A wet adhesive hydrogel material and its preparation method and application

Abstract

The present invention provides a wet adhesive hydrogel material. This material uses a polyvinyl alcohol (PVA) substrate with excellent biocompatibility as a base. Compounds containing catechol groups are doped to enhance the overall adhesion of the material, thereby preparing the PVA hydrogel. Laser direct writing is then used to process the hydrogel substrate surface to construct a microarray structure. Finally, under slightly alkaline conditions, dopamine is oxidized in situ to form polydopamine nanoparticles at the micrometer-scale structure, resulting in a hydrogel material with extremely strong adhesion. This hydrogel material is an ideal medical adhesive for use in clinical procedures or emergency situations, exhibiting suitable adhesion and excellent biocompatibility.

Description

Technical Field

[0001] The invention belongs to the field of gel materials, and in particular relates to a wet adhesive hydrogel material and a preparation method and application thereof. Background Art

[0002] Severe trauma caused by road traffic injuries and war, as well as uncontrollable bleeding during surgery, urgently require rapid wound closure. The suturing methods commonly used in clinical practice are not feasible outside the operating room and are not feasible in most emergency situations. With the development of materials science, many new materials have been used to quickly close wounds. Among them, hydrogel materials (Hydrogel) are widely used in biomaterials due to their characteristics similar to extracellular matrix. The adhesion strength of traditional hydrogels is usually weak. This is because a large amount of water forms a barrier between its surface and the substrate, preventing the two from direct contact, resulting in reduced surface energy and weakened adhesion. In addition, water molecules interact with the adhesion groups in the hydrogel through hydrogen bonds, significantly reducing the interfacial reaction between the hydrogel and the solid material.

[0003] Polyvinyl alcohol (PVA) is a water-soluble polymer obtained by the alcoholysis of polyvinyl acetate. It has excellent water solubility, is harmless to the human body, has no side effects, has good tissue compatibility, and is minimally polluting the environment. Hydrogels made from PVA have broad application prospects in biomedical fields such as ophthalmology, artificial cartilage, and wound dressings. However, PVA hydrogels inherently lack adhesion to biological substrates, necessitating material or structural modifications to enhance their wet adhesion (Chinese patents CN113201152A, CN113150326A, and CN113004543A).

[0004] In terms of material design, the adhesive proteins in mussel foot patches are rich in an amino acid called 3,4-dihydroxyphenylalanine (L-Dopa). Its unique catechol groups can participate in various interfacial interactions through hydrogen bonding, metal coordination, cation-π interactions, π-π interactions, and redox reactions. These interactions provide immediate and effective adhesion, which is further strengthened during subsequent curing. Furthermore, catechol groups are easily oxidized to quinones, allowing chemical crosslinking between catechol groups or with sulfhydryl and amino groups, achieving chemical adhesion to the substrate.

[0005] In terms of structural design, many organisms, such as octopuses, geckos, and tree frogs, possess unique wet surface adhesion capabilities, thanks to the specialized micro- and nanostructures of their feet. These micro- and nanostructures (such as spines, hairs, and protrusions) increase the contact area between the adhesion organ and the substrate, both increasing the number of contact points and assisting in maintaining negative pressure. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to construct a PVA hydrogel using a biomimetic approach to address its weak adhesion under wet conditions. The present invention provides a polyvinyl alcohol hydrogel for wet adhesion and its preparation method. The hydrogel utilizes a biocompatible PVA material as a substrate, and catechol groups are introduced into the material design to enhance adhesion. Regarding the structural design, laser direct writing is used to construct a 10-200μm microarray structure, and 50-500nm polydopamine nanoparticles are generated in situ, resulting in a hydrogel material with extremely strong adhesion.

[0007] One of the objects of the present invention is to provide a wet adhesive hydrogel material, wherein the hydrogel material contains the following structural fragments:

[0008]

[0009] In a preferred embodiment of the present invention, the hydrogel material comprises a polyvinyl alcohol hydrogel substrate obtained by blending polyvinyl alcohol and a compound containing a catechol structure, and polydopamine nanoparticles grown in situ on the surface of the substrate.

[0010] In a more preferred embodiment of the present invention, the substrate surface has a microarray structure, preferably, the size of the microarray structure is 10 to 200 μm, preferably 30 to 130 μm; the particle size of the polydopamine nanoparticles is 50 to 500 nm, preferably 100 to 300 nm.

