CN116407689A - Absorbable bioactive bone cement and preparation method and application thereof - Google Patents
Absorbable bioactive bone cement and preparation method and application thereof Download PDFInfo
- Publication number
- CN116407689A CN116407689A CN202111677281.0A CN202111677281A CN116407689A CN 116407689 A CN116407689 A CN 116407689A CN 202111677281 A CN202111677281 A CN 202111677281A CN 116407689 A CN116407689 A CN 116407689A
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- Prior art keywords
- bone cement
- cyclic
- component
- reaction
- mixed 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.)
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Links
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Abstract
The invention provides absorbable bioactive bone cement and a preparation method and application thereof; the bone cement preparation raw material comprises a component A and a component B; the component A comprises a cyclic ketoacetal compound and an oxidant; the component B comprises a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nanomaterial-loaded reducing agent. The bone cement provided by the invention is formed by in-situ solidification of free radical ring-opening polymerization reaction in human body environment, the reaction process is rapid, the reaction is slightly exothermic, the human body is not burned, and the loosening phenomenon can not occur in subsequent use. The added inorganic nano material has osteogenic activity, can be absorbed by human body, and can be degraded and absorbed with cyclic ketene acetal compound free radical ring-opening polymer in physiological environment, but the absorption time is longer, so that the defect of too fast degradation time of calcium phosphate bone cement and calcium sulfate bone cement is avoided, and the method is suitable for total joint replacement, vertebroplasty, bone defect reconstruction, infectious lesion treatment and the like.
Description
Technical Field
The invention belongs to the technical field of materials, and particularly relates to absorbable bioactive bone cement and a preparation method and application thereof.
Background
Bone cement is a medical material for bone surgery and is widely applied to bone injury diseases such as fracture surgery fixation, joint surgery fixation and the like. Bone cements typically comprise solid and liquid phase components which are mixed in proportions at room temperature to form a slurry which is injected into a complex, irregular bone defect site for in situ curing. Currently, the bone cements commonly used are mainly polymethyl methacrylate, calcium phosphate, calcium sulfate bone cements and the like. 1. Polymethyl methacrylate bone cement is a room temperature self-setting adhesive consisting of powder and liquid, and has the following disadvantages although the application is wide: (1) the bone grafting agent has no osteogenesis activity, can not form organic chemical interface combination with host bone tissue, and causes long-term existence of fracture around a defect part, and although a certain stability is obtained by virtue of microcosmic twist lock and volume filling action in a short period after operation, the stability of the defect part in a long period has hidden trouble along with reactions such as bone absorption of a later fracture interface. (2) The high elastic modulus and stress concentration of the composite material cannot be relieved for a long time due to no degradation, the fracture risk of adjacent parts is increased, and the composite material also brings difficulty to the treatment of degenerative diseases of the adjacent parts. (3) The curing polymerization reaction generates a large amount of heat, and the heat accumulation is easy to cause damage to surrounding tissues and bone marrow. And can fall back due to temperature difference, so that bone cement is contracted to cause the subsequent joint prosthesis to loosen. 2. The calcium phosphate bone cement is hydrated and hardened by adding two or more calcium phosphate powders into a liquid phase blending agent, so as to form the bone cement similar to the bone tissue structure of a human body. The material has the following defects: often poor injectability; the mechanical properties are low, and the alloy is difficult to apply to load parts; the degradation rate is too fast. 3. The calcium sulfate cement is similar to the calcium phosphate cement in terms of degradability and bone conductivity. The defects are that: longer setting time, large modulus, low mechanical strength and too high degradation speed. The calcium phosphate bone cement and the calcium sulfate bone cement have obvious defects and have few clinical applications.
Therefore, there is a need to develop new materials that can replace polymethyl methacrylate bone cements, which have both osteogenic activity and are absorbable, cure without generating a lot of heat, and shrink loose.
Disclosure of Invention
In view of the above, the present invention aims to provide an absorbable bioactive bone cement, a preparation method and application thereof, wherein the bone cement has bone formation activity, can absorb bone, and can be cured without generating a large amount of heat and shrink and loosen.
The invention provides absorbable bioactive bone cement, which is prepared from the following raw materials of A component and B component;
the component A comprises a cyclic ketoacetal compound and an oxidant;
the component B comprises a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nanomaterial-loaded reducing agent.
