CN110606477A - Preparation method of hydroxyapatite, composite material containing hydroxyapatite and application of composite material - Google Patents
Preparation method of hydroxyapatite, composite material containing hydroxyapatite and application of composite material Download PDFInfo
- Publication number
- CN110606477A CN110606477A CN201810612068.3A CN201810612068A CN110606477A CN 110606477 A CN110606477 A CN 110606477A CN 201810612068 A CN201810612068 A CN 201810612068A CN 110606477 A CN110606477 A CN 110606477A
- Authority
- CN
- China
- Prior art keywords
- hydroxyapatite
- composite material
- solution
- soaking
- aqueous solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 title claims abstract description 121
- 229910052588 hydroxylapatite Inorganic materials 0.000 title claims abstract description 118
- 239000002131 composite material Substances 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 52
- 238000000034 method Methods 0.000 claims abstract description 38
- 241001465754 Metazoa Species 0.000 claims abstract description 22
- 239000000463 material Substances 0.000 claims abstract description 21
- 238000000209 wet digestion Methods 0.000 claims abstract description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 230000008439 repair process Effects 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 230000003472 neutralizing effect Effects 0.000 claims abstract description 3
- 238000012545 processing Methods 0.000 claims abstract description 3
- 239000007864 aqueous solution Substances 0.000 claims description 30
- 238000002791 soaking Methods 0.000 claims description 26
- 239000000243 solution Substances 0.000 claims description 24
- 230000001954 sterilising effect Effects 0.000 claims description 17
- 238000004659 sterilization and disinfection Methods 0.000 claims description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 229920001661 Chitosan Polymers 0.000 claims description 13
- 108010010803 Gelatin Proteins 0.000 claims description 13
- 239000008273 gelatin Substances 0.000 claims description 13
- 229920000159 gelatin Polymers 0.000 claims description 13
- 235000019322 gelatine Nutrition 0.000 claims description 13
- 235000011852 gelatine desserts Nutrition 0.000 claims description 13
- 102000008186 Collagen Human genes 0.000 claims description 12
- 108010035532 Collagen Proteins 0.000 claims description 12
- 229920001436 collagen Polymers 0.000 claims description 12
- 239000000835 fiber Substances 0.000 claims description 11
- 239000004132 Calcium polyphosphate Substances 0.000 claims description 10
- 235000019827 calcium polyphosphate Nutrition 0.000 claims description 10
- 239000004094 surface-active agent Substances 0.000 claims description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000000872 buffer Substances 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- GUTLYIVDDKVIGB-OUBTZVSYSA-N Cobalt-60 Chemical compound [60Co] GUTLYIVDDKVIGB-OUBTZVSYSA-N 0.000 claims description 7
- 238000001291 vacuum drying Methods 0.000 claims description 7
- 239000012670 alkaline solution Substances 0.000 claims description 6
- 238000004140 cleaning Methods 0.000 claims description 5
- 230000029087 digestion Effects 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000003973 irrigation Methods 0.000 claims description 4
- 230000002262 irrigation Effects 0.000 claims description 4
- 238000006386 neutralization reaction Methods 0.000 claims description 4
- -1 polyethylene Polymers 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 239000004952 Polyamide Substances 0.000 claims description 3
- 239000004698 Polyethylene Substances 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 3
- 229920002647 polyamide Polymers 0.000 claims description 3
- 229920001610 polycaprolactone Polymers 0.000 claims description 3
- 239000004632 polycaprolactone Substances 0.000 claims description 3
- 229920000573 polyethylene Polymers 0.000 claims description 3
- 239000004626 polylactic acid Substances 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 claims description 2
- NECRQCBKTGZNMH-UHFFFAOYSA-N 3,5-dimethylhex-1-yn-3-ol Chemical compound CC(C)CC(C)(O)C#C NECRQCBKTGZNMH-UHFFFAOYSA-N 0.000 claims description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 2
- 229920002307 Dextran Polymers 0.000 claims description 2
- 241000270322 Lepidosauria Species 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- TVFDJXOCXUVLDH-RNFDNDRNSA-N cesium-137 Chemical compound [137Cs] TVFDJXOCXUVLDH-RNFDNDRNSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000010894 electron beam technology Methods 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 241000271566 Aves Species 0.000 claims 1
- 239000008187 granular material Substances 0.000 claims 1
- 241000282414 Homo sapiens Species 0.000 abstract description 8
- 230000009286 beneficial effect Effects 0.000 abstract description 7
- 230000010261 cell growth Effects 0.000 abstract description 5
- 230000011164 ossification Effects 0.000 abstract description 5
- 239000002086 nanomaterial Substances 0.000 abstract description 2
- 230000017423 tissue regeneration Effects 0.000 abstract description 2
- 239000012528 membrane Substances 0.000 description 21
- 108010022355 Fibroins Proteins 0.000 description 8
- 238000001878 scanning electron micrograph Methods 0.000 description 8
- 230000005855 radiation Effects 0.000 description 7
