Antibacterial gel composite material as well as preparation method and application thereof

By coating polydopamine in bioceramics and wrapping drug-loaded mesoporous materials with photocrosslinked hydrogels, the problem of stable ions release in drugs and bioceramics is solved, slow release and stable release are achieved, and the application effect of biocera in biomedicine is improved.

CN119524194APending Publication Date: 2025-02-28GUANGDONG PROV MEDICAL INSTR INST
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Patent Information

Application Number
CN202411454589.2
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-10-17
Publication Date
2025-02-28

AI Technical Summary

Technical Problem

The prior art is difficult to achieve the stable release of ions from bioceramics in drugs and bioceramics, which affects its application in biomedical science.

Method used

The drug-loaded mesoporous material is encapsulated with a photocrosslinked hydrogel. The drug-loaded mesoporous material includes polydopamine-coated mesoporous bioceramics and growth factors. The mesoporous bioceramics are encapsulated with growth factors and doped with antibacterial metal ions.

Benefits of technology

Through polydopamine coating and photocrosslinked hydrogel wrapping, the slow release of ionic products and antibacterial ions in drugs and bioceramics is achieved, which reduces sudden release, achieves stable release, and effectively regulates the release curve of drugs and ions.

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Abstract

The invention discloses an antibacterial gel composite material as well as a preparation method and application thereof. The antibacterial gel composite material comprises photo-crosslinking hydrogel, and the photo-crosslinking hydrogel is coated with a drug-loaded mesoporous material; the drug-loaded mesoporous material comprises polydopamine, mesoporous biological ceramic and a growth factor which are arranged in sequence; the surface of the mesoporous biological ceramic is coated with polydopamine; growth factors are encapsulated in the mesoporous biological ceramic; the mesoporous biological ceramic is doped with metal ions with an antibacterial effect. According to the antibacterial gel composite material provided by the invention, in the composite material, mesoporous biological ceramic is coated with polydopamine, so that ionic products and doped antibacterial ions in drugs and biological ceramic can be slowly released, the burst release is relatively small, and stable release is realized; in addition, by regulating and controlling the doping amount of the antibacterial ions in the porous biological ceramic and the mass of the medicine loaded in the doped mesoporous biological ceramic, the release curve of the medicine and the ions can be effectively regulated and controlled.
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Description

Technical Field

[0001] The invention belongs to the technical field of medical materials, and specifically relates to an antibacterial gel composite material and a preparation method and application thereof. Background Art

[0002] The skin is a barrier that protects internal organs from potential environmental hazards. The skin has excellent regenerative properties and can repair wounds through a series of complex physiological processes. However, in some cases, such as partial-thickness wounds, full-thickness wounds, and deep-thickness wounds, the skin tissue regeneration function is impaired, resulting in the inability of the wound to heal in time. Delayed healing will cause further deterioration of the wound, exposing the patient to major health risks. A series of measures, including surgical treatment, are often required to promote recovery. Therefore, the development of therapeutic treatments, tissue engineering, bioactive molecules, wound dressings, etc. is particularly necessary, which can be used to enhance the healing effect and shorten the healing time.

[0003] Wound dressings can be used to protect wounds from contamination and to deliver bioactive molecules to the wound site. Typical bioactive agents are delivered to wounds in the form of solutions, creams, and ointments, but these forms are not very effective. They quickly absorb exudate and cause the loss of bioactive agents. Solid wound dressings can better absorb wound exudate and remain stable at the wound site for a longer period of time. Hydrogels are a three-dimensional network structure formed by cross-linking linear polymer chains. Since hydrogels have strong hydrophilic groups inside, they have a special adsorption effect on water and usually have good water absorption properties, making hydrogels useful in preparing wound dressings that stay moist.

