An antibacterial hydrogel and a preparation method and application thereof

Abstract

The application provides an antibacterial hydrogel and a preparation method and application thereof, and belongs to the technical field of medical polymer materials, and the preparation method comprises the following steps: (1) mixing vanillin, a halogen-containing ester compound, a carbonate and an organic solvent, stirring, post-treatment, and obtaining a first intermediate product; (2) mixing the first intermediate product, sodium borohydride and an organic solvent, stirring, post-treatment, and obtaining a second intermediate product; (3) mixing the second intermediate product, a diamine compound and an organic solvent, reacting, post-treatment, and obtaining a third intermediate product; (4) mixing methacrylated hyaluronic acid, the third intermediate product, a first catalyst, dopamine hydrochloride and a solvent, then adding a pH regulator, further adding a second catalyst, stirring, post-treatment, and obtaining the antibacterial hydrogel. The antibacterial hydrogel is used for surface coating of bone implant instruments, and can improve the occurrence of bone implant instrument infection.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medical polymer materials, and relates to an antibacterial hydrogel as well as a preparation method and application thereof. BACKGROUND

[0002] Infection may occur after the implantation of a bone implant device into a human body, and the infection requires the opening of a wound for debridement and the re-implantation of the device, which causes secondary damage to the patient in terms of physiology, psychology, economy and the like.

[0003] At present, the antibacterial coating applied to the bone implant device is generally an antibiotic coating, a silver coating or an iodine coating. Each of the coatings has its own problems, for example, the antibiotic coating is prone to cause disordered release of antibiotics, further causing drug resistance; and the silver coating and the iodine coating are subject to high prices and potential biological toxicity. At present, the research on the application of hydrogel to the bone implant device is still less.

[0004] Therefore, in the field, it is expected to develop an antibacterial hydrogel which is used in the bone implant device, has the advantages of low toxicity, good biocompatibility and the like, can achieve ordered release of drugs, and is low in cost. SUMMARY

[0005] In view of the deficiencies of the prior art, the purpose of the application is to provide an antibacterial hydrogel as well as a preparation method and application thereof.

[0006] To achieve the purpose of the application, the following technical solutions are adopted:

[0007] In a first aspect, the application provides a preparation method of an antibacterial hydrogel, and the preparation method comprises the following steps:

[0008] (1) vanillin, a halogen-containing ester compound and a carbonate are mixed with an organic solvent, stirred, and post-treated to obtain a first intermediate product;

[0009] (2) the first intermediate product, sodium borohydride (NaBH4) and an organic solvent are mixed, stirred, and post-treated to obtain a second intermediate product;

[0010] (3) the second intermediate product and a diamine compound are mixed with an organic solvent, reacted, and post-treated to obtain a third intermediate product;

[0011] (4) methacrylated hyaluronic acid, the third intermediate product, a first catalyst, dopamine hydrochloride and a solvent are mixed, then a pH adjuster is added, a second catalyst is further added, stirred, and post-treated to obtain the antibacterial hydrogel.

[0012] The antibacterial hydrogel prepared by the preparation method has the advantages of low toxicity, good biocompatibility, being absorbed by human body, and being capable of loading drugs, and the like, and when the antibacterial hydrogel is used for a surface coating of a bone implant device, the occurrence of infection of the bone implant device can be improved, the antibacterial hydrogel has excellent mechanical properties and can achieve ordered release of drugs, and in addition, the antibacterial hydrogel is convenient to use and low in cost.

[0013] Preferably, the halogen-containing ester compound in step (1) comprises any one or a combination of at least two of 4-bromobutyric acid methyl ester, 3-bromopropionic acid methyl ester, and 5-bromovaleric acid methyl ester.

[0014] Preferably, the carbonate in step (1) comprises potassium carbonate and / or sodium carbonate.

[0015] Preferably, the organic solvent in step (1) comprises N,N-dimethylformamide (DMF).

[0016] Preferably, the molar ratio of vanillin to the halogen-containing ester compound in step (1) is 1:(1-1.2), such as 1:1, 1:1.1, 1:1.2, or the like.

[0017] Preferably, the molar ratio of vanillin to the carbonate in step (1) is 1:(1-1.2), such as 1:1, 1:1.1, 1:1.2, or the like.

[0018] Preferably, the amount of the organic solvent in step (1) is 8-12 mL, such as 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, or the like, based on the amount of 2 g of vanillin.