- 238000000634 powder X-ray diffraction Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 238000009826 distribution Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 239000010419 fine particle Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 229920001503 Glucan Polymers 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229910052586 apatite Inorganic materials 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 230000010478 bone regeneration Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 238000005485 electric heating Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000001027 hydrothermal synthesis Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000000120 microwave digestion Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 231100001223 noncarcinogenic Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000004820 osteoconduction Effects 0.000 description 1
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 229920001432 poly(L-lactide) Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000012113 quantitative test Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 238000003980 solgel method Methods 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000004804 winding 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
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B25/00—Phosphorus; Compounds thereof
- C01B25/16—Oxyacids of phosphorus; Salts thereof
- C01B25/26—Phosphates
- C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/10—Particle morphology extending in one dimension, e.g. needle-like
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/60—Particles characterised by their size
- C01P2004/64—Nanometer sized, i.e. from 1-100 nanometer
Abstract
Disclosed herein is a method of preparing hydroxyapatite, the method comprising: (1) providing ex vivo animal bone; (2) processing the isolated animal bone in the step (1) by adopting wet digestion; (3) and (3) neutralizing the animal bone treated in the step (2) to obtain hydroxyapatite, wherein the DNA residue in the obtained hydroxyapatite is not higher than (0.21 +/-0.07) ng/mg and the mass percentage of nitrogen is not higher than (1.35 +/-0.25)% per thousand. Also disclosed herein are composite materials comprising hydroxyapatite, and the use of the hydroxyapatite and composite materials in the preparation of bone repair materials. The prepared hydroxyapatite material has a nano structure, can simulate the hydroxyapatite structure of human bones, and the composite material containing the hydroxyapatite is beneficial to cell growth, tissue regeneration and osteogenesis.
Description
Technical Field
The invention relates to a preparation method of hydroxyapatite, a composite material containing the hydroxyapatite and application of the hydroxyapatite and the composite material in preparation of bone repair materials.
Background
Hydroxyapatite (HA for short) is the main inorganic component of bones and teeth of human beings and vertebrates, the content of the Hydroxyapatite in bone is about 69 wt%, the basic unit of the Hydroxyapatite is needle-shaped apatite crystal, the composition and the structure of the Hydroxyapatite are similar to natural bones, the Hydroxyapatite is nontoxic, harmless and non-carcinogenic to human bodies, the Hydroxyapatite HAs good biocompatibility, bioactivity, biocompatibility and osteoconduction, the surface of the Hydroxyapatite can selectively react with physiological environment to induce and promote the growth of bone tissues, and the Hydroxyapatite can be bonded with bone on an interface in a strong chemical way, so the Hydroxyapatite can be widely applied to the repair of the defect of hard tissues of the human bodies, and is the most ideal substitute material for the bones.
In animal hard tissue materials, HA is present as a composite. Human bone tissue is a geometric body formed by mutually twisting and winding microcrystalline HA and collagen fibers in a three-dimensional space, and the composite material is formed through complex and long biochemical reaction. There are data showing that although the bone growth ability of human beings is greatly different in different age groups, bone regeneration ability is still present in human to elderly, and bone changes occur.
Currently, most HA is prepared by a sol-gel method, a hydrothermal reaction method, a coprecipitation method, a solid-phase synthesis method and an ultrasonic synthesis method. The synthesis method for preparing HA is complex, impurities are easily introduced in the preparation process, the process parameters are difficult to control, the natural structure of HA cannot be completely copied, and the components and the structure of HA are easily changed. Meanwhile, the industrial mass production of the preparation methods also faces a plurality of difficulties. So far, it is still very difficult to obtain "ideal powder" (i.e. satisfying the harsh conditions of uniform components, fine particles, narrow particle size distribution, no agglomeration, large specific surface area, etc.) at the same time. More importantly, although it is not difficult to prepare high-quality hydroxyapatite nano-powder with a certain characteristic or characteristics, the cost is higher. Therefore, the preparation method of the nano hydroxyapatite with low industrialization cost is to be researched.