[0004] Mesoporous bioceramics, such as mesoporous bioglass, mesoporous calcium silicate, and mesoporous silicon, are a class of ceramic materials with nanopore structures and good biological activity. At present, there are studies reporting the application of mesoporous materials as drug carriers. In addition, metal ions with therapeutic effects, such as strontium, manganese, copper, and zinc ions, have been used in the material structure of bioceramics to give the materials new functionality and expand their applications in different biomedicines. However, how to achieve stable release of drugs and bioceramic ions from bioceramics is a problem that needs to be overcome in this field. Summary of the invention

[0005] In order to overcome the problems existing in the above-mentioned prior art, one of the purposes of the present invention is to provide an antibacterial gel composite material. The second purpose of the present invention is to provide a method for preparing the above-mentioned antibacterial gel composite material. The third purpose of the present invention is to provide an application of the above-mentioned antibacterial gel composite material.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is:

[0007] The first aspect of the present invention provides an antibacterial gel composite material, comprising a photo-crosslinked hydrogel, wherein the photo-crosslinked hydrogel is wrapped with a drug-loaded mesoporous material; the drug-loaded mesoporous material comprises polydopamine, a mesoporous bioceramic and a growth factor arranged in sequence; the surface of the mesoporous bioceramic is coated with polydopamine; the growth factor is encapsulated in the mesoporous bioceramic; the mesoporous bioceramic is doped with metal ions with antibacterial effects.

[0008] Preferably, the photo-crosslinked hydrogel is a methacrylated hydrogel, and the methacrylated hydrogel is selected from at least one of methacrylated hyaluronic acid, methacrylated silk fibroin, methacrylated chondroitin sulfate, methacrylated chitosan, and methacrylated gelatin.

[0009] Preferably, the mesoporous bioceramic is selected from at least one of mesoporous silicon, mesoporous calcium silicate, mesoporous magnesium silicate and mesoporous bioglass.

[0010] Preferably, the average pore size of the mesoporous bioceramic is 2 to 50 nm, and the specific surface area is 150 to 1000 m 2 / g, particle size is 20~1000nm.

[0011] Preferably, the growth factor is selected from at least one of vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor, keratinocyte growth factor and nerve growth factor.

[0012] Preferably, the metal ions having antibacterial effects are selected from at least one of silver ions, copper ions, iron ions, zinc ions, mercury ions, gallium ions and lead ions.

[0013] Preferably, the mass ratio of the mesoporous bioceramic to the growth factor is 1:(0.0002-0.02).

[0014] Preferably, the molar percentage of the metal ions with antibacterial effect in the mesoporous bioceramic is 0.5-20%.

[0015] Preferably, the mass ratio of the mesoporous bioceramic to dopamine is 1:(0.01-0.2).

[0016] Preferably, the mass ratio of the mesoporous bioceramic to the photo-crosslinked hydrogel is 1:(1.2-20).

[0017] The second aspect of the present invention provides a method for preparing the antibacterial gel composite material of the first aspect, comprising the following steps:

[0018] S1: immersing the mesoporous bioceramic in a solution containing growth factors to obtain a mesoporous bioceramic encapsulating the growth factors;

[0019] S2: immersing the mesoporous bioceramic encapsulating the growth factor in a solution containing dopamine to obtain a drug-loaded mesoporous material;

[0020] S3: mixing the drug-loaded mesoporous material, the photo-crosslinked hydrogel and the crosslinking agent, and performing photocuring to obtain the antibacterial gel composite material.

[0021] Preferably, in step S1, the immersion temperature is 0 to 40°C, and the immersion time is 2 to 24 hours.

[0022] Preferably, in step S1, the solvent of the solution containing the growth factor is water.

[0023] Preferably, in step S1, the concentration of the growth factor in the growth factor-containing solution is 0.2-2 mg / mL.

[0024] Preferably, in step S1, the usage ratio of the mesoporous bioceramic to the solution containing the growth factor is (25-100) mg: 1 mL.

[0025] Preferably, in step S1, the encapsulation rate of the growth factor is 40-80%.

[0026] Preferably, in step S2, the concentration of dopamine in the dopamine-containing solution is 0.2-2 mg / mL.

[0027] Preferably, in step S2, the immersion time is 3 to 24 hours.

[0028] Preferably, in step S3, the light curing time is 10 s to 5 min.

[0029] Preferably, in step S3, the light curing is performed using blue light.

[0030] The third aspect of the present invention provides the use of the antibacterial gel composite material of the first aspect in the preparation of medical materials.

[0031] Preferably, the medical material is a medical material that promotes wound surface and / or tissue repair, or a medical dressing that promotes wound surface and / or tissue regeneration.

