A reusable dual-network zwitterionic hydrogel adhesive and methods of making and using the same
The dual-network hydrogel adhesive formed by gelatin and zwitterionic monomers overcomes the shortcomings of hydrogels in terms of mechanical strength, toughness, antibacterial properties, and reusability, achieving high strength, antibacterial properties, and reusability, making it suitable for wound dressings in the biomedical field.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-05-30
- Publication Date
- 2026-03-24
AI Technical Summary
Existing hydrogel materials have shortcomings in mechanical strength, toughness, antibacterial ability, and reusability, which limits their application in the biomedical field.
A high-mechanical-strength antibacterial hydrogel adhesive was prepared by forming a dual-network structure using gelatin and zwitterionic monomers, and by physical cross-linking and interpenetration of copolymer networks. The properties of the gelatin network and zwitterionic monomers were utilized to improve the biocompatibility and reusability of the material.
It achieves high peel strength, good biocompatibility, antibacterial properties and reusability, and can effectively adhere to various substrates, promoting wound healing and inhibiting bacterial growth.
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Figure CN116425927B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application belongs to the technical field of biomedical materials, and particularly relates to a reusable double-network zwitterionic hydrogel adhesive as well as a preparation method and application thereof. BACKGROUND
[0002] Polymeric hydrogels have been widely used in wastewater treatment, agriculture and food chemistry, tissue scaffolds, drug delivery systems, biosensors and other fields. However, most polymeric hydrogels lack outstanding mechanical strength and toughness, and have limited recovery ability, which greatly limits their applications. Therefore, many people have devoted themselves to solving these problems. At present, many new tough hydrogels have been developed, such as topological hydrogels, double-network hydrogels and nanocomposite hydrogels.
[0003] Among these tough hydrogels, double-network hydrogels have become a powerful candidate for artificial connective tissue, which plays a major biomechanical role in the body and biosensors as well as wound dressings. Generally, double-network gels are composed of two networks with different physical properties, in which the first network is rigid and easily broken to dissipate energy, thereby improving the strength, while the second network is flexible to improve the tensile properties of the hydrogel and achieve a balance between stiffness and toughness.
[0004] The dipolarity of zwitterionic molecules enables zwitterionic hydrogels to establish good adhesion on many surfaces through ionic-dipole or dipole-dipole interactions and the ionic dipole and dipole-dipole interactions of the adherend, repeatedly adhering to various substrates. Zwitterionic polymers have hydrophilic anion and cation groups that can be highly hydrated, thereby having unique anti-biofouling properties. This feature makes such materials increasingly applied in the field of biomedicine and other related fields. SUMMARY
[0005] In view of the deficiencies of the prior art, the present application provides a reusable double-network zwitterionic hydrogel adhesive as well as a preparation method and application thereof, which solves the problems of high cytotoxicity, weak mechanical strength, limited antibacterial ability and non-reusability of the hydrogel in the prior art. The present application takes gelatin and zwitterionic monomers as main raw materials, and forms a high-mechanical-strength antibacterial hydrogel adhesive through physical crosslinking of the first layer of gelatin and interpenetration of the copolymer network formed by the second layer of zwitterionic monomers and acrylic acid monomers.
[0006] In order to solve the problems of the prior art, the technical scheme adopted by the present application is as follows:
[0007] The reusable double network zwitterionic hydrogel adhesive comprises the following components in mass fraction: gelatin 2-15%, zwitterionic monomer 20-30%, acrylic monomer 5-15%, initiator 0.1-1%, crosslinking agent 0.1-1%, and the rest is deionized water.
[0008] As an improvement, the zwitterionic monomer is a compound with positive and negative charge dipoles and is electrically neutral.
[0009] As an improvement, the zwitterionic monomer is one of 2-methacryloyloxyethyl phosphorylcholine, methacryloyl ethyl sulfobetaine, or carboxybetaine methyl methacrylate.