[0011] A second object of the present invention is to provide a method for preparing the wet-adhesive hydrogel material described in claim 1, comprising blending polyvinyl alcohol and a compound containing a catechol structure to obtain a polyvinyl alcohol hydrogel substrate, adding a dopamine compound by laser direct writing, and in situ generating polydopamine nanoparticles on the surface of the hydrogel substrate to obtain the wet-adhesive hydrogel material. Preferably, the preparation method specifically comprises the following steps:

[0012] Step 1: adding a compound containing a catechol structure to a polyvinyl alcohol solution and mixing the mixture uniformly to obtain a mixture A (PVA-DA);

[0013] Step 2: adding a crosslinking agent to the mixture A to undergo a crosslinking reaction to obtain a polyvinyl alcohol hydrogel B (PVA-DA Hydrogel);

[0014] Step 3: Processing the polyvinyl alcohol hydrogel B by laser direct writing to construct a polyvinyl alcohol hydrogel substrate with a microarray structure on the surface (PVA-DA-Laser Hydrogel);

[0015] Step 4: Apply the dopamine compound solution to the surface of the polyvinyl alcohol hydrogel substrate obtained in step 3 to generate polydopamine nanoparticles through polymerization reaction, thereby obtaining the wet adhesive hydrogel material (PVA-DA-Laser-PDAHydrogel).

[0016] In step 1 of the above preparation method, the concentration of the polyvinyl alcohol solution is 2 to 20 wt%, preferably 8 to 12 wt%; the polyvinyl alcohol solution is obtained by adding polyvinyl alcohol to water and heating and dissolving it. The temperature of heating and dissolving is not particularly limited, as long as the polyvinyl alcohol can be fully dissolved. For example, the heating temperature can be 75 to 95°C, preferably 80 to 90°C.

[0017] In step 1 of the above preparation method, the compound containing a catechol structure is selected from at least one of dopamine hydrochloride, 3,4-dihydroxybenzoic acid, 3,4-dihydroxyphenylacetic acid, and tannic acid; the amount of the compound containing a catechol structure is 5 to 50 wt% of the amount of polyvinyl alcohol, preferably 10 to 20 wt%.

[0018] In step 2 of the above preparation method, the cross-linking agent is selected from at least one of 1,4-butanediol glycidyl ether, glutaraldehyde, epichlorohydrin, and o-phthalaldehyde; the amount of the cross-linking agent is 5 to 30 wt% of the amount of polyvinyl alcohol, preferably 10 to 20 wt%.

[0019] In step 2 of the above preparation method, the cross-linking reaction temperature is 15-30°C and the reaction time is 4-36 hours; the polyvinyl alcohol hydrogel obtained after the cross-linking reaction also needs to be soaked and dialyzed with water to remove unreacted cross-linking agent. The specific soaking and dialysis operation is: the obtained polyvinyl alcohol hydrogel is soaked and dialyzed with deionized water for 3 days.

[0020] In step 3 of the above preparation method, the laser direct writing operation can adopt commonly used equipment and operating conditions. Preferably, a CO2 excimer laser beam with a wavelength of 5 to 20 μm and a power of 60 to 100 W is selected. The microarray structure constructed by laser direct writing can be a line array, a hole array, a circle array, a column array, a pattern array, etc.

[0021] In step 4 of the above preparation method, the concentration of the dopamine compound solution is 0.1 to 10 wt%, preferably 1 to 5 wt%; the solvent of the dopamine compound solution is an alkaline mixed solvent, preferably, the alkaline mixed solvent is a mixture of an alkaline compound, ethanol, and water; wherein the alkaline compound is selected from at least one of ammonia water, ethylenediamine, triethylamine, triethanolamine, 2-hydroxyethylamine, and isopropanolamine, and the dosage ratio of the alkaline compound: ethanol: water is 1: (20 to 60): (60 to 100), preferably 1: (30 to 50): (80 to 90).

[0022] In step 4 of the above preparation method, the polymerization reaction can be carried out at room temperature, preferably at room temperature in the dark for 10 to 50 hours. The polydopamine nanoparticles obtained after the polymerization reaction need to be washed and dried. Specifically, the gel surface can be washed with ethanol and then dried in air.

[0023] A third object of the present invention is to provide the wet adhesive hydrogel material or the wet adhesive hydrogel material obtained by the above preparation method for use in medical adhesives.