Meanwhile, in order to further improve the toughness, reduce the brittleness and further improve the shaping ability of a single hydroxyapatite material and improve the fatigue resistance in a physiological environment, the composite material containing hydroxyapatite is urgently needed in the field for repairing bone tissues such as bone defects and the like, and is particularly applied to repairing bones capable of bearing larger loads.
Disclosure of Invention
In one aspect, the present invention provides a method of preparing hydroxyapatite, the method comprising:
(1) providing ex vivo animal bone;
(2) processing the isolated animal bone in the step (1) by adopting wet digestion;
(3) and (3) neutralizing the animal bone treated in the step (2) to obtain hydroxyapatite, wherein the DNA residue in the obtained hydroxyapatite is not higher than (0.21 +/-0.07) ng/mg and the mass percentage of nitrogen is not higher than (1.35 +/-0.25)% per thousand.
In some embodiments, prior to performing the wet digestion treatment, the excised animal bone is washed, the washing comprising soaking the excised animal bone with water and/or soaking with an aqueous solution containing a surfactant and replacing the water for soaking or the aqueous solution containing the surfactant until the soaking solution is clear. And, the cleaning further comprises performing an irrigation and/or ultrasonic irrigation of the excised animal bone after the soaking. In some embodiments, the soaking lasts no more than 72 hours. The concentration of the surfactant in the aqueous solution containing the surfactant is 0.1g/100ml to 3g/100 ml. The surfactant is selected from: TritonX-100, Tween-80, Tween-40, Surfynol 485,ON-870, CHEMAL LA-9 and Brij 35.
In some embodiments, the wet digestion comprises digesting with an alkaline solution having a pH of not less than 9 at a temperature of 20 ℃ to 300 ℃ until the ex vivo animal bone is digested into particulate form. The digestion treatment lasts for 1 to 120 hours. The alkaline solution is selected from: aqueous NaOH solution, Ca (OH)2Aqueous solution, KOH aqueous solution, Na2CO3Aqueous solution, K2CO3Aqueous solution, NaHCO3Aqueous solution, aqueous ammonia solution and KHCO3An aqueous solution. The wet digestion is carried out by adopting an electric heating plate, a hole type digestion device or a microwave digestion device. In one embodiment, the wet digestion is carried out at a temperature of from 100 ℃ to 300 ℃, or from 100 ℃ to 200 ℃, or from 100 ℃ to 150 ℃; the pH of the alkaline solution is 9 to 12, or 9 to 11, or 9 to 10, or 10 to 12, or 10 to 11.
In some embodiments, the neutralization treatment comprises soaking the animal bone treated in step (2) with water or buffer at 4 ℃ to 30 ℃, and replacing the buffer for soaking one or more times until the pH value of the soaking solution is 7.0 to 7.4. The buffer is a PBS buffer with a pH value of 3.0 to 7.9.
In some embodiments, the above method for preparing hydroxyapatite further comprises: a drying treatment is performed after the neutralization treatment.
The ex vivo animal bone is derived from the bone of a mammal and/or bird and/or reptile and/or marine organism.
In another aspect, the present invention provides a purified hydroxyapatite prepared by the above method, wherein the purified hydroxyapatite has a DNA residue of not higher than (0.21 ± 0.07) ng/mg and a nitrogen content of not higher than (1.35 ± 0.25)% by mass.
In yet another aspect, the present invention provides a hydroxyapatite composite material comprising hydroxyapatite prepared by the above method and a carrier solution. In the hydroxyapatite composite material, the mass percentage of the hydroxyapatite is 1-90%.
In some embodiments, the carrier solution comprises 0.5% to 3% by weight of a carrier, and the carrier is selected from the group consisting of: polylactic acid, polycaprolactone, polyethylene, polyamide, collagen, chitosan, dextran, cellulose, calcium polyphosphate fiber, gelatin and glycerol.
In some embodiments, the composite is prepared by the steps of: providing the carrier solution, and mixing the carrier solution and the hydroxyapatite to obtain the free-flowing gel-state hydroxyapatite composite material.
