An absorbable bioactive bone cement and its preparation method and application

Abstract

The present invention provides an absorbable bioactive bone cement, its preparation method and application; the raw materials for preparing the bone cement include component A and component B; component A includes cycloalkenone acetal compounds and oxidants; component B includes hydrophobic vinyl monomers, hydrophilic crosslinking agents and inorganic nanomaterial-supported reducing agents. The bone cement provided by the present invention is formed by in-situ curing through a free radical ring-opening polymerization reaction under the human body environment. The reaction process is rapid, slightly exothermic, does not burn the human body, and there will be no loosening phenomenon during subsequent use. The added inorganic nanomaterials have osteogenic activity and can be absorbed by the human body. The free radical ring-opening polymer with cycloalkenone acetal compounds can be degraded and absorbed in the physiological environment, but the absorption time is longer, avoiding the deficiency of the too-fast degradation time of calcium phosphate bone cement and calcium sulfate bone cement, and is applicable to total joint replacement, vertebroplasty, bone defect reconstruction, treatment of infectious lesions, etc.

Description

Technical Field

[0001] The present invention belongs to the technical field of applied materials, and particularly relates to an absorbable bioactive bone cement, a preparation method thereof, and an application thereof. Background Art

[0002] Bone cement is a medical material used in orthopedic surgeries and is widely applied to bone injury diseases such as fracture surgery fixation and joint surgery fixation. Bone cement usually includes a solid-phase powder and a liquid-phase component. At room temperature, after mixing them in a certain proportion into a slurry, it is injected into a bone defect site with a complex and irregular shape for in-situ curing. Currently, commonly used bone cements mainly include polymethyl methacrylate, calcium phosphate, and calcium sulfate bone cements, etc. 1. Polymethyl methacrylate bone cement is a room-temperature self-curing binder composed of a powder and a liquid. Although it is widely used, it has the following deficiencies: ① It has no osteogenic activity and cannot form an organic chemical interface bond with the host bone tissue, resulting in the long-term existence of fractures around the defect site. Although a certain stability is obtained in the short term after surgery by means of microscopic interlocking and volume filling, with the subsequent bone resorption and other reactions at the fracture interface in the later stage, there are potential hazards to the long-term stability of the defect site. ② It is not degradable, causing its high elastic modulus and stress concentration to not be relieved for a long time, increasing the risk of fractures in adjacent parts and also bringing difficulties to the treatment of degenerative diseases in adjacent parts. ③ The curing polymerization reaction generates a large amount of heat, and the heat accumulation is likely to cause damage to the surrounding tissues and bone marrow. And due to the temperature difference drop, it will lead to the shrinkage of the bone cement and cause subsequent loosening of the joint prosthesis. 2. Calcium phosphate bone cement undergoes hydration hardening by adding two or more calcium phosphate powders to a liquid-phase conditioner to form a bone cement similar to the human bone tissue structure. The deficiencies of this material are: generally, its injectability is not good; its mechanical properties are low, and it is difficult to be applied to load-bearing parts; its degradation rate is too fast. 3. Calcium sulfate bone cement is similar to calcium phosphate bone cement and has degradability and osteoconductivity. The deficiencies are: the setting time is long, the modulus is large, the mechanical strength is low, and the degradation rate is too fast. The deficiencies of calcium phosphate bone cement and calcium sulfate bone cement are obvious, and their clinical applications are not many.

[0003] Therefore, it is urgent to develop new materials that can replace polymethyl methacrylate bone cement, which have osteogenic activity, can be absorbed, do not generate a large amount of heat during curing, and do not shrink and loosen. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide an absorbable bioactive bone cement, a preparation method thereof, and an application thereof. This bone cement has osteogenic activity, can be absorbed, does not generate a large amount of heat during curing, and does not shrink and loosen.

[0005] The present invention provides an absorbable bioactive bone cement, and the preparation raw materials include component A and component B;

[0006] Component A includes a cycloalkenone acetal compound and an oxidant;

[0007] Component B includes a hydrophobic vinyl monomer, a hydrophilic crosslinking agent, and a reducing agent supported on an inorganic nanomaterial.

[0008] In the present invention, the molar ratio of the hydrophobic vinyl monomer to the cycloalkenone acetal compound is 0.01 to 100:1;

[0009] The molar ratio of the hydrophilic crosslinking agent to the cycloalkenone acetal compound is 0.001 to 0.2:1.

