A highly wet tissue-adhesive, anti-swelling, conductive hydrogel and methods of making the same

Abstract

The application belongs to the technical field of polymer hydrogel, and particularly relates to a high-humidity tissue-adhesion anti-swelling conductive hydrogel. The high-humidity tissue-adhesion anti-swelling conductive hydrogel comprises a hydrophobic amino acid vinyl structural unit, a hydrophilic structural unit and a zwitterionic structural unit. The application constructs a conductive hydrogel with tissue matching, biological safety, high-humidity tissue adhesion and anti-swelling by free radical polymerization of the hydrophobic amino acid vinyl monomer, the hydrophilic monomer and the zwitterionic monomer.

Description

Technical Field

[0001] This invention belongs to the field of polymer hydrogel technology, specifically relating to a conductive hydrogel with high wet tissue adhesion and anti-swelling properties and its preparation method. Background Technology

[0002] Conductive hydrogels, due to their advantages such as tissue similarity, good biocompatibility, and rapid response to various external stimuli, have shown broad application prospects in fields such as human-machine interfaces, implantable electronic devices, and intelligent health diagnosis and treatment. However, whether used for physiological signal monitoring or tissue repair, conductive hydrogels are inevitably affected by different types of solutions (such as rainwater, sweat, and bodily fluids) during use. First, the numerous hydrophilic functional groups on the polymer backbone of traditional hydrogels cause the hydrogel to absorb a large number of water molecules upon contact with solutions, resulting in volume swelling and a significant reduction in the mechanical properties of the hydrogel. Second, water molecules can interfere with the direct contact or chemical bonding between the hydrogel and the substrate, reducing the adhesion strength between the hydrogel and the adhesive interface, thereby increasing the risk of human-machine interface failure or tissue fluid leakage due to sensor detachment during use. Therefore, to ensure that conductive hydrogels are not affected by different types of solutions when used in dynamic humid environments, it is crucial to synergistically enhance the anti-swelling properties of the hydrogel matrix and the adhesion to wet tissues at the interface.

[0003] To meet application requirements, researchers have recently improved the anti-swelling properties of hydrogels by encapsulating the hydrogel surface, introducing hydrophobic functional groups, and combining various interactions, thereby achieving structural and functional stability of conductive hydrogels in underwater environments. Professor Fei Chen of Xi'an Jiaotong University, in collaboration with Professor Bin Xu of Northumbria University, modified the surface of conductive hydrogels with hydrophobic ester gel coatings to give them unique anti-swelling properties (Adv. Funct. Mater. 2022, 32, 2201396). Professor Guanghui Gao and his team at Changchun University of Technology constructed a solvent-resistant conductive hydrogel that is stable in various organic solvents and exhibits no significant volume swelling by introducing the hydrophobic monomer 2-methoxyethyl acrylate into a hydrophilic polymer network (ACS Nano 2020, 14, 13709-13717). Professor Lü Shaoyu and his team at Lanzhou University copolymerized zwitterionic monomers with the hydrophobic monomer hydroxyethyl methacrylate and combined them with polyvinyl alcohol. Based on multiple hydrogen bonds, electrostatic interactions, and a dual-network structure, they designed an anti-swelling conductive hydrogel for underwater motion monitoring (Adv. Funct. Mater. 2022, 32, 2107404). However, the introduction of numerous hydrophobic functional groups and the high crosslinking density of the hydrogel hindered the mobility of polymer chains. While effectively preventing water molecules from penetrating into the gel, it also limited the migration of adhesive functional groups to the bonding interface, weakening the wet adhesion strength between the hydrogel and biological tissue. This insufficient interfacial wet tissue adhesion performance will severely limit the hydrogel's potential applications in underwater or physiological environments for tissue repair or flexible sensing.