[0032] The beneficial effects of the present invention are:

[0033] (1) The present invention provides an antibacterial gel composite material, in which polydopamine is used to coat bioceramics, so that drugs, ion products in bioceramics and doped antibacterial ions can be released slowly with less burst release, thereby achieving stable release; in addition, by regulating the doping amount of antibacterial ions in bioceramics and the mass of drugs loaded in doped mesoporous bioceramics, the release curves of drugs and ions can be effectively regulated.

[0034] (2) The raw materials used in the antibacterial gel composite material of the present invention are hydrogel and bioceramics. The prepared antibacterial gel dressing is not only injectable and in-situ moldable, but also has good biocompatibility. Moreover, under the action of dopamine and bioceramics, the antibacterial ions and growth factors have good ion and drug release properties and can be used for wound repair and regeneration. The antibacterial gel composite material of the present invention can be used alone or in combination with medical bandages, gauze, elastic sleeves, tapes, adhesive plasters, adhesive stickers, adhesive plasters and other medical devices. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 The in vitro ion release performance of the materials prepared in the examples and comparative examples;

[0036] Figure 2 The in vitro ion release performance of the materials prepared in Example 3 and Comparative Example 3;

[0037] Figure 3 The in vitro drug release properties of the materials prepared in the examples and comparative examples are shown. DETAILED DESCRIPTION

[0038] The present invention is further described in detail below through specific examples. The raw materials used in the following examples, unless otherwise specified, can be obtained from conventional commercial sources or prepared and separated by simple synthesis; the processes used, unless otherwise specified, are conventional processes in the art.

[0039] Example 1

[0040] This embodiment provides an antibacterial gel composite material, and the preparation method thereof is as follows:

[0041] S1. At 0°C, 100 mg of copper-doped mesoporous magnesium silicate powder (copper molar ratio of 8.47%) was dispersed in 2 mL of an aqueous solution containing 2 mg of keratinocyte growth factor by magnetic stirring, stirred for 24 h, centrifuged and washed, and freeze-dried to obtain drug-loaded copper-doped mesoporous magnesium silicate;

[0042] S2, dispersing 100 mg of drug-loaded copper-doped mesoporous magnesium silicate in 10 mL of an aqueous solution containing dopamine (concentration of 1.5 mg / mL), stirring for 10 h, centrifuging, and washing to obtain sealed drug-loaded copper-doped mesoporous magnesium silicate;

[0043] S3. Add 100 mg of sealed copper-doped mesoporous magnesium silicate loaded with drugs to 3 mL of 66.67% methacryloyl hyaluronic acid, and continue stirring for 60 min to obtain a copper-doped mesoporous magnesium silicate slurry loaded with drugs. After injection, blue light is cured for 3 min to form an antibacterial gel composite material, i.e., a gel dressing.

[0044] Example 2

[0045] This embodiment provides an antibacterial gel composite material, and the preparation method thereof is as follows:

[0046] S1. At 40° C., 100 mg of silver-doped mesoporous silica powder (silver molar ratio of 0.51%) was dispersed in 12 ml of an aqueous solution containing 0.5 mg of fibroblast growth factor by ultrasonication, shaken on a shaker for 2 h, centrifuged and washed, and freeze-dried to obtain drug-loaded silver-doped mesoporous silica;

[0047] S2, dispersing 100 mg of drug-loaded silver-doped mesoporous silica in 15 mL of an aqueous solution containing dopamine (concentration of 0.8 mg / mL), stirring for 3 h, centrifuging, and washing to obtain sealed drug-loaded silver-doped mesoporous silica;

[0048] S3. Add 100 mg of sealed drug-loaded silver-doped mesoporous silica to 6 mL of 66.67% methacrylylated silk fibroin and continue stirring for 45 min to obtain drug-loaded silver-doped mesoporous silica slurry. After injection, blue light is cured for 1.5 min to form an antibacterial gel composite material, i.e., gel dressing.

