An antibacterial low-adhesion strong and tough hydrogel as well as a preparation method and application thereof

Abstract

The application provides a preparation method of an antibacterial low-adhesion strong hydrogel, S1: 10-30 parts of polyvinyl alcohol and 50-1500 parts of a methacrylic acid sulfobetaine of a facultative ion are simultaneously added into deionized water at room temperature to obtain a mixed solution; S2: 1-20 parts of an initiator and 200-300 parts of a crosslinking agent are added into the mixed solution, stirring is conducted under the protection of nitrogen for 4-5 hours, and the temperature is kept at 85-95 DEG C; a hydrogel solution is obtained; S3: 10-30 parts of the hydrogel solution are introduced into a base material, then 1-5 parts of dopamine is added into the base material, soaking is conducted for 30-40 minutes, then repeated flushing is conducted with ultrapure water, and repeated oscillation is conducted on a shaking table for 30-60 minutes, so that the antibacterial low-adhesion strong hydrogel is prepared. The prepared hydrogel can simultaneously meet the effects of low adhesion, high tensile strength and antibiosis.

Description

Technical Field

[0001] This invention relates to hydrogels, specifically antibacterial, low-adhesion, and tough hydrogels, their preparation methods, and applications. Background Technology

[0002] Hydrogels are a class of highly hydrophilic three-dimensional network gels with a soft texture, variable properties, and physical properties similar to biological tissues. They exhibit excellent biocompatibility, with a water content exceeding 95% by weight, enabling them to dissolve and transport many ions and small molecules, demonstrating strong containment capabilities. Furthermore, their mechanical properties are tunable, making them excellent biomaterials. Since the invention of hydrogel contact lenses in 1960, extensive research and development have been conducted on medical hydrogels. In industrial applications, hydrogels are relatively new compared to metals, ceramics, and many other forms of polymers. The diversity of hydrogels, with their varied polymer topologies and chemical compositions, allows for their wide application across various fields. In the field of artificial cells, various molecular components are used to construct artificial cells to mimic the processes, behaviors, and structures of biological systems. Typically, artificial cells rely on a bilayered membrane chassis and possess a fluid-water internal structure. Due to the potential role of hydrogel structures in the origin of life, hydrogel structures are gradually becoming the basis for synthetic cells.

[0003] However, with the wider application of hydrogel materials, more and more problems are emerging. Hydrogel coatings rapidly absorb water and swell, and this volume change induces strong stress within the thin hydrogel layer. The hydrogel coating and the substrate are connected by non-covalent weak forces, making the coating prone to peeling. Therefore, it is necessary to attach the hydrogel to the matrix through stronger connections (such as covalent bonds).

[0004] Currently, the industry mainly uses methods such as stereocomplexation, inclusion complexes, metal-ligand coordination, and synthetic peptide chains to regulate the mechanical and degradation properties of hydrogels. For example, one major application of stereocomplexation is the preparation of injectable hydrogels by block copolymers of two amphiphilic copolymers, PLLA (polylactic acid) and PDLA (polylactic acid enantiomers). There is also research on constructing hydrogels with hydrophobic cavities capable of accommodating different molecules using cyclodextrin inclusion complexes. In genetic engineering, there is also research on constructing synthetic peptide (or protein) hydrogels using the folded structure of peptides. However, these hydrogels have weak binding ability with other materials and usually cannot allow target cells to directly adhere to the surface of the consumable. Furthermore, biofouling caused by foreign body reactions can reduce the lifespan of the material or even lead to its removal and replacement. Existing technology uses hydrogels combined with antibacterial materials to coat the substrate for antibacterial colonization, but this method has significant limitations for cell experiments, increasing the operational difficulty. Moreover, because antibacterial agents affect the tensile strength of the hydrogel, it is prone to detachment and breakage in practical applications. Summary of the Invention

[0005] The purpose of this invention is to provide an antibacterial, low-adhesion, and tough hydrogel, its preparation method, and its application to solve the problems in the prior art.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] A method for preparing an antibacterial, low-adhesion, and tough hydrogel includes the following steps:

[0008] S1: By weight, 10-30 parts of polyvinyl alcohol and 50-1500 parts of zwitterionic methacrylate sulfobetaine are simultaneously added to deionized water at room temperature to obtain a mixed solution.