In some embodiments, the composite is prepared by the steps of: providing the carrier solution, mixing the carrier solution and the hydroxyapatite, and freeze-drying or vacuum-drying the obtained mixture to obtain the porous reticular composite film-shaped hydroxyapatite composite material.
In some embodiments, the step of preparing the composite material may further comprise subjecting the composite material to a sterilization process. The sterilization treatment comprises irradiation sterilization with cobalt-60 or cesium-137 or electron beams, and the irradiation dose is 15 to 50 kGy.
In another aspect, the invention provides the application of the hydroxyapatite and the hydroxyapatite composite material in preparing bone repair materials.
The hydroxyapatite is prepared in a brand new mode, the prepared hydroxyapatite material has a nano structure and can simulate the hydroxyapatite structure of human bones, and the hydroxyapatite prepared by the invention has a needle-shaped structure which is unique to natural hydroxyapatite under a transmission electron microscope. Meanwhile, the invention provides a composite material obtained by mixing the prepared hydroxyapatite with one or more selected from polylactic acid, poly-L-lactic acid, polycaprolactone, polyethylene, polyamide, collagen, chitosan, glucan, cellulose, calcium polyphosphate fiber, gelatin and glycerol, the composite material can further improve the mechanical property of the hydroxyapatite, and can be prepared into a free-flowing gel state or porous reticular composite membrane, wherein the free-flowing gel state can be directly injected to a wound part, and the composite material has the advantages of simple operation, convenience in molding and the like and can be applied to filling of irregular defect sites; the porous structure in the porous reticular composite membrane is favorable for cell growth and tissue regeneration, the hydroxyapatite can form bone bonding with new bones, the bone formation is guided, the storage mode is simple, and the use is convenient.
Drawings
Figure 1 shows a transmission electron micrograph of purified hydroxyapatite material prepared according to one embodiment of the present invention.
Fig. 2 is an X-ray powder diffraction (XRD) pattern of purified hydroxyapatite prepared according to an embodiment of the present invention.
Fig. 3 is a scanning electron micrograph of a hydroxyapatite/chitosan porous mesh-like composite membrane according to an embodiment of the present invention.
Fig. 4 is a scanning electron micrograph of a hydroxyapatite/collagen porous mesh-like composite membrane according to an embodiment of the present invention.
Fig. 5 is a scanning electron micrograph of a hydroxyapatite/silk fibroin porous mesh-like composite membrane according to an embodiment of the present invention.
Fig. 6 is a scanning electron micrograph of a hydroxyapatite/calcium polyphosphate fiber/gelatin porous mesh-shaped composite film according to an embodiment of the present invention.
Detailed Description
The various aspects of the present invention will be described in detail with reference to specific examples, which are provided for illustration only and are not intended to limit the scope and spirit of the present invention.
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified. In the quantitative tests in the following examples, three replicates were set up and the results averaged.
EXAMPLE 1 preparation of hydroxyapatite
This example illustrates a method for preparing hydroxyapatite, the method comprising:
1) collecting fresh pig long bones which are just slaughtered from a slaughterhouse in standardized management, avoiding contacting pollutants as much as possible, and immediately freezing and storing after collection;
2) thawing frozen pig bone material, fully cleaning with water, cutting into 5cm blocks, and washing to remove surface attachments;
3) soaking the pig bone sample obtained in the step 2) for 10 hours by using clear water, and replacing a soak solution;
4) soaking the pig bone sample cleaned in the step 3) for 10 hours at the temperature of 20 +/-2 ℃ by using TritonX-100 aqueous solution with the concentration of 1g/100ml, and replacing the soaking solution;
5) soaking the pig bone sample cleaned and soaked in the step 4) with clear water for 10 hours, and replacing the soaking solution;
6) soaking the sample treated in the step 5) for 10 hours at the temperature of 20 +/-2 ℃ by using aqueous solution of TritonX-100 with the concentration of 1g/100 ml;
7) preparing a NaOH solution with the pH value of 10-12 by using 10g of NaOH, and digesting the sample in the step 6) for 30 minutes at the temperature of 100 +/-2 ℃ by using the NaOH solution so that the massive pig bone samples are digested into fine particles;
8) soaking and cleaning the product obtained in the step 7) by digestion treatment with PBS buffer solution with pH of 6.5 at 20 +/-2 ℃, soaking for 30min each time and replacing the buffer solution until the final pH is 7.0-7.4;
9) carrying out suction filtration treatment on the product obtained in the step 8);
10) and (3) carrying out vacuum drying on the product obtained in the step 9) for 5h at the temperature of 60 +/-2 ℃, and finally obtaining the dried hydroxyapatite.