In the invention, the mol ratio of the hydrophobic vinyl monomer to the cyclic ketoacetal compound is 0.01-100:1;
the molar ratio of the hydrophilic cross-linking agent to the cyclic ketoacetal compound is 0.001-0.2:1.
In the invention, the molar ratio of the oxidant to the cyclic enone acetal compound is 0.001-0.2:1;
the mol ratio of the oxidant to the reducer is 0.01-10:1.
In the present invention, the cyclic enones acetal compound is selected from one or more of 2-methylene-1, 3-dioxepane, 2-methylene-4-phenyl-1, 3-dioxepane, 5, 6-benzo-2-methylene-1, 3-dioxepane and 4, 7-dimethyl-2-methylene-1, 3-dioxepane;
the hydrophobic vinyl monomer comprises one or more of acrylic ester, methacrylic ester, N-tertiary butyl acrylamide, N-dodecyl acrylamide, 3- (methacryloyloxy) propyl trimethoxysilane and vinyl acetate;
the hydrophilic cross-linking agent comprises one or more of polyethylene glycol dimethacrylate, polyethylene glycol diacrylate, diacrylamide polyethylene glycol, dimethylacrylamide polyethylene glycol, phosphoric acid dimethacrylate and phosphoric acid diacrylate.
In the present invention, the oxidizing agent includes one or more of benzoyl peroxide, t-butyl hydroperoxide, ammonium persulfate and hydrogen peroxide;
the reducing agent in the reducing agent loaded by the inorganic nano material comprises one or more of N, N-dimethyl-p-toluidine, sodium metabisulfite, sodium bisulphite and ferrous sulfate;
the inorganic nano material in the reducing agent loaded by the inorganic nano material is selected from one or more of nano hydroxyapatite, nano calcium triphosphate and nano bioactive glass.
The invention provides a preparation method of absorbable bioactive bone cement, which comprises the following steps:
dissolving an oxidant in a cyclic ketoacetal compound to obtain a mixed solution A;
uniformly mixing a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nano material loaded reducing agent to obtain a mixed solution B;
and uniformly mixing the mixed solution A and the mixed solution B, and curing in situ to obtain the absorbable bioactive bone cement.
The invention provides application of the absorbable bioactive bone cement prepared by the technical scheme or the preparation method of the absorbable bioactive bone cement in preparation of bone cement products.
In the present invention, the bone cement product is filled to the site of bone injury during the toothpaste period;
the filling is performed in any of a variety of procedures including total joint replacement, vertebroplasty, bone defect reconstruction, and infectious disease treatment.
The invention provides absorbable bioactive bone cement, which is prepared from the following raw materials of A component and B component; the component A comprises a cyclic ketoacetal compound and an oxidant; the component B comprises a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nanomaterial-loaded reducing agent. The bone cement provided by the invention is formed by in-situ solidification of free radical ring-opening polymerization reaction in human body environment, the reaction process is rapid, the reaction is slightly exothermic, the human body is not burned, and the loosening phenomenon can not occur in subsequent use. The added inorganic nano material has osteogenic activity, can be absorbed by human body, and can be degraded and absorbed with cyclic ketene acetal compound free radical ring-opening polymer in physiological environment, but the absorption time is longer, so that the defect of too fast degradation time of calcium phosphate bone cement and calcium sulfate bone cement is avoided, and the method is suitable for total joint replacement, vertebroplasty, bone defect reconstruction, infectious lesion treatment and the like.
Drawings
FIG. 1 shows the structural formula of cyclic ketoacetals in the present invention;
FIG. 2 is a graph showing in vivo degradation test of the materials of comparative example 1 and examples 1 to 4 of the present invention;
FIG. 3 shows ALP activity assays in comparative example 1 and examples 1 to 4 of the present invention.
Detailed Description
The invention provides absorbable bioactive bone cement, which is prepared from the following raw materials of A component and B component;
the component A comprises a cyclic ketoacetal compound and an oxidant;
the component B comprises a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nanomaterial-loaded reducing agent.
The absorbable bioactive bone cement provided by the invention has the advantages of bone formation activity, absorption, no generation of a great amount of heat during solidification, no shrinkage and loosening, and suitability for total joint replacement, vertebroplasty, bone defect reconstruction, infectious lesion treatment and the like.