[0019] Preferably, the stirring temperature in step (1) is 20-25℃, such as 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, or the like, and the stirring time is 12-20 h, such as 12 h, 14 h, 16 h, 18 h, 20 h, or the like.

[0020] Preferably, the post-treatment in step (1) comprises precipitation, filtration, washing, and drying.

[0021] Preferably, the molar ratio of the first intermediate product to sodium borohydride in step (2) is 1:(1.4-1.6), such as 1:1.4, 1:1.5, 1:1.6, or the like.

[0022] Preferably, the organic solvent in step (2) comprises methanol and / or tetrahydrofuran, preferably a mixture of methanol and tetrahydrofuran.

[0023] Preferably, the amount of the organic solvent in step (2) is 20-40 mL, such as 20 mL, 25 mL, 30 mL, 35 mL, 40 mL, or the like, based on the amount of 2 g of the first intermediate product.

[0024] Preferably, the mixing in step (2) specifically comprises: mixing the first intermediate product with part of the organic solvent and controlling the mixing temperature to be 0-5℃ to obtain a first mixed solution, mixing sodium borohydride with the remaining organic solvent to obtain a second mixed solution, and slowly adding the second mixed solution into the first mixed solution. It should be noted that the amount of the part of the organic solvent is not specifically limited in the present application, as long as it can dissolve the first intermediate product and the remaining organic solvent can dissolve sodium borohydride.

[0025] Preferably, the temperature of the stirring in step (2) is 0-5℃, such as 0℃, 1℃, 2℃, 3℃, 4℃, 5℃, etc., and the stirring time is 2-4h, such as 2h, 3h, 4h, etc.

[0026] Preferably, the post-treatment in step (2) comprises removing the organic solvent, washing, and drying.

[0027] Preferably, the diamine compound in step (3) comprises any one or a combination of at least two of ethylenediamine, propylenediamine, and butylenediamine.

[0028] Preferably, the organic solvent in step (3) comprises methanol.

[0029] Preferably, the molar ratio of the second intermediate product to the diamine compound in step (3) is 1:(1-1.2), such as 1:1, 1:1.1, 1:1.2, etc.

[0030] Preferably, in step (3), the amount of the organic solvent is 20-40mL, such as 20mL, 25mL, 30mL, 35mL, 40mL, etc., based on the amount of 2g of the second intermediate product.

[0031] Preferably, the temperature of the reaction in step (3) is 70-80℃, such as 70℃, 75℃, 80℃, etc.

[0032] Preferably, the reaction in step (3) is a reaction until the raw material is no longer observed by using TLC (thin layer chromatography).

[0033] Preferably, the post-treatment in step (3) comprises removing the organic solvent, recrystallization, filtration, and drying.

[0034] Preferably, the first catalyst in step (4) comprises 1-hydroxybenzotriazole.

[0035] Preferably, the solvent in step (4) comprises deionized water.

[0036] Preferably, the pH adjuster in step (4) comprises hydrochloric acid.

[0037] Preferably, the pH regulator is used in an amount such that the pH value of the system is 4-5, for example 4, 4.2, 4.4, 4.6, 4.8, 5, etc.

[0038] Preferably, the second catalyst in step (4) comprises 1-ethyl-(3-dimethylaminopropyl) carbodiimide.

[0039] Preferably, the molar ratio of the methacrylated hyaluronic acid to the third intermediate product in step (4) is 1:(400-600), for example 1:400, 1:420, 1:440, 1:450, 1:460, 1:480, 1:500, 1:520, 1:540, 1:550, 1:560, 1:580, 1:600, etc.

[0040] Preferably, the molar ratio of the third intermediate product to the first catalyst in step (4) is 1:(1.6-1.8), for example 1:1.6, 1:1.7, 1:1.8, etc.

[0041] Preferably, the molar ratio of the third intermediate product to dopamine hydrochloride in step (4) is 1:(0.7-0.9), for example 1:0.7, 1:0.8, 1:0.9, etc.

[0042] Preferably, the amount of the solvent in step (4) is 40-60 mL, for example 40 mL, 45 mL, 50 mL, 55 mL, 60 mL, etc., based on the amount of the third intermediate product being 0.2 g.

