components and structures similar to natural bones, good biocompatibility and bioactivity, biodegradability more matched with new bone formation, and can well improve the problems of infection, immune rejection, slow degradation in ceramic biological materials and the like existing in bone transplantation, and is one of the biological materials most concerned in the field of bone repair.
The existing mineralized collagen material only achieves that the ratio of the inorganic component is consistent with that of the natural bone, but the fine component in the inorganic component is inconsistent with that of the natural bone, so that the osteogenic activity of the mineralized collagen material is poor. The inorganic component of the mineralized collagen material is a single calcium phosphate material, and trace elements in the inorganic component of the natural bone, including magnesium, strontium, iron and the like are absent. These microelements play an important role in the bone tissue regeneration process. For example, magnesium has effects of promoting stem cell proliferation and osteogenic differentiation, promoting angiogenesis at defect site, regulating nerve regeneration at defect site, inducing osteogenesis related gene expression, and enhancing mineralization of extracellular matrix. Magnesium phosphate (MGP) cements have been shown to promote proliferation and differentiation of human bone marrow stem cells. Magnesium is also involved in the biomineralization of bone and teeth and indirectly affects mineral metabolism, for example by activating alkaline phosphatase (ALP). Magnesium ions are also implanted into the material to promote bone formation, which can improve the problems of too poor mechanical strength of mineralized collagen and premature collapse during bone healing to some extent.
At present, effective solutions have not been proposed for solving the problems of single inorganic component, lack of active metal elements related to bone formation, low bone formation activity and the like in the existing mineralized collagen materials.
Disclosure of Invention
The application aims at overcoming the defects in the prior art and providing a calcium-magnesium mineralized collagen material, a preparation method and application thereof, so as to at least solve the problems of single inorganic component, lack of osteogenesis-related active metal elements and low osteogenesis activity in the related art.
In order to achieve the above purpose, the technical scheme adopted by the application is as follows:
in a first aspect, the present invention provides a method for preparing a calcium magnesium mineralized collagen material, comprising:
mixing type I collagen, a calcium source, a magnesium source, an acid and a glycerin solvent to obtain a first solution, wherein the glycerin solvent is glycerin or a mixed solvent of glycerin and water, and the pH value of the first solution is less than or equal to 7;
mixing an alkali, a phosphorus source and a glycerol solvent to obtain a second solution;
adding the second solution into the first solution and mixing the second solution at the temperature of less than or equal to 45 ℃ to obtain a third solution, wherein the pH value of the third solution is more than or equal to 7;
and (3) soaking the third solution in deionized water solvent to remove impurities so as to obtain the calcium-magnesium mineralized collagen gel.
In some of these embodiments, further comprising:
and freeze-drying the calcium-magnesium mineralized collagen gel to obtain the calcium-magnesium mineralized collagen scaffold.
In some of these embodiments, prior to immersing the third solution in deionized water solvent, further comprising:
the third solution was allowed to stand at room temperature.
In some of these embodiments, mixing the type I collagen, the calcium source, the magnesium source, the acid, and the glycerol solvent to obtain the first solution comprises:
dissolving type I collagen in an acid to obtain a collagen solution;
dissolving a calcium source and a magnesium source in a glycerol solvent to obtain a calcium-magnesium solution;
the calcium magnesium solution is mixed with the collagen solution to obtain a first solution.
In some embodiments, the concentration ratio of the calcium source to the magnesium source in the calcium magnesium solution is 1000: 1-2: 1.
in some of these embodiments, the dropping rate of the calcium-magnesium solution into the collagen solution is 0.1 to 10000mL/min.
In some of these embodiments, mixing includes one or a combination of stirring, vortexing, and sonication.
In some embodiments, the stirring time is more than or equal to 1min, and the stirring speed is 10-10000 revolutions/min.
In some embodiments, the mass ratio of the glycerol to the glycerol solvent is 0% to 100%.
In some embodiments, the mass ratio of the glycerol to the water is ≡1:10.
in some of these embodiments, the mass ratio of the glycerin to the water is 1: 10-10: 1.
in some of these embodiments, the mass ratio of the glycerin to the water is 1: 5-5: 1.
in some of these embodiments, the mass ratio of the glycerin to the water is 2:5 to 4:1.
in some of these embodiments, the mass ratio of the glycerin to the water is 1: 2-2: 1.
in some embodiments, the type I collagen is murine, bovine, porcine collagen or a combination of several thereof.
