CN106730025B - Preparation method of shell hydroxyapatite artificial bone repair material - Google Patents
Preparation method of shell hydroxyapatite artificial bone repair material Download PDFInfo
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- CN106730025B CN106730025B CN201710088929.8A CN201710088929A CN106730025B CN 106730025 B CN106730025 B CN 106730025B CN 201710088929 A CN201710088929 A CN 201710088929A CN 106730025 B CN106730025 B CN 106730025B
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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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
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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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- 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
Abstract
The invention relates to a preparation method of a shell hydroxyapatite artificial bone repair material, which comprises the steps of firstly synthesizing needle-shaped hydroxyapatite by taking shell powder as a main raw material and pullulan as an organic template, then taking the needle-shaped hydroxyapatite as a filler, and carrying out cross-linking reaction on the needle-shaped hydroxyapatite, the filler and composite collagen, chitosan and cellulose substances to prepare the artificial bone repair material which has a large number of mutually-communicated microporous structures and good mechanical properties. The preparation method has the advantages of simple preparation process, easily obtained raw materials and good production and application prospects.
Description
Technical Field
The invention relates to a biological material, in particular to a preparation method of a shell hydroxyapatite artificial bone repair material.
Background
The bone defect caused by accident or disease is the common clinical case, and the commonly used repair materials at present are autogenous bone, allogenic bone and artificial bone synthetic material, which are all insufficient to a certain extent and can not completely meet the clinical requirement. Natural bone itself is a composite material of nano-hydroxyapatite and collagen, so the nano-hydroxyapatite becomes the most important bone repair and substitute material. The artificial bone material made of nano-hydroxyapatite can replace Ca and P through normal metabolism after being implanted into a human body, can achieve perfect affinity with human tissues through hydrogen bonds formed by hydroxyl groups, has excellent biocompatibility and no immunological rejection phenomenon, is an artificial bone material with excellent biological performance, and is widely applied to clinic. However, the nano-hydroxyapatite belongs to a biological ceramic material, and inevitably has some performance defects, such as brittleness, lower bending strength, and incapability of being used for repairing bone defects of load-bearing parts, and the crystallinity after calcination is higher, so that the nano-hydroxyapatite is difficult to degrade and absorb by organisms.
At present, the success of preparing hydroxyapatite by taking biological materials such as coral, cuttlefish bone, sea urchin and the like as raw materials is reported. However, with the increasing severity of marine pollution, the material resources are limited, the acquisition cost is high, the clinical requirements are difficult to meet, and the technology for preparing the porous hydroxyapatite scaffold by using the waste marine resources as the raw materials is developed, so that the method has extremely high social and economic benefits and environmental protection significance, and conforms to the low-carbon development strategy.
Pullulan (Pullulan, abbreviated as Pu, Chinese is also translated into Pullulan or aureobasidium Pullulan which is extracellular polysaccharide produced by fermentation of aureobasidium pullulans, Pullulan is a linear straight-chain molecule, namely poly maltotriose connected by α - (1 → 6) glycosidic bond, three glucoses are connected by two α - (1 → 4) glycosidic bonds to form maltotriose, two ends of the maltotriose are connected by α - (1 → 6) glycosidic bonds to form a polymer, the ratio of α - (1 → 4) glycosidic bonds to α - - (1 → 6) glycosidic bonds is 2:1, the degree of polymerization is 100-5000, and the molecular weight is 4-200 ten thousand.
Therefore, the invention utilizes the marine waste shell resources, uses the pullulan as the organic template regulator to prepare the hydroxyapatite, and further compounds the collagen and the chitosan substance to synthesize the artificial bone repair material with good biocompatibility and high mechanical strength.
Disclosure of Invention
The invention aims to provide a preparation method of a shell hydroxyapatite artificial bone, which is an artificial bone repair material which is prepared by synthesizing needle-shaped hydroxyapatite with the particle size of 60-100nm by taking shell powder as one of raw materials and then compounding collagen and other substances to prepare a large number of mutually-communicated microporous structures and is suitable for cell growth and tissue repair.
In order to realize the purpose of the invention, the following technical scheme is adopted:
a preparation method of a shell hydroxyapatite artificial bone repair material comprises the following specific steps:
(1) respectively spreading shell powder and diammonium hydrogen phosphate powder at the bottoms of the container A and the container B;
(2) putting a container B into a container A, slowly adding a pullulan aqueous solution with pH =10, which is pre-adjusted by ammonia water, along the inner walls of the container A and the container B, enabling the solution to flow over the container B, sealing the container B by using a preservative film, standing for 14 days at normal temperature, respectively washing obtained precipitates for 3-4 times by using secondary distilled water and absolute ethyl alcohol, performing suction filtration, and putting a washing product into a 50 ℃ oven for overnight to obtain hydroxyapatite powder;
(3) dissolving chitosan and collagen in an acetic acid solution with the volume fraction of 1-2%;
(4) fully and uniformly mixing the hydroxyapatite obtained in the step (2), the solution obtained in the step (3) and the nano-cellulose by adopting a high-speed dispersion machine;
(5) freeze-drying the product obtained in the step (4) until the product is completely dehydrated, then placing the freeze-dried sample in 0.5-1.5 mol/L aqueous alkali for soaking for 8-15 h, repeatedly soaking and washing with deionized water until the product is neutral, soaking the obtained material in a cross-linking agent for cross-linking, wherein the cross-linking agent is glutaraldehyde with the volume fraction of 0.2-0.3%, and the cross-linking time is 12-24 h;
(6) drying the cross-linked product in a vacuum drying oven to obtain the artificial bone repair material, sterilizing with ethylene oxide, and packaging.