[0004] Hydrogel surfaces require a large number of adhesive functional groups to achieve multiple interactions between the hydrogel and the bonding matrix. However, adhesive functional groups often form a hydration layer at the interface due to their strong hydrophilicity, hindering direct contact between the hydrogel and the bonding matrix and severely weakening the adhesive strength at the interface. Therefore, to ensure that conductive hydrogels form stable and strong adhesions on the surface of wet and dynamic biological tissues, it is necessary to minimize the interference of the interfacial hydration layer on the interaction between the hydrogel and the target matrix. It is worth noting that organisms in nature often contain solutions to this problem. Inspired by marine mussels, Professor Cao Yi and his team at Nanjing University incorporated a catechol structure into a polymer backbone. The catechol structure can effectively penetrate the interfacial hydration layer and interact with biological tissues, thereby constructing a hydrogel tape that can quickly form a strong adhesion to wet tissues (Nat. Commun. 2021, 12, 7156). Professor Yan Xuehai and his team at the Institute of Process Engineering, Chinese Academy of Sciences, integrated polydopamine nanoparticles with a catechol structure into a hydrogel network, endowing it with stronger adhesion and lower impedance, thus avoiding interference from sweat during electroencephalography (EEG) signal monitoring (Adv. Mater. 2023, 35, 2209606). Inspired by barnacles, Professor Gong Jianping and her team at Hokkaido University, Japan, discovered that copolymerization of adjacent sequences of cationic and aromatic monomers endows hydrogels with the ability to rapidly and reversibly adhere to negatively charged substrates in seawater (Adv. Funct. Mater. 2021, 31, 2009334). However, the catechol groups are easily oxidized to quinones, leading to a reduction in the number of phenolic hydroxyl groups and a decrease in adhesion strength. In addition, cation-π interactions depend on complex structural design and are easily affected by factors such as temperature, pH, and ion concentration. Therefore, constructing a long-term stable conductive hydrogel with both high wet tissue adhesion and anti-swelling properties through a simple and effective method faces significant challenges. Summary of the Invention

[0005] To address the problem that existing conductive hydrogels have weak wet tissue adhesion and insufficient anti-swelling properties, making it difficult to meet the application requirements for tissue repair or stable transmission of various physiological signals in high humidity or underwater environments, this invention provides a conductive hydrogel with high wet tissue adhesion and anti-swelling properties.

[0006] This highly wet tissue-adhesive, anti-swelling conductive hydrogel comprises hydrophobic amino acid vinyl structural units, hydrophilic structural units, and zwitterionic structural units.

[0007] Furthermore, the ratio of the hydrophobic amino acid vinyl structural units to the hydrophilic structural units is 1:(8-20).

[0008] Furthermore, the ratio of the hydrophobic amino acid vinyl structural unit to the zwitterionic structural unit is 1:(0.9-3).

[0009] Furthermore, the hydrophobic amino acid vinyl monomer corresponding to the hydrophobic amino acid vinyl structural unit is selected from one or more of N-acryloylalanine, N-acryloylvaline, N-acryloylphenylalanine, N-acryloylleucine, N-acryloylisoleucine, N-acryloyltryptophan, N-acryloylmethionine, N-acryloylalanamide, N-acryloylvaline, and N-acryloylphenylalanamide;

[0010] The hydrophilic monomer corresponding to the hydrophilic structural unit is selected from one or more of the following: acrylic acid, methacrylic acid, 2-hydroxyethyl acrylate, hydroxyethyl methacrylate, acrylamide, N-trimethylolmethacrylamide, N,N-dimethylacrylamide, N-hydroxyethylacrylamide, 1-vinyl-2-pyrrolidone, N-acryloylaspartic acid, N-acryloylglutamic acid, N-acryloylglycine, N-acryloyltyrosine, N-acryloylserine, N-acryloylthreonine, and N-acryloylglutamine.

[0011] The zwitterionic monomer corresponding to the zwitterionic structural unit is selected from one or more of 2-methacryloyloxyethyl phosphorylcholine, 3-[[2-(methacryloyloxy)ethyl]dimethylammonium]propionate, [3-(methacryloylamino)propyl]dimethyl(3-thiopropyl)ammonium hydroxide and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide.

[0012] The present invention also provides a method for preparing a conductive hydrogel with high moisture adhesion and anti-swelling properties.

[0013] The preparation method of this highly moist tissue-adhesive, anti-swelling conductive hydrogel includes the following steps:

[0014] S1: Dissolve the hydrophobic amino acid vinyl monomer, the hydrophilic monomer, and the zwitterionic monomer fully in an aqueous solution to obtain a colorless and transparent mixture;

[0015] S2: At room temperature, add the initiator and initiator accelerator and mix evenly to complete the free radical polymerization;

[0016] S3: Immerse the polymer in deionized water to obtain the high-moisture-adhesion, anti-swelling conductive hydrogel.