In some embodiments, the calcium source is one or a combination of calcium chloride, calcium nitrate, calcium acetate, calcium bicarbonate, and calcium bisulfate.
In some embodiments, the magnesium source is one or a combination of magnesium chloride, magnesium nitrate, magnesium acetate, magnesium bicarbonate, magnesium bisulfate.
In some embodiments, the acid is one or a combination of acetic acid, hydrochloric acid, nitric acid, phosphoric acid.
In some embodiments, the concentration of type I collagen in the first solution is less than or equal to 100mg/mL.
In some embodiments, the concentration of calcium ions in the first solution is less than or equal to 5mol/L.
In some embodiments, the concentration of magnesium ions in the first solution is less than or equal to 5mol/L.
In some of these embodiments, the pH of the first solution is from 1 to 7.
In some embodiments, the base is one or a combination of sodium hydroxide, ammonia, potassium hydroxide.
In some embodiments, the phosphorus source is one or a combination of sodium phosphate, sodium phosphate monobasic, trisodium phosphate, phosphoric acid.
In some embodiments, the phosphate ion concentration in the second solution is less than or equal to 5mol/L.
In some embodiments, the phosphate ion concentration in the second solution is 3mol/L or less.
In some embodiments, the phosphate ion concentration in the second solution is less than or equal to 2mol/L.
In some embodiments, the phosphate ion concentration in the second solution is less than or equal to 1mol/L.
In some of these embodiments, the molar ratio of calcium ions to phosphate ions in the third solution is 1: 10-10: 1.
in some of these embodiments, the molar ratio of calcium ions to phosphate ions in the third solution is 3:10 to 6:1.
in some of these embodiments, the molar ratio of calcium ions to phosphate ions in the third solution is 1: 2-2: 1.
in some of these embodiments, the molar ratio of magnesium ions to phosphate ions in the third solution is 1: 10-10: 1.
in some of these embodiments, the molar ratio of magnesium ions to phosphate ions in the third solution is 3:10 to 6:1.
in some of these embodiments, the molar ratio of magnesium ions to phosphate ions in the third solution is 1: 2-2: 1.
in some of these embodiments, the second solution is added to the first solution at a dropping rate of 0.1 to 10000mL/min.
In some of these embodiments, the second solution is added to the first solution at a temperature of 5 to 30 ℃.
In some of these embodiments, the second solution is added to the first solution at a temperature of 10 to 20 ℃.
In a second aspect, the present invention provides a calcium magnesium mineralized collagen material, prepared by the preparation method of the first aspect.
In a third aspect, the present invention provides the use of a calcium-magnesium mineralized collagen according to the second aspect for preparing a material for repairing bone defects.
Compared with the related art, the calcium-magnesium mineralized collagen material, the preparation method and the application provided by the embodiment of the application have the advantages that a certain amount of magnesium ions are introduced into a reaction system, so that the mineralization process can be controlled, and the osteogenesis activity of the mineralized collagen material can be greatly improved; a certain amount of glycerol or glycerol aqueous solution is introduced into the reaction system, and the speed and the assembly structure of collagen and the nucleation condition of mineral substances in fibers are controlled by controlling the precipitation speed of the glycerol, so that the collagen can be mineralized deeply at the same time; the calcium-magnesium mineralized collagen material obtained by the method can be in a gel state, has good compression resistance and good plasticity, and can be made into different shapes to meet different medical requirements; after freeze drying, the porous block body is in a porous block body form (non-powder state), and the compression strength and the modulus are adjustable; under the condition of no artificial chemical crosslinking, the porous structure can still be reserved after water absorption is re-saturated, and the fiber has more excellent flexibility; the preparation method has the characteristics of simplicity, convenience, high efficiency and controllability, and utilizes the characteristic that glycerol can control the formation of calcium phosphate and simultaneously assemble collagen into a large-size continuous space structure to form a product which can be deeply and uniformly mineralized.