[0024] The present invention uses a biocompatible PVA material as a substrate. Compounds (DA) with catechol groups are doped to increase the overall material's adhesion, subsequently preparing a PVA-DA hydrogel. Laser direct writing is used to process the hydrogel substrate surface, creating a 10-200 μm microarray structure. Finally, under slightly alkaline conditions, dopamine hydrochloride is in situ oxidized to form 50-500 nm polydopamine (PDA) nanoparticles at the micron-sized structure, resulting in a highly adhesive hydrogel material (PVA-DA-PDA hydrogel). The resulting hydrogel material product has a brown to black appearance.

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

[0026] The present invention uses a PVA material with good biocompatibility as a substrate, and increases the overall adhesion of the material by doping a compound with a catechol group. The hydrogen bonds formed between the catechol group and the PVA matrix help anchor the DA molecules. Subsequently, a PVA-DA hydrogel is prepared. Drawing on the micro-nanostructure of gecko feet, the surface of the hydrogel substrate is processed by laser direct writing to construct microarray structures such as 10-200 μm hole arrays, column arrays, circular arrays, polygonal arrays, or pattern arrays. Finally, 50-500 nm polydopamine nanoparticles are generated on the micronized structure through in-situ oxidation and self-polymerization of dopamine hydrochloride, thereby obtaining a hydrogel material (PVA-DA-Laser-PDA Hydrogel) with extremely strong adhesion under humid conditions.

[0027] Drawing on the concept of biomimetic nature, this invention uses a simple method to construct a hydrogel material with strong adhesion to biological tissues, both in terms of material synthesis and structural construction. The prepared hydrogel material is an ideal medical adhesive for clinical applications or emergency situations, exhibiting suitable adhesion and good biocompatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Schematic diagram of the preparation process of the hydrogel material of the present invention;

[0029] Figure 2 is the adhesion strength of the hydrogel materials prepared in Example 1 and Comparative Example 1, wherein PVA is polyvinyl alcohol, PVA-DA is the composite polyvinyl alcohol hydrogel obtained in step 2 of Example 1, PVA-DA-Laser is the hydrogel with a microarray structure obtained in step 3 of Example 1, PVA-DA-PDA is the hydrogel material prepared in Comparative Example 1, and PVA-DA-Laser-PDA is the hydrogel material prepared in Example 1;

[0030] Figure 3 This is a scanning electron micrograph of the hydrogel material prepared in Example 1;

[0031] Figure 4 Transmission electron microscopy image of polydopamine nanoparticles. DETAILED DESCRIPTION

[0032] The present invention will be described in detail below with reference to specific embodiments. It is necessary to point out that the following embodiments are only used to further illustrate the present invention and are not to be construed as limiting the scope of protection of the present invention. Non-essential improvements and adjustments made by those skilled in the art to the present invention based on the contents of the present invention still fall within the scope of protection of the present invention.

[0033] The test instruments and test conditions used in the examples are as follows:

[0034] Polydopamine nanoparticle size: observation by transmission electron microscopy

[0035] Micrometer-scale structure of laser array structure: Observed by scanning electron microscopy

[0036] Adhesion performance test:

[0037] The adhesion strength of the hydrogel to wet pigskin was measured using a tensile adhesion test. The hydrogel sample was adhered to the wet pigskin surface with a bonding area of 8 mm x 10 mm. The sample was stretched to failure at a rate of 5 mm / min at room temperature using a servo tensile testing machine. The adhesion strength was defined as the load per unit area.

[0038] The raw materials used in the examples can be purchased directly or prepared according to the preparation methods disclosed in the prior art.

[0039] Example 1

[0040] Step 1: add 1 g of polyvinyl alcohol solid to 9 g of deionized water, heat to 95° C., stir thoroughly until completely dissolved, add 0.15 g of dopamine hydrochloride, stir and dissolve to obtain a first mixture (PVA-DA).

[0041] Step 2: add 0.1 g of 1,4-butanediol glycidyl ether to the first mixture, crosslink at 25° C. for 12 h, and soak the obtained polyvinyl alcohol hydrogel in deionized water for 3 days to obtain a composite polyvinyl alcohol hydrogel (PVA-DAHydrogel).

[0042] Step 3: The surface of the hydrogel substrate was processed by laser direct writing on the surface of the PVA-DA Hydrogel to construct a circular array structure (PVA-DA-Laser Hydrogel) with a diameter of 100 μm.