The preparation raw materials of the absorbable bioactive bone cement provided by the invention comprise a component A, wherein the component A comprises a cyclic enone acetal compound and an oxidant.
In the present invention, the cyclic enones acetal compound is selected from one or more of 2-methylene-1, 3-dioxepane (MDO), 2-methylene-4-phenyl-1, 3-dioxepane (MPDL), 5, 6-benzo-2-methylene-1, 3-dioxepane (BMDO) and 4, 7-dimethyl-2-methylene-1, 3-dioxepane (DMMDO); FIG. 1 shows the structural formula of the cyclic enones acetals of the above-mentioned type.
In the present invention, the oxidizing agent includes one or more of benzoyl peroxide, t-butyl hydroperoxide, ammonium persulfate and hydrogen peroxide;
the preparation raw materials of the absorbable bioactive bone cement provided by the invention comprise a component B; the component B comprises a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nanomaterial-loaded reducing agent.
In the present invention, the hydrophobic vinyl monomer is selected from one or more of acrylate, methacrylate, N-t-butyl acrylamide, N-dodecyl acrylamide, 3- (methacryloyloxy) propyl trimethoxysilane, and vinyl acetate; in specific embodiments, the hydrophobic vinyl monomer is 3- (methacryloyloxy) propyl trimethoxysilane, methyl methacrylate, N-t-butyl acrylamide, or vinyl acetate.
In the present invention, the hydrophilic crosslinking agent is a monomer containing two or more vinyl units; the hydrophilic cross-linking agent is selected from one or more of polyethylene glycol dimethacrylate, polyethylene glycol diacrylate, diacrylamide polyethylene glycol, dimethylacrylamide polyethylene glycol, phosphoric acid dimethacrylate and phosphoric acid diacrylate. In a specific embodiment, the hydrophilic cross-linking agent is selected from polyethylene glycol dimethacrylate.
In the invention, the reducing agent loaded by the inorganic nano material comprises one or more of N, N-dimethyl-p-toluidine, sodium metabisulfite, sodium bisulphite and ferrous sulfate; the inorganic nano material in the reducing agent loaded by the inorganic nano material is selected from one or more of nano hydroxyapatite, nano calcium triphosphate and nano bioactive glass. In specific embodiments, the inorganic nanomaterial-loaded reducing agent is bioactive glass-loaded N, N '-dimethyl-p-methylaniline, β -tricalcium phosphate-loaded N, N' -dimethyl-p-methylaniline, nano hydroxyapatite-loaded N, N '-dimethyl-p-methylaniline, or bioactive glass-loaded NN' -dimethyl-p-methylaniline.
In the invention, the molar ratio of the hydrophobic vinyl monomer to the cyclic ketoacetal compound is 0.01-100:1, preferably 0.1-10:1;
the molar ratio of the hydrophilic cross-linking agent to the cyclic ketoacetal compound is 0.001-0.2:1, preferably 0.005-0.05:1.
In the invention, the molar ratio of the oxidant to the cyclic enone acetal compound is 0.001-0.2:1; preferably 0.2 to 2:1.
The molar ratio of the oxidant to the reducing agent is 0.01-10:1, preferably 0.2-2:1.
The ratio of the mass of the inorganic nano material to the total mass of the hydrophobic vinyl monomer and the cyclic ketoacetal compound is 0.001-100:1; preferably 0.1 to 0.5:1;
the invention provides a preparation method of absorbable bioactive bone cement, which comprises the following steps:
dissolving an oxidant in a cyclic ketoacetal compound to obtain a mixed solution A;
uniformly mixing a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nano material loaded reducing agent to obtain a mixed solution B;
and uniformly mixing the mixed solution A and the mixed solution B, and curing in situ to obtain the absorbable bioactive bone cement.
In the invention, the oxidant in the A component and the reducing agent loaded by the inorganic nano material in the B component are used as oxidation-reduction free radical polymerization initiator; the in-situ curing is carried out to carry out ring-opening polymerization reaction; the ring-opening polymerization reaction is carried out under the initiation of an oxidation-reduction free radical polymerization initiator; with free radicals as active centers; the main chain of the component after free radical polymerization contains an ester bond structure.
The invention provides application of the absorbable bioactive bone cement prepared by the technical scheme or the preparation method of the absorbable bioactive bone cement in preparation of bone cement products.
