An asymmetric porous bilayer composite hydrogel, its preparation method and application

Abstract

This invention relates to an asymmetric porous bilayer composite hydrogel, its preparation method, and its applications, belonging to the field of medical materials technology. Specifically, the asymmetric porous bilayer composite hydrogel provided by this invention comprises a polyvinyl alcohol (PVA) hydrogel layer and an activated carbon / PVA composite hydrogel layer. The asymmetric porous bilayer composite hydrogel has a bi-asymmetric structure; the dense porous surface formed by the PVA hydrogel prevents tissue adhesion, while the loose porous surface formed by the activated carbon / PVA composite hydrogel promotes the repair of abdominal wall defects. More importantly, by introducing activated carbon into the PVA hydrogel system, reactive oxygen species (ROS) can be effectively adsorbed, simultaneously improving the cell adhesion and anti-swelling properties of the asymmetric porous bilayer composite hydrogel, further promoting tissue repair.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of surgical biomaterials, and more particularly to an asymmetric porous double-layer composite hydrogel and a preparation method and application thereof. BACKGROUND

[0002] Abdominal wall defect is a common disease, and tension-free repair based on high molecular materials is the main treatment method. At present, synthetic patches based on polypropylene and polyester are widely used in abdominal wall defect repair due to their high mechanical strength and anti-deformation advantages. However, up to 30% of abdominal wall defect patients are complicated with local pollution / infection, and synthetic patches implanted in the contaminated area can induce severe foreign body reactions. Biological patches have become the first choice for repairing contaminated abdominal wall defects due to their excellent biocompatibility and pollution resistance. Unfortunately, the existing biological patches will rapidly degrade in the body and lose their mechanical properties, which cannot provide biocompatible long-term mechanical support for abdominal wall defect reconstruction, resulting in a high recurrence rate and often requiring secondary surgery using synthetic patches to effectively reconstruct the abdominal wall. Therefore, how to reduce the foreign body reaction of high molecular materials has been a bottleneck problem in the field of abdominal wall defect repair.

[0003] Hydrogel materials are most likely to be developed for abdominal wall defect repair materials due to their good biocompatibility and functional diversity. Among them, polyvinyl alcohol (PVA) is a synthetic water-soluble polymer. The polyvinyl alcohol hydrogel formed by freeze-thaw method has good biocompatibility, excellent stability and physical and mechanical properties, and is widely used in postoperative anti-adhesion, wound repair and other biomedical application fields. Porous carbon materials are widely used in drug loading, adsorption and other biomedical fields due to their good compatibility and high specific surface area, but they have not been applied to abdominal wall defect repair materials. Although some related inventions have used hydrogel materials for abdominal wall defect repair, especially hydrogels with asymmetric porous structure have been proven to have excellent abdominal wall defect repair effect. However, most of the hydrogel materials have complex preparation process, solvent or impurity residues are difficult to remove, and are difficult to mass-produce, and even have the risk of inducing severe foreign body reactions; some hydrogel materials also add antibacterial / anti-inflammatory ingredients, which inevitably have certain biological toxicity, and the diversity and complexity of drug-device combination products also increase the difficulty and uncertainty of transformation. Therefore, it is still a great challenge to introduce porous carbon materials into hydrogels and develop a green and economical asymmetric porous composite hydrogel preparation method that is easy to mass-produce. SUMMARY

[0004] The purpose of the present application is to overcome the deficiencies in the prior art and provide an asymmetric porous double-layer composite hydrogel and a preparation method and application thereof.

[0005] In order to achieve the above object, the technical scheme adopted by the present application is to provide an asymmetric porous double-layer composite hydrogel, which comprises a first hydrogel layer and a second hydrogel layer, the first hydrogel layer is a polyvinyl alcohol hydrogel layer, and the second hydrogel layer is an activated carbon / polyvinyl alcohol composite hydrogel layer.

[0006] The asymmetric porous double-layer composite hydrogel has a double-sided asymmetric structure, comprising a loose porous surface and a dense porous surface.

[0007] In the technical scheme, the asymmetric porous double-layer composite hydrogel adopts a polyvinyl alcohol hydrogel system, which ensures the biocompatibility and good mechanical properties of the composite hydrogel as a whole; further, the asymmetric porous double-layer composite hydrogel comprises a polyvinyl alcohol hydrogel layer and an activated carbon / polyvinyl alcohol composite hydrogel layer, the polyvinyl alcohol hydrogel layer provides a dense porous surface, which ensures good biocompatibility, excellent stability and mechanical properties when used as a biomedical material, and avoids postoperative adhesion and other problems; at the same time, the activated carbon / polyvinyl alcohol composite hydrogel layer provides a loose porous surface, which effectively promotes cell proliferation and adhesion, and the introduction of activated carbon can effectively remove ROS and improve the anti-swelling properties of the hydrogel.