[0043] Preferably, the molar ratio of the third intermediate product to the second catalyst in step (4) is 1:(0.9-1.1), for example 1:0.9, 1:1, 1:1.1, etc.

[0044] Preferably, the temperature of the stirring in step (4) is 20-25℃, for example 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, etc., and the time of the stirring is 45-55 h, for example 45 h, 46 h, 48 h, 50 h, 52 h, 53 h, 55 h, etc.

[0045] Preferably, the stirring in step (4) is carried out in the dark.

[0046] Preferably, the post-treatment in step (4) comprises purification.

[0047] Preferably, the purification comprises dialysis.

[0048] As a preferred technical scheme of the present application, the preparation method comprises the following steps:

[0049] (1) vanillin, halogen-containing ester compound, carbonate and organic solvent are mixed, stirred at 20-25℃ for 12-20h, then the reaction solution is poured into deionized water to stand for precipitation, filtration, washing, drying, to obtain a first intermediate product;

[0050] (2) the first intermediate product is mixed with organic solvent, and the mixing temperature is controlled at 0-5℃ to obtain a first mixed solution, sodium borohydride is mixed with organic solvent to obtain a second mixed solution, the second mixed solution is added into the first mixed solution, stirred at 0-5℃ for 2-4h, the organic solvent is removed, washed, dried, to obtain a second intermediate product;

[0051] (3) the second intermediate product, diamine compound and organic solvent are mixed, reacted at 70-80℃ until no raw material is observed by using thin layer chromatography, the organic solvent is removed, recrystallized, filtered, dried, to obtain a third intermediate product;

[0052] (4) methacrylated hyaluronic acid, the third intermediate product, a first catalyst, dopamine hydrochloride and a solvent are mixed, then a pH regulator is added to make the pH value of the system 4-5, a second catalyst is added, stirred at 20-25℃ in dark for 45-55h, purified, to obtain the antibacterial hydrogel.

[0053] In the second aspect, the present application provides an antibacterial hydrogel, which is prepared by the preparation method in the first aspect.

[0054] In the third aspect, the present application provides an application of the antibacterial hydrogel in the second aspect to a bone implant device.

[0055] Compared with the prior art, the present application has the following beneficial effects:

[0056] The antibacterial hydrogel prepared by the preparation method provided by the present application has the advantages of low toxicity, good biocompatibility, being absorbed by the human body, being able to load drugs, etc., and when used as a surface coating of a bone implant device, the antibacterial hydrogel can improve the occurrence of infection of the bone implant device, and the antibacterial hydrogel provided by the present application has excellent mechanical properties, can achieve ordered release of drugs, in addition, it is convenient to use and has low cost. BRIEF DESCRIPTION OF DRAWINGS

[0057] Figure 1 The nuclear magnetic spectrum of the first intermediate product provided for Example 1.

[0058] Figure 2 The nuclear magnetic spectrum of the second intermediate product provided for Example 1.

[0059] Figure 3 The nuclear magnetic spectrum of the third intermediate product provided for Example 1.

[0060] Figure 4 NMR spectrum of the antibacterial hydrogel provided for Example 1.

[0061] Figure 5A Figure 5B Figure 5C The test result figures of the fluorescence staining experiment at the 1st, 3rd and 7th days in the compatibility experiment of the antibacterial hydrogel with cells provided for Example 1, respectively.

[0062] Figure 6 The comparison figure of the ultraviolet absorption spectrum result of the CCK8 experiment in the compatibility experiment of the antibacterial hydrogel with cells provided for Example 1. DETAILED DESCRIPTION

[0063] The technical solutions of the present application will be further described below through specific embodiments. Those skilled in the art should understand that the embodiments are only to help understand the present application and should not be regarded as specific limitations on the present application.

[0064] Example 1

[0065] In the present embodiment, an antibacterial hydrogel is provided, and the preparation method comprises the following steps:

[0066] (1) 2 g (13.1 mmol, 1 eq) of vanillin, 2.6 g (14.4 mmol, 1.1 eq) of methyl 4-bromobutyrate, and 2.2 g (15.7 mmol, 1.2 eq) of potassium carbonate are weighed and dissolved in 10 mL of DMF. After stirring at 25°C for 16 h, the reaction solution is poured into 100 mL of 0°C deionized water, and the material is allowed to precipitate after standing for 15 min. The precipitate is filtered and washed with deionized water. Then it is dissolved in dichloromethane and dried with anhydrous magnesium sulfate. Finally, the dichloromethane is removed to obtain a white solid product, which is the first intermediate product;