[0010] In the present invention, the molar ratio of the oxidizing agent to the cycloalkenone acetal compound is 0.001 to 0.2:1;

[0011] The molar ratio of the oxidizing agent to the reducing agent is 0.01 to 10:1.

[0012] In the present invention, the cycloalkenone acetal compound is selected from one or more of 2-methylene-1,3-dioxepane, 2-methylene-4-phenyl-1,3-dioxolane, 5,6-benzo-2-methylene-1,3-dioxepane, and 4,7-dimethyl-2-methylene-1,3-dioxepane;

[0013] The hydrophobic vinyl monomer includes one or more of acrylate, methacrylate, N-tert-butylacrylamide, N-dodecylacrylamide, 3-(methacryloyloxy)propyltrimethoxysilane, and vinyl acetate;

[0014] The hydrophilic crosslinking agent includes one or more of polyethylene glycol dimethacrylate, polyethylene glycol diacrylate, polyethylene glycol diacrylamide, polyethylene glycol dimethacrylamide, dimethacrylic acid phosphate, and diacrylic acid phosphate.

[0015] In the present invention, the oxidizing agent includes one or more of benzoyl peroxide, tert-butyl hydroperoxide, ammonium persulfate, and hydrogen peroxide;

[0016] The reducing agent in the reducing agent supported on the inorganic nanomaterial includes one or more of N,N-dimethyl-p-toluidine, sodium metabisulfite, sodium bisulfite, and ferrous sulfate;

[0017] The inorganic nanomaterial in the reducing agent supported on the inorganic nanomaterial is selected from one or more of nano-hydroxyapatite, nano-tricalcium phosphate, and nano-bioactive glass.

[0018] The present invention provides a method for preparing the absorbable bioactive bone cement according to the above technical solution, comprising the following steps:

[0019] Dissolve the oxidizing agent in the cycloalkenone acetal compound to obtain a mixed solution A;

[0020] Mix the hydrophobic vinyl monomer, hydrophilic crosslinking agent, and the reducing agent supported on the inorganic nanomaterial uniformly to obtain the mixed solution B;

[0021] Mix the mixed solution A and the mixed solution B uniformly, and obtain the absorbable bioactive bone cement after in-situ curing.

[0022] The present invention provides an application of the absorbable bioactive bone cement described in the above technical solution or the absorbable bioactive bone cement prepared by the preparation method described in the above technical solution in the preparation of bone cement products.

[0023] In the present invention, the bone cement product is filled into the bone injury site in the toothpaste stage;

[0024] The filling is carried out in any one of total joint replacement, vertebroplasty, bone defect reconstruction, and treatment of infectious lesions.

[0025] The present invention provides an absorbable bioactive bone cement, and the preparation raw materials include component A and component B; component A includes cycloalkenone acetal compounds and oxidants; component B includes hydrophobic vinyl monomers, hydrophilic crosslinking agents, and reducing agents supported on inorganic nanomaterials. The bone cement provided by the present invention is formed by in-situ curing through a free radical ring-opening polymerization reaction in the human body environment. The reaction process is rapid, the reaction is slightly exothermic, and it will not burn the human body. There will be no loosening phenomenon during subsequent use. The added inorganic nanomaterials have osteogenic activity and can be absorbed by the human body. The free radical ring-opening polymer with cycloalkenone acetal compounds can be degraded and absorbed in the physiological environment, but the absorption time is longer, avoiding the deficiency of too fast degradation time of calcium phosphate bone cement and calcium sulfate bone cement, and is applicable to total joint replacement, vertebroplasty, bone defect reconstruction, treatment of infectious lesions, etc. Description of the Drawings

[0026] Figure 1 It is the structural formula of the cycloalkenone acetal compound in the present invention;

[0027] Figure 2 It is the in-vivo degradation test chart of the materials in Comparative Example 1 and Examples 1-4 of the present invention;

[0028] Figure 3 It is the detection of ALP activity in Comparative Example 1 and Examples 1-4 of the present invention. Detailed Embodiments

[0029] The present invention provides an absorbable bioactive bone cement, and the preparation raw materials include component A and component B;

[0030] Component A includes cycloalkenone acetal compounds and oxidants;

[0031] The component B includes hydrophobic vinyl monomers, hydrophilic crosslinking agents, and reducing agents supported on inorganic nanomaterials.