[0008] Another object of the present application is to provide a preparation method of the asymmetric porous double-layer composite hydrogel, comprising the following steps:

[0009] (1) dissolving polyvinyl alcohol in water to obtain a polyvinyl alcohol aqueous solution;

[0010] (2) adding activated carbon to the polyvinyl alcohol aqueous solution and stirring to mix uniformly, and then freezing to obtain an activated carbon / polyvinyl alcohol composite hydrogel;

[0011] (3) placing the activated carbon / polyvinyl alcohol composite hydrogel prepared in step (2) to melt, uniformly scraping polyvinyl alcohol aqueous solution on the surface of the melted activated carbon / polyvinyl alcohol composite hydrogel, and then placing to level, then repeating the freezing-melting treatment of the activated carbon / polyvinyl alcohol composite hydrogel with the surface uniformly scraped with polyvinyl alcohol aqueous solution, and then freeze-drying and rehydrating in a phosphate buffer to obtain the asymmetric porous double-layer composite hydrogel.

[0012] Preferably, the polyvinyl alcohol used in the technical scheme has a polymerization degree ranging from 1700 to 4500 and an alcoholysis degree ranging from 97% to 99%.

[0013] Further preferably, the polyvinyl alcohol has a polymerization degree of 1700 and an alcoholysis degree of 99%.

[0014] Further, in the step (1), the mass fraction of the polyvinyl alcohol aqueous solution is 5% to 15%.

[0015] Further, in the step (2), the mass ratio of the activated carbon to the polyvinyl alcohol aqueous solution is (0.5-2):100.

[0016] Further, in the step (3), the mass ratio of the scraped polyvinyl alcohol aqueous solution to the activated carbon / polyvinyl alcohol composite hydrogel is 1:(3-4).

[0017] Further, in the step (1), the polyvinyl alcohol aqueous solution is prepared by stirring and mixing uniformly at 90-100 ℃.

[0018] Further, in the step (2), the mesh number of the activated carbon is 100-400 meshes; and the step of stirring and mixing uniformly is stirring at a speed of 10,000-13,000 r / min for 10-20 min.

[0019] Preferably, in the step (2), the activated carbon / polyvinyl alcohol composite hydrogel is prepared by freezing at-30--10 ℃ for 10-16 h.

[0020] Preferably, in the step (3), the activated carbon / polyvinyl alcohol composite hydrogel prepared in the step (2) is thawed at 20-30 ℃ for 1-3 h, the polyvinyl alcohol aqueous solution is uniformly scraped on the surface of the thawed activated carbon / polyvinyl alcohol composite hydrogel, the surface of the activated carbon / polyvinyl alcohol composite hydrogel with the uniformly scraped polyvinyl alcohol aqueous solution is placed at-30--10 ℃ for 10-16 h, and then thawed at 20-30 ℃ for 1-3 h, the freezing-thawing step is repeated for 3-5 times, and then the asymmetric porous double-layer composite hydrogel is prepared by freeze-drying for 22-26 h, rehydrating in a phosphate buffer at 20-35 ℃.

[0021] Preferably, in the step (3), the polyvinyl alcohol aqueous solution uniformly scraped on the surface of the activated carbon / polyvinyl alcohol composite hydrogel has a mass fraction of 5%-15%.

[0022] Still another purpose of the present application is to provide an asymmetric porous double-layer composite hydrogel prepared by the preparation method of the asymmetric porous double-layer composite hydrogel.

[0023] Still another purpose of the present application is to provide the application of the asymmetric porous double-layer composite hydrogel in biomedical materials.

[0024] Preferably, the present application further provides the application of the asymmetric porous double-layer composite hydrogel in soft tissue defect repair patches, and the soft tissue includes heart, intestine, artery, lung, stomach, peritoneum, liver and kidney, etc.