[0010] As an improvement, the acrylic monomer is zinc methacrylate.
[0011] As an improvement, the initiator is one of potassium persulfate, ammonium persulfate or cumene hydroperoxide.
[0012] As an improvement, the crosslinking agent is N,N －_ Methylene bisacrylamide.
[0013] The preparation method of the double network zwitterionic hydrogel adhesive described in any of the above, comprising the following steps:
[0014] Step one, dissolve gelatin in deionized water until completely dissolved;
[0015] Step two, at room temperature, disperse the crosslinking agent in deionized water until completely dissolved;
[0016] Step three, add the zwitterionic monomer, acrylic monomer and initiator to the solution of step two in sequence and mix uniformly;
[0017] Step four, pour the solution of step one into the solution of step three and stir for 10 min, then pour into a glass mold and trigger at 75℃ for 3h to obtain the double network zwitterionic hydrogel adhesive.
[0018] The above double network zwitterionic hydrogel adhesive is applied in a medical adhesive, which is an antibacterial hydrogel adhesive.
[0019] As an improvement, the antibacterial hydrogel adhesive can be used as an antibacterial dressing. Advantages
[0020] Compared with the prior art, the reusable double-network zwitterionic hydrogel adhesive and the preparation method and application thereof have the double-network structure, good biocompatibility of the hydrogel, a maximum peel strength of 26 Kpa, and an antibacterial efficiency of more than 95% on E. coli and S. aureus, the adhesive can absorb the body fluid secreted from a wound and be reused, and wound healing is promoted, due to the excellent hydrophilic performance and special structure of the gelatin network and the zwitterion. BRIEF DESCRIPTION OF DRAWINGS
[0021] Figure 1 A peel strength detection result graph of the hydrogel adhesive prepared for the inventive examples 1-5 and the control example 1;
[0022] Figure 2 An antibacterial efficiency detection result graph of the hydrogel adhesive prepared for the inventive examples 1-5 and the control example 2;
[0023] Figure 3 A repeated adhesion ability detection result graph of the hydrogel adhesive prepared for the inventive example 4;
[0024] Figure 4 An experimental mechanism graph of the inventive reusable double-network zwitterionic hydrogel adhesive. DETAILED DESCRIPTION
[0025] The present application can be better understood according to the following examples. However, it is readily apparent to a person skilled in the art that the content described in the examples is only for illustrating the present application and should not and will not limit the present application described in detail in the claims.
[0026] The experimental methods described in the examples are all conventional methods unless otherwise specified; and the reagents and materials described are all commercially available or can be simply prepared by the prior art unless otherwise specified. Example 1
[0027] A gelatin solution was prepared by dissolving 4% gelatin in 5 mL deionized water, stirring at 60°C for 1 h to completely dissolve the gelatin, then 0.2% crosslinking agent N,N-methylene bisacrylamide was dissolved in 5 mL deionized water, 30% methacryloyl ethyl sulfobetaine, 10% zinc methacrylate and 1% initiator ammonium persulfate were sequentially added at room temperature, the gelatin solution was added after complete dissolution, stirred for 10 min, poured into a glass mold and triggered at 75°C for 3 h to obtain the hydrogel adhesive. Example 2
[0028] Dissolve 6% gelatin in 5 mL deionized water, stir at 60 °C for 1 h to make it completely dissolved, get gelatin solution, then dissolve 0.2% crosslinker N,N-methylene bisacrylamide in 5 mL deionized water, add 30% methacryloyl ethyl sulfobetaine, 10% zinc methacrylate and 1% initiator ammonium persulfate in turn at room temperature, after all dissolved, add gelatin solution, pour into glass mold after stirring for 10 min and trigger at 75 °C for 3 h to get hydrogel adhesive. Example 3