Drawings
The accompanying drawings, which are included to provide a further understanding of the application and are incorporated in and constitute a part of this application, illustrate embodiments of the application and together with the description serve to explain the application and do not constitute an undue limitation to the application. In the drawings:
FIG. 1 is a scanning electron microscope image of a calcium magnesium mineralized collagen material according to the invention;
FIG. 2 is an X-ray diffraction pattern of a calcium-magnesium mineralized collagen material according to the invention;
FIG. 3 is a thermogravimetric analysis of the calcium magnesium mineralized collagen material according to the invention;
FIG. 4 is a schematic illustration of mineralized collagen hydrogel obtained by the method for preparing calcium-magnesium mineralized collagen material according to the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present application more apparent, the present application is described and illustrated below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the present application. All other embodiments, which can be made by one of ordinary skill in the art without undue burden on the person of ordinary skill in the art based on the embodiments provided herein, are intended to be within the scope of the present application.
It is apparent that the drawings in the following description are only some examples or embodiments of the present application, and it is possible for those of ordinary skill in the art to apply the present application to other similar situations according to these drawings without inventive effort. Moreover, it should be appreciated that while such a development effort might be complex and lengthy, it would nevertheless be a routine undertaking of design, fabrication, or manufacture for those of ordinary skill having the benefit of this disclosure, and thus should not be construed as having the benefit of this disclosure.
Reference in the specification to "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the application. The appearances of such phrases in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. It is to be expressly and implicitly understood by those of ordinary skill in the art that the embodiments described herein can be combined with other embodiments without conflict.
Unless defined otherwise, technical or scientific terms used herein should be given the ordinary meaning as understood by one of ordinary skill in the art to which this application belongs. Reference to "a," "an," "the," and similar terms herein do not denote a limitation of quantity, but rather denote the singular or plural. The terms "comprising," "including," "having," and any variations thereof, are intended to cover a non-exclusive inclusion; for example, a process, method, system, article, or apparatus that comprises a list of steps or modules (elements) is not limited to only those steps or elements but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus. The terms "connected," "coupled," and the like in this application are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. The term "plurality" as used herein refers to two or more. "and/or" describes an association relationship of an association object, meaning that there may be three relationships, e.g., "a and/or B" may mean: a exists alone, A and B exist together, and B exists alone. The character "/" generally indicates that the context-dependent object is an "or" relationship. The terms "first," "second," "third," and the like, as used herein, are merely distinguishing between similar objects and not representing a particular ordering of objects.
Example 1
This example is an illustrative example of the invention, and relates to a mineralized collagen material, a method of preparation, and applications thereof.
A method for preparing a calcium-magnesium mineralized collagen material, comprising the following steps:
step S102, mixing type I collagen, a calcium source, a magnesium source and an acid with a glycerol solvent to obtain a first solution, wherein the glycerol solvent is glycerol or a mixed solvent of glycerol and water, and the pH value of the first solution is less than or equal to 7;
step S104, mixing an alkali, a phosphorus source and a glycerol solvent to obtain a second solution;
step S106, adding the second solution into the first solution and mixing the second solution under the condition that the temperature is less than or equal to 45 ℃ to obtain a third solution, wherein the pH value of the third solution is more than or equal to 7;
and S108, soaking the third solution in a deionized water solvent to remove impurities so as to obtain the calcium-magnesium mineralized collagen gel.
Wherein the mixing comprises one or a combination of a plurality of stirring method, vortex oscillation method and ultrasonic method.
Wherein, under the condition of mixing by adopting a stirring method, the stirring time is more than or equal to 1min, and the stirring speed is 10-10000 revolutions per minute.
In some of these embodiments, step S102 includes:
step S102a, dissolving type I collagen in acid to obtain a collagen solution;
step S102b, dissolving a calcium source and a magnesium source in a glycerol solvent to obtain a calcium-magnesium solution;
step S102c, mixing the calcium-magnesium solution with the collagen solution to obtain a first solution.
In step S102a, the type I collagen is one or a combination of several of murine collagen, bovine collagen and porcine collagen.
In step S102a, the concentration of type I collagen in the collagen solution is less than or equal to 100mg/mL. Preferably, the concentration of type I collagen is 1-100 mg/mL. More preferably, the concentration of type I collagen is 5 to 50mg/mL. More preferably, the concentration of type I collagen is 10 to 30mg/mL.
In step S102a, the acid is one or a combination of several of acetic acid, hydrochloric acid, nitric acid, and phosphoric acid.
In step S102a, the concentration of the acid is 0.1 to 1mol/L.
