Underwater adhesion-on-demand debonding wet tissue adhesive and preparation method thereof

Abstract

The invention discloses a preparation method of an underwater adhesion-on-demand debonding wet tissue adhesive. The preparation method comprises the following steps: 1, preparing an imitated byssus protein aggregate solution: respectively dissolving a short-chain high-molecular polymer and a natural polyphenol compound in deionized water to obtain the imitated byssus protein aggregate solution; 2, preparation of a powerful wet tissue adhesive: adding a long-chain high-molecular polymer, a cross-linking agent and a free radical initiator into the byssus-like protein aggregate solution to obtain the powerful wet tissue adhesive; and 3, preparing the underwater adhesion-on-demand debonding wet tissue adhesive: introducing the natural polysaccharide into the powerful wet tissue adhesive, and blending to obtain the underwater adhesion-on-demand debonding wet tissue adhesive. According to the preparation method of the underwater adhesion-on-demand debonding wet tissue adhesive provided by the invention, powerful adhesion can be realized in an underwater environment, so that a hemostatic effect is quickly achieved; and meanwhile, the device has the characteristic of instant debonding according to needs, so that rapid debonding can be realized when the wounded person is transferred to the back for further treatment.

Description

Technical Field

[0001] The present invention belongs to the technical field of tissue adhesives, and relates to an underwater adhesion-on-demand debonding wet tissue adhesive. The present invention also relates to a preparation method of the adhesive. Background Art

[0002] In the marine environment, workers or divers who sustain injuries are vulnerable to exposure to high osmotic pressure, weak alkalinity (≈8.1), and a high concentration of pathogenic bacteria in seawater, increasing the risk of infection and inflammation. Traditional adhesives, however, debond underwater due to low cohesion, preventing effective hemostasis. The development of highly efficient underwater wet tissue adhesives with on-demand adhesion and debonding is urgently needed. Furthermore, when patients are transferred to a remote location for further treatment, the conflict between strong adhesion and instantaneous debonding is faced. Therefore, instantaneous debonding is crucial to minimizing secondary wound damage.

[0003] Currently, existing hemostatic dressings primarily include alginate dressings, hydrocolloid wound dressings, and film-based hemostatic dressings. However, these dressings primarily operate on land and in sanitary environments, and each has its own limitations and hazards. For example, alginate dressings have drawbacks such as odor, increased risk of wound infection, and secondary damage during replacement. Hydrocolloid wound dressings are unsuitable for wounds with high exudate and infection. Film-based hemostatic dressings have drawbacks such as poor absorption and inability to maintain strong adhesion underwater.

[0004] Therefore, the development of highly efficient underwater adhesives that adhere and debond on demand is crucial. These adhesives not only quickly stop bleeding and prevent wound infection, but also reduce secondary wound damage when the injured person needs to be transferred to a remote location for follow-up treatment. This significantly improves the patient's chance of survival in emergency situations and the effectiveness of subsequent treatment.

[0005] A Chinese invention patent application, "A Method for Preparing a Demand-Removable Hydrogel Tissue Adhesive," filed on November 9, 2022, with application number CN202211397046.2, discloses a method for preparing a demand-removable hydrogel tissue adhesive. This method triggers a transient gel-sol-gel transition by adding cyclodextrin (γ-CD), enabling on-demand disassembly of the hydrogel tissue adhesive. However, the hydrogel's adhesive properties are insufficient to adhere firmly to wounds underwater and cannot effectively prevent wound infection, making it difficult to meet the requirements for strong underwater adhesion.

[0006] The Chinese invention patent "A dual-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch and its preparation method" with an application date of June 8, 2022 and application number CN202210638254.0 discloses a dual-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch and its preparation method. The method is to mix the hydrogel material of mussel biomimetic components and gelatin powder and dissolve them in a PBS solution to obtain a composite tissue adhesive precursor solution, which is then added to the octopus suction cup biomimetic structure positive mold template, irradiated for cross-linking, and dried to obtain the dual-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch. However, in the marine environment, after workers or divers are injured, dressings need to be changed frequently to prevent wound infection. This characteristic of not being able to be debonded on demand is obviously not suitable for underwater wound treatment scenarios and is not conducive to the patient's recovery.

