CN114209878B - Solid phase powder for bone cement composite material, bone cement composite material and application - Google Patents

Solid phase powder for bone cement composite material, bone cement composite material and application Download PDF

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CN114209878B
CN114209878B CN202111439934.1A CN202111439934A CN114209878B CN 114209878 B CN114209878 B CN 114209878B CN 202111439934 A CN202111439934 A CN 202111439934A CN 114209878 B CN114209878 B CN 114209878B
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phosphate
bone cement
powder
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cement composite
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CN114209878A (en
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李梅
张海燕
李祥瑞
董骧
许书富
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Beijing Natong Medical Research Institute Co ltd
Tianjin Zhengtian Medical Instrument Co Ltd
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Tianjin Zhengtian Medical Instrument Co Ltd
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    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
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    • 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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Abstract

The invention discloses a bone cement composite material, which comprises solid phase powder and curing liquid, wherein the solid phase powder comprises calcium phosphate powder, calcium sulfate hemihydrate powder, bioglass and hydroxyapatite, and the calcium phosphate powder comprises the following components in percentage by weight: beta-tricalcium phosphate, tetracalcium phosphate, and monocalcium phosphate monohydrate. Wherein the solid phase powder comprises 10-80% of calcium phosphate powder, 5-50% of bioglass, 10-25% of calcium sulfate hemihydrate powder and 5-15% of hydroxyapatite by mass percentage. The bone cement prepared from the composite material has high strength, good antibacterial property and injectability, keeps good biological activity, is not easy to collapse in the using process, and can be applied to filling and repairing of bone defect parts in the fields of orthopedics, plastic surgery, dentistry and the like.

Description

Solid phase powder for bone cement composite material, bone cement composite material and application
Technical Field
The invention belongs to the field of bone repair materials, particularly relates to solid-phase powder for a bone cement composite material, and particularly relates to the bone cement composite material and application thereof.
Background
Bone cement is a common orthopedic repair material and is widely applied to the fields of bone defects, dentistry, plastic surgery and the like. Currently, the most common bone cement material on the market is polymethylmethacrylate bone cement (PMMA). The material system is non-absorbable, has low bioactivity and no good bone induction capability, and releases a large amount of heat in the curing process to cause damage to surrounding tissues. Therefore, a more suitable orthopedic repair material is sought.
The calcium phosphate cement consists of solid calcium phosphate powder and liquid phase, and the mixture of the solid calcium phosphate powder and the liquid phase can be solidified in physiological environment. The curing process has no great heat generation, and the product is hydroxyapatite similar to inorganic components in human skeleton. In addition, the material system has good biological activity, osteoinductivity and absorbability, and can stimulate the rapid generation of new bone tissues when being implanted into a body. Although calcium phosphate cement is more suitable for bone repair than polymethylmethacrylate bone cement in a material system, the traditional calcium phosphate bone cement still has some problems and cannot meet clinical requirements. Firstly, the strength is low, the mechanical property of the calcium phosphate cement is close to that of cancellous bone, and the calcium phosphate cement can only be used for bone defect of a non-bearing part and cannot meet the requirement of clinical load-bearing bone repair. Secondly, the curing time is not matched with clinical requirements, the ideal cement curing time in the operation is 15-30 min, and the curing time of different calcium phosphate systems is too fast or too slow to adapt to the clinical requirements on the curing time. And thirdly, the injection performance is poor, the solid-liquid separation phenomenon is easy to occur in the injection process, the injection rate is low, the material waste is caused, and the clinical requirement of the minimally invasive surgery cannot be met. Then, the medicine is easy to be dispersed, and the medicine is washed by body fluid or blood and cannot be shaped in the operation process. Finally, the calcium phosphate bone cement has no antibacterial property, inflammation caused by bacterial infection is a key factor causing operation failure in an orthopedic implantation operation, the traditional calcium phosphate bone cement has no good antibacterial property, and if the bone cement has the good antibacterial property, the inflammatory reaction caused by the bacterial infection can be effectively reduced, the bone healing is promoted, and the success rate of the operation is improved. Therefore, there is a need to develop a new bone cement material to meet the current clinical needs.
Disclosure of Invention
The present invention is based on the discovery and recognition by the inventors of the following facts and problems: the traditional calcium phosphate bone cement has low strength, poor injectability, easy collapsibility, unmatched curing time with ideal requirements of operations, no antibacterial property and incapability of meeting clinical requirements.