In step S102b, the calcium source is one or a combination of several of calcium chloride, calcium nitrate, calcium acetate, calcium bicarbonate and calcium bisulfate.
In step S102b, the concentration of calcium ions in the calcium-magnesium solution is 5mol/L or less. Preferably, the calcium ion concentration is less than or equal to 3mol/L. More preferably, the calcium ion concentration is 2mol/L or less.
In step S102b, the magnesium source is one or a combination of magnesium chloride, magnesium nitrate, magnesium acetate, magnesium bicarbonate, and magnesium bisulfate.
In step S102b, the concentration of magnesium ions in the calcium-magnesium solution is 5mol/L or less. Preferably, the magnesium ion concentration is less than or equal to 3mol/L. More preferably, the magnesium ion concentration is 2mol/L or less.
In step S102b, the mass ratio of glycerin to glycerin solvent is 0% -100%.
In step S102b, the mass ratio of glycerin to water is equal to or greater than 1:10. more preferably, the mass ratio of glycerin to water is 1: 10-10: 1. more preferably, the mass ratio of glycerin to water is 1: 5-5: 1. more preferably, the mass ratio of glycerin to water is 2:5 to 4:1. more preferably, the mass ratio of glycerin to water is 1: 2-2: 1.
in step S102b, in the calcium-magnesium solution, the mass ratio of the calcium source to the magnesium source is 1000: 1-2: 1.
in step S102c, the dropping speed of adding the calcium-magnesium solution into the collagen solution is 0.1-10000 mL/min.
In step S104, the alkali is one or a combination of several of sodium hydroxide, ammonia water and potassium hydroxide.
In step S104, the concentration of the alkali in the second solution is 0.1 to 1mol/L.
In step S104, the phosphorus source is one or a combination of several of sodium phosphate, sodium phosphate monobasic, trisodium phosphate, and phosphoric acid.
In step S104, in the second solution, the phosphate ion concentration is 5mol/L or less. Preferably, the phosphate ion concentration is 3mol/L or less. More preferably, the phosphate ion concentration is 2mol/L or less. More preferably, the phosphate ion concentration is 1mol/L or less.
In step S106, the second solution is added to the first solution at a dropping rate of 0.1-10000 mL/min.
In step S106, in the third solution, the molar ratio of calcium ions to phosphate ions is 1: 10-10: 1. preferably, the molar ratio of calcium ions to phosphate ions is 3:10 to 6:1. more preferably, the molar ratio of calcium ions to phosphate ions is 1: 2-2: 1.
in step S106, in the third solution, the molar ratio of magnesium ions to phosphate ions is 1: 10-10: 1. preferably, the molar ratio of magnesium ions to phosphate ions is 3:10 to 6:1. more preferably, in the third solution, the molar ratio of magnesium ions to phosphate ions is 1: 2-2: 1.
in step S106, the second solution is preferably added to the first solution at a temperature of 5 to 30 ℃. More preferably, the second solution is added to the first solution at a temperature of 10 to 20 ℃.
In step S106, the third solution is in a substantially gel-like form.
In step S108, the third solution is placed in deionized water solvent for the purpose of removing impurities including glycerin, alkali, salts (substantially inorganic salts) formed by the reaction of alkali and acid, unreacted calcium source, unreacted magnesium source, and unreacted phosphorus source.
In some of these embodiments, the third solution is repeatedly soaked in deionized water solvent.
Specifically, after the third solution is soaked in deionized water solvent for a certain time, the third solution is taken out, and is soaked in new deionized water solvent again for a plurality of times.
Further, before step S108, the method further includes:
the third solution was allowed to stand at room temperature.
Wherein the purpose of the third solution is to make the third solution gel-like.
Wherein the standing time is more than or equal to 8 hours.
Preferably, the standing time is not less than 24 hours.
Further, after step S108, the method further includes:
and step S110, freeze-drying the calcium-magnesium mineralized collagen gel to obtain the calcium-magnesium mineralized collagen scaffold.
In step S110, the prepared calcium-magnesium mineralized collagen scaffold is porous, the specific surface area of the scaffold is increased, and the bone defect position is easier to repair.
In some embodiments, the degree of mineralization of the calcium-magnesium mineralized collagen gel and the calcium-magnesium mineralized collagen scaffold is > 1%.
Preferably, the degree of mineralization of the calcium-magnesium mineralized collagen gel and the calcium-magnesium mineralized collagen scaffold is > 40%.