[0049] Example 3

[0050] This embodiment provides an antibacterial gel composite material, and the preparation method thereof is as follows:

[0051] S1. At 4°C, 100 mg of silver-doped mesoporous bioglass powder (silver molar ratio of 1.46%) was dispersed in 1.5 mL of an aqueous solution containing 1 mg of vascular endothelial growth factor by magnetic stirring, stirred for 18 h, centrifuged and washed, and freeze-dried to obtain drug-loaded silver-doped mesoporous bioglass;

[0052] S2, dispersing 100 mg of drug-loaded silver-doped mesoporous bioglass in 8 mL of an aqueous solution containing dopamine (at a concentration of 1 mg / mL), stirring for 12 h, centrifuging, and washing to obtain sealed drug-loaded silver-doped mesoporous bioglass;

[0053] S3. Add 100 mg of sealed drug-loaded silver-doped mesoporous bioglass into 4 mL of 40% methacryloyl hyaluronic acid and continue stirring for 15 min to obtain drug-loaded silver-doped mesoporous bioglass slurry. After injection, blue light is cured for 2 min to form an antibacterial gel composite material, i.e., gel dressing.

[0054] Example 4

[0055] This embodiment provides an antibacterial gel composite material, and the preparation method thereof is as follows:

[0056] S1. At 37°C, 100 mg of zinc-doped mesoporous calcium silicate powder (zinc molar ratio of 15.67%) was dispersed in 10 mL of an aqueous solution containing 0.1 mg of epidermal growth factor by magnetic stirring, stirred for 4 h, centrifuged and washed, and freeze-dried to obtain drug-loaded zinc-doped mesoporous calcium silicate;

[0057] S2, dispersing 100 mg of drug-loaded zinc-doped mesoporous calcium silicate in 5 mL of an aqueous solution containing dopamine (concentration of 0.2 mg / mL), stirring for 24 h, centrifuging, and washing to obtain sealed drug-loaded zinc-doped mesoporous calcium silicate;

[0058] S3. Add 100 mg of sealed drug-loaded zinc-doped mesoporous calcium silicate into 12 mL of 12.5% ​​methacrylated gelatin and continue stirring for 30 min to obtain drug-loaded zinc-doped mesoporous calcium silicate slurry. After injection, blue light is cured for 0.5 min to form an antibacterial gel composite material, i.e., a gel dressing.

[0059] Example 5

[0060] This embodiment provides an antibacterial gel composite material, and the preparation method thereof is as follows:

[0061] S1. At 15°C, 100 mg of zinc-doped mesoporous bioglass powder (zinc molar ratio of 20.04%) was dispersed in 0.1 mL of an aqueous solution containing 2 ug of vascular endothelial growth factor by ultrasonication, shaken on a shaker for 5 h, centrifuged and washed, and freeze-dried to obtain drug-loaded zinc-doped mesoporous bioglass;

[0062] S2, dispersing 100 mg of drug-loaded zinc-doped mesoporous bioglass in 10 mL of an aqueous solution containing dopamine (concentration of 2 mg / mL), stirring for 3 h, centrifuging, and washing to obtain sealed drug-loaded zinc-doped mesoporous bioglass;

[0063] S3. Add 100 mg of sealed drug-loaded zinc-doped mesoporous bioglass into 1.5 mL of 12.5% ​​methacryloyl chondroitin sulfate, and continue stirring for 30 minutes to obtain drug-loaded zinc-doped mesoporous bioglass slurry. After injection, blue light is cured for 5 minutes to form an antibacterial gel composite material, i.e., gel dressing.

[0064] Comparative Example 1

[0065] This comparative example provides a gel composite material, and its preparation method is substantially the same as that of Example 3, except that no drug is loaded. The specific steps are as follows:

[0066] S1. Disperse 100 mg of silver-doped mesoporous bioglass (silver molar ratio of 1.46%) in 8 mL of an aqueous solution containing dopamine (concentration of 1 mg / mL), stir for 12 h, centrifuge, and wash to obtain sealed silver-doped mesoporous bioglass;

[0067] S2. Add 100 mg of sealed silver-doped mesoporous bioglass into 4 mL of 40% methacrylated hyaluronic acid and continue stirring for 15 min to obtain silver-doped mesoporous bioglass slurry. After injection, blue light is cured for 2 min to form a gel composite material.