[0017] Furthermore, the total concentration of the hydrophobic amino acid vinyl monomer and the hydrophilic monomer is 4.4–8.8 mol / L;

[0018] The concentration of the zwitterionic monomer is 0.2–1.8 mol / L.

[0019] Furthermore, the initiator is selected from one or more of potassium persulfate, ammonium persulfate, and azobisisobutyrazoline hydrochloride;

[0020] The initiator / promoter is N,N,N',N'-tetramethylethylenediamine.

[0021] Furthermore, the amount of the initiator added is 0.5% to 2% of the total mass of the hydrophobic amino acid vinyl monomer, the hydrophilic monomer, and the zwitterionic monomer;

[0022] The amount of the initiator accelerator added is 0-30% of the mass of the initiator.

[0023] Furthermore, in step S1, the method of achieving complete dissolution is selected from one or more of heating, ultrasonication, and vortex oscillation;

[0024] In step S2, the polymerization temperature is 20–80℃, and the polymerization reaction time is 2–12 h;

[0025] In step S3, the soaking time is 21 to 24 hours.

[0026] Compared with existing technologies, the conductive hydrogel with high wet tissue adhesion and anti-swelling properties provided by this invention has the following advantages:

[0027] 1) The hydrogel provided by this invention is convenient and quick to use, with strong and stable tissue adhesion. It can form a firm and long-term stable bond with moist biological tissue with only 5 kPa stress for 20 seconds, and the bonding interface is not affected by external water molecules. Furthermore, the hydrogel also exhibits firm and stable wet adhesion behavior to various internal organs and tissues, including the heart, liver, arteries, lungs, and stomach, and has the potential to achieve rapid hemostasis and promote tissue repair.

[0028] 2) The hydrogel provided by the present invention has stable anti-swelling properties underwater. No matter whether it is soaked in deionized water solution or simulated seawater solution for 10 days, the mass and volume of the hydrogel will not change significantly.

[0029] 3) The hydrogel provided by this invention has stable and effective underwater sensing capabilities. In an underwater environment, the hydrogel can not only monitor changes in electrical signals generated by human joint activity, but also collect physiological signals such as human pulse, electrocardiogram, and electromyography, providing a new option for clinical use to replace traditional adhesive tape-type commercial electrode pads.

[0030] 4) The hydrogel provided by this invention has good biocompatibility. The hydrogel patch obtained by free radical polymerization of amino acid derivatives, hydrophilic monomers and zwitterionic monomers has excellent biocompatibility, which is conducive to clinical translation and provides a new option for replacing surgical sutures to achieve wound closure and rapid hemostasis in clinical practice. Attached Figure Description

[0031] Figure 1 The graph shows the wet bond strength test results of the hydrogels and pigskin provided in Examples 2, 5, 6, and 7.

[0032] Figure 2 The graph shows the test results of wet bonding strength and bonding interface toughness of the hydrogel provided in Example 2 with various porcine tissues.

[0033] Figure 3 The graph shows the swelling rate changes of the hydrogel provided in Example 2 after immersion in deionized water and seawater solutions.

[0034] Figure 4 The image shows the results of electromyography (EMG) signal changes when hydrogel electrode patches and commercial electrode patches are attached to the human forearm and immersed in an aqueous solution. Detailed Implementation

[0035] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings, but this should not be construed as limiting the scope of the present invention.

[0036] To address the shortcomings of existing technologies, this invention proposes a strategy of synergistic reinforcement between the hydrogel interface and the matrix, controlling the steric hindrance of polymer side chains and the spatial effects of hydrophilic and hydrophobic groups. Through free radical polymerization of hydrophobic amino acid vinyl monomers with hydrophilic monomers and zwitterionic monomers, a conductive hydrogel with tissue compatibility, biocompatibility, high wet tissue adhesion, and anti-swelling properties can be simply and efficiently constructed.