The present invention is directed to solving, at least to some extent, one of the technical problems in the related art.
Therefore, the solid phase powder for the bone cement composite material provided by the embodiment of the invention improves the components of the calcium phosphate material to perform multiphase curing reaction, so that the strength is improved, and the solid phase powder applied to the calcium phosphate bone cement not only has high strength, good antibacterial property and injectability, but also maintains good biological activity and is not easy to collapse in the using process, so that the solid phase powder can be applied to filling and repairing of bone defect parts in the fields of orthopedics, plastic surgery, dentistry and the like.
The solid phase powder for the bone cement composite material comprises calcium phosphate powder, calcium sulfate hemihydrate powder, bioglass and hydroxyapatite, wherein the calcium phosphate powder comprises the following components in parts by weight: beta-tricalcium phosphate, tetracalcium phosphate, and monocalcium phosphate monohydrate.
The solid-phase powder for the bone cement composite material of the embodiment of the invention brings advantages and technical effects, 1, in the embodiment of the invention, through the design of the components of the solid-phase powder, the multiphase solidification reaction is carried out in the reaction phase, so that the strength can be improved multiple times, beta-tricalcium phosphate and calcium dihydrogen phosphate monohydrate in a calcium phosphate material system can quickly react in a liquid phase environment to generate calcium hydrogen phosphate dihydrate, and the generated calcium hydrogen phosphate dihydrate and tetracalcium phosphate slowly carry out chemical reaction in the liquid phase environment to generate hydroxyapatite, wherein the reaction rate of the beta-tricalcium phosphate and the calcium dihydrogen phosphate monohydrate in the calcium phosphate system is high, the solidification time is short, the reaction can be completed in about 1min, and the reaction rate of the calcium hydrogen phosphate dihydrate and the tetracalcium phosphate is low, the solidification time is long, and the calcium phosphate dihydrate and the tetracalcium phosphate are solidified in about 50-120 min; 2. in the embodiment of the invention, the hydroxyapatite added in the solid phase powder can provide nucleation sites for the hydroxyapatite generated by the reaction in the system, accelerate the reaction of calcium hydrophosphate dihydrate and tetracalcium phosphate to generate the hydroxyapatite and shorten the curing time; 3. in the embodiment of the invention, when the solid-phase powder is applied to the bone cement composite material, the calcium sulfate hemihydrate reacts with the liquid phase to generate the calcium sulfate dihydrate, the calcium sulfate has higher degradation rate in body fluid, and the degradation performance of the bone cement can be directionally prepared by doping the calcium sulfate hemihydrate in a calcium phosphate system so as to be matched with the growth of human bones; 4. in the embodiment of the invention, the bioglass in the solid phase powder has higher activity, can better stimulate and induce osteoblast gene expression and promote cell ossification, and meanwhile, the bioglass has good antibacterial performance and can improve the antibacterial performance of bone cement when being doped into calcium phosphate bone cement.
In some embodiments, the solid phase powder comprises 10-80% of calcium phosphate powder, 5-50% of bioglass, 10-25% of calcium sulfate hemihydrate powder and 5-15% of hydroxyapatite by mass percentage.
In some embodiments, the calcium phosphate powder comprises 5-20% of beta-tricalcium phosphate, 60-90% of tetracalcium phosphate and 5-20% of monocalcium phosphate monohydrate by mass percentage.
The embodiment of the invention also provides application of the solid-phase powder for the bone cement composite material in preparing a bone repair material. The solid phase powder provided by the embodiment of the invention can be used for preparing a bone repair material, and the bone repair material has the corresponding advantages brought by the solid phase powder provided by the embodiment of the invention, and is not described again.
The embodiment of the invention also provides a bone cement composite material which comprises the solid-phase powder and the curing liquid. The composite material disclosed by the embodiment of the invention has excellent biocompatibility, the curing time can meet the ideal requirement of a surgical operation, and meanwhile, the antibacterial property and the injectability are maintained, so that the composite material can be applied to filling and repairing of bone defect parts in the fields of orthopedics, plastic surgery, dentistry and the like.
In some embodiments, the liquid-solid ratio of the solidification liquid to the solid-phase powder is 0.5ml/g to 1ml/g.
In some embodiments, the curing liquid comprises dipotassium hydrogen phosphate, potassium dihydrogen phosphate, citric acid, and water.