[0032] The absorbable bioactive bone cement provided by the present invention has osteogenic activity, is absorbable, does not generate a large amount of heat during curing, does not shrink or loosen, and is applicable to total joint replacement, vertebroplasty, bone defect reconstruction, treatment of infectious lesions, etc.

[0033] The raw materials for preparing the absorbable bioactive bone cement provided by the present invention include component A, and the component A includes cycloalkenone acetal compounds and oxidants.

[0034] In the present invention, the cycloalkenone acetal compounds are selected from one or more of 2-methylene-1,3-dioxepane (MDO), 2-methylene-4-phenyl-1,3-dioxolane (MPDL), 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), and 4,7-dimethyl-2-methylene-1,3-dioxepane (DMMDO); Figure 1 are the structural formulas of the above types of cycloalkenone acetal compounds.

[0035] In the present invention, the oxidants include one or more of benzoyl peroxide, tert-butyl hydroperoxide, ammonium persulfate, and hydrogen peroxide;

[0036] The raw materials for preparing the absorbable bioactive bone cement provided by the present invention include component B; the component B includes hydrophobic vinyl monomers, hydrophilic crosslinking agents, and reducing agents supported on inorganic nanomaterials.

[0037] In the present invention, the hydrophobic vinyl monomers are selected from one or more of acrylates, methacrylates, N-tert-butylacrylamide, N-dodecylacrylamide, 3-(methacryloyloxy)propyltrimethoxysilane, and vinyl acetate; in specific embodiments, the hydrophobic vinyl monomers are 3-(methacryloyloxy)propyltrimethoxysilane, methyl methacrylate, N-tert-butylacrylamide, or vinyl acetate.

[0038] In the present invention, the hydrophilic crosslinking agent is a monomer containing two or more vinyl units; the hydrophilic crosslinking agent is selected from one or more of polyethylene glycol dimethacrylate, polyethylene glycol diacrylate, dipropylene glycol acrylamide, dimethacrylamide polyethylene glycol, dimethacrylic acid phosphate, and diacrylic acid phosphate. In specific embodiments, the hydrophilic crosslinking agent is selected from polyethylene glycol dimethacrylate.

[0039] In the present invention, the reducing agent in the inorganic nanomaterial-supported reducing agent includes one or more of N,N-dimethyl-p-toluidine, sodium metabisulfite, sodium bisulfite, and ferrous sulfate; the inorganic nanomaterial in the inorganic nanomaterial-supported reducing agent is selected from one or more of nano-hydroxyapatite, nano-tricalcium phosphate, and nano-bioactive glass. In a specific embodiment, the inorganic nanomaterial-supported reducing agent is N,N'-dimethyl-p-methylaniline supported by bioactive glass, N,N'-dimethyl-p-methylaniline supported by β-tricalcium phosphate, N,N'-dimethyl-p-methylaniline supported by nano-hydroxyapatite, or NN'-dimethyl-p-methylaniline supported by bioactive glass.

[0040] In the present invention, the molar ratio of the hydrophobic vinyl monomer to the cycloalkenone acetal compound is 0.01 to 100:1, preferably 0.1 to 10:1;

[0041] The molar ratio of the hydrophilic crosslinking agent to the cycloalkenone acetal compound is 0.001 to 0.2:1, preferably 0.005 to 0.05:1.

[0042] In the present invention, the molar ratio of the oxidizing agent to the cycloalkenone acetal compound is 0.001 to 0.2:1; preferably 0.2 to 2:1.

[0043] The molar ratio of the oxidizing agent to the reducing agent is 0.01 to 10:1, preferably 0.2 to 2:1.

[0044] The ratio of the mass of the inorganic nanomaterial to the total mass of the hydrophobic vinyl monomer and the cycloalkenone acetal compound is 0.001 to 100:1; preferably 0.1 to 0.5:1;

[0045] The present invention provides a method for preparing the absorbable bioactive bone cement according to the above technical solution, comprising the following steps:

[0046] Dissolve the oxidizing agent in the cycloalkenone acetal compound to obtain a mixed solution A;

[0047] Mix the hydrophobic vinyl monomer, the hydrophilic crosslinking agent, and the inorganic nanomaterial-supported reducing agent evenly to obtain a mixed solution B;

[0048] Mix the mixed solution A and the mixed solution B evenly, and obtain the absorbable bioactive bone cement after in-situ curing.