[0037] This invention provides a conductive hydrogel with high adhesion to moist tissues and resistance to swelling, as well as its preparation method. The hydrogel is obtained through free radical polymerization of hydrophobic amino acid vinyl monomers, hydrophilic monomers, and zwitterionic monomers in an aqueous solution. When in contact with moist biological tissues, the hydrogel effectively eliminates the interfacial hydration layer through the hydrophobic effect of its hydrophobic groups, and then combines with the non-covalent interactions between various hydrophilic groups and biological tissues to achieve rapid and firm adhesion to various biological tissues in a moist environment. Simultaneously, based on the hydrophobic effect, multiple intermolecular hydrogen bonds, and electrostatic interactions, the hydrogel exhibits stable and durable underwater anti-swelling properties, effectively resisting the penetration of external water molecules in high humidity or underwater environments. Furthermore, due to the introduction of conductive functional groups such as carboxyl and sulfonic acid groups, the hydrogel possesses excellent conductivity and bioelectric signal sensing capabilities, enabling stable transmission of various physiological signals in high humidity or underwater environments. The hydrogel prepared by this invention uses inexpensive and readily available raw materials, exhibits excellent mechanical properties, and good biocompatibility, which facilitates clinical translation and provides new options for applications in clinical emergency hemostasis, tissue damage repair, and flexible biosensing.

[0038] This highly wet tissue-adhesive, anti-swelling conductive hydrogel comprises hydrophobic amino acid vinyl structural units, hydrophilic structural units, and zwitterionic structural units.

[0039] In one embodiment, the ratio of hydrophobic amino acid vinyl structural units to hydrophilic structural units is 1:(8-20);

[0040] The ratio of hydrophobic amino acid vinyl structural units to zwitterionic structural units is 1:(0.9–3).

[0041] In one embodiment, the hydrophobic amino acid vinyl monomer corresponding to the hydrophobic amino acid vinyl structural unit is selected from one or more of N-acryloylalanine (AL), N-acryloylvaline (AV), N-acryloylphenylalanine (APA), N-acryloylleucine (ALE), N-acryloylisoleucine (AIL), N-acryloyltryptophan (ATP), N-acryloylmethionine (AMT), N-acryloylalanamide (ALN), N-acryloylvaline (AVN), and N-acryloylphenylalanamide (APN).

[0042] In one embodiment, the hydrophilic monomer corresponding to the hydrophilic structural unit is selected from one or more of acrylic acid (AA), methacrylic acid (MAA), 2-hydroxyethyl acrylate (HEA), hydroxyethyl methacrylate (HEMA), acrylamide (AM), N-trimethylolmethacrylamide (THMA), N,N-dimethylacrylamide (DMA), N-hydroxyethylacrylamide (HEAA), 1-vinyl-2-pyrrolidone (NVP), N-acryloylaspartic acid (AASP), N-acryloylglutamic acid (AGLU), N-acryloylglycine (AG), N-acryloyltyrosine (AT), N-acryloylserine (AS), N-acryloylthreonine (AT), and N-acryloylglutamine (AGT).

[0043] In one embodiment, the zwitterionic monomer corresponding to the zwitterionic structural unit is selected from one or more of 2-methacryloyloxyethyl phosphorylcholine (MPC), 3-[[2-(methacryloyloxy)ethyl]dimethylammonium]propionate (CBMA), [3-(methacryloylamino)propyl]dimethyl(3-thiopropyl)ammonium hydroxide (SBAA), and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA).

[0044] The preparation method of this highly moist tissue-adhesive, anti-swelling conductive hydrogel includes the following steps:

[0045] S1: A colorless and transparent mixture is obtained by fully dissolving hydrophobic amino acid vinyl monomers, hydrophilic monomers, and zwitterionic monomers in an aqueous solution.

[0046] S2: At room temperature, add the initiator and initiator accelerator and mix evenly to complete the free radical polymerization;

[0047] S3: Immerse the polymer in deionized water to obtain the high-moisture-adhesion, anti-swelling conductive hydrogel.

[0048] In one embodiment, the total concentration of the hydrophobic amino acid vinyl monomer and the hydrophilic monomer is 4.4–8.8 mol / L;

[0049] The concentration of the zwitterionic unit monomer is 0.2–1.8 mol / L.