[0029] Dissolve 8% gelatin in 5 mL deionized water, stir at 60 °C for 1 h to make it completely dissolved, get gelatin solution, then dissolve 0.2% crosslinker N,N-methylene bisacrylamide in 5 mL deionized water, add 30% methacryloyl ethyl sulfobetaine, 10% zinc methacrylate and 1% initiator ammonium persulfate in turn at room temperature, after all dissolved, add gelatin solution, pour into glass mold after stirring for 10 min and trigger at 75 °C for 3 h to get hydrogel adhesive. Example 4
[0030] Dissolve 10% gelatin in 5 mL deionized water, stir at 60 °C for 1 h to make it completely dissolved, get gelatin solution, then dissolve 0.2% crosslinker N,N-methylene bisacrylamide in 5 mL deionized water, add 30% methacryloyl ethyl sulfobetaine, 10% zinc methacrylate and 1% initiator ammonium persulfate in turn at room temperature, after all dissolved, add gelatin solution, pour into glass mold after stirring for 10 min and trigger at 75 °C for 3 h to get hydrogel adhesive. Example 5
[0031] Dissolve 12% gelatin in 5 mL deionized water, stir at 60 °C for 1 h to make it completely dissolved, get gelatin solution, then dissolve 0.2% crosslinker N,N-methylene bisacrylamide in 5 mL deionized water, add 30% methacryloyl ethyl sulfobetaine, 10% zinc methacrylate and 1% initiator ammonium persulfate in turn at room temperature, after all dissolved, add gelatin solution, pour into glass mold after stirring for 10 min and trigger at 75 °C for 3 h to get hydrogel adhesive.
[0032] Comparative Example 1
[0033] The mass fraction 0.2% crosslinking agent N, N-methylene bisacrylamide was dissolved in 5 mL deionized water, and the mass fraction 30% methacryloyl ethyl sulfobetaine, the mass fraction 10% zinc methacrylate and the mass fraction 1% initiator ammonium persulfate were sequentially added at room temperature, and the rest was deionized water. After stirring for 10 min, it was poured into a glass mold and triggered at 75°C for 3 h to obtain a hydrogel adhesive.
[0034] Comparative Example 2
[0035] The mass fraction 10% gelatin was dissolved in 5 mL deionized water, and the gelatin solution was obtained by stirring at 60°C for 1 h. Then the mass fraction 0.2% crosslinking agent N, N-methylene bisacrylamide was dissolved in 5 mL deionized water, and the mass fraction 30% methacryloyl ethyl sulfobetaine and the mass fraction 1% initiator ammonium persulfate were added at room temperature. After all were dissolved, the gelatin solution was added, stirred for 10 min, poured into a glass mold and triggered at 75°C for 3 h to obtain a hydrogel adhesive.
[0036] The zwitterionic hydrogel adhesives prepared in Examples 1-5 and Comparative Examples 1-2 were characterized in terms of peel strength, repeated peeling, cytotoxicity and antibacterial efficiency, and the specific test methods are as follows:
[0037] The characterization method of peel strength: the hydrogel adhesive was applied on the treated fresh pigskin, and the peel strength, i.e. the adhesion strength of the adhesive, was tested by lap shear test. The fresh pigskin was pretreated and cut into 5 cm x 2.5 cm strips, washed with 0.9% normal saline, and finally soaked in PBS buffer solution with pH = 7 for 12 hours to keep the pigskin in a wet state. Take two pieces of pigskin after treatment, evenly brush the hydrogel adhesive on the surface of one wet pigskin, then paste the two pieces of pigskin and apply 10N pressure to make the adhesive sample fully contact with the pigskin surface. The peel strength test was carried out with a universal electronic tensile testing machine (WDW-5) at a rate of 10 mm / min.
[0038] The characterization method of repeated peeling: the adhesive after the initial peeling experiment was re-adhered between the two pieces of pigskin, and a 500g weight was pressed for 1h. The peel strength was measured with a universal testing machine (WDW-5) at a rate of 10 mm / min, and the repeated adhesion performance of the adhesive was obtained after multiple tests. The results within 15% of the original peel strength were recorded as valid data.