[0025] Compared with the prior art, the present application has the following beneficial effects:

[0026] (1) The present application provides an asymmetric porous double-layer composite hydrogel, which adopts a polyvinyl alcohol hydrogel system to ensure the overall biocompatibility and good mechanical properties of the composite hydrogel; further, the asymmetric porous double-layer composite hydrogel comprises a polyvinyl alcohol hydrogel layer and an activated carbon / polyvinyl alcohol composite hydrogel layer, the polyvinyl alcohol hydrogel layer provides a dense porous surface, which ensures good biocompatibility, excellent stability and mechanical properties when used as a biomedical material, and avoids postoperative adhesion and other problems; at the same time, the activated carbon / polyvinyl alcohol composite hydrogel layer provides a loose porous surface, which effectively promotes cell proliferation and adhesion, and the introduction of activated carbon can effectively remove ROS and improve the anti-swelling properties of the hydrogel.

[0027] (2) The present application also provides a preparation method of the asymmetric porous double-layer composite hydrogel, which comprises uniformly mixing activated carbon and a polyvinyl alcohol aqueous solution, freezing to obtain an activated carbon / polyvinyl alcohol composite hydrogel, uniformly coating a polyvinyl alcohol aqueous solution on the obtained activated carbon / polyvinyl alcohol composite hydrogel, and further preparing the asymmetric porous double-layer composite hydrogel by using a freeze-thaw method, which is simple, efficient, economical, easy to mass-produce and has good application prospects. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 A scanning electron microscope image of the asymmetric porous double-layer composite hydrogel PVA / PVA-AC10 prepared in Example 2;

[0029] Figure 2 A swelling rate curve of the asymmetric porous double-layer composite hydrogels PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 prepared in Examples 1-3;

[0030] Figure 3 A ROS removal curve of the asymmetric porous double-layer composite hydrogels PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 prepared in Examples 1-3;

[0031] Figure 4 A cell compatibility diagram of the asymmetric porous double-layer composite hydrogels PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 prepared in Examples 1-3;

[0032] Figure 5 A cell adhesion fluorescence diagram of the asymmetric porous double-layer composite hydrogel PVA / PVA-AC10 prepared in Example 2;

[0033] Figure 6 Figure 1 shows the repair of a rat abdominal wall defect using the asymmetric porous double-layer composite hydrogel PVA / PVA-AC10 prepared in Example 2. DETAILED DESCRIPTION

[0034] It should be noted that the following detailed description is merely exemplary and is intended to provide further description of the application. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0035] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments in accordance with the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising," when used in this specification, specify the presence of stated features, steps, operations, elements, components, and / or groups thereof, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof.

[0036] The application will be further described with reference to the following examples without however, such examples constraining the application in any way. The test samples and test procedures used in the following examples include the following (if the specific conditions of the experiment are not marked in the examples, the general conditions are usually used, or the conditions recommended by the reagent company; the reagents, consumables, etc. used in the following examples can be obtained from commercial channels if not specifically stated).

[0037] Example 1

[0038] The present embodiment provides a preparation method of an asymmetric porous double-layer composite hydrogel, comprising the following steps:

[0039] (1) 10 g of polyvinyl alcohol was added to 90 g of water, and stirred and mixed uniformly at 90-100 °C to obtain a 10% polyvinyl alcohol aqueous solution;

[0040] (2) 0.25 g of medicinal activated carbon was mixed with 50 g of the 10% polyvinyl alcohol aqueous solution under high-speed stirring at 12000 rpm for 15 min, poured into a mold, and frozen at -20 °C for 12 h to obtain an activated carbon / polyvinyl alcohol composite hydrogel PVA-AC5;

[0041] (3) melt 3 g of the activated carbon / polyvinyl alcohol composite hydrogel PVA-AC5 at 20-30 °C for 1-3 h, uniformly scrape coat 1 g of 10% polyvinyl alcohol aqueous solution on the surface of the activated carbon / polyvinyl alcohol composite hydrogel, level, freeze at -20 °C for 12 h, then melt at 25 °C for 2 h, repeat the freezing-melting step for 5 times, then freeze dry for 24 h, rehydrate in the phosphate buffer at 20-35 °C, to obtain the asymmetric porous double-layer composite hydrogel PVA / PVA-AC5.