In the present invention, the bone cement product is filled to the site of bone injury during the toothpaste period;
the filling is performed in any of a variety of procedures including total joint replacement, vertebroplasty, bone defect reconstruction, and infectious lesion treatment.
In order to further illustrate the present invention, the following examples are provided to illustrate the invention in more detail, but are not to be construed as limiting the scope of the invention.
Example 1
The preparation process of the cyclic ketoacetal compound MDO comprises the following steps:
2-bromo-1, 1' -dimethoxyethane (65 g,0.4 mol), 1, 4-butanediol (36 g,0.51 mol) and Dowex 50 acidic ion exchange resin (0.5 g) were added into a reaction flask, the reaction temperature was set to 115 ℃, methanol as a by-product was continuously collected by a water separator during the reaction, the reaction progress was judged according to the amount of methanol collected, the reaction was continued for about 4 hours, after the reaction was completed, the acidic resin was removed by filtration, and the obtained crude product was distilled under reduced pressure to collect a 95℃fraction; the product (35 g,0.18 mol) obtained above was dissolved in 70ml of dry tetrahydrofuran and placed in a reaction flask, aliquat 336 (1.67 g, 0.04 mol) was added, the reaction temperature was reduced to 0 ℃, t-BuOK (40.41 g,0.36 mol) was gradually added, the reaction was maintained at the temperature for 2 hours, after the reaction was completed, the solid was removed by filtration, the organic phase was concentrated, and the obtained crude product was distilled, and the fraction at 25℃was collected to obtain the product MDO.
The cyclic enone acetal compound MDO (11.4 g,0.1 mol) and dibenzoyl peroxide (BPO, 0.48g, 0.002mol) are evenly mixed to obtain a mixed solution A; uniformly mixing vinyl monomer 3- (methacryloyloxy) propyl trimethoxysilane (24.8 g,0.1 mol), 2mol% polyethylene glycol dimethacrylate crosslinker and bioactive glass (particle size 45 μm,5 wt%) supported N, N' -dimethyl-p-methylaniline (DMPT, 1 mol%) to obtain a mixed solution B; rapidly mixing the mixed solution A and the mixed solution B, and curing in situ to obtain absorbable bioactive bone cement; sucking the bone cement by a syringe and injecting the bone cement in the toothpaste stage to a required position with the aid of the image.
Example 2
The preparation process of the cyclic ketoacetal compound MPDL comprises the following steps:
2-bromo-1, 1' -dimethoxyethane (65 g,0.4 mol), 1-phenyl-1, 2-ethylene glycol (69 g,0.5 mol) and Dowex 50 acidic ion exchange resin (0.5 g) were added to a reaction flask, the reaction temperature was set to 120 ℃, methanol as a by-product was continuously collected by a water separator during the reaction, the progress of the reaction was judged according to the amount of methanol collected, the reaction was continued for about 4 hours, after the completion of the reaction, the acidic resin was removed by filtration, and the obtained crude product was distilled under reduced pressure to collect a fraction around 70 ℃; the product (43.77 g,0.18 mol) obtained above was dissolved in 70ml of dry tetrahydrofuran, placed in a reaction flask, aliquat 336 (1.67 g, 0.04 mol) was added, the reaction temperature was reduced to 0 ℃, t-BuOK (40.41 g,0.36 mol) was gradually added, the reaction was maintained at the temperature for 2 hours, after the reaction was completed, the solid was filtered off, the organic phase was concentrated, and the obtained crude product was distilled, and the fraction around 50℃was collected to obtain the product MPDL.
MPDL (16.2 g,0.1 mol) of cyclic enone acetal compound and dibenzoyl peroxide (BPO, 0.48g, 0.002mol) are uniformly mixed to obtain a mixed solution A; uniformly mixing vinyl monomer methyl methacrylate (10 g,0.1 mol), 2mol% polyethylene glycol dimethacrylate cross-linking agent and beta-tricalcium phosphate (30 mu m,5 wt%) loaded N, N' -dimethyl-p-methylaniline (DMPT, 1 mol%) to obtain a mixed solution B; rapidly mixing the mixed solution A and the mixed solution B, and curing in situ to obtain absorbable bioactive bone cement; sucking the bone cement by a syringe and injecting the bone cement in the toothpaste stage to a required position with the aid of the image.