[0007] The Chinese invention patent application, "Preparation Method and Application of a Sericin Adhesive," filed on June 30, 2021, with application number CN202110740024.0, discloses a method for preparing and applying a sericin adhesive. This method promotes drainage from tissue surfaces by adjusting the hydrophilic and hydrophobic balance of the adhesive components, providing high-strength adhesion. However, due to the high humidity and salinity in the marine environment, this adhesive struggles to maintain its high-strength adhesion underwater, as it does in terrestrial environments, making it ineffective for hemostasis and infection prevention. Summary of the Invention

[0008] The first objective of the present invention is to provide a method for preparing an underwater adhesion-on-demand debonding wet tissue adhesive that can achieve strong adhesion in an underwater environment, thereby quickly achieving a hemostatic effect; at the same time, it has the characteristic of instantaneous debonding on demand, facilitating rapid debonding when the injured person is transferred to the rear for further treatment.

[0009] The second object of the present invention is to provide an underwater adhesion-on-demand debonding wet tissue adhesive prepared according to the above-mentioned method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive.

[0010] The first technical solution adopted by the present invention is a method for preparing an underwater adhesion-on-demand debonding wet tissue adhesive, the specific method is as follows: Step 1, preparing a byssin-mimicking protein aggregate solution: dissolving a short-chain high molecular weight polymer and a natural polyphenol compound in deionized water to obtain a byssin-mimicking protein aggregate solution; Step 2, preparing a strong wet tissue adhesive: adding a long-chain high molecular weight polymer, a cross-linking agent, and a free radical initiator to the byssus protein aggregate solution to obtain a strong wet tissue adhesive; Step 3: preparing an underwater adhesion-on-demand debonding wet tissue adhesive: introducing a natural polysaccharide into a strong wet tissue adhesive and blending them together to obtain an underwater adhesion-on-demand debonding wet tissue adhesive.

[0011] The present invention is also characterized in that: The specific method of step 1 is as follows: The short-chain high molecular polymer is dissolved in deionized water and stirred at 60-80°C and 300 rpm for 2-3 hours to form a first homogeneous solution; then, the natural polyphenol compound is added to the first homogeneous solution and stirred at 25-40°C and 300 rpm for 2-3 hours to form a foot silk protein aggregate solution.

[0012] The concentration of the short-chain high molecular polymer is 2% to 3% w / v, and the concentration of the natural polyphenol compound is 2% to 3% w / v.

[0013] The short-chain high molecular polymer is any one of polyvinyl pyrrolidone, polyethylene glycol or polyvinyl alcohol; The natural polyphenol compound is any one of tannic acid, polyglutamic acid or dopamine.

[0014] The specific method of step 2 is as follows: A long-chain polymer is added to the byssin-like protein coacervate solution, followed by the addition of a cross-linking agent and a free radical initiator, and the mixture is stirred at 70-80°C for 1-3 hours to uniformly disperse the long-chain polymer in the coacervate solution, thereby obtaining a strong wet tissue adhesive.

[0015] The mass ratio of the long-chain polymer to the byssin-mimicking protein aggregate solution is 10%-30%, the mass ratio of the crosslinking agent to the byssin-mimicking protein aggregate solution is 0.02%-0.04%, and the mass ratio of the free radical initiator to the byssin-mimicking protein aggregate solution is 0.05%-0.15%.

[0016] The long-chain high molecular polymer is any one of polymaleic acid, polymethacrylic acid or polyacrylic acid; The cross-linking agent is any one of N,N′-bis(acryloyl)cysteine, 4,4′-dimercaptodibenzamide or 3,3′-dimercaptodipropionic acid; The free radical initiator is any one of 2,2′-azobis(2-methylpropionamide) dihydrochloride, ammonium persulfate or N-hydroxysuccinimide.

[0017] The specific method of step 3 is as follows: The natural polysaccharide was introduced into a strong wet tissue adhesive and mixed, and stirred at 60-80°C and 290-310 rpm for 2-3 hours to form a second homogeneous solution. Subsequently, a 0.05-0.15 mol / L CaCl2 solution was added and stirred for 10-30 minutes for cross-linking to obtain an underwater adhesion-on-demand debonding wet tissue adhesive. Apply the cross-linked adhesive solution to the surface to be adhered, or pour it into a mold to form it; when debonding is required, soak the adhesive part in ethylenediaminetetraacetic acid solution for 1 to 2 minutes to complete the debonding.

[0018] The natural polysaccharide is any one of sodium alginate, chitosan or hyaluronic acid. The mass ratio of the natural polysaccharide to the strong wet tissue adhesive is 3% to 5%, and the mass ratio of the natural polysaccharide to the CaCl2 solution is 3 to 9.01:1.

[0019] The concentration of EDTA solution is 0.4~0.6mol / L.

[0020] The second technical solution adopted by the present invention is to prepare the underwater adhesion-on-demand debonding wet tissue adhesive according to the preparation method of the above-mentioned underwater adhesion-on-demand debonding wet tissue adhesive.