[0049] In the present invention, the oxidant in component A and the reducing agent supported by the inorganic nanomaterial in component B serve as an oxidation-reduction free radical polymerization initiator; the in-situ curing is to carry out a ring-opening polymerization reaction; the ring-opening polymerization reaction is carried out under the initiation of the oxidation-reduction free radical polymerization initiator; it is carried out with free radicals as the active center; after the component free radical polymerization, the main chain contains a structure with an ester bond.

[0050] The present invention provides an application of the absorbable bioactive bone cement described in the above technical solution or the absorbable bioactive bone cement prepared by the preparation method described in the above technical solution in the preparation of bone cement products.

[0051] In the present invention, the bone cement product is filled into the bone injury site at the toothpaste stage;

[0052] The filling is carried out in any one of total joint replacement, vertebroplasty, bone defect reconstruction, and treatment of infectious lesions.

[0053] In order to further illustrate the present invention, the following is a detailed description of an absorbable bioactive bone cement provided by the present invention, its preparation method and application in conjunction with embodiments, but they cannot be understood as limiting the protection scope of the present invention.

[0054] Example 1

[0055] Preparation process of the cycloalkenone acetal compound MDO:

[0056] Add 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) into the reaction flask, set the reaction temperature to 115 °C, continuously collect the by-product methanol by using a water separator during the reaction, and judge the reaction progress according to the amount of methanol collected. The reaction lasts for about 4 h. After the reaction is completed, filter out the acidic resin, and carry out vacuum distillation on the obtained crude product to collect the fraction at 95 °C; dissolve the obtained product above (35 g, 0.18 mol) in 70 ml of dry tetrahydrofuran and place it in the reaction flask, add Aliquat 336 (1.67 g, 0.004 mol), lower the reaction temperature to 0 °C, gradually add t-BuOK (40.41 g, 0.36 mol), maintain the temperature and react for 2 h. After the reaction is completed, filter out the solid, concentrate the organic phase, and carry out distillation on the obtained crude product to collect the fraction at 25 °C, which is the product MDO.

[0057] The cyclic enone acetal compound MDO (11.4 g, 0.1 mol) and benzoyl peroxide (BPO, 0.48 g, 0.002 mol) were mixed evenly to obtain mixture A; the vinyl monomer 3-(methacryloyloxy)propyltrimethoxysilane (24.8 g, 0.1 mol), 2 mol% polyethylene glycol dimethacrylate crosslinking agent, and N,N'-dimethyl-p-toluidine (DMPT, 1 mol%) supported on bioactive glass (particle size 45 μm, 5 wt%) were mixed evenly to obtain mixture B; the mixture A and mixture B were quickly mixed and in-situ cured to obtain an absorbable bioactive bone cement; the bone cement was aspirated with a syringe and injected into the desired site with the assistance of imaging in the toothpaste stage.

[0058] Example 2

[0059] Preparation process of cyclic enone acetal compound MPDL:

[0060] 2-Bromo-1,1'-dimethoxyethane (65 g, 0.4 mol), 1-phenyl-1,2-ethanediol (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 at 120 °C, and the by-product methanol was continuously collected using a water separator during the reaction, and the reaction progress was judged according to the amount of methanol collected. The reaction continued for about 4 h. After the reaction was completed, the acidic resin was removed by filtration, and the obtained crude product was subjected to vacuum distillation to collect the fraction around 70 °C; the obtained product (43.77 g, 0.18 mol) was dissolved in 70 ml of dry tetrahydrofuran and placed in a reaction flask, Aliquat 336 (1.67 g, 0.004 mol) was added, the reaction temperature was lowered to 0 °C, and t-BuOK (40.41 g, 0.36 mol) was gradually added, and the temperature was maintained for reaction for 2 h. After the reaction was completed, the solid was removed by filtration, the organic phase was concentrated, and the obtained crude product was distilled to collect the fraction around 50 °C, which was the product MPDL.

[0061] The cyclic enone acetal compound MPDL (16.2 g, 0.1 mol) and benzoyl peroxide (BPO, 0.48 g, 0.002 mol) were mixed evenly to obtain mixture A; the vinyl monomer methyl methacrylate (10 g, 0.1 mol), 2 mol% polyethylene glycol dimethacrylate crosslinking agent, and N,N'-dimethyl-p-toluidine (DMPT, 1 mol%) supported on β-tricalcium phosphate (30 μm, 5 wt%) were mixed evenly to obtain mixture B; the mixture A and mixture B were quickly mixed and in-situ cured to obtain an absorbable bioactive bone cement; the bone cement was aspirated with a syringe and injected into the desired site with the assistance of imaging in the toothpaste stage.

