CN110694106A - Composite bone cement with high bioactivity and high strength and preparation method thereof - Google Patents

Composite bone cement with high bioactivity and high strength and preparation method thereof Download PDF

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CN110694106A
CN110694106A CN201810754251.7A CN201810754251A CN110694106A CN 110694106 A CN110694106 A CN 110694106A CN 201810754251 A CN201810754251 A CN 201810754251A CN 110694106 A CN110694106 A CN 110694106A
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bone cement
powder
composite
liquid
composite bone
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赵立升
杨烁
李俊杰
温宁
顾斌
王宇
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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
    • A61L27/20—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
    • A61L27/02—Inorganic materials
    • A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
    • 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
    • A61L27/50—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
    • 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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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Transplantation (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The invention discloses a composite bone cement with high bioactivity and high strength and a preparation method thereof. The preparation method comprises the following steps: (1) preparing a composite bone cement liquid; (2) mixing the composite bone cement powder and the liquid to prepare composite bone cement; (3) placing the composite bone cement in a mould, and drying and solidifying in a vacuum drying oven to obtain the composite bone cement. The invention compounds calcium phosphate and strontium-containing pectin solution with high bioactivity to obtain the high-bioactivity and high-strength composite bone cement, wherein the compressive strength of the composite bone cement is more than 15MPa, the porosity is 50-75%, and the pore diameter is 200-600 mu m. The composite bone cement with high bioactivity and high strength can repair bone defects in any shapes and can induce bone formation.