[0050] In one embodiment, the concentration of the zwitterionic monomer is 0.2–1.8 mol / L;

[0051] In one embodiment, the initiator is selected from one or more of potassium persulfate, ammonium persulfate, and azobisisobutyrazoline hydrochloride;

[0052] The initiator / promoter is N,N,N',N'-tetramethylethylenediamine.

[0053] In one embodiment, the amount of the initiator added is 0.5% to 2% of the total mass of the hydrophobic amino acid vinyl monomer, the hydrophilic monomer, and the zwitterionic monomer;

[0054] The amount of the initiator accelerator added is 0-30% of the mass of the initiator.

[0055] In one embodiment, in step S1, the method of achieving complete dissolution is selected from one or more of heating, ultrasonication, and vortex oscillation;

[0056] In step S2, the polymerization temperature is 20–80℃, and the polymerization reaction time is 2–12 h;

[0057] In step S3, the soaking time is 21 to 24 hours.

[0058] Examples 1-19 are provided based on the preparation method of the high-moisture-adhesion, anti-swelling conductive hydrogel provided above.

[0059] The hydrophobic amino acid vinyl monomer mentioned in this invention is obtained according to the methods described in Biomacromolecules 2021, 22, 1297-1304; Sci. Adv. 2023, 9, eadg4031.

[0060] Example 1: P(APA) 0.7 -AA 7.0 -SBMA 0.6 )

[0061] Free radical copolymerization was carried out using APA, AA, and SBMA monomers: 153 mg APA, 504 mg AA, and 168 mg SBMA were dissolved in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.7 mol / L, the concentration of AA was 7.0 mol / L, and the concentration of SBMA was 0.6 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 8.3 mg ammonium persulfate was added as an initiator, and 2.5 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0062] Example 2: P(APA) 0.7 -AA 7.0 -SBMA 1.2 )

[0063] Free radical copolymerization was carried out using APA, AA, and SBMA monomers: 153 mg APA, 504 mg AA, and 335 mg SBMA were dissolved in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.7 mol / L, the concentration of AA was 7.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 9.9 mg ammonium persulfate was added as an initiator, and 3.0 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0064] Example 3: P(APA) 0.7 -AA 7.0 -SBMA 1.8 )

[0065] Free radical copolymerization was carried out using APA, AA, and SBMA monomers: 153 mg APA, 504 mg AA, and 503 mg SBMA were dissolved together in 1 mL of deionized water by heating at 60 °C, so as to make the concentration of APA 0.7 mol / L, the concentration of AA 7.0 mol / L, and the concentration of SBMA 1.8 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 11.6 mg ammonium persulfate was added as an initiator, and 3.5 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in an oven at 60 °C and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified high-moisture tissue adhesion anti-swelling conductive hydrogel.

[0066] Example 4: P(APA) 0.4 -AA 4.0 -SBMA 1.2 )

[0067] Free radical copolymerization was carried out using APA, AA, and SBMA monomers: 88 mg APA, 288 mg AA, and 335 mg SBMA were dissolved in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.4 mol / L, the concentration of AA was 4.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 7.1 mg ammonium persulfate was added as an initiator, and 2.1 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0068] Example 5: P(APA) 0.5 -AA 5.0 -SBMA 1.2 )

[0069] Free radical copolymerization was carried out using APA, AA, and SBMA monomers: 110 mg APA, 360 mg AA, and 335 mg SBMA were dissolved together in 1 mL of deionized water by heating at 60 °C, so as to make the concentration of APA 0.5 mol / L, the concentration of AA 5.0 mol / L, and the concentration of SBMA 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 8.0 mg ammonium persulfate was added as an initiator, and 2.4 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0070] Example 6: P(APA) 0.6 -AA 6.0 -SBMA 1.2 )

[0071] Free radical copolymerization was carried out using APA, AA, and SBMA monomers: 131 mg APA, 432 mg AA, and 335 mg SBMA were dissolved together in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.6 mol / L, the concentration of AA was 6.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 9.0 mg ammonium persulfate was added as an initiator, and 2.7 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0072] Example 7: P(APA) 0.8 -AA 8.0 -SBMA 1.2 )