Wherein the calcium-phosphorus atomic ratio of the shell powder to the diammonium hydrogen phosphate powder is 1.67;
wherein the mass fraction of the pullulan aqueous solution is 0.3-0.7%;
wherein, the hydroxyapatite, the collagen, the cellulose and the chitosan are mixed according to the mass ratio of 45-55:15-20:7-10: 20-28.
Compared with the prior art, the invention has the following advantages:
(1) according to the invention, the pulullan is used as an organic template, and the needle-shaped hydroxyapatite is synthesized by a biomineralization method, has a high length-diameter ratio, can block the dislocation motion of a matrix, and can disperse stress, so that the pulullan is used as a filler, and the mechanical property of the composite material can be enhanced;
(2) the invention constructs a novel collagen-chitosan-hydroxyapatite composite material which can be completely degraded in vivo and has a three-dimensional pore structure, and when the collagen-chitosan-hydroxyapatite composite material is transplanted into a human body, cells can grow in pores so as to form close combination with human tissues;
(3) the artificial bone repair material prepared by the invention has the advantages of good mechanical property, high tensile strength, good wear resistance, high corrosion resistance, easy molding and good biocompatibility.
Drawings
Fig. 1 is a TEM image of the synthesized hydroxyapatite in example 1.
Detailed Description
For further disclosure, but not limitation, the present invention is described in further detail below with reference to examples.
Example 1
A preparation method of a shell hydroxyapatite artificial bone repair material comprises the following specific steps:
(1) respectively paving shell powder and diammonium hydrogen phosphate powder at the bottoms of the container A and the container B according to the calcium-phosphorus atomic ratio of 1.67;
(2) putting a container B into a container A, slowly adding a 0.3 mass percent pullulan aqueous solution with pH =10, which is pre-adjusted by ammonia water, along the inner walls of the container A and the container B, enabling the solution to flow over the container B, sealing the container B by using a preservative film, standing for 14 days at normal temperature, respectively washing obtained precipitates for 4 times by using secondary distilled water and absolute ethyl alcohol, carrying out suction filtration, and putting a washing product into a 50 ℃ oven for overnight to obtain hydroxyapatite powder;
(3) dissolving chitosan and collagen in 1% volume fraction acetic acid solution;
(4) fully and uniformly mixing the hydroxyapatite obtained in the step (2), the solution obtained in the step (3) and the nano-cellulose by adopting a high-speed dispersion machine;
(5) freeze-drying the product obtained in the step (4) until the product is completely dehydrated, then placing the freeze-dried sample in 0.5mol/L aqueous alkali for soaking for 8 hours, repeatedly soaking and washing the sample with deionized water until the sample is neutral, soaking the obtained material in a cross-linking agent for cross-linking, wherein the cross-linking agent is glutaraldehyde with the volume fraction of 0.2%, and the cross-linking time is 12 hours;
(6) drying the cross-linked product in a vacuum drying oven to obtain the artificial bone repair material, packaging, and sterilizing with gamma-ray.
Wherein, the hydroxyapatite, the collagen, the cellulose and the chitosan are mixed according to the mass ratio of 45:20:7: 28.
In fig. 1, a and b are transmission electron micrographs of the hydroxyapatite prepared, and it is known that the hydroxyapatite prepared is needle-shaped.
Example 2
A preparation method of a shell hydroxyapatite artificial bone repair material comprises the following specific steps:
(1) respectively paving shell powder and diammonium hydrogen phosphate powder at the bottoms of the container A and the container B according to the calcium-phosphorus atomic ratio of 1.67;
(2) putting a container B into a container A, slowly adding a 0.5 mass percent pullulan aqueous solution with pH =10, which is pre-adjusted by ammonia water, along the inner walls of the container A and the container B, enabling the solution to flow over the container B, sealing the container B by using a preservative film, standing for 14 days at normal temperature, respectively washing obtained precipitates for 4 times by using secondary distilled water and absolute ethyl alcohol, carrying out suction filtration, and putting a washing product into a 50 ℃ oven for overnight to obtain hydroxyapatite powder;
(3) dissolving chitosan and collagen in 1% volume fraction acetic acid solution;
(4) fully and uniformly mixing the hydroxyapatite obtained in the step (2), the solution obtained in the step (3) and the nano-cellulose by adopting a high-speed dispersion machine;
(5) freeze-drying the product obtained in the step (4) until the product is completely dehydrated, then placing the freeze-dried sample in 0.5mol/L aqueous alkali for soaking for 10 hours, repeatedly soaking and washing the sample with deionized water until the sample is neutral, soaking the obtained material in a cross-linking agent for cross-linking, wherein the cross-linking agent is glutaraldehyde with the volume fraction of 0.2%, and the cross-linking time is 16 hours;
(6) drying the cross-linked product in a vacuum drying oven to obtain the artificial bone material, packaging, and sterilizing with gamma-ray.