Example 3
The preparation process of the cyclic ketoacetal compound BMDO comprises the following steps:
2-bromo-1, 1' -dimethoxyethane (65 g,0.4 mol), phthalic acid dimethanol (69 g,0.5 mol) and Dowex 50 acidic ion exchange resin (0.5 g) are added into a reaction bottle, the reaction temperature is set to 120 ℃, a water separator is used for continuously collecting byproduct methanol during the reaction, the reaction progress is judged according to the amount of the collected methanol, the reaction lasts for about 8 hours, after the reaction is completed, the acidic resin is removed by filtration, the obtained crude product is distilled under reduced pressure, and fractions near 160 ℃ are collected; the product (43.77 g,0.18 mol) obtained above was dissolved in 70ml of dry tetrahydrofuran and placed in a reaction flask, aliquat 336 (1.67 g, 0.04 mol) was added, the reaction temperature was lowered to 0 ℃, t-BuOK (40.41 g,0.36 mol) was gradually added, the reaction was maintained at the temperature for 2 hours, after the reaction was completed, the solid was filtered off, the organic phase was concentrated, and the obtained crude product was distilled, and fractions around 96-99℃were collected to obtain the product BMDO.
The cyclic enone acetal compound BMDO (16.2 g,0.1 mol) and dibenzoyl peroxide (BPO, 0.48g, 0.002mol) are evenly mixed to obtain a mixed solution A; comonomer N-tert-butyl acrylamide (12.7 g,0.1 mol), 2mol% polyethylene glycol dimethacrylate cross-linking agent and nano hydroxyapatite (80 μm,5 wt%) loaded N, N' -dimethyl-p-methylaniline (DMPT, 1 mol%) are uniformly mixed to obtain a mixed solution B; rapidly mixing the mixed solution A and the mixed solution B, and curing in situ to obtain absorbable bioactive bone cement; sucking the bone cement by a syringe and injecting the bone cement in the toothpaste stage to a required position with the aid of the image.
Example 4
The preparation process of the cyclic ketoacetal compound DMMDO comprises the following steps:
2, 5-hexanediol (1.2 g,10.2 mmol) was dissolved in dichloromethane (170 ml) and pyridine (7.5 ml,91.5 mmol), the reaction system was placed in-20deg.C for replacement of argon, then triphosgene (4.55 g,15.2 mmol) in dichloromethane (90 ml) was added dropwise, after the addition was completed, the reaction was allowed to proceed to room temperature for 20min, then the reaction was quenched with saturated ammonium chloride solution (100 ml), the product mixture was extracted with dichloromethane, the obtained organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was removed in vacuo after filtration, and the fraction near 95deg.C was collected by distillation under reduced pressure; the product (0.023 g,0.16 mmol) obtained above was dissolved in a mixed solvent of tetrahydrofuran/toluene (1:1), petasis reagent (2 ml,0.5mmol, 5wt% tetrahydrofuran/toluene mixed solution) was added, the reaction system was replaced with argon, the reaction was conducted at 60-65℃for 20 hours in the absence of light, n-hexane (10 ml) was added after the completion of the reaction to form a yellow precipitate, and the filtrate was concentrated after filtration to obtain DMMDO.
Mixing cycloketal compound DMMDO (14.2 g,0.1 mol) and dibenzoyl peroxide (BPO, 0.48g,0.002 mol) uniformly to obtain a mixed solution A; vinyl acetate (8.6 g,0.1 mol) was uniformly mixed, and then 2mol% of polyethylene glycol dimethacrylate cross-linking agent and N, N' -dimethyl-p-methylaniline (DMPT, 1 mol%) loaded with bioactive glass (45 μm,5 wt%) were added to be uniformly mixed to obtain a mixed solution B; rapidly mixing the mixed solution A and the mixed solution B, and curing in situ to obtain absorbable bioactive bone cement; sucking the bone cement by a syringe and injecting the bone cement in the toothpaste stage to a required position with the aid of the image.
Comparative example 1
Commercially available bone cements
After the solid phase and the liquid phase are uniformly mixed according to the instruction of use, the bone cement is sucked by a syringe and injected into the required position in the toothpaste stage with the assistance of the image.