[0073] Free radical copolymerization was carried out using APA, AA, and SBMA monomers: 175 mg APA, 576 mg AA, and 335 mg SBMA were dissolved in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.8 mol / L, the concentration of AA was 8.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 10.9 mg ammonium persulfate was added as an initiator, and 3.3 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0074] Example 8: P(AL) 0.7 -AA 7.0 -SBMA 1.2 )

[0075] Free radical copolymerization was carried out using AL, AA, and SBMA monomers: 100 mg AL, 504 mg AA, and 335 mg SBMA were dissolved together in 1 mL of deionized water by heating at 60 °C, so as to make the concentration of AL 0.7 mol / L, the concentration of AA 7.0 mol / L, and the concentration of SBMA 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 9.4 mg ammonium persulfate was added as an initiator, and 2.8 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in an oven at 60 °C and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly wettable, tissue-adhesive, anti-swelling conductive hydrogel.

[0076] Example 9: P(AV) 0.7 -AA 7.0 -SBMA 1.2 )

[0077] Free radical copolymerization was carried out using AV, AA, and SBMA monomers: 120 mg AV, 504 mg AA, and 335 mg SBMA were dissolved together in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of AV was 0.7 mol / L, the concentration of AA was 7.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 9.6 mg ammonium persulfate was added as an initiator, and 2.9 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly wettable, tissue-adhesive, anti-swelling conductive hydrogel.

[0078] Example 10: P(ALE) 0.7 -AA 7.0 -SBMA 1.2 )

[0079] Free radical copolymerization was carried out using ALE, AA, and SBMA monomers: 130 mg ALE, 504 mg AA, and 335 mg SBMA were dissolved together in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of ALE was 0.7 mol / L, the concentration of AA was 7.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 9.7 mg ammonium persulfate was added as an initiator, and 2.9 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0080] Example 11: P(AIL) 0.7 -AA 7.0 -SBMA 1.2 )

[0081] Free radical copolymerization was carried out using AIL, AA, and SBMA monomers: 130 mg AIL, 504 mg AA, and 335 mg SBMA were dissolved in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of AIL was 0.7 mol / L, the concentration of AA was 7.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 9.7 mg ammonium persulfate was added as an initiator, and 2.9 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0082] Example 12: P(ATP) 0.7 -AA 7.0 -SBMA 1.2 )

[0083] Free radical copolymerization was carried out using ATP, AA, and SBMA monomers: 181 mg ATP, 504 mg AA, and 335 mg SBMA were dissolved together in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing to achieve a concentration of 0.7 mol / L for ATP, 7.0 mol / L for AA, and 1.2 mol / L for SBMA. After complete dissolution, the mixed solution was cooled to room temperature, and 10.2 mg ammonium persulfate was added as an initiator, along with 3.1 mg N,N,N',N'-tetramethylethylenediamine as an initiator accelerator. After thorough mixing, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. This hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0084] Example 13: P(APA) 0.7 -MAA 7.0 -SBMA 1.2 )

[0085] Free radical copolymerization was carried out using APA, MAA, and SBMA monomers: 153 mg APA, 603 mg MAA, and 335 mg SBMA were dissolved together in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.7 mol / L, the concentration of MAA was 7.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 10.9 mg ammonium persulfate was added as an initiator, and 3.3 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in an oven at 60 °C and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0086] Example 14: P(APA) 0.7 -HEAA 7.0 -SBMA 1.2 )

[0087] Free radical copolymerization was carried out using APA, HEAA, and SBMA monomers: 153 mg APA, 806 mg HEAA, and 335 mg SBMA were dissolved in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.7 mol / L, the concentration of HEAA was 7.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 12.9 mg ammonium persulfate was added as an initiator, and 3.9 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0088] Example 15: P(APA) 0.7 -AG 7.0 -SBMA 1.2 )

[0089] Free radical copolymerization was carried out using APA, AG, and SBMA monomers: 153 mg APA, 904 mg AG, and 335 mg SBMA were dissolved in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.7 mol / L, the concentration of AG was 7.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 13.9 mg ammonium persulfate was added as an initiator, and 4.2 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0090] Example 16: P(APA) 0.7 -AASP 7.0 -SBMA 1.2 )