The purified hydroxyapatite material prepared by the steps is observed under a transmission electron microscope, as shown in figure 1, the hydroxyapatite material has the advantages of uniform shape distribution, fine particles, narrow particle size distribution, no agglomeration, large specific surface area, typical rod-shaped structure, length of about 200nm and width of about 30 nm.
Fig. 2 is an X-ray powder diffraction (XRD) pattern of the purified hydroxyapatite prepared in this example. As shown in fig. 2, the XRD diffraction peaks are consistent with hexagonal hydroxyapatite crystal with space group P63m in standard XRD card (a ═ b ═ 9.418 a; c ═ 6.884a, PDF card No. 09-432). The crystal planes of the hydroxyapatite such as (002), (211), (112), (300), (202), (310), (222), (213) and (004) have clear characteristic diffraction peaks, which shows that the crystallization effect is better, and no diffraction peaks of other phases exist, which shows that no products of other phases exist.
DNA residue detection was performed on the purified hydroxyapatite material prepared in this example, and the result was (0.15. + -. 0.05) ng/mg, indicating complete removal of the genetic material.
The purified hydroxyapatite material prepared in this example was subjected to kjeldahl analysis, and the test result shows that the mass percentage of nitrogen in the hydroxyapatite material is (1.01 ± 0.53)% o, which indicates that the organic components are completely removed and only the hydroxyapatite material remains.
It can be seen from the above preparation method and detection results that the purified hydroxyapatite of the present invention has high purity, complete removal of DNA, complete removal of organic components, and good crystallization effect due to the adoption of specific preparation process and process parameters, and can be prepared from widely available natural bone materials, the preparation method is simple, and is easy for industrial mass production, and the difficulty of industrial difficulty in the present preparation of hydroxyapatite is solved.
EXAMPLE 2 preparation of hydroxyapatite/Chitosan free-flowing gel-state composite
Preparing an aqueous solution containing 3% of chitosan by mass (chitosan is purchased from Shanghai province shellfish ocean biology engineering Co., Ltd., deacetylation is more than or equal to 90%); the hydroxyapatite prepared in example 1 (added in an amount of 60% of the total mass of the aqueous chitosan solution and the hydroxyapatite material) was then added to the aqueous solution, and after being uniformly mixed, the mixture was injected into a syringe prepared in advance. Subsequently, the mixture was subjected to radiation sterilization treatment by cobalt-60 irradiation at a dose of 25 KGy.
The hydroxyapatite composite material prepared by the embodiment is in a gel state capable of flowing freely, can be directly injected to a wound part, and has the advantages of being simple to operate, convenient to mold and the like.
Example 3 preparation of hydroxyapatite/Chitosan porous reticular composite Membrane
The flow type composite material prepared in example 2 was subjected to vacuum drying for 24 hours to obtain a hydroxyapatite/chitosan porous mesh composite membrane, which was subjected to irradiation sterilization by cobalt-60 irradiation at an irradiation dose of 25 KGy. In the hydroxyapatite/chitosan porous reticular composite membrane, the chitosan provides a flexible support, and the hydroxyapatite is attached to the surface of the bracket to play a role in guiding bones.
Fig. 3 is a scanning electron micrograph of the hydroxyapatite/chitosan porous mesh composite membrane prepared in this example. As shown in FIG. 3, the prepared porous reticular composite membrane has a porous structure, which is beneficial to the growth of cells and the regeneration of tissue; the hydroxyapatite is uniformly adsorbed on the surface of the bracket to provide mechanical support, which is beneficial to guiding osteogenesis.
Example 4 preparation of hydroxyapatite/collagen porous mesh composite Membrane
Preparing a collagen aqueous solution containing 4 wt% (wherein collagen is purchased from Aselmi Biotechnology Ltd, and the molecular weight is about 30 KDa), adding the hydroxyapatite prepared in example 1 (the addition amount is 60% of the total mass of the collagen aqueous solution and the hydroxyapatite) into the collagen aqueous solution, uniformly mixing, and performing vacuum drying on the sample for 24 hours to obtain a hydroxyapatite/collagen porous mesh composite membrane; then carrying out radiation sterilization, wherein the sterilization can be cobalt-60 radiation sterilization, and the radiation dose is specifically 25 KGy.