[0039] Method for characterizing cytotoxicity: L929 (mouse fibroblast) cells (commercial product) were added to a culture dish containing DMEM medium as the experimental cells, and the cytotoxicity of the adhesive was tested by live and dead cell staining. The cells were placed in each well of a well plate containing the adhesive sample, and incubated in a cell incubator at 37°C for 24 hours. Then the DMEM medium was removed, and calcein AM and propidium iodide were added for live and dead cell staining, and incubated in the dark for 30 minutes. After the incubation, the live and dead cells were observed under an inverted fluorescence microscope.
[0040] Method for characterizing antibacterial efficiency: Escherichia coli and Staphylococcus aureus were used as target bacteria, and the adhesive sample was contacted with the bacterial solution for different times, then plated and cultured, and the number of colonies was counted. The bacterial solution concentration was calculated according to the number of colonies, and Y represents the antibacterial efficiency; Wt represents the number of colonies of the bacteria grown on the material; W0 represents the number of colonies of the bacteria grown in the control group 2. The antibacterial rate was calculated according to the following formula.
[0041] Y (%) = (1 - (W0 - Wt) / W0) x 100%
[0042] The test results are shown in Table 1.
[0043] Table 1. Performance characterization of zwitterionic hydrogel adhesives prepared under different parameters
[0044]
[0045] As can be seen from Table 1, the zwitterionic hydrogel adhesive obtained by polymerizing the zwitterionic monomer methacryloyl ethyl sulfobetaine and the acrylic acid monomer in Comparative Example 1 has no cytotoxicity, but has poor peel strength and repeatability. By adding the content of the gelatin network component, the performance of the zwitterionic hydrogel adhesive can be effectively changed. As can be seen from Comparative Example 2, without adding the acrylic acid monomer, the peel strength, antibacterial efficiency and repeatability of the hydrogel adhesive are poor, and cannot meet the actual demand. However, the zwitterionic hydrogel adhesive prepared under the experimental conditions of the present application has high adhesive strength, good repeatability, good antibacterial ability and no cytotoxicity, and can meet the demand of practical application.
Claims
1. A reusable dual-network zwitterionic hydrogel adhesive, characterized in that, The product comprises the following components by mass fraction: 2%~15% gelatin, 20%~30% zwitterionic monomer, 5%~15% zinc methacrylate, 0.1%~1% initiator, 0.1%~1% crosslinking agent, and the remainder being deionized water; wherein the zwitterionic monomer is one of 2-methacryloyloxyethyl phosphorylcholine, methacryloylethyl sulfobetaine, or carboxylate betaine methyl methacrylate.
2. The dual-network zwitterionic hydrogel adhesive according to claim 1, characterized in that, The initiator is one of potassium persulfate, ammonium persulfate, or cumene hydroperoxide.
3. The dual-network zwitterionic hydrogel adhesive according to claim 1, characterized in that, The crosslinking agent is N,N-methylenebisacrylamide.
4. A method for preparing a dual-network zwitterionic hydrogel adhesive according to any one of claims 1-3, characterized in that, Includes the following steps: Step 1: Dissolve gelatin in deionized water until completely dissolved; Step 2: At room temperature, disperse the crosslinking agent in deionized water until it is completely dissolved; Step 3: Add the zwitterionic monomer, zinc methacrylate, and initiator to the solution from Step 2 in sequence, and stir until homogeneous; Step 4: Pour the solution from Step 1 into the solution from Step 3 and stir for 10 minutes. Then pour the mixture into a glass mold and trigger the reaction at 75°C for 3 hours to obtain a double-network zwitterionic hydrogel adhesive.
5. The application of the dual-network zwitterionic hydrogel adhesive according to claim 1 in medical adhesives, characterized in that, The medical adhesive is an antibacterial hydrogel adhesive.
6. The application according to claim 5, characterized in that, The antibacterial hydrogel adhesive is used as an antibacterial dressing.