In some embodiments, the solidifying fluid further comprises a polymeric compound comprising at least one of sodium alginate or hyaluronic acid.
In some embodiments, the curing liquid comprises 5-20% of dipotassium phosphate, 5-20% of monopotassium phosphate, 5-10% of citric acid, 1-5% of high molecular compounds and the balance of water by mass percentage.
The invention also provides application of the bone cement composite material in preparing a bone repair material. The composite material provided by the embodiment of the invention can be used for preparing a bone repair material, has the corresponding advantages brought by the composite material provided by the embodiment of the invention, and is not described again.
Drawings
FIG. 1 is an XRD pattern of a solidified liquid and a solid powder described in example 1 at different times after mixing;
FIG. 2 is a graph showing a test of setting time of a bone cement composite according to an embodiment of the present invention;
FIG. 3 is a graph of the compressive strength of a bone cement composite of an embodiment of the present invention after hydration for 24 hours;
FIG. 4 is a graph of the activity of cellular ALP after 7 days of co-culture of a bone cement composite with BMSCs cells according to an embodiment of the present invention;
FIG. 5 is a graph of time versus mass loss for a bone cement composite soaked in an SBF solution according to an embodiment of the present invention;
FIG. 6 is the OD value measured at 475nm wavelength after 48h of co-culture of the bone cement composite material of the example of the present invention with Staphylococcus aureus.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings. The embodiments described below with reference to the accompanying drawings are illustrative and intended to explain the present invention and should not be construed as limiting the present invention.
The solid phase powder for the bone cement composite material comprises calcium phosphate powder, calcium sulfate hemihydrate powder, bioglass and hydroxyapatite, wherein the calcium phosphate powder comprises: beta-tricalcium phosphate, tetracalcium phosphate and monocalcium phosphate monohydrate.
The solid-phase powder for the bone cement composite material provided by the embodiment of the invention has the advantages that through the design of components of the solid-phase powder, multiphase solidification reaction is carried out in a reaction phase, so that the strength can be improved in multiple ways, beta-tricalcium phosphate and monohydrated monocalcium phosphate in a calcium phosphate material system can quickly react in a liquid-phase environment to generate calcium hydrophosphate dihydrate, and the generated calcium hydrophosphate and tetracalcium phosphate slowly carry out chemical reaction in the liquid-phase environment to generate hydroxyapatite, wherein the reaction rate of the beta-tricalcium phosphate and the monohydrated monocalcium phosphate in the calcium phosphate system is high, the solidification time is short, the reaction rate of the calcium hydrophosphate dihydrate and the tetracalcium phosphate is slow, and the solidification time is long; in the embodiment of the invention, the hydroxyapatite added into the solid phase powder can provide nucleation sites for the hydroxyapatite generated by the reaction in the system, accelerate the reaction of calcium hydrogen phosphate dihydrate and tetracalcium phosphate to generate hydroxyapatite and shorten the curing time; in the embodiment of the invention, when the solid-phase powder is applied to the bone cement composite material, the calcium sulfate hemihydrate reacts with the liquid phase to generate the calcium sulfate dihydrate, the calcium sulfate has higher degradation rate in body fluid, and the degradation performance of the bone cement can be directionally prepared by doping the calcium sulfate hemihydrate in a calcium phosphate system so as to be matched with the growth of human bones; in the embodiment of the invention, the bioglass in the solid phase powder has higher activity, can better stimulate and induce osteoblast gene expression and promote cell ossification, and meanwhile, the bioglass has good antibacterial performance and can improve the antibacterial performance of the bone cement when being doped into calcium phosphate bone cement.
The reaction equation involved in the examples of the present invention is as follows:
in the calcium phosphate material system, beta-tricalcium phosphate and calcium dihydrogen phosphate monohydrate can react quickly in a liquid phase environment to generate calcium hydrogen phosphate dihydrate.
β-Ca 3 (PO 4 ) 2 +Ca(H 2 PO 4 ) 2 ·H 2 O+7H 2 O→4CaHPO 4 ·2H 2 O (1)
Subsequently, as shown in reaction equations (2) and (3), the generated calcium hydrogen phosphate dihydrate and tetracalcium phosphate slowly undergo a chemical reaction in a liquid phase environment to generate hydroxyapatite.