[0062] Example 3

[0063] Preparation process of cycloalkenone acetal compound BMDO:

[0064] Add 2-bromo-1,1'-dimethoxyethane (65 g, 0.4 mol), o-phthalic alcohol (69 g, 0.5 mol) and Dowex 50 acidic ion exchange resin (0.5 g) into the reaction flask, set the reaction temperature to 120 °C, continuously collect the by-product methanol using a water separator during the reaction, and judge the reaction progress according to the amount of methanol collected. The reaction lasts for about 8 h. After the reaction is completed, filter off the acidic resin, and perform vacuum distillation on the obtained crude product to collect the fraction around 160 °C; dissolve the obtained product above (43.77 g, 0.18 mol) in 70 ml of dry tetrahydrofuran and place it in the reaction flask, add Aliquat 336 (1.67 g, 0.004 mol), lower the reaction temperature to 0 °C, gradually add t-BuOK (40.41 g, 0.36 mol), maintain the temperature and react for 2 h. After the reaction is completed, filter off the solid, concentrate the organic phase, and perform distillation on the obtained crude product to collect the fraction around 96 - 99 °C, which is the product BMDO.

[0065] Mix cycloalkenone acetal compound BMDO (16.2 g, 0.1 mol) and benzoyl peroxide (BPO, 0.48 g, 0.002 mol) evenly to obtain mixture A; mix the comonomer N-tert-butylacrylamide (12.7 g, 0.1 mol), 2 mol% polyethylene glycol dimethacrylate crosslinking agent and N,N'-dimethyl-p-toluidine (DMPT, 1 mol%) supported on nano-hydroxyapatite (80 μm, 5 wt%) evenly to obtain mixture B; quickly mix the mixture A and mixture B, and after in-situ curing, obtain an absorbable bioactive bone cement; suck the bone cement with a syringe and inject the bone cement in the toothpaste state into the required site with the assistance of imaging.

[0066] Example 4

[0067] Preparation process of cycloalkenone acetal compound DMMDO:

[0068] Dissolve 2,5 - hexanediol (1.2 g, 10.2 mmol) in dichloromethane (170 ml) and pyridine (7.5 ml, 91.5 mmol). Place the reaction system in an argon - purged environment at - 20 °C, and then slowly add a dichloromethane (90 ml) solution of triphosgene (4.55 g, 15.2 mmol) dropwise. After the addition is complete, restore the temperature to room temperature and react for 20 min. Then quench the reaction with saturated ammonium chloride solution (100 ml). Extract the product mixture with dichloromethane. Wash the obtained organic phase with saturated brine, dry it over anhydrous sodium sulfate, filter, remove the solvent under vacuum, and perform vacuum distillation to collect the fraction around 95 °C. Dissolve the product obtained above (0.023 g, 0.16 mmol) in a mixed solvent of tetrahydrofuran / toluene (1:1), add Petasis reagent (2 ml, 0.5 mmol, a 5 wt% tetrahydrofuran / toluene mixed solution), purge the reaction system with argon, and react under light - free conditions at 60 - 65 °C for 20 h. After the reaction is completed, add n - hexane (10 ml) to form a yellow precipitate. Filter and concentrate the filtrate to obtain the product DMMDO.

[0069] Mix the cyclic enone acetal compound DMMDO (14.2 g, 0.1 mol) and benzoyl peroxide (BPO, 0.48 g, 0.002 mol) evenly to obtain mixture A; mix vinyl acetate (8.6 g, 0.1 mol) evenly, then add 2 mol% polyethylene glycol dimethacrylate cross - linker and add N,N’ - dimethyl - p - toluidine (DMPT, 1 mol%) supported on bioactive glass (45 μm, 5 wt%) and mix evenly to obtain mixture B; quickly mix the mixture A and mixture B, and after in - situ curing, obtain an absorbable bioactive bone cement; suck the bone cement with a syringe and inject the bone cement in the toothpaste - like stage into the required site with the assistance of imaging.

[0070] Comparative Example 1

[0071] Commercially available bone cement According to the instruction manual, evenly mix the solid phase and the liquid phase, then suck the bone cement with a syringe and inject the bone cement in the toothpaste - like stage into the required site with the assistance of imaging.