Fig. 4 is a scanning electron micrograph of the hydroxyapatite/collagen porous mesh composite membrane prepared in this example. As shown in fig. 4, the prepared porous reticular composite membrane has a porous structure, which is beneficial to the growth of cells and the regeneration of tissue; the hydroxyapatite is uniformly adsorbed on the surface of the bracket to provide mechanical support, which is beneficial to guiding osteogenesis.
Example 5 preparation of hydroxyapatite/Silk fibroin porous reticular composite Membrane
Preparing a silk fibroin aqueous solution containing 4 wt% (wherein the silk fibroin is purchased from Siam Siji Biotechnology Ltd., molecular weight is 500-10000, content is 98%), adding hydroxyapatite (the addition amount of which is 70% of the total mass of the silk fibroin aqueous solution and the hydroxyapatite) prepared in the example 1 into the silk fibroin aqueous solution, uniformly mixing, carrying out vacuum drying on a sample for 24 hours to obtain a hydroxyapatite/silk fibroin porous reticular composite membrane, and carrying out irradiation sterilization, wherein the sterilization can be cobalt-60 irradiation sterilization, and the irradiation dose is specifically 25 KGy.
Fig. 5 is a scanning electron micrograph of the hydroxyapatite/silk fibroin porous mesh composite membrane prepared in this example. As shown in fig. 5, the prepared porous reticular composite membrane has a porous structure, which is beneficial to the growth of cells and the regeneration of tissue; the hydroxyapatite is uniformly adsorbed on the surface of the bracket to provide mechanical support, which is beneficial to guiding osteogenesis.
Example 6 hydroxyapatite/calcium polyphosphate fiber/gelatin porous mesh composite film
Preparing a gelatin aqueous solution with the mass percentage content of 20% (wherein gelatin is purchased from Qinghai gelatin corporation, and the content is 99.0%), then adding hydroxyapatite and calcium polyphosphate fiber (the mass ratio of gelatin to hydroxyapatite is 2:1, and the mass ratio of calcium polyphosphate fiber to hydroxyapatite is 3:1) into the gelatin aqueous solution, uniformly mixing, and then carrying out vacuum drying on the sample for 36 hours to obtain the hydroxyapatite/calcium polyphosphate fiber/gelatin porous reticular composite membrane. Then carrying out radiation sterilization, wherein the sterilization can be cobalt-60 radiation sterilization, and the radiation dose is specifically 25 KGy.
Fig. 6 is a scanning electron micrograph of the hydroxyapatite/calcium polyphosphate fiber/gelatin porous mesh composite membrane prepared in this example. As shown in FIG. 6, the hydroxyapatite/calcium polyphosphate fiber/gelatin porous reticular composite membrane has a three-dimensional connected micropore structure, and the distribution of internal micropores is relatively uniform, and the size of the micropores is between 200 and 450 μm. The three-dimensional communicated micropore reticular space structure can provide proper nutrient delivery conditions, space conditions and excretion and exchange conditions for the growth and the propagation of tissue cells, and is favorable for bone tissues to exert specific physiological functions.
The present invention has been described in detail with reference to the specific embodiments, which are exemplary only, and are not intended to limit the scope of the present invention, and those skilled in the art may make various modifications, changes, or alterations to the present invention without departing from the spirit and scope of the present invention. Therefore, various equivalent changes made in accordance with the present invention are also within the scope of the present invention.
Claims (27)
1. A method of preparing hydroxyapatite, the method comprising:
(1) providing ex vivo animal bone;
(2) processing the isolated animal bone in the step (1) by adopting wet digestion;
(3) neutralizing the animal bone digested in the step (2) to obtain hydroxyapatite, wherein the DNA residue in the obtained hydroxyapatite is not higher than (0.21 +/-0.07) ng/mg, and the mass percentage content of nitrogen is not higher than (1.35 +/-0.25)% per thousand.
2. The method of claim 1, further comprising: washing the ex vivo animal bone provided in step (1) before the wet digestion treatment.
3. The method of claim 2, wherein the cleaning comprises soaking the excised animal bone with water and/or soaking with an aqueous solution containing a surfactant and replacing the water for soaking or the aqueous solution containing the surfactant until the soaking solution is clear.