[0067] (2) 2 g (6.7 mmol, 1 eq) of the first intermediate product is dissolved in 20 mL of a 1:1 volume ratio methanol / tetrahydrofuran mixed solvent, and the solution temperature is controlled at 0°C. Then 0.38 g (10 mmol, 1.5 eq) of sodium borohydride is dissolved in 10 mL of a 1:1 volume ratio methanol / tetrahydrofuran solvent, and the solution containing sodium borohydride is slowly added to the previous 0°C solution. After the addition is completed, stirring is continued at 0°C for 3 h. After the reaction is completed, the methanol and tetrahydrofuran are removed, and 50 mL of deionized water and 50 mL of dichloromethane are added for washing, which is repeated 3 times. The dichloromethane solution obtained after the last washing is dried with anhydrous magnesium sulfate. Finally, the dichloromethane is removed to obtain a yellow solid product, which is the second intermediate product;

[0068] ​​(3) Take 2 g (6.7 mmol, 1 eq) of the second intermediate product and 0.24 g (7.3 mmol, 1.1 eq) of ethylenediamine, dissolve them in 30 mL of methanol, and reflux at 75°C until no raw material is observed by TLC method, and the reaction is completed. Remove the methanol to obtain the crude product, dissolve it in as little methanol as possible, and recrystallize it with ethyl acetate. Filter the obtained crystals and dry them under vacuum for 12 h to obtain a yellow solid product, which is the third intermediate product;

[0069] (4) Take 0.4 g (0.001 mmol) of methacrylated hyaluronic acid, 0.2 g (0.65 mmol) of the third intermediate product, 0.15 g (1.1 mmol) of 1-hydroxybenzotriazole, and 0.1 g (0.53 mmol) of dopamine hydrochloride, dissolve them in 50 mL of deionized water, adjust the pH of the solution to 4.5 with hydrochloric acid, then add 0.1 g (0.64 mmol) of 1-ethyl-(3-dimethylaminopropyl) carbodiimide, and stir at 25°C in the dark for 48 h. Perform dialysis using a 3500 Da dialysis bag and distilled water with pH = 5 for 4 days, with water changes every 3 h on the first day and every 8 h thereafter. After dialysis, freeze-drying is performed to obtain a black final product, which is the antibacterial hydrogel.

[0070] The synthesis route of the antibacterial hydrogel provided by the present embodiment is shown below:

[0071] .

[0072] The nuclear magnetic resonance spectra of the first intermediate product, the second intermediate product, the third intermediate product, and the antibacterial hydrogel provided by the present embodiment are shown in Figures 1-4 .

[0073] Example 2

[0074] The difference between the present embodiment and Example 1 is that the 4-bromobutyl acid methyl ester in step (1) is replaced with an equal molar amount of 3-bromopropyl acid methyl ester, and the molar amount of the intermediate product used in the subsequent steps remains the same as in Example 1.

[0075] Example 3

[0076] The difference between the present embodiment and Example 1 is that the ethylenediamine in step (3) is replaced with an equal molar amount of propylenediamine, and the molar amount of the third intermediate product used in step (4) remains the same as in Example 1.

[0077] Comparative Example 1

[0078] The difference between the present comparative example and Example 1 is that no methacrylated hyaluronic acid is added in step (4).

[0079] Comparative Example 2

[0080] The only difference between the present comparative example and Example 1 is that no dopamine hydrochloride is added in step (4).

[0081] Performance test

[0082] (1) Mechanical property test

[0083] First, prepare a 0.25% initiator standard solution: take two standard phosphate buffer solutions (20 mL in total), add to a brown bottle containing 0.05 g of initiator lithium phenyl (2,4,6-trimethylbenzoyl) phosphate salt (LAP), and then heat to dissolve at 45°C for 30 min, with multiple shaking during the period to ensure that the LAP is fully dissolved, to obtain a LAP solution;

[0084] Respectively, 0.1 g of the antibacterial hydrogel provided by the above examples and comparative examples is added to 0.4 g of the LAP solution, and swelled at 60°C until completely swelled; after complete swelling, the curing is completed under 405 nm, 955 mw / cm 2 light intensity for 60 s, and then the tensile shear strength and bulk tensile strength of the cured sample are tested, wherein the tensile shear strength is tested according to GB / T 7124, and the bulk tensile strength is tested according to GB / T 1040.