[0072] (1) Maximum curing temperature and setting time

[0073] After the solid and liquid phases of the bone cement materials in the examples and comparative examples were contacted and mixed evenly, they were immediately injected into a prefabricated mold and timing was started. The temperature was continuously measured using a thermocouple and observed in real time. The test was terminated after the temperature began to drop. According to the curve of temperature change over time obtained, the peak value was read as the highest curing temperature. At the same time, the setting time of the bone cement was defined as the time corresponding to the average curing temperature (the average of the highest curing temperature and room temperature) on the curve. The highest curing temperatures and setting times of the materials in Comparative Example 1 and Examples 1 to 4 are shown in Table 1.

[0074] Table 1 The highest curing temperatures and setting times of the bone cement materials in the examples and comparative examples.

[0075]

[0076] The results show that compared with the traditional PMMA bone cement, the curing temperature of the absorbable bioactive bone cement of the present invention is significantly reduced; a large amount of heat is not generated during the curing of the shown examples, and the highest curing temperature does not exceed 42 °C. Especially in Example 1, the highest temperature is 37.2 °C, which is very close to the normal human body temperature. At the same time, the shortened setting time window can also meet the clinical operation requirements.

[0077] (2) Mechanical property test of bone cement

[0078] The mechanical properties of the bone cement were tested according to ISO5833-2002. After the solid and liquid phases of the bone cement materials in the examples and comparative examples were contacted and mixed evenly, they were immediately injected into a cylindrical mold with a diameter of 5 mm and a height of 10 mm. After curing, the mold was removed. The prepared specimens were subjected to compression tests on a universal testing machine (LD-5 type of LLOYD company, the sensor was 2.5 kN). The loading speed was 5 mm / min, and the test was stopped when the compression rate reached 30%. The compressive strength value and the elastic modulus of the bone cement were calculated according to the stress-strain curve. There were 5 parallel samples in each group, and the results were averaged. Another rectangular sample strip was prepared and the flexural strength of the bone cement was measured by the three-point bending test method. The loading speed was 5 mm / min, and the loading was continued until the sample strip broke and the test was stopped. There were 5 parallel samples in each group, and the results were averaged. The compressive strength, elastic modulus and flexural strength of the bone cement are shown in Table 2.

[0079] Table 2 The mechanical properties of the bone cement materials in the examples and comparative examples.

[0080]

[0081] The results show that compared with the commercially available bone cement products, the absorbable bioactive bone cement in the present invention has improved compressive strength and flexural strength, and the material has higher toughness.

[0082] (3) In vivo degradation experiment

[0083] Balb / c mice (20 g, female) had their back hair removed in a sterile environment, the skin was cleaned, and then they were placed in a chamber of an isoflurane anesthesia machine for anesthesia and fixed on the operating table, with an anesthesia mask maintaining the anesthesia. The skin around the back was disinfected with iodophor, and an incision (~1 cm) was made on the back with a scalpel. The fascia between the skin and muscle was separated with scissors and forceps to form a small pocket. The solidified samples in Comparative Example 1 and Examples 1-4 were made into discs with a diameter of 5 mm and a height of 2 mm, and implanted subcutaneously in the back. The tissue was sutured and disinfected again with iodophor. Six mice were randomly implanted in each case. After 8 weeks of feeding, the mice were euthanized, and the samples in Comparative Example 1 and Examples 1-4 were taken out. The morphology of the samples was observed, the weight of the samples was measured, and the degradation rate was calculated by comparing with the samples before implantation.

[0084] The in vivo degradation test of the materials in Comparative Example 1 and Examples 1-4 was as Figure 2 shown.

[0085] As Figure 2 shown: The materials in Examples 1-4 all showed good degradation rates after being maintained for 8 weeks in the physiological environment. The degradation of the material in Example 2 was the most obvious, and the degradation rate could reach 26.86%; it was shown that the introduction of the MDO ring-opening polymer provided better degradation performance for the material; in addition, the degradation rate of the material in Comparative Example 1 after 8 weeks was 1.49%, and the degradability of the material was poor, far lower than that of Examples 1-4, indicating that the bone cement constructed in the present invention has excellent in vivo degradation performance.

[0086] (4) Osteogenic activity experiment

[0087] ALP activity detection: Osteoblasts MC3T3 were cultured on the prefabricated Examples 1-4 and Comparative Example 1 for 7 days and 14 days respectively. The old culture medium was removed, and the cells were washed 1-3 times with PBS. Then RIAP cell lysate was added. After the cells were fully lysed, the cell lysate was centrifuged, and the supernatant was taken. The activity of cell ALP was detected according to the instructions of the AKP / ALP kit.