4. The method of claim 3, wherein said cleaning further comprises performing an irrigation and/or ultrasonic irrigation of said ex vivo animal bone after said soaking.
5. The method of claim 3, wherein the soaking lasts no more than 72 hours.
6. The method of claim 3, wherein the surfactant concentration in the surfactant-containing aqueous solution is 0.1g/100ml to 3g/100 ml.
7. The method of claim 6, wherein the surfactant is selected from the group consisting of: TritonX-100, Tween-80, Tween-40, Surfynol 485,ON-870, CHEMAL LA-9 and Brij 35.
8. The method according to claim 1, wherein the wet digestion comprises digestion treatment with an alkaline solution having a pH of not less than 9 at a temperature of 20 ℃ to 300 ℃ until the ex vivo animal bone is digested into granules.
9. The method of claim 8, wherein the wet digestion is carried out at a temperature of 100 ℃ to 300 ℃, or 100 ℃ to 200 ℃, or 100 ℃ to 150 ℃.
10. The method of claim 8, wherein the alkaline solution has a pH of 9 to 12, or 9 to 11, or 9 to 10, or 10 to 12, or 10 to 11.
11. The method of claim 8, wherein the digestion process lasts for 1 to 120 hours.
12. The method of claim 10, wherein the alkaline solution is selected from the group consisting of: aqueous NaOH solution, Ca (OH)2Aqueous solution, KOH aqueous solution, Na2CO3Aqueous solution, K2CO3Aqueous solution, NaHCO3Aqueous solution, aqueous ammonia solution and KHCO3An aqueous solution.
13. The method of claim 8, wherein the wet digestion is performed using a hotplate, a well digester, or a microwave digester.
14. The method according to claim 1, wherein the neutralization treatment comprises soaking the treated animal bone in the step (2) with water or buffer at 4-30 ℃ and replacing the buffer for soaking one or more times until the pH value of the soaking solution is 7.0-7.4.
15. The method of claim 14, wherein the buffer is a PBS buffer having a pH of 3.0 to 7.9.
16. The method of claim 1, further comprising: a drying treatment is performed after the neutralization treatment.
17. The method according to any one of claims 1 to 16, wherein the ex vivo animal bone is from the bone of a mammal and/or an avian and/or a reptile and/or a marine organism.
18. A purified hydroxyapatite prepared by the method of any one of claims 1 to 17.
19. A hydroxyapatite composite material comprising hydroxyapatite prepared by the method of any one of claims 1 to 17 and a carrier solution.
20. The hydroxyapatite composite material according to claim 19, wherein the hydroxyapatite composite material has a mass percentage of the hydroxyapatite of 1% to 90%.
21. The hydroxyapatite composite material according to claim 19, wherein the carrier in the carrier solution is present in an amount of 0.5% to 3% by mass, and the carrier is selected from the group consisting of: polylactic acid, polycaprolactone, polyethylene, polyamide, collagen, chitosan, dextran, cellulose, calcium polyphosphate fiber, gelatin and glycerol.
22. The hydroxyapatite composite material according to any one of claims 19 to 21, wherein the composite material is prepared by: providing the carrier solution, and mixing the carrier solution and the hydroxyapatite to obtain the free-flowing gel-state hydroxyapatite composite material.
23. The hydroxyapatite composite material according to any one of claims 19 to 21, wherein the composite material is prepared by: providing the carrier solution, mixing the carrier solution and the hydroxyapatite, and freeze-drying or vacuum-drying the obtained mixture to obtain the porous reticular composite film-shaped hydroxyapatite composite material.
24. The hydroxyapatite composite material according to claim 22 or 23, wherein the step further comprises subjecting the composite material to a sterilization treatment.
25. The hydroxyapatite composite material according to claim 24, wherein the sterilization treatment comprises irradiation sterilization with cobalt-60 or cesium-137 or electron beams and an irradiation dose is from 15kGy to 50 kGy.
26. Use of hydroxyapatite prepared by a method according to any one of claims 1 to 17 in the preparation of bone repair material.