(1) Maximum curing temperature and setting time
The solid phase and the liquid phase of the bone cement materials of the examples and the comparative examples are contacted and mixed uniformly and then are immediately injected into a prefabricated mould, timing is started, the temperature is continuously measured by a thermocouple and observed in real time, and the test is stopped after the temperature begins to drop. And according to the obtained curve of temperature change along with time, reading the peak value to obtain the highest curing temperature. The setting time of bone cement is defined as the time corresponding to the average setting temperature (average of the highest setting temperature and room temperature) on the curve. The maximum curing temperatures and curing times of the materials in comparative example 1 and examples 1 to 4 are shown in Table 1.
Table 1 the highest setting temperature and setting time of the example and comparative bone cement materials.
The result shows that compared with the traditional PMMA bone cement, the absorbable bioactive bone cement has obviously reduced curing temperature; the curing of the examples does not generate a great amount of heat, the highest curing temperature is not more than 42 ℃, especially in the example 1, the highest temperature is 37.2 ℃ which is very close to the normal temperature of the human body, and the shortened solidification time window can meet the clinical operation requirement.
(2) Bone cement mechanical property test
The mechanical properties of bone cements were tested according to IS05833-2002, and the solid phase and the liquid phase of the bone cement materials of the examples and the comparative examples were mixed uniformly by contact and then immediately poured into a cylindrical mold having a diameter of 5mm and a height of 10mm, and the mold was removed after curing. The prepared sample was subjected to compression test on a universal tester (model LD-5, model LLOYD, sensor 2.5 kN). The loading speed was 5mm/min and the test was stopped when the compression rate was 30%. And calculating the compressive strength value and the elastic modulus of the bone cement according to the stress-strain curve. The results were averaged for 5 replicates per group. And (3) preparing rectangular sample strips, measuring the bending strength of the bone cement by adopting a three-point bending test method, wherein the loading speed is 5mm/min, continuously loading until the sample strips are broken, stopping testing 5 parallel samples in each group, and taking an average value of the results. The compressive strength and elastic modulus and flexural strength of the bone cements are shown in Table 2.
Table 2 mechanical properties of the example and comparative bone cement materials.
The results show that the absorbable bioactive bone cement of the invention has improved compressive and flexural strength and higher toughness than commercially available bone cement products.
(3) In vivo degradation experiments
Balb/c mice (20 g, females) were shaved back in a sterile environment, cleaned skin, then placed in an isoflurane-containing anesthesia machine box for anesthesia, and secured to an operating table with a respiratory mask to maintain anesthesia. The skin around the back was sterilized with iodophor, and an opening (-1 cm) was cut into the back with a scalpel, and fascia between the skin and muscle was separated with scissors and forceps, forming a small pocket. The cured samples of comparative example 1 and examples 1-4 were fabricated into wafers 5mm in diameter and 2mm in height, and implanted subcutaneously into the back, the tissue was sutured, and again sterilized with iodophor. Each of the 6 mice were randomly implanted, after 8 weeks of rearing, the mice were euthanized, the samples of comparative example 1 and examples 1 to 4 were taken out, the morphology of the samples was observed, the weight of the samples was weighed, and the degradation rate was calculated by comparing with the samples before the implantation.
The in vivo degradation test of the materials in comparative example 1 and examples 1 to 4 is shown in fig. 2.
As shown in fig. 2: the materials in examples 1-4 show good degradation rate after being maintained for 8 weeks in a physiological environment, and the degradation rate of the material in example 2 is most obvious, and can reach 26.86%; the introduction of MDO ring-opening polymer provides better degradation performance for the material; in addition, the degradation rate of the material of the comparative example 1 for 8 weeks is 1.49%, and the degradation of the material is poor and is far lower than that of examples 1-4, which shows that the bone cement constructed by the invention has excellent in vivo degradation performance.
(4) Osteogenic Activity assay
ALP Activity assay: after osteoblast MC3T3 was cultured on prefabricated examples 1 to 4 and comparative example 1 for 7 days and 14 days, respectively, the old medium was removed, washed 1 to 3 times with PBS, then RIAP cell lysate was added, after the cells were sufficiently lysed, the cell lysate was centrifuged, and the supernatant was taken, and the activity of cellular ALP was examined according to the AKP/ALP kit instructions.
The ALP activity assays for the materials of comparative example 1 and examples 1-4 are shown in FIG. 3.