[0088] The ALP activity detection of the materials in Comparative Example 1 and Examples 1-4 was as Figure 3 shown.

[0089] As Figure 3 shown: The cell ALP activity in the test of the materials in Examples 1-4 was significantly higher than that in Comparative Example 1. This was because the absorbable bioactive bone cement in the present invention added inorganic nano materials with osteogenic activity. The inorganic nano materials with bioactivity could be gradually exposed or released with the degradation of the bone cement in vivo, so as to show osteogenic activity when contacting with the surrounding tissue environment.

[0090] As can be seen from the above embodiments, the present invention provides an absorbable bioactive bone cement, and the preparation raw materials include component A and component B; component A includes cycloalkenone acetal compounds and oxidants; component B includes hydrophobic vinyl monomers, hydrophilic crosslinking agents and reducing agents loaded on inorganic nanomaterials. The bone cement provided by the present invention is formed by in-situ curing through a free radical ring-opening polymerization reaction in a human body environment. The reaction process is rapid, slightly exothermic, does not burn the human body, and there will be no loosening phenomenon in subsequent use. The added inorganic nanomaterials have osteogenic activity and can be absorbed by the human body. The free radical ring-opening polymer with cycloalkenone acetal compounds can be degraded and absorbed in a physiological environment, but the absorption time is longer, avoiding the deficiency of too fast degradation time of calcium phosphate bone cement and calcium sulfate bone cement, and is applicable to total joint replacement, vertebroplasty, bone defect reconstruction, treatment of infectious lesions, etc.

[0091] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be regarded as the protection scope of the present invention.

Claims

1. A bioabsorbable bioactive bone cement, the raw materials for preparation including component A and component B; Component A includes cycloalkenone acetal compounds and oxidants; the cycloalkenone acetal compounds are selected from one or more of 2-methylene-1,3-dioxepane, 2-methylene-4-phenyl-1,3-dioxolane, 5,6-benzo-2-methylene-1,3-dioxepane, and 4,7-dimethyl-2-methylene-1,3-dioxepane; Component B includes hydrophobic vinyl monomers, hydrophilic crosslinkers, and inorganic nanomaterial-supported reducing agents; The hydrophobic vinyl monomers include one or more of acrylate, methacrylate, N-tert-butylacrylamide, N-dodecylacrylamide, 3-(methacryloyloxy)propyltrimethoxysilane, and vinyl acetate; The hydrophilic crosslinker is polyethylene glycol dimethacrylate; The oxidants include one or more of benzoyl peroxide, tert-butyl hydroperoxide, ammonium persulfate, and hydrogen peroxide; The reducing agents in the inorganic nanomaterial-supported reducing agents include one or more of N,N-dimethyl-p-toluidine, sodium metabisulfite, sodium bisulfite, and ferrous sulfate; The inorganic nanomaterials in the inorganic nanomaterial-supported reducing agents are selected from one or more of nano-hydroxyapatite, nano-tricalcium phosphate, and nano-bioactive glass; 2. The absorbable bioactive bone cement according to claim 1, characterized in that, The molar ratio of the hydrophobic vinyl monomers to the cycloalkenone acetal compounds is 0.01~100:1; The molar ratio of the hydrophilic crosslinker to the cycloalkenone acetal compounds is 0.001~0.2:1; 3. The absorbable bioactive bone cement according to claim 1, characterized in that, The molar ratio of the oxidants to the cycloalkenone acetal compounds is 0.001~0.2:1; The molar ratio of the oxidants to the reducing agents is 0.01~10:1; 4. A preparation method of the bioabsorbable bioactive bone cement according to any one of claims 1~3, comprising the following steps: Dissolve the oxidant in the cycloalkenone acetal compounds to obtain mixture A; Mix the hydrophobic vinyl monomers, hydrophilic crosslinkers, and inorganic nanomaterial-supported reducing agents evenly to obtain mixture B; Mix mixture A and mixture B evenly, and obtain the bioabsorbable bioactive bone cement after in-situ curing; 5. An application of the bioabsorbable bioactive bone cement according to any one of claims 1~3 or the bioabsorbable bioactive bone cement prepared by the preparation method according to claim 4 in the preparation of bone cement products.

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