27. Use of a hydroxyapatite composite material according to any one of claims 19 to 25 in the preparation of a bone repair material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810612068.3A CN110606477A (en) | 2018-06-14 | 2018-06-14 | Preparation method of hydroxyapatite, composite material containing hydroxyapatite and application of composite material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810612068.3A CN110606477A (en) | 2018-06-14 | 2018-06-14 | Preparation method of hydroxyapatite, composite material containing hydroxyapatite and application of composite material |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110606477A true CN110606477A (en) | 2019-12-24 |
Family
ID=68887551
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810612068.3A Pending CN110606477A (en) | 2018-06-14 | 2018-06-14 | Preparation method of hydroxyapatite, composite material containing hydroxyapatite and application of composite material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110606477A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114569796A (en) * | 2022-03-04 | 2022-06-03 | 大连大学 | Biodegradable bone repair internal fixation material and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101462707A (en) * | 2007-12-18 | 2009-06-24 | 孙炜 | Natural high-purity nano hydroxylapatite leaching technology |
| CN105816919A (en) * | 2016-05-23 | 2016-08-03 | 烟台正海生物科技股份有限公司 | Composite material containing natural nano-hydroxyapatite and preparation method of composite material |
-
2018
- 2018-06-14 CN CN201810612068.3A patent/CN110606477A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101462707A (en) * | 2007-12-18 | 2009-06-24 | 孙炜 | Natural high-purity nano hydroxylapatite leaching technology |
| CN105816919A (en) * | 2016-05-23 | 2016-08-03 | 烟台正海生物科技股份有限公司 | Composite material containing natural nano-hydroxyapatite and preparation method of composite material |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114569796A (en) * | 2022-03-04 | 2022-06-03 | 大连大学 | Biodegradable bone repair internal fixation material and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ibekwe et al. | Synthesis and characterization of chitosan/gum arabic nanoparticles for bone regeneration | |
| CN107952115B (en) | Bionic biomineralization artificial bone repair material and preparation method and application thereof | |
| Chang et al. | Fabrication and properties of chitin/hydroxyapatite hybrid hydrogels as scaffold nano-materials | |
| Qin et al. | Development and application of fish scale wastes as versatile natural biomaterials | |
| Muthukumar et al. | Collagen/chitosan porous bone tissue engineering composite scaffold incorporated with Ginseng compound K | |
| Xing et al. | Chitin-hydroxyapatite-collagen composite scaffolds for bone regeneration | |
| CN105816919B (en) | A kind of composite material and preparation method containing natural nano hydroxyapatite | |
| KR101053118B1 (en) | Method for preparing silk / hydroxyapatite composite nanofiber support for bone regeneration | |
| CN106729982A (en) | A kind of preparation method of silk fibroin nanosphere | |
| JP6157351B2 (en) | Bioresorbable inclined porous composite, artificial bone using the same, and production method thereof | |
| WO2007011172A1 (en) | Preparation method of porous beta tricalcium phosphate granules | |
| Van Ho et al. | Novel TOCNF reinforced injectable alginate/β-tricalcium phosphate microspheres for bone regeneration | |
| Do Amaral et al. | In vitro and in vivo response of composites based on chitosan, hydroxyapatite and collagen | |
| Hu et al. | Fabrication and characterization of chitosan-silk fibroin/hydroxyapatite composites via in situ precipitation for bone tissue engineering | |
| Zakharov et al. | Synthesis and properties of calcium hydroxyapatite/silk fibroin organomineral composites | |
| CN101856515B (en) | Method for preparing artificial bone from chitosan and shell powder serving as raw materials | |
| CN102167843B (en) | Method for preparing collagen modified polycaprolactone/bioactive glass composite material | |
| Mudhafar et al. | Preparation and characterization of beads of fish scales hydroxyapatite/collagen/silver nanoparticles by using infiltration method | |
| CN110606477A (en) | Preparation method of hydroxyapatite, composite material containing hydroxyapatite and application of composite material | |
| Ataie et al. | Carboxymethyl carrageenan immobilized on 3D-printed polycaprolactone scaffold for the adsorption of calcium phosphate/strontium phosphate adapted to bone regeneration | |
| CN112076350B (en) | Biomimetic mineralized hydrogel with nano-micron composite structure and high mineral density as well as preparation method and application thereof | |
| CN110947034B (en) | Bioactive calcium phosphate/fibrin compounded injectable bone repair hydrogel | |
| KR101381108B1 (en) | Nano ceramic bone cement using animal bone and method for preparing the same | |
| Kanjwal et al. | Fabrication of poly (caprolactone) nanofibers containing hydroxyapatite nanoparticles and their mineralization in a simulated body fluid | |
| JP2013121496A (en) | Artificial cartilage and method for manufacturing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20191224 |