[0009] S2: By weight, add 1-20 parts of initiator and 200-300 parts of crosslinking agent to the mixed solution, stir under nitrogen protection for 4-5 hours, and maintain the temperature at 85-95℃ to obtain a hydrogel solution;

[0010] S3: Introduce 10-30 parts of the hydrogel solution into the substrate, then add 1-5 parts of dopamine to the substrate and soak for 30-40 minutes, then rinse repeatedly with ultrapure water, and repeatedly oscillate on a shaker for 30-60 minutes to obtain the antibacterial, low-adhesion, and tough hydrogel.

[0011] Furthermore, the crosslinking agent is tannic acid.

[0012] Furthermore, the initiator is copper sulfate and hydrogen peroxide in a mass ratio of 1:400.

[0013] An antibacterial, low-adhesion, and tough hydrogel was prepared using the method described above.

[0014] An antibacterial, low-adhesion, and tough hydrogel is applied to three-dimensional cell culture.

[0015] The beneficial effects of this invention are as follows:

[0016] 1. Compared to traditional methods, this invention offers higher toughness and stronger adhesion to the substrate. It employs a dual-network preparation method. The first step involves adding polyvinyl alcohol (PVA) and tannic acid (TA) to obtain a tightly cross-linked, rigid yet brittle polyelectrolyte network structure through free radical polymerization, forming the first network layer. Then, the hydrogel based on this first network layer is immersed in a high-concentration solution of betaine SBMA and dopamine (DA). A large amount of betaine SBMA and dopamine (DA) swells within the first network layer, polymerizing to form a loosely cross-linked second network layer. Finally, the resulting hydrogel is placed in water to swell, yielding the final dual-network hydrogel. The concentration of the second network layer is typically 20 to 30 times that of the first network layer. This allows for tight cross-linking of polyvinyl alcohol (PVA) and tannic acid (TA). Furthermore, the strong adhesion of dopamine (DA) in the second network layer results in an extremely strong and tough hydrogel. When tested under a universal testing machine, its tensile strength reaches 0.22 N / mm², which is more than ten times stronger than the hydrogel prepared using only polyvinyl alcohol (PVA) and tannic acid (TA).

[0017] 2. This invention uses tannic acid as a crosslinking agent to prepare a gel with water-absorbing and swelling properties. Therefore, the hydrogel prepared can greatly reduce the chance of the hydrogel bursting due to excessive water absorption. At the same time, since tannic acid is natural and non-toxic, it can greatly simplify the process of washing off the crosslinking agent in the later stage of gel preparation. Compared with other crosslinking agents, it can greatly improve the preparation efficiency of hydrogel coating and reduce its washing cost.

[0018] 3. This invention uses electrically neutral zwitterionic polysulfonate betaine, whose molecular chain serves as a grafting chain to connect the polyvinyl alcohol (PVA) and tannic acid (TA) network structures of the first layer of the hydrogel. Through electrostatic forces and hydrogen bonds, it binds water molecules on the surface of the hydrogel to form a hydrated layer. At the same time, tannic acid has antioxidant, antibacterial, anti-inflammatory and biodegradable effects, which can degrade large molecular proteins adsorbed on the gel surface and resist the adsorption of small molecular proteins on the gel surface. It can also resist inflammation and bacterial contamination caused by protein adsorption.

[0019] 4. The dopamine (DA)-based hydrogel used in this invention possesses self-healing properties and various biological characteristics (such as tissue adhesion, biocompatibility, and cell adhesion), ensuring not only the self-healing of mechanical properties but also other properties to adapt to the human body environment. First, the polydopamine produced after the oxidative polymerization of dopamine contains highly active phenolic hydroxyl groups, which can form various non-covalent synergistic effects with the hydrogel polymer network, achieving reversible non-covalent bond reconstruction at the fracture surface and endowing the dopamine hydrogel with excellent self-healing properties. Second, the phenolic hydroxyl groups in polydopamine can interact with the surface of biological tissues covalently or non-covalently, giving the hydrogel good tissue adhesion. The highly active phenolic hydroxyl groups can also endow the hydrogel with superior cell affinity and cell adhesion.