[0042] Example 2

[0043] The present embodiment is a preferred embodiment, and also provides a preparation method of an asymmetric porous double-layer composite hydrogel, comprising the following steps:

[0044] (1) add 10 g of polyvinyl alcohol into 90 g of water, mix uniformly at 90-100 °C under stirring, to obtain a 10% polyvinyl alcohol aqueous solution;

[0045] (2) mix 0.5 g of medicinal activated carbon with 50 g of the 10% polyvinyl alcohol aqueous solution under high-speed stirring at 12000 rpm for 15 min, pour into a mold, freeze at -20 °C for 12 h, to obtain an activated carbon / polyvinyl alcohol composite hydrogel PVA-AC10;

[0046] (3) melt 3 g of the activated carbon / polyvinyl alcohol composite hydrogel PVA-AC10 at 20-30 °C for 1-3 h, uniformly scrape coat 1 g of 10% polyvinyl alcohol aqueous solution on the surface of the activated carbon / polyvinyl alcohol composite hydrogel, level, freeze at -20 °C for 12 h, then melt at 25 °C for 2 h, repeat the freezing-melting step for 5 times, then freeze dry for 24 h, rehydrate in the phosphate buffer at 20-35 °C, to obtain the asymmetric porous double-layer composite hydrogel PVA / PVA-AC10.

[0047] Example 3

[0048] The present embodiment provides a preparation method of an asymmetric porous double-layer composite hydrogel, comprising the following steps:

[0049] (1) add 10 g of polyvinyl alcohol into 90 g of water, mix uniformly at 90-100 °C under stirring, to obtain a 10% polyvinyl alcohol aqueous solution;

[0050] (2) mix 0.5 g of medicinal activated carbon with 50 g of the 10% polyvinyl alcohol aqueous solution under high-speed stirring at 12000 rpm for 15 min, pour into a mold, freeze at -20 °C for 12 h, to obtain an activated carbon / polyvinyl alcohol composite hydrogel PVA-AC10;

[0051] (3) Melt 3 g of activated carbon / polyvinyl alcohol composite hydrogel PVA-AC20 at 20~30 ℃ for 1~3 h, then uniformly coat 1 g of 10% polyvinyl alcohol aqueous solution on the surface of activated carbon / polyvinyl alcohol composite hydrogel, let it stand and level, freeze at -20 ℃ for 12 h and then melt at 25 ℃ for 2 h, repeat the freeze-thaw step 5 times, then freeze dry for 24 h and rehydrate in phosphate buffer at 20~35 ℃ to obtain asymmetric porous bilayer composite hydrogel PVA / PVA-AC20.

[0052] Comparative Example 1

[0053] This comparative example provides a method for preparing a PVA composite hydrogel, comprising the following steps:

[0054] (1) Add 10 g of polyvinyl alcohol to 90 g of water and stir and mix evenly at 90~100 °C to obtain a 10% polyvinyl alcohol aqueous solution;

[0055] (2) Mix 50 g of 10% polyvinyl alcohol aqueous solution at 12000 rpm for 15 min, pour into a mold, and freeze at -20 ℃ for 12 h to obtain PVA hydrogel;

[0056] (3) Melt 3 g of PVA hydrogel at 20~30 ℃ for 1~3 h, then evenly coat 1 g of 10% polyvinyl alcohol aqueous solution on the surface of PVA hydrogel, let it stand and level, freeze at -20 ℃ for 12 h and then melt at 25 ℃ for 2 h. Repeat the freeze-thaw step 5 times, then freeze dry for 24 h and rehydrate in phosphate buffer at 20~35 ℃ to obtain PVA composite hydrogel.

[0057] To better illustrate the technical effects of this application, the PVA composite hydrogel prepared in Comparative Example 1, and the PVA / PVA-AC5, PVA / PVA-AC10, and PVA / PVA-AC20 prepared in Examples 1-3 were subjected to morphological characterization, swelling rate experiment, in vitro ROS scavenging experiment, cell compatibility experiment, cell adhesion experiment, and animal experiment.

[0058] Example 1

[0059] This example uses scanning electron microscopy to characterize the morphology of PVA / PVA-AC10 prepared in Example 2, and the results are as follows: Figure 1 As shown. According to Figure 1 It can be seen that PVA / PVA-AC10 has a double-sided asymmetric structure. The dense porous surface is dense and smooth with a pore size distribution of 0.5-2 μm, while the loose porous surface is loose and porous with a pore size greater than 10 μm.