Wherein, the hydroxyapatite, the collagen, the cellulose and the chitosan are mixed according to the mass ratio of 48:20:8: 24.
Example 3
A preparation method of a shell hydroxyapatite artificial bone repair material comprises the following specific steps:
(1) respectively paving shell powder and diammonium hydrogen phosphate powder at the bottoms of the container A and the container B according to the calcium-phosphorus atomic ratio of 1.67;
(2) putting a container B into a container A, slowly adding a 0.7 mass percent pullulan aqueous solution with pH =10, which is pre-adjusted by ammonia water, along the inner walls of the container A and the container B, enabling the solution to flow over the container B, sealing the container B by using a preservative film, standing for 14 days at normal temperature, respectively washing obtained precipitates for 4 times by using secondary distilled water and absolute ethyl alcohol, carrying out suction filtration, and putting a washing product into a 50 ℃ oven for overnight to obtain hydroxyapatite powder;
(3) dissolving chitosan and collagen in 2% volume fraction acetic acid solution;
(4) fully and uniformly mixing the hydroxyapatite obtained in the step (2), the solution obtained in the step (3) and the nano-cellulose by adopting a high-speed dispersion machine;
(5) freeze-drying the product obtained in the step (4) until the product is completely dehydrated, then placing the freeze-dried sample in 0.5mol/L aqueous alkali for soaking for 8 hours, repeatedly soaking and washing the sample with deionized water until the sample is neutral, soaking the obtained material in a cross-linking agent for cross-linking, wherein the cross-linking agent is glutaraldehyde with the volume fraction of 0.2%, and the cross-linking time is 18 hours;
(6) drying the cross-linked product in a vacuum drying oven to obtain the artificial bone material, and sterilizing by gamma-ray.
Wherein, the hydroxyapatite, the collagen, the cellulose and the chitosan are mixed according to the mass ratio of 55:15:10: 20.
The mechanical strength chart of the artificial bone repair composite material of the invention is as follows:
the above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the present invention.
Claims (3)
1. A preparation method of a shell hydroxyapatite artificial bone repair material is characterized by comprising the following steps: the method comprises the following specific steps:
(1) respectively spreading shell powder and diammonium hydrogen phosphate powder at the bottoms of the container A and the container B;
(2) putting a container B into a container A, slowly adding a pullulan aqueous solution with the pH =10 pre-adjusted by ammonia water along the inner walls of the container A and the container B, enabling the solution to flow over the container B, sealing the container B by a preservative film, standing for 14 days at normal temperature, respectively washing obtained precipitates for 3-4 times by using secondary distilled water and absolute ethyl alcohol, performing suction filtration, and putting a washing product into a 50 ℃ oven for overnight to obtain hydroxyapatite powder;
(3) dissolving chitosan and collagen in an acetic acid solution with the volume fraction of 1-2%;
(4) fully and uniformly mixing the hydroxyapatite obtained in the step (2), the solution obtained in the step (3) and the nano-cellulose by adopting a high-speed dispersion machine;
(5) freeze-drying the product obtained in the step (4) until the product is completely dehydrated, then placing the freeze-dried sample in 0.5-1.5 mol/L aqueous alkali for soaking for 8-15 h, repeatedly soaking and washing with deionized water until the sample is neutral, and soaking the obtained material in a cross-linking agent for cross-linking;
drying the cross-linked product in a vacuum drying oven to obtain the artificial bone material, sterilizing by gamma-ray, and packaging; the mass fraction of the pullulan aqueous solution is 0.3-0.7%;
according to the mass ratio, the hydroxyapatite: collagen protein: nano-cellulose: chitosan =45-55:15-20:7-10: 20-28.
2. The preparation method of the shell hydroxyapatite artificial bone repair material according to claim 1, which is characterized by comprising the following steps: the calcium-phosphorus atomic ratio of the shell powder to the diammonium phosphate powder is 1.67.
3. The preparation method of the shell hydroxyapatite artificial bone repair material according to claim 1, which is characterized by comprising the following steps:
the cross-linking agent is glutaraldehyde with volume fraction of 0.2-0.3%; the crosslinking time is 12-24 h.
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