2Ca 4 (PO 4 ) 2 O+2CaHPO 4 ·2H 2 O→Ca 10 (PO 4 ) 6 (OH) 2 +4H 2 O+2XCa(OH) 2 (2)
2Ca 4 (PO 4 ) 2 O+2CaHPO 4 ·2H 2 O→Ca 10-X (HPO 4 ) X (PO 4 ) 6-X (OH) 2-X +XCa(OH) 2 +(4-X)H 2 O(3)
The tricalcium phosphate and the monocalcium phosphate monohydrate in the calcium phosphate system of the embodiment of the invention have high reaction rate, and can react in about 1min, and the calcium hydrogen phosphate dihydrate and the tetracalcium phosphate have relatively low reaction rate and long curing time, and are primarily cured in about 50-120 min.
Meanwhile, when the calcium sulfate hemihydrate is applied to the bone cement composite material, the calcium sulfate hemihydrate in the solid-phase powder reacts with the liquid phase to generate calcium sulfate dihydrate, as shown in the formula (4), so that the degradation performance of the bone cement composite material can be effectively adjusted.
CaSO 4 ·0.5H 2 O+1.5H 2 O→CaSO 4 ·2H 2 O (4)
In some embodiments, the solid phase powder comprises 10-80% of calcium phosphate powder, 5-50% of bioglass, 10-25% of calcium sulfate hemihydrate powder and 5-15% of hydroxyapatite by mass percentage. More preferably, the calcium phosphate powder comprises 5-20% of beta-tricalcium phosphate, 60-90% of tetracalcium phosphate and 5-20% of monocalcium phosphate monohydrate by mass percentage. Too much hydroxyapatite can affect the mechanical property of the bone cement, and too little hydroxyapatite can reduce the provided nucleation sites, which is not beneficial to effectively promoting the solidification reaction. The pure calcium sulfate hemihydrate system has the advantages of fast degradation, short setting time and lower mechanical property than a calcium phosphate system, and the excessive addition of the calcium sulfate hemihydrate can shorten the setting time, accelerate the degradation speed and reduce the mechanical property of the bone cement. The bioglass has good biological activity and antibacterial property, but the mechanical property of the bone cement is reduced due to excessive addition. In the embodiment of the invention, the dosage of each substance in the solid phase powder is optimized, and the comprehensive performance of the bone cement is effectively improved.
The preparation method of the solid phase powder for the bone cement composite material comprises the following steps:
a. preparing calcium phosphate powder: mixing and grinding beta-tricalcium phosphate, tetracalcium phosphate and monocalcium phosphate monohydrate in a designed proportion, and uniformly mixing to obtain calcium phosphate powder;
b. preparing solid-phase powder: and c, mixing and grinding the calcium phosphate powder which is prepared in the step a and can be subjected to multi-step curing reaction, calcium sulfate hemihydrate powder, bioglass and hydroxyapatite according to a designed proportion, and uniformly mixing to obtain solid-phase powder.
The preparation method of the solid phase powder provided by the embodiment of the invention is simple and easy to operate, only needs grinding and mixing, and is easy for industrial application.
The embodiment of the invention also provides a bone cement composite material which comprises the solid-phase powder and the curing liquid. The composite material provided by the embodiment of the invention has excellent biocompatibility, the curing time can meet the ideal requirements of surgical operations, and meanwhile, the antibacterial property and the injectability are maintained, so that the composite material can be applied to the filling and repairing of bone defect parts in the fields of orthopedics, plastic surgery, dentistry and the like.
In some embodiments, the liquid-solid ratio of the solidification liquid to the solid-phase powder is 0.5ml/g to 1ml/g. If the liquid-solid ratio is too high, the setting time is prolonged, and if the water solution is too high, too many pores are left after the bone cement is cured, so that the mechanical property is reduced. If the liquid-solid ratio is too low, the solid-liquid phase mixing can not form uniform paste, thereby affecting the bone cement reaction, reducing the injectability and causing the reduction of the mechanical and anti-collapsibility performance of the bone cement. In the embodiment of the invention, the liquid-solid ratio of the curing liquid to the solid-phase powder is optimized, and the mechanical property and the injectability of the bone cement are further improved.