[0043] Step 4: Ammonia water: ethanol: deionized water are added to a beaker in a mass ratio of 1:40:90. Dopamine hydrochloride powder is dissolved in deionized water and then added to the above mixed solvent to obtain a 1% dopamine hydrochloride solution. The solution is applied to the surface of the PVA-DA-Laser Hydrogel having a microarray structure and reacted in the dark at room temperature for 24 hours to generate polydopamine nanoparticles with a median particle size of 200 nm at the micron-sized structure. After the reaction, the gel surface is washed with ethanol and dried in air to obtain a hydrogel material with extremely strong adhesion (PVA-DA-Laser-PDA Hydrogel).

[0044] Example 2

[0045] Step 1: add 1.5 g of polyvinyl alcohol solid to 8.5 g of deionized water, heat to 95° C., stir thoroughly until completely dissolved, add 0.15 g of tannic acid and dissolve to obtain a first mixture (PVA-DA).

[0046] Step 2: add 0.15 g of 1,4-butanediol glycidyl ether to the first mixture, crosslink at 25° C. for 24 h, and soak the obtained polyvinyl alcohol hydrogel in deionized water for 3 days to obtain a composite polyvinyl alcohol hydrogel (PVA-DAHydrogel).

[0047] Step 3: The surface of the hydrogel substrate was processed by laser direct writing on the surface of the PVA-DA Hydrogel to construct a column array structure (PVA-DA-Laser Hydrogel) with a diameter of 80 μm.

[0048] Step 4: Add ethylenediamine:ethanol:deionized water in a mass ratio of 1:40:90 to a beaker, dissolve dopamine hydrochloride powder in deionized water, and then add it to the above mixed solvent to obtain a 2% dopamine hydrochloride solution, which is applied to the surface of the PVA-DA Hydrogel with a microarray structure. The solution is reacted at room temperature in the dark for 36 hours to generate polydopamine nanoparticles with a median particle size of 220 nm at the micron-sized structure. After the reaction, the gel surface is washed with ethanol and dried in air to obtain a hydrogel material with extremely strong adhesion (PVA-DA-Laser-PDA Hydrogel).

[0049] Example 3

[0050] Step 1: add 1 g of polyvinyl alcohol solid to 9 g of deionized water, heat to 95° C., stir thoroughly until completely dissolved, add 0.2 g of 3,4-dihydroxybenzoic acid and dissolve to obtain a first mixture (PVA-DA).

[0051] Step 2: adding 0.15 g of glutaraldehyde to the first mixture, cross-linking at 25° C. for 18 h, and soaking the obtained polyvinyl alcohol hydrogel in deionized water for 3 days to obtain a composite polyvinyl alcohol hydrogel (PVA-DA Hydrogel).

[0052] Step 3: The surface of the hydrogel substrate was processed by laser direct writing on the surface of the PVA-DA Hydrogel to construct a pore array structure with a diameter of 50 μm (PVA-DA-Laser Hydrogel).

[0053] Step 4: Add ethylenediamine:ethanol:deionized water in a mass ratio of 1:40:85 to a beaker, dissolve dopamine hydrochloride powder in deionized water and then add it to the above mixed solvent to obtain a 1% dopamine hydrochloride solution, which is applied to the surface of the PVA-DA Hydrogel with a microarray structure. The solution is reacted at room temperature in the dark for 12 hours to generate polydopamine nanoparticles (PDA) with a median particle size of 180 nm at the micron-sized structure. After the reaction, the gel surface is washed with ethanol and dried in air to obtain a hydrogel material with extremely strong adhesion (PVA-DA-Laser-PDA Hydrogel).

[0054] Comparative Example 1

[0055] Step 1: add 1 g of polyvinyl alcohol solid to 9 g of deionized water, heat to 95° C., stir thoroughly until completely dissolved, add 0.15 g of dopamine hydrochloride, stir and dissolve to obtain a first mixture (PVA-DA).

[0056] Step 2: add 0.1 g of 1,4-butanediol glycidyl ether to the first mixture, crosslink at 25° C. for 12 h, and soak the obtained polyvinyl alcohol hydrogel in deionized water for 3 days to obtain a composite polyvinyl alcohol hydrogel (PVA-DAHydrogel).

[0057] Step 3: Add ammonia water: ethanol: deionized water in a mass ratio of 1:40:90 to a beaker, dissolve the dopamine hydrochloride powder in deionized water, and then add it to the above mixed solvent to obtain a 1% dopamine hydrochloride solution, which is applied to the surface of the PVA-DA Hydrogel. The solution is reacted at room temperature in the dark for 24 hours. After the reaction, the gel surface is washed with ethanol and dried in air to obtain a hydrogel material (PVA-DA-PDA Hydrogel).