[0085] The performance test results are shown in Table 1.

[0086] Table 1

[0087]

[0088] As can be seen from Table 1, the antibacterial hydrogels provided by the examples have high tensile shear strength (47-52 kPa) and bulk tensile strength (3-4 MPa).

[0089] Compared with Example 1, the antibacterial hydrogel provided by Comparative Example 1 cannot form a hydrogel due to the absence of methacrylated hyaluronic acid, and has almost no mechanical strength. The antibacterial hydrogel provided by Comparative Example 2 has a small tensile shear strength, although its bulk tensile strength is not affected, which also shows that dopamine helps the adhesion strength, which may be due to the hydroxyl group of dopamine can form hydrogen bond or stronger intermolecular force with the polar groups on the surface of the adhesive.

[0090] (2) Compatibility experiment of hydrogel and cells

[0091] Fluorescent staining experiment: the antibacterial hydrogel provided in Example 1 was used to culture cells, which specifically included the following steps: the antibacterial hydrogel provided in Example 1 was dissolved in PBS containing a photoinitiator to obtain a gel solution with a final concentration of 5wt%; the gel solution was added to a six-well plate (1mL / well) and cured using an ultraviolet lamp for 1min, and then BMSCs cell suspension (1*10 5 6 / well) was added to each well. At 1, 3 and 7 days, the cells were stained using a CAM / PI staining kit to detect their survival status (green represents live cells and red represents dead cells). The test results at 1, 3 and 7 days are shown in FIGS. Figures 5A-5C Figures 5A-5C It can be seen that,

[0092] CCK8 experiment: the antibacterial hydrogel provided in Example 1 was added to DMEM high-sugar culture medium containing 10% fetal bovine serum to obtain a gel solution with a final concentration of 5wt%, which was placed on a 37℃ shaking bed for 24h to allow it to dissolve completely. Mouse BMSCs were uniformly spread in a 96-well plate at a density of 5*10 3 6 / well. Blank medium was added to the well plate as a control group, and the gel solution was added to another well plate as the experimental group of Example 1. At 1, 3 and 7 days, CCK8 detection solution was added, and the absorbance was detected at 450nm using an enzyme marker after incubation at 37℃ for 2h (live cells have absorbance and dead cells do not).

[0093] The CCK-8 test results of cell culture at 1, 3 and 7 days are shown in FIG. Figure 6 It can be seen that the absorbance of the experimental group with the antibacterial hydrogel provided in Example 1 is close to that of the blank control group, and the absorbance of the experimental group at 7 days is within 85% of that of the blank control group, indicating that the antibacterial hydrogel provided in Example 1 has qualified biological toxicity and cell compatibility.

[0094] The applicant declares that the antibacterial hydrogel, its preparation method and application of the present application are illustrated by the above examples, but the present application is not limited to the above examples, i.e. it does not mean that the present application must rely on the above examples to be implemented. It should be understood by those skilled in the art that any improvement of the present application, equivalent replacement of the selected materials of the present application, addition of auxiliary ingredients, selection of specific methods, etc. fall within the protection scope and disclosure scope of the present application.​

Claims

1. A method for preparing an antibacterial hydrogel, characterized in that, The preparation method includes the following steps: (1) Vanillin, halogenated ester compounds, carbonates and organic solvents are mixed, stirred and post-treated to obtain the first intermediate product; (2) The first intermediate product, sodium borohydride and organic solvent are mixed, stirred and post-treated to obtain the second intermediate product; (3) The second intermediate product, the diamine compound and the organic solvent are mixed, reacted and post-treated to obtain the third intermediate product; (4) Mix methacrylamide hyaluronic acid, the third intermediate product, the first catalyst, dopamine hydrochloride and solvent, then add pH adjuster, then add second catalyst, stir, and post-process to obtain the antibacterial hydrogel. The molar ratio of methacrylated hyaluronic acid to the third intermediate in step (4) is 1:(400-600); The molar ratio of the third intermediate product to dopamine hydrochloride in step (4) is 1:(0.7-0.9); The post-processing described in step (4) includes purification.