In some embodiments, the curing liquid comprises dipotassium hydrogen phosphate, potassium dihydrogen phosphate, citric acid, and water. Preferably, the solidifying solution further comprises a high molecular compound, and the high molecular compound comprises at least one of sodium alginate or hyaluronic acid. More preferably, the curing liquid comprises 5-20% of dipotassium hydrogen phosphate, 5-20% of monopotassium phosphate, 5-10% of citric acid, 1-5% of high molecular compound and the balance of water by mass percentage. In the embodiment of the invention, the potassium dihydrogen phosphate in the curing liquid can ionize dihydrogen phosphate to promote the reaction of beta-tricalcium phosphate and calcium dihydrogen phosphate monohydrate, the dipotassium hydrogen phosphate and the citric acid can promote the reaction of calcium hydrogen phosphate dihydrate and tetracalcium phosphate, and the dipotassium hydrogen phosphate ionizes hydrogen phosphate ions in the solution, so that the hydroxyapatite can be accelerated to be generated by the calcium hydrogen phosphate dihydrate and the tetracalcium phosphate, meanwhile, the generation of the calcium hydrogen phosphate dihydrate can be inhibited, and the over-short curing time can be avoided. The multiple gradient chemical reaction designed in the embodiment of the invention is a step continuous reaction, and preferably dipotassium hydrogen phosphate, citric acid and potassium dihydrogen phosphate are adopted in the curing liquid to better promote and coordinate the multiple gradient chemical reaction in the embodiment of the invention, so that the curing time of the bone cement is optimized.
The preparation method of the bone cement composite material provided by the embodiment of the invention comprises the following steps: the dipotassium hydrogen phosphate, the monopotassium phosphate, the citric acid and the high molecular compound in the designed proportion are dissolved in deionized water and stirred until the mixture is uniformly mixed to obtain a curing liquid, and the curing liquid is mixed with the solid phase powder to obtain the composite material. The preparation method of the composite material provided by the embodiment of the invention is simple and easy to operate, and has a wide application prospect. The invention is described in detail below with reference to the figures and examples.
Example 1
1g of beta-tricalcium phosphate, 8g of tetracalcium phosphate and 1g of monocalcium phosphate monohydrate are ground into powder, and the powder is stirred and mixed uniformly to obtain 10g of calcium phosphate powder. And (3) stirring and grinding 5g of the obtained calcium phosphate powder, 3g of bioglass, 1g of calcium sulfate hemihydrate powder and 1g of hydroxyapatite into powder, and uniformly stirring and mixing to obtain solid-phase powder.
Dissolving 1.25g of dipotassium hydrogen phosphate, 1.25g of monopotassium phosphate, 0.75g of citric acid and 0.25g of hyaluronic acid in 5mL of deionized water, uniformly mixing, adding deionized water to dilute the mixed solution, increasing the volume of the obtained mixed solution to 10mL, and uniformly mixing and stirring to obtain a curing solution;
and mixing the curing liquid and the solid-phase powder according to the proportion of 0.7ml/g to form pasty bone cement paste, thereby obtaining the bone cement composite material.
As shown in FIG. 1, this is an XRD pattern of the mixture of the solidified liquid and the solid phase powder in the present example. After the solidification liquid and the solid-phase powder are mixed for 1min, beta-tricalcium phosphate and monocalcium phosphate monohydrate which belong to a trigonal system can be found in an XRD (X-ray diffraction) pattern, which indicates that the first step of a multiphase solidification reaction just starts, and calcium sulfate hemihydrate can be found in the pattern, which indicates that the calcium sulfate hemihydrate and the liquid phase do not completely react; after the curing liquid and the solid-phase powder are mixed for 10min, the XRD (X-ray diffraction) diagram shows that the beta-tricalcium phosphate and the monohydrate monocalcium phosphate are completely consumed, which indicates that the first step of a plurality of curing reactions is completed, and the content of the hydroxyapatite is 10% by full-peak fitting calculation; after the curing liquid and the solid-phase powder are mixed for 1 hour, the content of the hydroxyapatite is 24 percent through full-peak fitting calculation, and the comparison shows that the second step of the multiphase curing reaction is in progress; after the curing liquid and the solid-phase powder are mixed for 10 hours, the calcium sulfate hemihydrate phase cannot be found in an XRD (X-ray diffraction) pattern, only the calcium sulfate dihydrate phase exists, which indicates that the calcium sulfate hemihydrate and the liquid phase completely react to generate the calcium sulfate dihydrate, and meanwhile, the hydroxyapatite phase is observed to be continuously increased, and the calcium hydrogen phosphate dihydrate phase is continuously reduced. From this, it can be seen that calcium sulfate hemihydrate is already complete and the reaction of tetracalcium phosphate and dicalcium phosphate dihydrate is proceeding in the heterogeneous setting reaction; after the solidification liquid and the solid-phase powder are mixed for 24 hours, the calcium hydrophosphate dihydrate phase disappears, and only a tetracalcium phosphate phase which is not completely consumed and a newly produced hydroxyapatite phase exist, which indicates that a plurality of solidification reactions are basically completed.