[0060] Example 2

[0061] The swelling rate of PVA composite hydrogel prepared in Comparative Example 1, PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 prepared in Examples 1-3 was measured by using the weighing method. The specific test method was as follows: PVA, PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 were divided into 4 groups, each group had 4 samples, after rehydrating in PBS for 24 hours, the surface water was wiped off, the wet mass of the sample was weighed and recorded as w0, ultraviolet sterilization was performed for 30 minutes, and the operation was performed in a super-clean bench, 3 mL of PBS buffer was added to each sample, and the sample was placed in a 37 ℃ shaking bed, and the sample was taken out at 7, 14, 21 and 28 days, the surface water was wiped off, and the weight was weighed and recorded as w t . The swelling rate was recorded as Δw, which was calculated according to the following formula.

[0062]

[0063] The results are shown in Figure 2 The introduction of activated carbon can improve the anti-swelling performance of PVA hydrogel, and the higher the content of activated carbon, the lower the swelling rate of the hydrogel.

[0064] Effect Example 3

[0065] In this effect example, PVA composite hydrogel prepared in Comparative Example 1, PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 prepared in Examples 1-3 were subjected to in vitro ROS removal experiment. The specific test method was as follows: 15 mm*15 mm*1 mm PVA, PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 were immersed in 2 mL DPPH ethanol solution, and the solution was shaken in the dark (120 rpm, 37 ℃). After a predetermined time, the absorbance at 515 nm was measured by ultraviolet-visible spectrometer. The DPPH removal efficiency of the sample was calculated according to the formula.

[0066]

[0067] The results are shown in Figure 3 PVA / PVA-AC10 and PVA / PVA-AC20 have excellent DPPH adsorption performance, and the removal efficiency of DPPH in 48 hours is more than 90%.

[0068] Effect Example 4

[0069] The effect example carries out cell compatibility experiment to commercial PCO patch (Kewei), PVA composite hydrogel prepared in Comparative Example 1, PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 prepared in Examples 1-3. The specific test method is: after PCO, PVA, PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 are co-cultured with L929 fibroblasts for 1, 2, 3 days, the proliferation activity is detected by CCK-8 method.

[0070] The results are shown in Figure 4 As shown, the cell growth trend of each group is good, and there is no significant difference among each group at 1, 2, 3 days. It is proved that PVA / PVA-AC5, PVA / PVA-AC10 and PVA / PVA-AC20 do not affect the proliferation activity of cells, and have good cell compatibility.

[0071] Effect Example 5

[0072] The effect example carries out cell adhesion experiment to commercial PCO patch (Kewei), PVA composite hydrogel prepared in Comparative Example 1, PVA / PVA-AC10 prepared in Example 2. The specific test method is: PCO collagen surface, PVA dense porous surface and loose porous surface, PVA / PVA-AC10 dense porous surface and loose porous surface are set as 4 groups of parallel experiments, the samples are sterilized by ultraviolet lamp irradiation for 1 h and then placed in the hole plate, then 4 x 10 5 The density of cells per hole is that L929 mouse fibroblasts are inoculated on the sample, the hole plate is placed in a 37 ℃, 5% carbon dioxide incubator for static culture for 48 h, then the culture medium is removed and washed with PBS for 3 times, Calcein AM live and dead fluorescent dye is added for incubation in dark for 15 min, the cell adhesion is observed and photographed under an inverted fluorescence microscope.

[0073] The results are shown in Figure 5 As shown, PCO collagen surface, PVA dense porous surface and PVA / PVA-AC10 dense porous surface have only a small amount of cell adhesion, showing good cell adhesion prevention performance; while PVA / PVA-AC10 loose porous surface has more cell adhesion than PVA loose porous surface, indicating that the introduction of activated carbon has good promotion effect on cell proliferation and adhesion.

[0074] Effect Example 6

[0075] The effect example carries commercial PP patch (Zhonghui Xixi), commercial PCO patch (Ke Hui), PVA composite hydrogel prepared in Comparative Example 1, PVA / PVA-AC10 prepared in Example 2 to animal experiment. The specific test method is: construct rat abdominal wall defect animal model, all rats are anesthetized by intraperitoneal injection of sodium pentobarbital in the anesthesia room, under aseptic surgical technique, a circular defect with a diameter of 1 cm is formed in the middle of the abdominal wall by a standard biopsy punch. The peritoneum and full-thickness abdominal wall muscle are excised, but the skin is completely reserved, the PP patch, the PCO patch, the PVA hydrogel and the PVA / PVA-AC10 hydrogel are respectively sutured to repair the defect, and then the wound is sutured. On the 10th day and the 28th day after the operation, the animals are humanely euthanized according to the relevant requirements. After the skin is peeled off, the suture line is reopened, the repaired site is exposed, and the formation of adhesion and the results of defect healing are evaluated.