More preferably, the degree of mineralization of the calcium-magnesium mineralized collagen gel and the calcium-magnesium mineralized collagen scaffold is > 65%.
For the prepared calcium-magnesium mineralized collagen material, the calcium-magnesium mineralized collagen material comprises calcium-magnesium mineralized collagen gel and calcium-magnesium mineralized collagen scaffold.
The calcium-magnesium mineralized collagen material can be applied to preparing materials for repairing bone defects. .
Specifically, the mineralized collagen material may be used as a single component, or may be used in combination with other components.
Specifically, as shown in fig. 1, a scanning electron microscope image of the calcium-magnesium mineralized collagen material prepared by the method shows that calcium phosphate uniformly and completely wraps all collagen fibers.
As shown in fig. 2, XRD of the calcium magnesium mineralized collagen material prepared by the present method showed typical amorphous phase, confirming that the mineralizer is amorphous calcium phosphate. The two characterization modes are combined mutually to show that the mineralized collagen material has the characteristics of high mineralization degree, uniformity and completeness.
As shown in FIG. 3, thermogravimetric analysis shows that the mineralization degree of the calcium-magnesium mineralized collagen material by the method is higher than 65%.
As shown in figure 4, the mineralized collagen hydrogel prepared by the method has certain mechanical strength without crosslinking, and can maintain the self integrity.
In the invention, by adding the magnesium element, a more proper local environment can be provided for the bone mineralization process, and magnesium ions can not only control the assembly speed of collagen and influence the assembly structure of collagen, but also control the nucleation and crystallization process of minerals. The magnesium element has the functions of promoting the angiogenesis of defect parts, promoting the proliferation and osteogenesis differentiation of stem cells, inducing the expression of osteogenesis related genes, enhancing the mineralization of extracellular matrixes and the like.
The structural components of the mineralized collagen material containing magnesium in the invention are close to natural bones, so that the mechanical property and the osteoinductive property of the mineralized collagen material can be obviously improved, and the regeneration of bone tissues can be promoted. The invention can be used for repairing bone defect caused by wound, infection, tumor and the like, can effectively solve the problems of insufficient self bone supply, immune rejection and the like, and has wide clinical application prospect.
The invention provides a preparation method of calcium-magnesium mineralized collagen, the calcium-magnesium mineralized collagen and application thereof. Specifically, a certain amount of magnesium ions are introduced into the reaction system, so that the mineralization process can be controlled, and the osteogenesis activity of the mineralized collagen material can be greatly improved. In addition, a certain amount of glycerin or glycerin water solution is introduced into the reaction system, and the speed and the assembly structure of collagen and the nucleation condition of mineral substances in fibers are controlled by controlling the glycerin precipitation speed, so that the collagen can be mineralized deeply at the same time. The calcium-magnesium mineralized collagen material obtained by the method can be in a gel state, has good compression resistance and good plasticity, and can be made into different shapes to meet different medical requirements; after freeze drying, the porous block body is in a porous block body form (non-powder state), and the compression strength and the modulus are adjustable; in the absence of artificial chemical crosslinking, after re-saturation of the water uptake, the porous structure can be maintained, and the flexibility is more excellent. The preparation method has the characteristics of simplicity, convenience, high efficiency and controllability, and utilizes the characteristic that glycerol can control the formation of calcium phosphate and simultaneously assemble collagen into a large-size continuous space structure to form a product which can be deeply and uniformly mineralized.
Example 2
This embodiment is one embodiment of the present invention.
Under the stirring of a magnetic stirring rod at room temperature (the rotating speed is 500-600 rpm), dissolving the porcine-derived type I collagen into 0.1M acetic acid to prepare a collagen solution, wherein the collagen concentration is 25mg/ml;
adding a glycerol solution containing calcium ions and magnesium ions into the collagen solution, and stirring vigorously by using a magnetic stirrer at a temperature of less than or equal to 24 ℃ under the best use of an ice bath, wherein the concentration ratio of the calcium ions to the magnesium ions is Ca: mg=4: 1, a step of;
continuously stirring the calcium-magnesium solution in a magnetic stirrer, slowly dropwise adding a mixed glycerol solution of trisodium phosphate 0.63M and sodium hydroxide 0.4M at the temperature of less than or equal to 24 ℃, wherein a white suspension appears in a mixed system, and the molar ratio of the adding amount of phosphate ions to the adding amount of calcium ions is 0.1-10: 1.
standing the solution for 1 day, taking out the content, repeatedly cleaning with deionized water for three times, and performing low-temperature vacuum freeze drying to obtain the magnesium-containing mineralized collagen scaffold.