Description

Composite bone cement with high bioactivity and high strength and preparation method thereof
Technical Field
The invention relates to a bone repair material and a preparation method thereof, in particular to a preparation method of composite bone cement with high bioactivity and high strength and a product prepared by the method, belonging to the field of artificial bone repair materials.
Background
The calcium phosphate bone cement is considered as a bone defect repair material with bright prospect, and at present, partial products are applied to clinical treatment to obtain certain curative effect. Although calcium phosphate bone cement has many advantages such as good biocompatibility and bone conduction performance, calcium phosphate bone cement has low strength and can only be used in non-bearing areas; in addition, the degradation speed of the collagen in vivo is too slow, which is not beneficial to the generation of new bones, and the biocompatibility of the collagen is still to be further improved (such as US 7229971, US20170255422, JP 2003073304 and the like), which limits the wide application of the collagen in clinic. At present, the curing liquid of calcium phosphate cement is mainly water or diluted phosphoric acid, and the curing liquid only has the function of simply promoting curing. Pectin is a natural water-soluble polysaccharide present in plant cell walls and has a structure very similar to that of polysaccharides in mammalian extracellular matrices. The pectin has good biocompatibility and can support the adhesion and growth of various cells. For example, Tuukkanen (Kokkonen H, Cassinelli C, Verhoef R, et al. differentiation of Osteoplasts on Pectin-coated titanium, Biomacromolecules 2008; 9: 2369-2376.) found that Pectin nano-coated titanium alloy can improve its biocompatibility as a bone and dental implant material.
The pectin is used as polysaccharide with good biocompatibility, and has a natural grid structure after being formed into gel, so that the physical and chemical properties of the calcium phosphate material can be improved, and the capability of slowly releasing trace elements is loaded, so that the osteogenesis is further promoted. Therefore, the pectin-rich composite calcium phosphate bone repair material has a relatively ideal prospect.
Disclosure of Invention
The invention aims to solve the technical problems of low biological activity, poor strength and incapability of supporting at the initial stage of implantation of the existing bone repair material, and the physicochemical property of bone cement is enhanced by using the mastiff combination property and the gelling property of pectin and calcium ions; strontium ions are introduced into the bone cement by utilizing the grid adsorption effect of the pectin solution, so that the bone forming efficiency and the material degradation rate are promoted, and the composite bone cement with high bioactivity and high strength is provided.
The technical problem to be solved by the invention is realized by the following technical scheme:
a composite bone cement with high bioactivity and high strength and a preparation method thereof comprise the following steps:
(1) preparing bone cement powder;
(2) preparing bone cement liquid;
(3) mixing the bone cement powder and the liquid to obtain the final product.
Wherein the composite bone cement powder in the step (1) is composed of equal molar tetracalcium phosphate (TTCP) and anhydrous calcium hydrogen phosphate (DCPA). Tetracalcium phosphate (TTCP) is prepared from equimolar calcium carbonate (CaCO)3) And calcium hydrogen phosphate Dihydrate (DCPA) powder, ball-milling, mixing, and sintering at high temperature.
Preferably, the high-temperature sintering in step (1) comprises: heating the uniformly-milled calcium phosphates in a muffle furnace to 1300-1600 ℃ for sintering to obtain tetracalcium phosphate powder; preferably, the sintering time is 6 to 20 hours, more preferably 8 to 12 hours.
And (2) when the high-temperature sintering in the step (1) is finished, rapidly cooling the sintered product to room temperature, rapidly taking out the sintered product from the furnace or adopting vacuum sintering during sintering, and cooling along with the furnace. And nitrogen can be filled to protect the product after the reaction is finished, so that the phase change during slow temperature reduction is prevented.
Mixing the cooled tetracalcium phosphate and anhydrous calcium hydrophosphate in equal proportion, and performing ball milling for 12-14h to obtain powder.
In order to achieve better effect, during high-temperature sintering, the temperature is rapidly increased to 1450-1600 ℃, and then the temperature is kept for 8-10 hours; meanwhile, the finally obtained bone cement powder is preferably stored in a vacuum seal mode.
The preparation method of the bone cement liquid in the step (2) comprises the following steps: 1-10g of pectin powder (degree of esterification > 50%, degree of polymerization 200-600) was slowly dissolved in 100ml of deionized water, and stirring was continued until complete dissolution. The liquid was left to stand in a refrigerator environment at 4 ℃ for 12 hours, allowing it to swell and completely eliminate air bubbles.
Weighing a certain amount of strontium chloride powder to prepare a solution containing strontium ions at 0.5 mol/L. Mixing the solution with pectin solution at a ratio of 20: 1, standing in 4 deg.C refrigerator for 12 hr.
The solid-to-liquid ratio (g/ml) of the powder and the liquid mixed in the step (3) is 1/0.4-1/1.0; preferably 1/0.8.
The invention obtains the bone cement powder of a tetracalcium phosphate system by sintering calcium phosphates at high temperature, and then compounds the bone cement powder with strontium-containing pectin liquid with high bioactivity to obtain the composite bone cement with high bioactivity and high strength, wherein the compressive strength of the composite bone cement is more than 15MPa, the porosity is 50-75%, and the pore diameter is 200-600 mu m. The composite bone cement with high bioactivity and high strength can repair various bone defects and induce osteogenesis.