The pasty bone cement paste prepared in this example was injected into a syringeAfter 5min, the injectability is measured to be99％；
The bone cement composite material prepared by the embodiment is placed in a simulated human body environment with 36.5 ℃ and 100% humidity, and the curing time test is carried out, the result is shown in figure 2, and the curing time is 15min; and after the hydration is continued for 24 hours, taking out the product, placing the product in a universal testing machine, and measuring the compressive strength of the product to be 25MPa, wherein the test result is shown in figure 3.
The bone cement composite material prepared in the embodiment is co-cultured with osteoblasts for 7 days, the test result is shown in FIG. 4, the ALP content is 6.72 +/-0.69 mg/ml, and the bone cement composite material has better cell activity.
After the bone cement composite material prepared in the embodiment is soaked in simulated body fluid for 28 days, the weight loss is measured to be 5.86 +/-0.55%, and the result is shown in fig. 5, and the bone cement composite material has good degradation performance.
Staphylococcus aureus was inoculated in sterilized Nutrient Broth (NB) configured to an initial colony concentration of 1.85 x 10 9 The absorbance (OD) value of the bone cement composite material prepared in the embodiment after the CFU/ml staphylococcus aureus liquid is co-cultured with the staphylococcus aureus liquid for 48 hours at a wavelength of 475nm is 0.21 +/-0.08, and the test result is shown in figure 6. The OD value of the bone cement composite material prepared by the embodiment is obviously lower than that of a pure CPC group, and the bone cement composite material has good antibacterial property.
Example 2
The solid phase powder was prepared in the same manner as in example 1, except that the solidifying agent was ionized water.
And mixing the curing liquid and the solid-phase powder according to the proportion of 0.7ml/g to form pasty bone cement paste, thereby obtaining the bone cement composite material.
The bone cement composite material prepared by the embodiment has the injectability of 80 percent, the curing time of 50min and the compressive strength of 20MPa after hydration for 24 h.
Example 3
The solid phase powder was prepared in the same manner as in example 1, except that the amount of Hydroxyapatite (HA) added to the solid phase powder was 0.5g, i.e., the content of hydroxyapatite in the solid phase powder was 5%.
A curing fluid and a bone cement composite were prepared in the same manner as in example 1.
The injectability of the test sample is 99 percent, the curing time is 20min, and the compressive strength of the test sample after hydration for 24h is 30MPa by adopting the same method as that of the test sample in the example 1.
Example 4
The solid phase powder was the same as in example 1, except that the amount of bioglass added to the solid phase powder was 1g, i.e., the bioglass content in the solid phase powder was 10%.
A curing fluid and a bone cement composite were prepared in the same manner as in example 1.
The injectability is 99 percent, the curing time is 15min, and the compressive strength is 35MPa after hydration for 24 h.
After the bone cement composite material prepared in this example was co-cultured with osteoblasts for 7 days, the ALP activity of the cells was 4.01. + -. 0.46mg/mL. After being co-cultured with staphylococcus aureus liquid for 48 hours, the OD value under the wavelength of 475nm is measured to be 0.36 +/-0.04.
Example 5
The solid phase powder was the same as in example 1 except that the amount of calcium sulfate hemihydrate added was 2g in the solid phase powder, i.e., the content of calcium sulfate hemihydrate in the solid phase powder was 20%.
A curing fluid and a bone cement composite were prepared in the same manner as in example 1.
The test was carried out in the same manner as in example 1, and the injectability was 90%, the curing time was 12min, and the compressive strength after hydration for 24h was 18MPa.
After soaking in simulated body fluid for 28 days, the mass loss was tested to be 8.12 ± 0.65%.
Comparative example 1
The solid phase powder was prepared in the same manner as in example 1, except that the calcium phosphate powder was not supplemented with β -tricalcium phosphate and monocalcium phosphate monohydrate, and calcium hydrogen phosphate dihydrate in a plasma amount was added.
A curing fluid and a bone cement composite were prepared in the same manner as in example 1.
The injectability is 99 percent, the curing time is 13min, and the compressive strength is 20MPa after hydration for 24 h.