Example 3
This embodiment is one embodiment of the present invention.
Under the stirring of a magnetic stirring rod at room temperature (the rotating speed is 500-600 rpm), dissolving the porcine-source type I collagen solution into 0.05M acetic acid to prepare a collagen solution, wherein the collagen concentration is 20mg/ml;
dissolving calcium chloride and magnesium chloride in a mixed solution of glycerin and water (the mass ratio of glycerin to water is 2:3), wherein the concentration ratio of the calcium and the magnesium in the mixed solution is about 35:1, obtaining 0.5M calcium-magnesium mixed solution;
3g of collagen solution and 2g of calcium-magnesium mixed solution are mixed under the stirring of a magnetic stirring rod at the temperature of 5 ℃ for 0.5h;
slowly dripping 4g of mixed solution of trisodium phosphate and sodium hydroxide (mixed solution of trisodium phosphate 0.4M and sodium hydroxide 1.27M) into the collagen calcium magnesium mixed solution under the stirring of a magnetic stirring rod at the temperature of 5 ℃ and stirring (800-1000 rpm), and fully mixing until white precipitate is generated;
standing the solution for 1 day, taking out the content, repeatedly soaking the content in deionized water, and freeze-drying to obtain the magnesium-containing mineralized collagen scaffold.
Example 4
This embodiment is one embodiment of the present invention.
Under the stirring of a magnetic stirring rod at room temperature (the rotating speed is 500-600 rpm), dissolving the murine I-type collagen solution in 0.1M acetic acid to prepare a collagen solution, wherein the collagen concentration is 5mg/ml;
dissolving calcium chloride and magnesium chloride in a mixed solution of glycerin and water (the mass ratio of glycerin to water is 1:1), wherein the concentration ratio of the calcium to the magnesium in the mixed solution is about 3:2, obtaining 0.1M calcium-magnesium mixed solution;
3g of collagen solution and 2g of calcium-magnesium mixed solution are mixed under the stirring of a magnetic stirring rod at the temperature of 10 ℃ for 0.5h;
slowly dripping 4g of mixed solution of trisodium phosphate and sodium hydroxide (mixed solution of trisodium phosphate 0.05M and sodium hydroxide 0.5M) into the collagen calcium magnesium mixed solution under the stirring of a magnetic stirring rod at 10 ℃ at 800-1000 rpm, and fully mixing to obtain a mixed solution containing white precipitate;
standing the solution for 3 days, taking out the content, repeatedly soaking the content in deionized water, and freeze-drying to obtain the magnesium-containing mineralized collagen scaffold.
Example 5
This embodiment is one embodiment of the present invention.
Under the stirring of a magnetic stirring rod at room temperature (the rotating speed is 500-600 r/min), dissolving bovine-derived type I collagen solution in 0.1M acetic acid to prepare collagen solution, wherein the collagen concentration is 30mg/ml;
dissolving calcium nitrate and magnesium nitrate in a mixed solution of glycerin and water (the mass ratio of glycerin to water is 2:3), wherein the concentration ratio of the calcium to the magnesium in the mixed solution is about 9:1, obtaining 0.5M calcium-magnesium mixed solution;
3g of collagen solution and 2g of calcium-magnesium mixed solution are mixed under the stirring of a magnetic stirring rod at the temperature of 5 ℃ for 0.5h;
slowly dripping 5g of mixed solution of sodium dihydrogen phosphate and ammonia water (mixed solution of sodium dihydrogen phosphate and ammonia water with the concentration of 0.4M and 1.2M) into the mixed solution of collagen calcium and magnesium under the stirring of a magnetic stirring rod at the temperature of 5 ℃ and fully mixing to obtain a mixed solution containing white precipitate;
standing the solution for 7 days, taking out the content, repeatedly soaking the content in deionized water, and freeze-drying to obtain the magnesium-containing mineralized collagen scaffold.
Example 6
This embodiment is one embodiment of the present invention.