[0021] The beneficial effects of the present invention are: (1) The present invention relates to a method for preparing an underwater adhesion-on-demand debonding wet tissue adhesive. This method develops an ion-responsive tissue adhesive that combines strong underwater wet adhesion with instant on-demand debonding. Interfacial water removal is achieved through interactions between hydrophobic groups. Simultaneously, hydrogen bonds formed between catechol and hydroxyl groups synergistically construct a dynamic reversible network. When mechanically damaged, this network structure dissipates energy through the reversible breaking and reconstruction of hydrogen bonds, thereby endowing the adhesive with self-healing properties and ensuring its stability and reliability in complex environments. (2) The preparation method of the underwater adhesion-on-demand debonding wet tissue adhesive of the present invention, the long-chain polymer and the short-chain polymer are combined by covalent bonds and penetrate into the cohesive network by means of chemical cross-linking reaction, thereby forming a mixed double network structure. In this process, the two networks are intertwined and act synergistically, so that when the adhesive is subjected to external force, it can dissipate energy by sacrificing part of the network while maintaining the integrity of the overall structure. Finally, the carboxyl group of the natural polysaccharide and the Ca 2+ The ionic cross-linking reaction between the adhesive and the bonding agent not only enhances the mechanical properties of the adhesive but also gives it the ability to debond on demand. (3) In the preparation method of the underwater adhesion-on-demand debonding wet tissue adhesive of the present invention, EDTA (a strong chelating agent) will preferentially bind to Ca 2+ Combines to form a stable chelate [Ca(EDTA)] 2- , which can effectively remove Ca in the cross-linked network 2+ , thereby destroying the ionic crosslinks and disintegrating the three-dimensional network, ultimately achieving on-demand debonding. Furthermore, the debonding process is not restricted by external conditions such as temperature and pH. This characteristic is particularly important in clinical practice, improving the safety and convenience of surgery and wound treatment while significantly reducing patient pain and the risk of complications. DETAILED DESCRIPTION

[0022] The present invention is described in detail below with reference to specific embodiments.

[0023] The preparation method of the underwater adhesion-on-demand debonding wet tissue adhesive of the present invention is as follows: Step 1: Prepare a solution of mimetic byssin protein aggregates: Dissolve the short-chain polymer and the natural polyphenol compound in deionized water to obtain a solution of mimetic byssin protein aggregates. The specific method is as follows: The short-chain high molecular polymer is dissolved in deionized water and stirred at 60-80°C and 300 rpm for 2-3 hours to form a first homogeneous solution; then, the natural polyphenol compound is added to the first homogeneous solution and stirred at 25-40°C and 300 rpm for 2-3 hours to form a foot silk protein aggregate solution.

[0024] The short-chain polymer is any one of polyvinyl pyrrolidone, polyethylene glycol or polyvinyl alcohol, and the concentration of the short-chain polymer is 2% to 3% w / v; The natural polyphenol compound is any one of tannic acid, polyglutamic acid or dopamine, and the concentration of the natural polyphenol compound is 2% to 3% w / v.

[0025] Step 2: Preparation of a strong wet tissue adhesive: Adding a long-chain polymer, a crosslinking agent, and a free radical initiator to the byssin-like protein aggregate solution to obtain a strong wet tissue adhesive; the specific method is as follows: A long-chain polymer is added to the byssin-like protein coacervate solution, followed by the addition of a cross-linking agent and a free radical initiator, and the mixture is stirred at 70-80°C for 1-3 hours to uniformly disperse the long-chain polymer in the coacervate solution, thereby obtaining a strong wet tissue adhesive.

[0026] Wherein, the long-chain high molecular polymer is any one of polymaleic acid, polymethacrylic acid or polyacrylic acid; The cross-linking agent is any one of N,N′-bis(acryloyl)cysteine, 4,4′-dimercaptodibenzamide or 3,3′-dimercaptodipropionic acid; The free radical initiator is any one of 2,2′-azobis(2-methylpropionamide) dihydrochloride, ammonium persulfate or N-hydroxysuccinimide.

[0027] The mass ratio of the long-chain polymer to the byssin-mimicking protein aggregate solution is 10%-30%, the mass ratio of the crosslinking agent to the byssin-mimicking protein aggregate solution is 0.02%-0.04%, and the mass ratio of the free radical initiator to the byssin-mimicking protein aggregate solution is 0.05%-0.15%.

[0028] Step 3: Preparation of underwater adhesion-on-demand debonding wet tissue adhesive: Introduce natural polysaccharide into strong wet tissue adhesive and blend them to obtain underwater adhesion-on-demand debonding wet tissue adhesive. The specific method is as follows: Natural polysaccharides are introduced into a strong wet tissue adhesive and blended, stirred at 60-80°C and 290-310 rpm for 2-3 hours to form a second homogeneous solution. Subsequently, 0.05-0.15 mol / LCaCl2 solution is added and stirred for 10-30 minutes for cross-linking.