As shown in fig. 3: the cellular ALP activity in the test of the materials in examples 1 to 4 is significantly higher than that of comparative example 1, since the absorbable bioactive bone cement of the present invention is added with an inorganic nanomaterial having osteogenic activity. The inorganic nanomaterial with biological activity can be gradually exposed or released along with degradation of bone cement in vivo, so that the inorganic nanomaterial with biological activity can be contacted with surrounding tissue environment to display osteogenic activity.
From the above examples, the present invention provides an absorbable bioactive bone cement, the preparation raw materials comprising a component a and a component B; the component A comprises a cyclic ketoacetal compound and an oxidant; the component B comprises a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nanomaterial-loaded reducing agent. The bone cement provided by the invention is formed by in-situ solidification of free radical ring-opening polymerization reaction in human body environment, the reaction process is rapid, the reaction is slightly exothermic, the human body is not burned, and the loosening phenomenon can not occur in subsequent use. The added inorganic nano material has osteogenic activity, can be absorbed by human body, and can be degraded and absorbed with cyclic ketene acetal compound free radical ring-opening polymer in physiological environment, but the absorption time is longer, so that the defect of too fast degradation time of calcium phosphate bone cement and calcium sulfate bone cement is avoided, and the method is suitable for total joint replacement, vertebroplasty, bone defect reconstruction, infectious lesion treatment and the like.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (8)
1. An absorbable bioactive bone cement is prepared from component A and component B;
the component A comprises a cyclic ketoacetal compound and an oxidant;
the component B comprises a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nanomaterial-loaded reducing agent.
2. The resorbable bioactive bone cement of claim 1, wherein the molar ratio of the hydrophobic vinyl monomer to the cyclic enone acetal compound is 0.01-100:1;
the molar ratio of the hydrophilic cross-linking agent to the cyclic ketoacetal compound is 0.001-0.2:1.
3. The absorbable bioactive bone cement of claim 1, wherein the molar ratio of the oxidizing agent to cyclic enone acetal compound is 0.001-0.2:1;
the mol ratio of the oxidant to the reducer is 0.01-10:1.
4. The resorbable bioactive bone cement of claim 1 wherein said cyclic enones acetal compound is selected from one or more of 2-methylene-1, 3-dioxepan, 2-methylene-4-phenyl-1, 3-dioxepan, 5, 6-benzo-2-methylene-1, 3-dioxepan and 4, 7-dimethyl-2-methylene-1, 3-dioxepan;
the hydrophobic vinyl monomer comprises one or more of acrylic ester, methacrylic ester, N-tertiary butyl acrylamide, N-dodecyl acrylamide, 3- (methacryloyloxy) propyl trimethoxysilane and vinyl acetate;
the hydrophilic cross-linking agent comprises one or more of polyethylene glycol dimethacrylate, polyethylene glycol diacrylate, diacrylamide polyethylene glycol, dimethylacrylamide polyethylene glycol, phosphoric acid dimethacrylate and phosphoric acid diacrylate.
5. The resorbable bioactive bone cement of claim 1, wherein the oxidizing agent comprises one or more of benzoyl peroxide, t-butyl hydroperoxide, ammonium persulfate, and hydrogen peroxide;
the reducing agent in the reducing agent loaded by the inorganic nano material comprises one or more of N, N-dimethyl-p-toluidine, sodium metabisulfite, sodium bisulphite and ferrous sulfate;
the inorganic nano material in the reducing agent loaded by the inorganic nano material is selected from one or more of nano hydroxyapatite, nano calcium triphosphate and nano bioactive glass.
6. A method of preparing the resorbable bioactive bone cement of any one of claims 1-5, comprising the steps of:
dissolving an oxidant in a cyclic ketoacetal compound to obtain a mixed solution A;
uniformly mixing a hydrophobic vinyl monomer, a hydrophilic cross-linking agent and an inorganic nano material loaded reducing agent to obtain a mixed solution B;
and uniformly mixing the mixed solution A and the mixed solution B, and curing in situ to obtain the absorbable bioactive bone cement.
7. Use of an absorbable bioactive bone cement as defined in any one of claims 1 to 5 or prepared by the method of preparation as defined in claim 6 in the preparation of a bone cement product.
8. The use of claim 7, wherein the bone cement product fills the bone injury site during the toothpaste period;
the filling is performed in any of a variety of procedures including total joint replacement, vertebroplasty, bone defect reconstruction, and infectious disease treatment.
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