Under the stirring of a magnetic stirring rod at room temperature (the rotating speed is 500-600 rpm), dissolving the porcine-source type I collagen solution into 0.05M acetic acid to prepare a collagen solution, wherein the collagen concentration is 15mg/ml;
dissolving calcium acetate and magnesium acetate in a mixed solution of glycerin and water (the mass ratio of glycerin to water is 1:3), wherein the concentration ratio of calcium and magnesium in the mixed solution is about 9:1, obtaining a 2M calcium-magnesium mixed solution;
3g of collagen solution and 2g of calcium-magnesium mixed solution are mixed under the stirring of a magnetic stirring rod at the temperature of 10 ℃ for 0.5h;
slowly dripping 4g of mixed solution of trisodium phosphate and sodium hydroxide (mixed solution of 1M trisodium phosphate and 1M sodium hydroxide) into the collagen calcium magnesium mixed solution under the stirring of a magnetic stirring rod at 10 ℃ for 800-1000 revolutions per minute, and fully mixing to obtain a mixed solution containing white precipitate;
standing the solution for 5 days, taking out the content, repeatedly soaking the content in deionized water, and freeze-drying to obtain the magnesium-containing mineralized collagen scaffold.
Example 7
This embodiment is one embodiment of the present invention.
Under the stirring of a magnetic stirring rod at room temperature (the rotating speed is 500-600 r/min), dissolving bovine-derived type I collagen solution in 0.1M acetic acid to prepare collagen solution, wherein the collagen concentration is 20mg/ml;
dissolving calcium chloride and magnesium chloride in a mixed solution of glycerin and water (the mass ratio of glycerin to water is 1:3), wherein the concentration ratio of the calcium to the magnesium in the mixed solution is about 4:1, obtaining a 1M calcium-magnesium mixed solution;
3g of collagen solution and 2g of calcium-magnesium mixed solution are mixed under the stirring of a magnetic stirring rod at the temperature of 10 ℃ for 0.5h;
slowly dripping 4g of mixed solution of trisodium phosphate and sodium hydroxide (mixed solution of trisodium phosphate 0.1M and sodium hydroxide 0.5M) into the collagen calcium magnesium mixed solution under the stirring of a magnetic stirring rod at 10 ℃ at 800-1000 rpm, and fully mixing to obtain a mixed solution containing white precipitate;
standing the solution for 1 day, taking out the content, repeatedly soaking the content in deionized water, and freeze-drying to obtain the magnesium-containing mineralized collagen scaffold.
Example 8
This embodiment is one embodiment of the present invention.
Under the stirring of a magnetic stirring rod at room temperature (the rotating speed is 500-600 rpm), dissolving the porcine-source type I collagen solution into 0.1M acetic acid to prepare a collagen solution, wherein the collagen concentration is 10mg/ml;
dissolving calcium chloride and magnesium chloride in a mixed solution of glycerin and water (the mass ratio of glycerin to water is 1:3), wherein the concentration ratio of the calcium to the magnesium in the mixed solution is about 35:1, obtaining 0.3M calcium-magnesium mixed solution;
3g of collagen solution and 2g of calcium-magnesium mixed solution are mixed under the stirring of a magnetic stirring rod at the temperature of 10 ℃ for 0.5h;
slowly dripping 8g of mixed solution of trisodium phosphate and sodium hydroxide (mixed solution of trisodium phosphate 3M and sodium hydroxide 0.5M) into the collagen calcium magnesium mixed solution under the stirring of a magnetic stirring rod at 10 ℃ and fully mixing to obtain a mixed solution containing white precipitate;
standing the solution for 1 day, taking out the content, repeatedly soaking the content in deionized water, and freeze-drying to obtain the magnesium-containing mineralized collagen scaffold.
Example 9
This embodiment is one embodiment of the present invention.