[0068] Comparative Example 2

[0069] This comparative example provides a gel composite material, and its preparation method is substantially the same as that of Example 3, except that it does not contain doped mesoporous bioceramics. The specific steps are as follows:

[0070] S1. Disperse 1 mg of vascular endothelial growth factor in 8 mL of an aqueous solution containing dopamine (at a concentration of 1 mg / mL), stir for 12 h, centrifuge, and wash to obtain polydopamine-encapsulated vascular endothelial growth factor;

[0071] S2. Add 100 mg of polydopamine-encapsulated vascular endothelial growth factor into 4 mL of 40% methacryloyl hyaluronic acid and continue stirring for 15 min to obtain a drug-loaded slurry. After injection, blue light is cured for 2 min to form a gel composite material.

[0072] Comparative Example 3

[0073] This comparative example provides a gel composite material, and its preparation method is substantially the same as that of Example 3, except that: it does not contain polydopamine, and the mesoporous bioceramic is doped without sealing. The specific steps are as follows:

[0074] S1. At 4°C, 100 mg of silver-doped mesoporous bioglass powder (silver molar ratio of 1.46%) was dispersed in 1.5 mL of an aqueous solution containing 1 mg of vascular endothelial growth factor by magnetic stirring, stirred for 18 h, centrifuged and washed, and freeze-dried to obtain drug-loaded silver-doped mesoporous bioglass;

[0075] S2. Add 100 mg of drug-loaded silver-doped mesoporous bioglass into 4 mL of 40% methacryloyl hyaluronic acid and continue stirring for 15 min to obtain drug-loaded silver-doped mesoporous bioglass slurry. After injection, blue light is cured for 2 min to form a gel composite material.

[0076] Comparative Example 4

[0077] This comparative example provides a gel composite material, and its preparation method is substantially the same as that of Example 3, except that it does not contain drugs and doped mesoporous bioceramics. The specific steps are as follows:

[0078] 8 mg of dopamine was added to 4 mL of 40% methacryloyl hyaluronic acid and stirred for 15 min to obtain a gel slurry containing dopamine. After injection, the slurry was cured with blue light for 2 min to form a gel composite material.

[0079] Comparative Example 5

[0080] This comparative example provides a gel composite material, and its preparation method is substantially the same as that of Example 3, except that the mesoporous ceramic is not doped with silver ions. The specific steps are as follows:

[0081] S1. At 4°C, 100 mg of mesoporous bioglass powder was dispersed in 1.5 mL of an aqueous solution containing 1 mg of vascular endothelial growth factor by magnetic stirring, stirred for 18 h, centrifuged and washed, and freeze-dried to obtain drug-loaded mesoporous bioglass;

[0082] S2, dispersing 100 mg of drug-loaded mesoporous bioglass in 8 mL of an aqueous solution containing dopamine (at a concentration of 1 mg / mL), stirring for 12 h, centrifuging, and washing to obtain sealed drug-loaded mesoporous bioglass;

[0083] S3. Add 100 mg of sealed drug-loaded mesoporous bioglass into 4 mL of 40% methacryloyl hyaluronic acid and continue stirring for 15 min to obtain drug-loaded mesoporous bioglass slurry. After injection, blue light is cured for 2 min to form an antibacterial gel composite material, i.e., gel dressing.

[0084] Experimental analysis

[0085] The gel materials prepared in Examples 1-4 and Comparative Examples 1-3 were evaluated for their properties as follows: Figures 1 to 3 .

[0086] 1. In vitro cytotoxicity evaluation

[0087] The prepared gel was evaluated and scored according to the requirements of GB / T 16886.5.

[0088] L929 mouse fibroblasts that had been cultured for 24 hours and were growing vigorously were digested and prepared to a density of 1.0×10 5 100 μL / mL was inoculated in a 96-well plate. After the cells grew into a monolayer, the original culture medium was removed and 100 μL of the test sample extract, blank control solution, positive control solution and negative control solution were added respectively, with 6 replicates in each group. After the addition of samples, the 96-well plate was placed in a 37°C, 5% CO2 incubator for 24 hours.