ALP of the cells was 6.69. + -. 0.59mg/ml measured 7 days after co-culture with osteoblasts, and OD of the cells was 0.22. + -. 0.06 after co-culture with Staphylococcus aureus solution for 48 hours.
Comparative example 2
8g of tetracalcium phosphate and 2g of calcium hydrogen phosphate dihydrate are stirred and ground into powder, and the powder is uniformly mixed to obtain solid-phase powder.
A curing fluid and a bone cement composite were prepared in the same manner as in example 1.
The calcium phosphate-bioglass cement composite was obtained by performing the test in the same manner as in example 1.
The injectability is 80 percent, the curing time is 30min, and the compressive strength is 22MPa after hydration for 24 h.
After the composite material prepared in comparative example 2 was co-cultured with osteoblasts for 7 days, ALP activity of the test cells was 3.60 ± 0.28; after soaking in simulated body fluid for 28 days, the mass loss is tested to be 3.32 +/-0.66%, and the OD value is 0.53 +/-0.10 after the mass loss is co-cultured with staphylococcus aureus liquid for 48 hours.
As can be seen from the above examples and comparative examples, in example 1, the mechanical properties of the bone cement are effectively improved by the multi-phase curing reaction, and compared with the single-phase curing reaction in comparative example 1, the mechanical properties can be improved from 20MPa to 25MPa, and the improvement range is 25%. Compared with the comparative example 2, the injectable property of the embodiment 1 is effectively improved, the curing time is shortened, the compressive strength is improved, and the cell activity, the antibacterial property and the degradation property are all better than those of the comparative example 2. Compared with the embodiment 2, the embodiment 1 has the advantages that the phosphate, the citric acid and the hyaluronic acid are added into the curing liquid, so that the curing time is obviously shortened, the mechanical property and the injectability are improved, and therefore, the phosphate, the citric acid and the hyaluronic acid are added into the curing liquid, the cement solidification reaction can be promoted, and the mechanical property and the injectability of the cement are improved. In example 1, compared with example 3, the content of Hydroxyapatite (HA) in the solid phase powder was increased, and the curing time was shortened, but the mechanical properties were decreased. Compared with the embodiment 4, the embodiment 1 has the advantages that the addition amount of the bioglass is increased, the mechanical property is reduced, the ALP activity of cells is effectively increased, the osteogenic property is improved, and the antibacterial property is greatly improved. Compared with the embodiment 5, the embodiment 1 reduces the dosage of the calcium sulfate hemihydrate, has slower degradation speed, but improves the injection performance and the mechanical property of the bone cement composite material.
In the present disclosure, the terms "one embodiment," "some embodiments," "example," "specific example," or "some examples" and the like mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present disclosure. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Moreover, various embodiments or examples and features of various embodiments or examples described in this specification can be combined and combined by one skilled in the art without being mutually inconsistent.
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.

Claims (6)

1. The bone cement composite material is characterized by comprising solid-phase powder and curing liquid, wherein,
the solid phase powder comprises 10-80% of calcium phosphate powder, 10-25% of calcium sulfate hemihydrate powder, 5-50% of bioglass and 5-15% of hydroxyapatite by mass percent, wherein the calcium phosphate powder comprises the following components: beta-tricalcium phosphate, tetracalcium phosphate, and monocalcium phosphate monohydrate;
the curing liquid comprises dipotassium hydrogen phosphate, potassium dihydrogen phosphate, citric acid and water.
2. The bone cement composite material as claimed in claim 1, wherein the calcium phosphate powder comprises 5% to 20% of β -tricalcium phosphate, 60% to 90% of tetracalcium phosphate, and 5% to 20% of monocalcium phosphate monohydrate by mass percentage.
3. The bone cement composite material as claimed in claim 1, wherein the liquid-solid ratio of the curing liquid to the solid phase powder is 0.5ml/g to 1ml/g.
4. The bone cement composite of claim 1, wherein the setting fluid further comprises a polymeric compound comprising at least one of sodium alginate or hyaluronic acid.
5. The bone cement composite material as claimed in claim 4, wherein the curing liquid comprises 5-20% of dipotassium hydrogen phosphate, 5-20% of monopotassium phosphate, 5-10% of citric acid, 1-5% of high molecular compound and the balance of water by mass percentage.
6. Use of a bone cement composite according to any one of claims 1-5 for the preparation of a bone repair material.
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