[0020] 5. The dopamine (DA) used in this invention has a similar structure to the adhesive proteins of mussels. When used with betaine as a raw material for hydrogels, it exhibits strong adhesion and good cell affinity to most biological consumables surfaces, but lacks biocompatibility and cannot solve the problem of biofouling caused by bacterial growth. Tannic acid (TA), on the other hand, is a natural polyphenol antibacterial molecule with antioxidant, antibacterial, anti-inflammatory, and biodegradable properties. It can exert good antibacterial effects even in the absence of antibiotics. Furthermore, tannic acid contains a large number of phenolic groups, providing various interaction sites, including hydrogen bonds, ionic bonds, coordination bonds, and hydrophilic-hydrophobic interactions, thus exhibiting strong biocompatibility and making it highly suitable as a raw material for hydrogels.

[0021] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, the preferred embodiments of the present invention are described in detail below. Attached Figure Description Detailed Implementation

[0022] The specific embodiments of the present invention will be described in further detail below with reference to the examples. These examples are for illustrative purposes only and are not intended to limit the scope of the invention.

[0023] Example 1:

[0024] A method for preparing an antibacterial, low-adhesion, and tough hydrogel includes the following steps:

[0025] S1: By weight, 25 parts of polyvinyl alcohol and 1000 parts of zwitterionic methacrylate sulfobetaine were simultaneously added to deionized water at room temperature to obtain a mixed solution.

[0026] S2: By weight, 5 parts of initiator and 200 parts of tannic acid were added to the mixed solution, and stirred for 5 hours under nitrogen protection while maintaining the temperature at 95°C to obtain a hydrogel solution.

[0027] S3: The 25 parts of hydrogel solution are introduced into the substrate, then 5 parts of dopamine are added to the substrate and soaked for 35 minutes. Then, the substrate is repeatedly rinsed with ultrapure water and repeatedly shaken on a shaker for 45 minutes to obtain the antibacterial, low-adhesion, and tough hydrogel.

[0028] The initiator is copper sulfate and hydrogen peroxide in a mass ratio of 1:400.

[0029] Comparative Example 1:

[0030] A method for preparing an antibacterial, low-adhesion, and tough hydrogel includes the following steps:

[0031] S1: By weight, 5 parts of polyvinyl alcohol and 1000 parts of zwitterionic methacrylate sulfobetaine were simultaneously added to deionized water at room temperature to obtain a mixed solution.

[0032] S2: By weight, 5 parts of initiator and 200 parts of tannic acid were added to the mixed solution, and stirred for 5 hours under nitrogen protection while maintaining the temperature at 95°C to obtain a hydrogel solution.

[0033] S3: The 25 parts of hydrogel solution are introduced into the substrate, then 5 parts of dopamine are added to the substrate and soaked for 35 minutes. Then, the substrate is repeatedly rinsed with ultrapure water and repeatedly shaken on a shaker for 45 minutes to obtain the antibacterial, low-adhesion, and tough hydrogel.

[0034] The initiator is copper sulfate and hydrogen peroxide in a mass ratio of 1:400.

[0035] Comparative Example 2:

[0036] 1: By weight, 25 parts of polyvinyl alcohol and 1000 parts of zwitterionic methacrylate sulfobetaine were simultaneously added to deionized water at room temperature to obtain a mixed solution;

[0037] S2: By weight, 5 parts of initiator and 200 parts of NN methylenebisacrylamide were added to the mixed solution, and stirred for 5 hours under nitrogen protection while maintaining the temperature at 95°C to obtain a hydrogel solution.

[0038] S3: The 25 parts of hydrogel solution are introduced into the substrate, then 5 parts of dopamine are added to the substrate and soaked for 35 minutes. Then, the substrate is repeatedly rinsed with ultrapure water and repeatedly shaken on a shaker for 45 minutes to obtain the antibacterial, low-adhesion, and tough hydrogel.

[0039] The initiator is copper sulfate and hydrogen peroxide in a mass ratio of 1:400.

[0040] Comparative Example 3:

[0041] A method for preparing an antibacterial, low-adhesion, and tough hydrogel includes the following steps:

[0042] S1: By weight, 25 parts of dopamine and 1000 parts of zwitterionic methacrylate sulfobetaine were simultaneously added to deionized water at room temperature to obtain a mixed solution.

[0043] S2: By weight, 5 parts of initiator and 200 parts of tannic acid were added to the mixed solution, and stirred for 5 hours under nitrogen protection while maintaining the temperature at 95°C to obtain a hydrogel solution.

[0044] S3: The 25 parts of hydrogel solution are introduced into the substrate, then 5 parts of dopamine are added to the substrate and soaked for 35 minutes. Then, the substrate is repeatedly rinsed with ultrapure water and repeatedly shaken on a shaker for 45 minutes to obtain the antibacterial, low-adhesion, and tough hydrogel.