[0091] Free radical copolymerization was carried out using APA, AASP, and SBMA monomers: 153 mg APA, 1310 mg AASP, and 335 mg SBMA were dissolved together in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.7 mol / L, the concentration of AASP was 7.0 mol / L, and the concentration of SBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 18.0 mg ammonium persulfate was added as an initiator, and 5.4 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0092] Example 17: P(APA) 0.7 -AA 7.0 -MPC 1.2 )

[0093] Free radical copolymerization was carried out using APA, AA, and MPC monomers: 153 mg APA, 504 mg AA, and 354 mg MPC were dissolved together in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.7 mol / L, the concentration of AA was 7.0 mol / L, and the concentration of MPC was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 10.1 mg ammonium persulfate was added as an initiator, and 3.0 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0094] Example 18: P(APA) 0.7 -AA 7.0 -CBMA 1.2 )

[0095] Free radical copolymerization was carried out using APA, AA, and CBMA monomers: 153 mg APA, 504 mg AA, and 275 mg CBMA were dissolved in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.7 mol / L, the concentration of AA was 7.0 mol / L, and the concentration of CBMA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 9.3 mg ammonium persulfate was added as an initiator, and 2.8 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0096] Example 19: P(APA) 0.7 -AA 7.0 -SBAA 1.2 )

[0097] Free radical copolymerization was carried out using APA, AA, and SBAA monomers: 153 mg APA, 504 mg AA, and 351 mg SBAA were dissolved in 1 mL of deionized water by heating at 60 °C, sonication, and vortexing, so that the concentration of APA was 0.7 mol / L, the concentration of AA was 7.0 mol / L, and the concentration of SBAA was 1.2 mol / L. After complete dissolution, the mixed solution was cooled to room temperature, and 10.1 mg ammonium persulfate was added as an initiator, and 3.0 mg N,N,N',N'-tetramethylethylenediamine was added as an initiator accelerator. After mixing evenly, the mixture was placed in a 60 °C oven and allowed to stand for 3 h to initially obtain a hydrogel. The hydrogel was then immersed in deionized water for 24 h to finally obtain a purified, highly moist, tissue-adhesive, anti-swelling conductive hydrogel.

[0098] Effect test:

[0099] Figure 1 The wet bond strength of the hydrogels provided in Examples 2, 5, 6, and 7 to pigskin was demonstrated. The wet bond strength gradually increased with increasing content of hydrophobic amino acid vinyl monomers and hydrophilic monomers. The hydrogel provided in Example 7 exhibited a wet bond strength as high as 93 kPa, showing a significant advantage over catechol-based hydrogel patches (Adv. Mater. 2023, 35, 2209606; Biomaterials 2023, 301, 122240).

[0100] Figure 2 The hydrogel provided in Example 2 demonstrated strong wet adhesion strength and robust bonding interface toughness with different porcine tissues (including liver, lungs, heart, stomach, arteries, and skin).

[0101] Figure 3 The swelling rate changes of the hydrogel provided in Example 2 when immersed in deionized water and simulated seawater solutions are demonstrated. The hydrogel exhibits anti-swelling properties in aqueous solutions, with a swelling rate of less than 4% after 10 days of immersion; furthermore, the hydrogel exhibits anti-dehydration properties in simulated seawater solutions, with a water loss rate of less than 1% after 10 days of immersion.

[0102] Figure 4 This study demonstrates a comparative test of electromyography (EMG) signal collection using a modified hydrogel electrode patch (provided in Example 2) and an unmodified commercial electrode patch (from Hangzhou Xunda Radio Equipment Co., Ltd.), both attached to the forearm and immersed in an aqueous solution. The hydrogel electrode patch was obtained by replacing the adhesive tape and conductive hydrogel of the commercial electrode patch with the hydrogel provided in Example 2. The weight lifted by the forearm in the test was 2.5 kg. During the test, the hydrogel electrode patch exhibited stable signal output and maintained a consistently high signal-to-noise ratio, while the commercial electrode patch showed significant signal attenuation and ultimately exhibited a lower signal-to-noise ratio. These results indicate that the hydrogel provided by this invention possesses stable and durable underwater conductivity and sensing capabilities.