The specific implementation mode is as follows:
the invention will be further described with reference to specific embodiments, and the advantages and features of the invention will become apparent as the description proceeds. These examples are illustrative only and do not limit the scope of the present invention in any way.
Example 1
(1) Weighing 0.1 mol of each of calcium carbonate and calcium hydrophosphate dihydrate, and ball-milling with corundum for 12 hours to obtain mixed powder.
(2) And placing the mixed powder in a corundum crucible, placing the corundum crucible in a muffle furnace, quickly heating to 1400 ℃, and preserving heat for 8 hours. And opening the furnace, taking out the crucible, and rapidly cooling the crucible to room temperature in the air to obtain the tetracalcium phosphate.
(3) Weighing 0.01 mol of tetracalcium phosphate and anhydrous calcium hydrophosphate by an electronic balance, and performing ball milling for 12-14 hours to obtain the bone cement powder.
(4) Weighing 0.6g of pectin powder, dissolving in 30ml of deionized water on a magnetic stirrer at room temperature, and stirring continuously to obtain a 2% pectin solution; 3.9 g of strontium chloride powder is weighed and dissolved in 50ml of deionized water on a magnetic stirrer at room temperature, and stirring is carried out continuously to obtain 0.5mol/L strontium-containing solution. Mixing the solution with pectin solution at a ratio of 20: 1(v/v), standing at 4 deg.C in refrigerator for 12 hr.
(5) Weighing 1g of powder and 0.8ml of 2% strontium-containing pectin solution according to the solid-liquid ratio of 1/0.8, uniformly mixing, placing in a cylindrical mold, and curing to obtain a cylindrical composite bone cement sample.
The composite bone cement prepared in the embodiment has the following compressive strength after being tested: 10.24 +/-1.05 MPa;
the activity detection method of the composite bone cement prepared in the embodiment is as follows:
1. culturing human adipose mesenchymal stem cells:
the human adipose-derived mesenchymal stem cells are derived from adipose tissues of young healthy people, and the induction medium is an alpha-MEM (alpha-MEM) medium which contains 10% fetal calf serum, 100U/ml cyan/streptomycin, 0.05g/L ascorbic acid and 10mmol/L beta-sodium glycerophosphate.
The composite bone cement disc samples prepared in this example were placed in a 24-well plate and sterilized by irradiation with Co 60. Experiment 1X 10 inoculations per well in 24-well plates5And 4, cells grow and reproduce faster. 37 ℃ and 5% CO2Culturing in 100% humidity incubator, and changing the culture medium every 3 days.
2. Alkaline phosphatase activity assay:
the medium was discarded, washed 3 times with PBS, cells were digested by adding 0.25% trypsin solution to each well, and 1ml of medium was added to each well after the cells were completely detached. Transfer well liquid and sample into centrifuge tube, add cell lysate, centrifuge at 1000rpm for 10min, carefully aspirate supernatant. Adding 10 μ l of supernatant into 96-well plate, adding 100 μ l of substrate into each well, shaking in 37 deg.C constant temperature water bath shaker for 60min, and measuring absorbance with excitation wavelength of 405 nm. The absolute amount of alkaline phosphatase was calculated against a standard curve. The number of measurements for each sample was 3.
The detection result is as follows: the alkaline phosphatase (ALP (Protein) activities of the cells cultured on the composite bone cement disk prepared in this example were 10.30. + -. 1.21U/L Protein, 16.78. + -. 4.34U/L Protein, and 44.26. + -. 4.32U/L Protein, respectively, after 7 days, 14 days, and 21 days of induction culture.
Example 2
(1) Weighing 0.1 mol of each of calcium carbonate and calcium hydrophosphate dihydrate, and ball-milling with corundum for 12 hours to obtain mixed powder.
(2) And (3) placing the mixed powder into a corundum crucible, placing the corundum crucible into a muffle furnace, quickly heating to 1600 ℃, and preserving heat for 8 hours. And opening the furnace, taking out the crucible, and rapidly cooling the crucible to room temperature in the air to obtain the tetracalcium phosphate.
(3) Weighing 0.01 mol of tetracalcium phosphate and anhydrous calcium hydrophosphate by an electronic balance, and performing ball milling for 12-14 hours to obtain the bone cement powder.
(4) Weighing 1.2g of pectin powder, dissolving in 30ml of deionized water on a magnetic stirrer at room temperature, and stirring continuously to obtain a 4% pectin solution; 3.9 g of strontium chloride powder is weighed and dissolved in 50ml of deionized water on a magnetic stirrer at room temperature, and stirring is carried out continuously to obtain 0.5mol/L strontium-containing solution. Mixing the solution with pectin solution at a ratio of 20: 1(v/v), standing at 4 deg.C in refrigerator for 12 hr.
(5) Weighing 1g of solid-phase powder and 0.8ml of 4% strontium-containing pectin solution according to the solid-liquid ratio of 1/0.8, uniformly mixing, placing in a mold, and curing to obtain a cylindrical or disk-shaped composite bone cement sample.
The compressive strength of the cylindrical composite bone cement prepared in the embodiment is tested as follows: 28.76 +/-8.18 MPa;
the method for measuring the activity of the composite bone cement prepared in this example is the same as in example 1.
The detection result is as follows: the alkaline phosphatase (ALP (Protein) activities of the cells induced and cultured on the composite bone cement disk prepared in this example for 7 days, 14 days and 21 days were 11.47 + -0.44U/L Protein, 20.77 + -3.40U/L Protein and 51.65 + -3.81U/L Protein, respectively.