Claims

1. A wet adhesive hydrogel material, comprising the following structural fragments: The hydrogel material comprises a polyvinyl alcohol hydrogel substrate obtained by blending polyvinyl alcohol and a compound containing a catechol structure, and polydopamine nanoparticles in situ grown on the surface of the substrate; the surface of the substrate has a microarray structure.

2. The hydrogel material according to claim 1, characterized in that The size of the microarray structure is 10 to 200 μm; and / or, The particle size of the polydopamine nanoparticles is 50 to 500 nm.

3. The hydrogel material according to claim 2, characterized in that The size of the microarray structure is 30 to 130 μm; and / or, The particle size of the polydopamine nanoparticles is 100-300 nm.

4. A method for preparing the wet adhesive hydrogel material according to any one of claims 1 to 3, comprising blending polyvinyl alcohol and a compound containing a catechol structure to obtain a polyvinyl alcohol hydrogel substrate, applying a dopamine compound solution by laser direct writing, and in situ generating polydopamine nanoparticles on the surface of the hydrogel substrate to obtain the wet adhesive hydrogel material.

5. The preparation method according to claim 4, characterized in that The preparation method specifically comprises the following steps: Step 1, adding a compound containing a catechol structure to a polyvinyl alcohol solution and mixing uniformly to obtain a mixture A; Step 2: adding a crosslinking agent to the mixture A to obtain a polyvinyl alcohol hydrogel B through a crosslinking reaction; Step 3: Processing the polyvinyl alcohol hydrogel B by laser direct writing to construct a polyvinyl alcohol hydrogel substrate with a microarray structure on the surface; Step 4: Apply the dopamine compound solution to the surface of the polyvinyl alcohol hydrogel substrate obtained in step 3, and generate polydopamine nanoparticles through polymerization reaction to obtain the wet adhesive hydrogel material.

6. The preparation method according to claim 5, characterized in that In step 1: The concentration of the polyvinyl alcohol solution is 2 to 20 wt%; and / or, The compound containing a catechol structure is selected from at least one of dopamine hydrochloride, 3,4-dihydroxybenzoic acid, 3,4-dihydroxyphenylacetic acid, and tannic acid; and / or The amount of the compound containing catechol structure is 5 to 50 wt % of the amount of polyvinyl alcohol.

7. The preparation method according to claim 6, characterized in that In step 1: The concentration of the polyvinyl alcohol solution is 8 to 12 wt%; and / or, The amount of the compound containing catechol structure is 10 to 20 wt % of the amount of polyvinyl alcohol.

8. The preparation method according to claim 5, characterized in that In step 2: The cross-linking agent is selected from at least one of 1,4-butanediol glycidyl ether, glutaraldehyde, epichlorohydrin, and o-phthalaldehyde; and / or, The amount of the cross-linking agent is 5 to 30 wt% of the amount of the polyvinyl alcohol; and / or, The cross-linking reaction temperature is 15 to 30° C., and the cross-linking reaction time is 4 to 36 hours; and / or, The polyvinyl alcohol hydrogel B obtained after the cross-linking reaction needs to be immersed in water and dialyzed.

9. The preparation method according to claim 8, characterized in that In step 2: The amount of the cross-linking agent used is 10-20 wt% of the amount of polyvinyl alcohol used.

10. The preparation method according to claim 5, characterized in that In step 4: The concentration of the dopamine compound solution is 0.1-10 wt %; and / or, The solvent of the dopamine compound solution is an alkaline mixed solvent; and / or, The polydopamine nanoparticles obtained after the polymerization reaction need to be washed and dried.

11. The preparation method according to claim 10, characterized in that: In step 4: The concentration of the dopamine compound solution is 1 to 5 wt%; and / or, The alkaline mixed solvent is a mixture of alkaline compounds, ethanol and water.

12. The preparation method according to claim 11, characterized in that The alkaline compound is selected from at least one of ammonia, ethylenediamine, triethylamine, triethanolamine, 2-hydroxyethylamine, and isopropanolamine; and / or, The dosage ratio of the alkaline compound: ethanol: water is 1: (20-60): (60-100).

13. The preparation method according to claim 12, characterized in that The dosage ratio of the alkaline compound: ethanol: water is 1: (30-50): (80-90).

14. A wet adhesive hydrogel material according to any one of claims 1 to 3 or a wet adhesive hydrogel material obtained by the preparation method according to any one of claims 4 to 13, used in medical adhesives.

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