[0089] After 24 hours of culture, the original culture medium was aspirated, and 50 μL of MTT (1 mg / mL) was added to each well. The culture was continued for 2 hours. After the end, the supernatant was aspirated and 100 μL of 99.5% pure isopropanol was added to dissolve the crystals; the absorbance value was measured on an ELISA instrument with 570 nm as the main absorption wavelength and 650 nm as the reference wavelength to calculate the cell survival rate.

[0090] The cell viability was calculated according to the following formula: Cell viability (%) = 100 × OD 570e / OD570 b

[0091] OD 570e It is the average optical density of the test sample or control sample extract.

[0092] OD 570b is the average optical density of the blank.

[0093] The experimental results are shown in Table 1:

[0094] Table 1 In vitro cell survival rate of the scaffolds prepared in the examples and comparative examples

[0095]

[0096] It can be seen from the in vitro cytotoxicity evaluation results of the examples and comparative examples (Table 1) that the composite gels prepared by the method of the present invention are non-cytotoxic.

[0097] 2. Hemolytic performance test

[0098] Blood was collected from the heart of healthy rabbits according to the amount of blood used in the experiment. For example, 10 mL of blood was collected, and 0.5 mL of potassium oxalate solution with a mass concentration of 20 g / L was added to prepare fresh anticoagulated rabbit blood. Take 8 mL of fresh anticoagulated rabbit blood and dilute it with 10 mL of sodium chloride injection with a mass concentration of 9 g / L. The test sample group was added with the test sample according to the extraction ratio, and then 10 mL of sodium chloride injection was added; 10 mL of sodium chloride was added to each tube of the negative control group; 10 mL of distilled water was added to each tube of the positive control group. Three tubes were operated in parallel for each group. After all the test tubes were placed in a constant temperature water bath at (37±1)℃ for 30 minutes, 0.2 mL of diluted rabbit blood was added to each test tube, gently mixed, and placed in a (37±1)℃ water bath for another 60 minutes. Pour out the liquid in the tube and centrifuge at 800g for 5 minutes. Aspirate the supernatant and transfer it to a cuvette, and measure the absorbance at a wavelength of 545 nm using a spectrophotometer. The absorbance of the test group and the control group is the average value of the three tubes. The absorbance of the negative control tube should not be greater than 0.03; the absorbance of the positive control tube should be 0.8±0.3, otherwise the test should be repeated. Calculate according to the following formula:

[0099]

[0100] The experimental results are shown in Table 2:

[0101] Table 2 Hemolysis rate of materials obtained in Examples and Comparative Examples

[0102]

[0103]

[0104] From the hemolysis rate evaluation results of the examples and comparative examples (Table 2), it can be seen that the hemolysis rate of the hydrogel prepared by the method of the present invention is less than 5%, and there is no hemolysis risk.

[0105] 3. Ion release performance test

[0106] 30 mg of the composite gel prepared in Examples 1-5 and Comparative Examples 1 and 3 was placed in 15 mL of simulated body fluid and incubated on a shaker at 37°C and 120 rpm for 0 min, 30 min, 12 h, 1 d, 3 d, 5 d, and 7 d. The supernatant was collected at different time periods, and the concentration of antibacterial metal ions in the SBF solution collected at each time point was detected by inductively coupled plasma optical emission spectrometry (ICP-OES).

[0107] The in vitro ion release results of the materials prepared in the examples and comparative examples are as follows: Figure 1 and Figure 2 As shown, the materials can continuously release Ag + , Cu 2+ 、Zn 2+ , indicating that all materials have antibacterial potential. Figure 2 It is shown that the use of polydopamine to coat drug-loaded mesoporous materials can slowly release drugs, ion products in bioceramics and doped antibacterial ions.

[0108] 4. In vitro drug release performance test

[0109] The composite gels prepared in Examples 1-5 and Comparative Examples 2-4 were evaluated for in vitro solute release. The evaluation method was as follows: the in vitro solute release experiment was conducted in a constant temperature shaker at 37°C and 60rpm. 500 mg of the scaffold was immersed in 200 mL of PBS (pH = 7.4), the test solution was collected regularly, and an equal amount of PBS was supplemented. The collected test solution was measured for solute content by high performance liquid chromatography (HPLC). The absorbance of the solute at a certain time point was substituted into its standard curve to obtain the actual amount of solute released at this time point. The actual amount was divided by the total amount of solute loaded in the material to obtain the cumulative release of the solute at this time point.