[0045] The initiator is copper sulfate and hydrogen peroxide in a mass ratio of 1:400.

[0046] Comparative Example 4:

[0047] A method for preparing an antibacterial, low-adhesion, and tough hydrogel includes the following steps:

[0048] S1: By weight, 25 parts of polyvinyl alcohol and 1000 parts of zwitterionic methacrylate sulfobetaine were simultaneously added to deionized water at room temperature to obtain a mixed solution.

[0049] S2: By weight, 5 parts of initiator and 200 parts of tannic acid were added to the mixed solution, and stirred for 5 hours under nitrogen protection while maintaining the temperature at 95°C to obtain a hydrogel solution.

[0050] S3: The 25 parts of hydrogel solution are introduced into the substrate, then soaked for 35 minutes, then rinsed repeatedly with ultrapure water, and repeatedly shaken on a shaker for 45 minutes to obtain the antibacterial, low-adhesion, and tough hydrogel.

[0051] The initiator is copper sulfate and hydrogen peroxide in a mass ratio of 1:400.

[0052] The antibacterial, low-adhesion, and tough hydrogels obtained in Example 1 and Comparative Examples 1-4 were subjected to tensile strength tests.

[0053] The test results are shown in Table 1 below.

[0054] Example 1 0.2 Comparative Example 1 0.04 Comparative Example 2 0.01 Comparative Example 3 0.05 Comparative Example 4 0.02

[0055] Table 1

[0056] As shown in Table 1, Comparative Example 1 had a relatively low amount of PVA, which prevented the formation of a dense network, resulting in decreased mechanical properties. Comparative Example 2, due to the change of crosslinking agent, could not achieve the tensile strength of the present invention. Comparative Example 3 replaced PVA with dopamine, leading to a decrease in the mechanical properties of the formed hydrogel. Comparative Example 4 lacked dopamine, preventing the formation of a double network structure, which also resulted in decreased mechanical properties.

[0057] The antibacterial, low-adhesion, and tough hydrogels obtained in Example 1 and Comparative Examples 1-4 were subjected to antibacterial tests. The test procedure was as follows: the antibacterial, low-adhesion, and tough hydrogels were adhered to sterilized LB medium. Then, diluted bacterial solution was inoculated onto the medium, spread evenly, and incubated overnight at 37°C. The test results are shown in Table 2 below:

[0058] Escherichia coli inhibition rate 99.99％ 96.5％ 82.1％ 96.3％ 98.2％ Staphylococcus aureus inhibition rate 99.99％ 94.9％ 81.2％ 97.3％ 97.2％ Salmonella inhibition rate 99.99％ 95.2％ 84.％ 96.8％ 97.9％

[0059] Table 2

[0060] As can be seen from Table 2, tannic acid plays an effective antibacterial role, and the composition of the double network structure of the hydrogel affects the antibacterial effect of tannic acid.

[0061] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0062] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A method for preparing an antibacterial, low-adhesion, and tough hydrogel, characterized in that, Includes the following steps: S1: By weight, 10-30 parts of polyvinyl alcohol and 1000 parts of zwitterionic methacrylate sulfobetaine are simultaneously added to deionized water at room temperature to obtain a mixed solution. S2: By weight, add 1-20 parts of initiator and 200-300 parts of crosslinking agent to the mixed solution, stir under nitrogen protection for 4-5 hours, and maintain the temperature at 85-95°C to obtain a hydrogel solution; S3: Introduce 10-30 parts of the hydrogel solution into the substrate, then add 1-5 parts of dopamine to the substrate and soak for 30-40 minutes, then rinse repeatedly with ultrapure water, and repeatedly oscillate on a shaker for 30-60 minutes to obtain the antibacterial, low-adhesion, and tough hydrogel. The crosslinking agent is tannic acid.

2. The method for preparing an antibacterial, low-adhesion, and tough hydrogel according to claim 1, characterized in that, The initiator is copper sulfate and hydrogen peroxide in a mass ratio of 1:

400.

3. An antibacterial, low-adhesion, and tough hydrogel, characterized in that, Prepared using the preparation method described in any one of claims 1 to 2.

4. An application of the antibacterial, low-adhesion, and tough hydrogel as described in claim 3, characterized in that, It is used in three-dimensional cell culture.