Under the stirring of a magnetic stirring rod at room temperature (the rotating speed is 500-600 r/min), dissolving bovine-derived type I collagen solution in 0.1M acetic acid to prepare collagen solution, wherein the collagen concentration is 20mg/ml;
dissolving calcium chloride and magnesium chloride in a mixed solution of glycerin and water (the mass ratio of glycerin to water is 1:1), wherein the concentration ratio of the calcium to the magnesium in the mixed solution is about 9:1, obtaining a 1M calcium-magnesium mixed solution;
3g of collagen solution and 2g of calcium-magnesium mixed solution are mixed under the stirring of a magnetic stirring rod at the temperature of 10 ℃ for 0.5h;
slowly dripping 4g of mixed solution of trisodium phosphate and sodium hydroxide (mixed solution of trisodium phosphate 0.5M and sodium hydroxide 0.3M) into the collagen calcium magnesium mixed solution under the stirring of a magnetic stirring rod at 10 ℃ at 800-1000 rpm, and fully mixing to obtain a mixed solution containing white precipitate;
standing the solution for 1 day, taking out the content, repeatedly soaking the content in deionized water, and freeze-drying to obtain the magnesium-containing mineralized collagen scaffold.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples merely represent a few embodiments of the present application, which are described in more detail and are not to be construed as limiting the scope of the invention. It should be noted that it would be apparent to those skilled in the art that various modifications and improvements could be made without departing from the spirit of the present application, which would be within the scope of the present application. Accordingly, the scope of protection of the present application is to be determined by the claims appended hereto.
Claims (10)
1. A method for preparing a calcium-magnesium mineralized collagen material, comprising the steps of:
mixing type I collagen, a calcium source, a magnesium source, an acid and a glycerin solvent to obtain a first solution, wherein the glycerin solvent is glycerin or a mixed solvent of glycerin and water, and the pH value of the first solution is less than or equal to 7;
mixing an alkali, a phosphorus source and a glycerol solvent to obtain a second solution;
adding the second solution into the first solution and mixing the second solution at the temperature of less than or equal to 45 ℃ to obtain a third solution, wherein the pH value of the third solution is more than or equal to 7;
and (3) soaking the third solution in deionized water solvent to remove impurities so as to obtain the calcium-magnesium mineralized collagen gel.
2. The method of manufacturing according to claim 1, further comprising:
and freeze-drying the calcium-magnesium mineralized collagen gel to obtain the calcium-magnesium mineralized collagen scaffold.
3. The method of preparing according to claim 1, further comprising, prior to immersing the third solution in deionized water solvent:
the third solution was allowed to stand at room temperature.
4. The method of preparing according to claim 1, wherein mixing type I collagen, a calcium source, a magnesium source, an acid, and a glycerol solvent to obtain the first solution comprises:
dissolving type I collagen in an acid to obtain a collagen solution;
dissolving a calcium source and a magnesium source in a glycerol solvent to obtain a calcium-magnesium solution;
the calcium magnesium solution is mixed with the collagen solution to obtain a first solution.
5. The method of claim 1, wherein mixing comprises one or a combination of stirring, vortex shaking, and sonication; and/or
The mass ratio of the glycerol to the glycerol solvent is 0-100%.
6. The method of any one of claims 1 to 5, wherein, in the first solution:
the concentration of the type I collagen is less than or equal to 100mg/mL; and/or
The concentration of calcium ions is less than or equal to 5mol/L; and/or
The concentration of magnesium ions is less than or equal to 5mol/L; and/or
The ratio of calcium ion concentration to magnesium ion concentration was 1000: 1-2: 1, a step of; and/or
The type I collagen is one or a combination of more of murine collagen, bovine collagen and porcine collagen; and/or
The calcium source is one or more of calcium chloride, calcium nitrate, calcium acetate, calcium bicarbonate and calcium bisulfate; and/or
The magnesium source is one or more of magnesium chloride, magnesium nitrate, magnesium acetate, magnesium bicarbonate and magnesium bisulfate; and/or
The acid is one or a combination of several of acetic acid, hydrochloric acid, nitric acid and phosphoric acid.
7. The method of any one of claims 1 to 5, wherein, in the second solution:
the concentration of phosphate radical ions is less than or equal to 5mol/L; and/or
The alkali is one or a combination of sodium hydroxide, ammonia water and potassium hydroxide; and/or
The phosphorus source is one or a combination of sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate and phosphoric acid.
8. The method of any one of claims 1 to 5, wherein in the third solution:
the molar ratio of calcium ions to phosphate ions is 1: 10-10: 1, a step of; and/or
The molar ratio of magnesium ions to phosphate ions is 1: 10-10: 1.
9. a calcium magnesium mineralized collagen material, prepared by the preparation method according to any one of claims 1 to 8.
10. Use of the calcium-magnesium mineralized collagen according to claim 9 for preparing a material for repairing bone defects.
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