[0110] The in vitro drug release performance test results are as follows Figure 3As shown, compared with Example 3, Comparative Example 2 does not contain silver-doped mesoporous bioglass, and the drug is loaded in the hydrogel after being wrapped by polydopamine, and its burst release is the highest and the drug release period is the shortest; compared with Example 3, the silver-doped mesoporous bioglass in Comparative Example 3 is not sealed, and its burst release and drug release period are between Example 3 and Comparative Example 2; the mesoporous ceramics in Comparative Example 5 are not doped with silver ions, and its burst release is higher than that in Example 3; it shows that loading drugs in silver-doped mesoporous bioglass and using polydopamine for sealing can effectively improve drug release performance, reduce burst release, and prolong drug release period.

[0111] The above is a preferred embodiment of the present invention. It should be pointed out that a person skilled in the art can make several improvements and modifications without departing from the principle of the present invention. These improvements and modifications are also considered to be within the scope of protection of the present invention.

Claims

1. An antibacterial gel composite material, characterized in that: It comprises a photo-crosslinked hydrogel, wherein the photo-crosslinked hydrogel is wrapped with a drug-loaded mesoporous material; the drug-loaded mesoporous material comprises polydopamine, a mesoporous bioceramic and a growth factor arranged in sequence; the surface of the mesoporous bioceramic is coated with polydopamine; the growth factor is encapsulated in the mesoporous bioceramic; and the mesoporous bioceramic is doped with metal ions having an antibacterial effect.

2. The antibacterial gel composite material according to claim 1, characterized in that: The photo-crosslinked hydrogel is a methacrylated hydrogel, and the methacrylated hydrogel is selected from at least one of methacrylated hyaluronic acid, methacrylated silk fibroin, methacrylated chondroitin sulfate, methacrylated chitosan, and methacrylated gelatin; And / or, the mesoporous bioceramic is selected from at least one of mesoporous silicon, mesoporous calcium silicate, mesoporous magnesium silicate and mesoporous bioglass.

3. The antibacterial gel composite material according to claim 1, characterized in that: The growth factor is selected from at least one of vascular endothelial growth factor, epidermal cell growth factor, fibroblast growth factor, keratinocyte growth factor and nerve growth factor; And / or, the metal ions having antibacterial effect are selected from at least one of silver ions, copper ions, iron ions, zinc ions, mercury ions, gallium ions and lead ions.

4. The antibacterial gel composite material according to claim 1, characterized in that: The mass ratio of the mesoporous bioceramic to the growth factor is 1:(0.0002-0.02); And / or, the molar percentage of the metal ions with antibacterial effect in the mesoporous bioceramic is 0.5-20%.

5. The antibacterial gel composite material according to claim 1, characterized in that: The mass ratio of the mesoporous bioceramic to dopamine is 1:(0.01-0.2); And / or, the mass ratio of the mesoporous bioceramic to the photo-crosslinked hydrogel is 1:(1.2-20).

6. The method for preparing the antibacterial gel composite material according to claims 1 to 5, characterized in that: The steps include: S1: immersing the mesoporous bioceramic in a solution containing growth factors to obtain a mesoporous bioceramic encapsulating the growth factors; S2: immersing the mesoporous bioceramic encapsulating the growth factor in a solution containing dopamine to obtain a drug-loaded mesoporous material; S3: mixing the drug-loaded mesoporous material, the photo-crosslinked hydrogel and the crosslinking agent, and performing photocuring to obtain the antibacterial gel composite material.

7. The method for preparing the antibacterial gel composite material according to claim 6, characterized in that: In step S1, the immersion temperature is 0 to 40°C, and the immersion time is 2 to 24 hours.

8. The method for preparing the antibacterial gel composite material according to claim 6, characterized in that: In step S2, the concentration of dopamine in the dopamine-containing solution is 0.2-2 mg / mL.

9. The method for preparing the antibacterial gel composite material according to claim 6, characterized in that: In step S3, the light curing time is 10 seconds to 5 minutes.

10. Use of the antibacterial gel composite material according to any one of claims 1 to 5 in the preparation of medical materials.

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