[0076] The results are shown in Table 1. Figure 6 As shown in Table 1, the PVA / PVA-AC10 has good anti-visceral adhesion effect, which is better than the commonly used PP patch and PCO patch in clinic.

[0077] Obviously, the above embodiments of the present application are only examples for clearly illustrating the technical solutions of the present application, and are not intended to limit the specific embodiments of the present application. Any modification, equivalent replacement and improvement made within the spirit and principle of the present application should be included in the protection scope of the present application.

Claims

1. A method for preparing an asymmetric porous double-layer composite hydrogel, characterized in that: The asymmetric porous double-layer composite hydrogel comprises a first hydrogel layer and a second hydrogel layer, the first hydrogel layer is a polyvinyl alcohol hydrogel layer, and the second hydrogel layer is an activated carbon / polyvinyl alcohol composite hydrogel layer. The asymmetric porous double-layer composite hydrogel has a double-face asymmetric structure, comprising a loose porous face and a dense porous face. The preparation process comprises the following steps: (1) dissolving polyvinyl alcohol in water, stirring and mixing to obtain a polyvinyl alcohol aqueous solution; (2) adding activated carbon into the polyvinyl alcohol aqueous solution and stirring and mixing uniformly, and then freezing to obtain an activated carbon / polyvinyl alcohol composite hydrogel; (3) placing the activated carbon / polyvinyl alcohol composite hydrogel prepared in step (2) to be melted, uniformly scraping the polyvinyl alcohol aqueous solution obtained in step (1) on the surface of the melted activated carbon / polyvinyl alcohol composite hydrogel, and then placing the activated carbon / polyvinyl alcohol composite hydrogel with the surface uniformly scraped with the polyvinyl alcohol aqueous solution to be repeatedly frozen-melted, and then freeze-drying and rehydrating in a phosphate buffer to obtain the asymmetric porous double-layer composite hydrogel. In step (2), the mesh number of the activated carbon is 100-400.

2. The method of claim 1, wherein the asymmetric porous double-layer composite hydrogel is prepared by the steps of: In step (1), the mass fraction of the polyvinyl alcohol aqueous solution is 5%-15%.

3. The method of claim 1, wherein the asymmetric porous double-layer composite hydrogel is prepared by the steps of: In step (2), the mass ratio of the activated carbon to the polyvinyl alcohol aqueous solution is (0.5-2):

100.

4. The method of claim 1, wherein the asymmetric porous double-layer composite hydrogel is prepared by the steps of: In step (3), the mass ratio of the scraped polyvinyl alcohol aqueous solution to the activated carbon / polyvinyl alcohol composite hydrogel is 1:(3-4).

5. The method for preparing an asymmetric porous double-layer composite hydrogel according to any one of claims 1-4, characterized in that, In step (1), the polyvinyl alcohol aqueous solution is prepared by stirring and mixing at 90-100 ℃.

6. The method of preparing an asymmetric porous double-layer composite hydrogel according to any one of claims 1-4, characterized in that, In step (2), the stirring and mixing uniformly is performed by stirring at a speed of 10,000-13,000 r / min for 10-20 min.

7. The method of preparing an asymmetric porous double-layer composite hydrogel according to any one of claims 1-4, characterized in that, In step (2), the activated carbon / polyvinyl alcohol composite hydrogel is prepared by freezing at-30--10 ℃ for 10-16 h.

8. The method of preparing an asymmetric porous double-layer composite hydrogel according to any one of claims 1-4, characterized in that, In step (3), the activated carbon / polyvinyl alcohol composite hydrogel prepared in step (2) is melted at 20-30 ℃ for 1-3 h, the polyvinyl alcohol aqueous solution is uniformly scraped on the surface of the melted activated carbon / polyvinyl alcohol composite hydrogel, and then the activated carbon / polyvinyl alcohol composite hydrogel with the surface uniformly scraped with the polyvinyl alcohol aqueous solution is placed at-30--10 ℃ to be frozen for 10-16 h, and then melted at 20-30 ℃ for 1-3 h, and the freezing-melting step is repeated for 3-5 times, and then freeze-drying is continued for 22-26 h, and then rehydrating in a phosphate buffer at 20-35 ℃ to prepare the asymmetric porous double-layer composite hydrogel.

9. The asymmetric porous double-layer composite hydrogel prepared by the preparation method according to any one of claims 1-8 is used for preparing a soft tissue defect repair patch.

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