[0103] The conductive hydrogel with high moisture adhesion and anti-swelling properties provided by this invention can achieve rapid and firm adhesion to moist biological tissues. Simultaneously, this hydrogel exhibits stable and durable underwater anti-swelling properties, effectively resisting the penetration of external water molecules in high humidity or underwater environments. Furthermore, this hydrogel possesses long-term stable conductivity and bioelectric signal sensing capabilities, enabling stable transmission of various physiological signals from the human body in high humidity or underwater environments. The hydrogel prepared by this invention uses inexpensive and readily available raw materials, exhibits excellent mechanical properties, and demonstrates good biocompatibility, facilitating clinical translation and providing new options for applications in clinical emergency hemostasis, tissue damage repair, and flexible biosensing.

Claims

1. A conductive hydrogel with high wet tissue adhesion and anti-swelling properties, characterized in that, It includes hydrophobic amino acid vinyl structural units, hydrophilic structural units, and zwitterionic structural units; The ratio of the hydrophobic amino acid vinyl structural units to the hydrophilic structural units is 1: (8~20); The ratio of the hydrophobic amino acid vinyl structural unit to the zwitterionic structural unit is 1:(0.9~3); The hydrophobic amino acid vinyl monomer corresponding to the hydrophobic amino acid vinyl structural unit is selected from one or more of N-acryloylalanine, N-acryloylvaline, N-acryloylphenylalanine, N-acryloylleucine, N-acryloylisoleucine, N-acryloyltryptophan, N-acryloylmethionine, N-acryloylalanamide, N-acryloylvaline, and N-acryloylphenylalanamide. The hydrophilic monomer corresponding to the hydrophilic structural unit is selected from one or more of the following: acrylic acid, methacrylic acid, 2-hydroxyethyl acrylate, hydroxyethyl methacrylate, acrylamide, N-trimethylolmethacrylamide, N,N-dimethylacrylamide, N-hydroxyethylacrylamide, 1-vinyl-2-pyrrolidone, N-acryloylaspartic acid, N-acryloylglutamic acid, N-acryloylglycine, N-acryloyltyrosine, N-acryloylserine, N-acryloylthreonine, and N-acryloylglutamine. The zwitterionic monomer corresponding to the zwitterionic structural unit is selected from one or more of 2-methacryloyloxyethyl phosphorylcholine, 3-[[2-(methacryloyloxy)ethyl]dimethylammonium]propionate, [3-(methacryloylamino)propyl]dimethyl(3-thiopropyl)ammonium hydroxide and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide.

2. A method for preparing a conductive hydrogel with high wet tissue adhesion and anti-swelling properties as described in claim 1, characterized in that, Includes the following steps: S1: A colorless and transparent mixture is obtained by fully dissolving hydrophobic amino acid vinyl monomers, hydrophilic monomers, and zwitterionic monomers in an aqueous solution. S2: At room temperature, add the initiator and initiator accelerator and mix evenly to complete the free radical polymerization; S3: Soak the polymer in deionized water to obtain the high-moisture-adhesion, anti-swelling conductive hydrogel. The total concentration of the hydrophobic amino acid vinyl monomer and the hydrophilic monomer is 4.4~8.8 mol / L; The concentration of the zwitterionic unit monomer is 0.2~1.8 mol / L.

3. The method for preparing the conductive hydrogel with high moisture adhesion and anti-swelling properties as described in claim 2, characterized in that, The initiator is selected from one or more of potassium persulfate, ammonium persulfate, and azobisisobutyrazoline hydrochloride; The initiator / promoter is N,N,N',N'-tetramethylethylenediamine.

4. The method for preparing the conductive hydrogel with high moisture adhesion and anti-swelling properties as described in claim 2, characterized in that, The amount of the initiator added is 0.5% to 2% of the total mass of the hydrophobic amino acid vinyl monomer, the hydrophilic monomer, and the zwitterionic monomer; The amount of the initiator accelerator added is 0-30% of the mass of the initiator.

5. The method for preparing the conductive hydrogel with high moisture adhesion and anti-swelling properties as described in claim 2, characterized in that, In step S1, the method of complete dissolution is selected from one or more of heating, ultrasonication, and vortex oscillation; In step S2, the polymerization temperature is 20~80 ℃, and the polymerization reaction time is 2~12 h; In step S3, the soaking time is 21~24 h.

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