2. The preparation method according to claim 1, characterized in that, The halogenated ester compounds in step (1) include any one or a combination of at least two of methyl 4-bromobutyrate, methyl 3-bromopropionate, and methyl 5-bromopentanoate; The carbonate in step (1) includes potassium carbonate and / or sodium carbonate; The organic solvent in step (1) includes N,N-dimethylformamide; The molar ratio of vanillin to halogenated ester compounds in step (1) is 1:(1-1.2); The molar ratio of vanillin to carbonate in step (1) is 1:(1-1.2); In step (1), the amount of vanillin used is 2g, and the amount of organic solvent used is 8-12mL.

3. The preparation method according to claim 1, characterized in that, The stirring temperature in step (1) is 20-25℃, and the stirring time is 12-20h; The post-processing in step (1) includes precipitation, filtration, washing, and drying.

4. The preparation method according to claim 1, characterized in that, In step (2), the molar ratio of the first intermediate product to sodium borohydride is 1:(1.4-1.6); The organic solvent in step (2) includes methanol and / or tetrahydrofuran; In step (2), based on the amount of the first intermediate product being 2g, the amount of the organic solvent being used is 20-40mL; The mixing in step (2) specifically includes: mixing the first intermediate product with a portion of the organic solvent and controlling the mixing temperature to 0-5℃ to obtain a first mixture; mixing sodium borohydride with the remaining organic solvent to obtain a second mixture; and adding the second mixture to the first mixture. The stirring temperature in step (2) is 0-5℃, and the stirring time is 2-4h; The post-processing in step (2) includes removing organic solvents, washing, and drying.

5. The preparation method according to claim 1, characterized in that, The diamine compound in step (3) includes any one or a combination of at least two of ethylenediamine, propylenediamine, and butylenediamine; The organic solvent in step (3) includes methanol; In step (3), the molar ratio of the second intermediate product to the diamine compound is 1:(1-1.2); In step (3), based on the amount of the second intermediate product being 2g, the amount of the organic solvent being 20-40mL; The reaction temperature in step (3) is 70-80℃; The post-processing in step (3) includes removing organic solvents, recrystallization, filtration, and drying.

6. The preparation method according to claim 1, characterized in that, Step (4) The first catalyst comprises 1-hydroxybenzotriazole; The solvent in step (4) includes deionized water; The pH adjuster in step (4) includes hydrochloric acid; The amount of pH adjuster used in step (4) is such that the pH value of the system is 4-5; Step (4) The second catalyst comprises 1-ethyl-(3-dimethylaminopropyl)carbodiimide; The molar ratio of the third intermediate to the first catalyst in step (4) is 1:(1.6-1.8); In step (4), the amount of solvent used is 40-60 mL, based on the amount of the third intermediate product being 0.2 g. The molar ratio of the third intermediate to the second catalyst in step (4) is 1:(0.9-1.1).

7. The preparation method according to claim 1, characterized in that, The stirring temperature in step (4) is 20-25℃, and the stirring time is 45-55h; The stirring in step (4) is carried out under light-protected conditions.

8. A preparation method as described in claim 1, characterized in that, The preparation method includes the following steps: (1) Mix vanillin, halogenated ester compounds, carbonates and organic solvents, stir at 20-25℃ for 12-20h, then pour the reaction solution into deionized water to stand and precipitate, filter, wash and dry to obtain the first intermediate product; (2) Mix the first intermediate product with an organic solvent and control the mixing temperature at 0-5℃ to obtain a first mixture. Mix sodium borohydride with an organic solvent to obtain a second mixture. Add the second mixture to the first mixture and stir at 0-5℃ for 2-4 hours. Remove the organic solvent, wash, and dry to obtain the second intermediate product. (3) The second intermediate product, the diamine compound and the organic solvent are mixed and reacted at 70-80°C until the raw material is no longer observed by thin-layer chromatography. The organic solvent is removed, recrystallized, filtered and dried to obtain the third intermediate product. (4) Mix methacrylated hyaluronic acid, the third intermediate product, the first catalyst, dopamine hydrochloride and solvent, then add a pH adjuster to make the pH of the system 4-5, then add the second catalyst, stir at 20-25℃ in the dark for 45-55h, purify, and obtain the antibacterial hydrogel.

9. An antibacterial hydrogel, characterized in that, The antibacterial hydrogel is prepared using the preparation method described in any one of claims 1-8.

10. The application of the antibacterial hydrogel as described in claim 9 in bone implant devices.

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