Claims (7)

1. A preparation method of composite bone cement with high bioactivity and high strength comprises the following steps:
(1) preparation of bone cement powder
(2) Preparing bone cement liquid;
(3) mixing the bone cement powder and the liquid according to a certain proportion, self-solidifying, and sterilizing to obtain the final product.
2. The method of claim 1, wherein: the composite bone cement is prepared by compounding calcium phosphate and pectin.
3. The method of claim 1, wherein: the bone cement powder in the step (1) is calcium phosphate and comprises the following components: tetracalcium phosphate, tricalcium phosphate, composite calcium phosphates, and the like. Preferably, the calcium phosphate is composed of tetracalcium phosphate (TTCP) and anhydrous Dibasic Calcium Phosphate (DCPA) in equimolar amounts. Tetracalcium phosphate (TTCP) is prepared from equimolar calcium carbonate (CaCO)3) And calcium hydrogen phosphate Dihydrate (DCPA) powder, ball-milling and uniformly mixing, and carrying out high-temperature solid-phase reaction to obtain the DCPA powder. Ball-milling the composite calcium phosphate powder for 20-32h and mixing uniformly.
4. The method of claim 1, wherein: the bone cement liquid in the step (2) is strontium-doped pectin solution, and the concentration range of the strontium-doped pectin solution is 1% -7%, and the concentration range of the strontium-doped pectin solution is more preferably 5% -7%. The preparation method comprises the following steps:
(1) weighing corresponding medicinal pectin with esterification degree higher than 50% and polymerization degree of 200-600, dissolving in deionized water, slowly adding pectin powder into deionized water, and stirring until completely dissolved.
(2) The liquid was left to stand in a refrigerator environment at 4 ℃ for 12 hours, allowing it to swell and completely eliminate air bubbles.
(3) Weighing a certain amount of strontium chloride powder to prepare a solution containing strontium ions at 0.5 mol/L.
(4) Mixing the solutions (2) and (3) at a ratio of 20: 1, standing in a refrigerator environment at 4 deg.C for 12 hr.
5. The method of claim 1, wherein: the solid-to-liquid ratio (g/ml) of the powder and the liquid mixed in the step (3) is 1/0.4-1/1.0; preferably 1/0.8. The method comprises the following steps:
(1) mixing calcium phosphate with 5-7% strontium-doped pectin solution at a solid-to-liquid ratio of 1/0.8 to obtain composite calcium phosphate.
(2) Placing the composite calcium phosphate in an incubator at 40 ℃, curing for 8-20 minutes, packaging, and sterilizing with ethylene oxide.
6. The product obtained by the process of any one of claims 1 to 7.
7. Use of the product of claim 6 in the preparation of a material for repairing bone repair.
CN201810754251.7A 2018-07-10 2018-07-10 Composite bone cement with high bioactivity and high strength and preparation method thereof Pending CN110694106A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115737932A (en) * 2022-11-23 2023-03-07 国纳之星(上海)纳米科技发展有限公司 Preparation of bone cement loaded with X-ray induced photodynamic therapy/radiotherapy collaborative diagnosis and treatment integrated probe, product and application

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115737932A (en) * 2022-11-23 2023-03-07 国纳之星(上海)纳米科技发展有限公司 Preparation of bone cement loaded with X-ray induced photodynamic therapy/radiotherapy collaborative diagnosis and treatment integrated probe, product and application
CN115737932B (en) * 2022-11-23 2024-04-26 国纳之星(上海)纳米科技发展有限公司 Preparation, product and application of bone cement loaded with X-ray induced photodynamic therapy/radiotherapy cooperative diagnosis and treatment integrated probe

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