[0029] The natural polysaccharide is any one of sodium alginate, chitosan or hyaluronic acid, the mass ratio of the natural polysaccharide to the strong wet tissue adhesive is 3% to 5%, and the mass ratio of the natural polysaccharide to the CaCl2 solution is 3 to 9.01:1.

[0030] The concentration of ethylenediaminetetraacetic acid (EDTA) solution is 0.4~0.6mol / L.

[0031] Apply the cross-linked adhesive solution to the surface to be adhered, or pour it into a mold to form it; when debonding is required, soak the adhesive part in EDTA solution for 1~2 minutes to remove Ca 2+ , which leads to network dissociation and debonding.

[0032] This invention combines the strong underwater adhesion of mussels with an ion-responsive dynamic cross-linking mechanism to develop an underwater, highly efficient adhesion-on-demand wet tissue adhesive: First, the interaction between hydrophobic groups removes interfacial water. Simultaneously, the hydrogen bonds formed between catechol and hydroxyl groups synergize to form a dynamic, reversible network structure. When mechanically damaged, the hydrogen bonds within this structure reversibly break and reconstruct, dissipating energy and achieving self-healing properties, ensuring the adhesive's stability and reliability in complex environments.

[0033] Secondly, long-chain polymers and short-chain polymers are covalently bonded and penetrate the aggregate network through chemical cross-linking reactions, forming a complex hybrid dual-network structure. These two networks intertwine and act synergistically. When the tissue adhesive is subjected to external forces, it can dissipate energy by sacrificing parts of the network while maintaining the integrity of the overall structure.

[0034] Finally, the carboxyl groups of natural polysaccharides react with Ca 2+ The ionic cross-linking reaction between the adhesive and the EDTA can enhance the mechanical properties of the adhesive and give it the characteristic of on-demand debonding. On-demand debonding is achieved by EDTA, which is a strong chelating agent that preferentially binds to Ca 2+ Combines to form a stable chelate [Ca(EDTA)] 2- This process can convert Ca 2+By removing the cross-linked polysaccharide from the natural polysaccharide network, the cross-links are broken, leading to the disintegration of the three-dimensional network and achieving on-demand debonding. Furthermore, this debonding process is not restricted by external conditions such as temperature and pH. This on-demand debonding property is of great significance in clinical applications, improving the safety and convenience of surgery and wound treatment, and reducing pain and complications for patients.

[0035] Example 1 Step 1: Preparation of foot silk protein aggregate solution Polyvinylpyrrolidone (PVP) (2.5% w / v) was dissolved in deionized water (DI) and stirred at 80°C and 300 rpm for 2 hours until it was completely dissolved to form a homogeneous solution. Subsequently, tannic acid (2.5% w / v) was added to the above polymer solution and stirred at 40°C and 300 rpm for 2 hours to form a viscous coacervate solution. Step 2: Prepare a strong wet tissue adhesive 10% polymaleic acid (PMAA) was added to the coacervate solution, and 0.03% N,N′-bis(acryloyl)cysteine ​​(BAC) and 0.15% 2,2′-azobis(2-methylpropionamide) dihydrochloride (AIBN) were added. The mixture was stirred at 70°C for 2 h to allow the polymaleic acid (PMAA) to be uniformly dispersed in the coacervate solution and to initiate polymerization. Step 3: Prepare underwater adhesion-on-demand debonding wet tissue adhesive 5% sodium alginate was introduced into the tissue adhesive and mixed, stirring at 60°C and 300 rpm for 2 hours until the sodium alginate was completely dissolved and a homogeneous solution was formed. Subsequently, 0.1 M CaCl2 was added and stirred for 10 minutes to ensure sufficient cross-linking.

[0036] Apply the cross-linked adhesive solution to the surface to be adhered, or pour it into a mold to form it. When debonding is required, soak the adhesive part in EDTA solution (0.5 mol / l) for 1 minute to remove Ca 2+ , leading to network disintegration.

[0037] Example 2 Step 1: Preparation of foot silk protein aggregate solution The specific steps are as follows: polyvinyl alcohol (PVA) (2% w / v) was dissolved in deionized water (DI) and stirred at 60°C and 300 rpm for 3 hours until it was completely dissolved to form a homogeneous solution; then, tannic acid (2% w / v) was added to the above polymer solution and stirred at 30°C and 300 rpm for 3 hours to form a viscous coacervate solution; Step 2: Prepare a strong wet tissue adhesive The specific steps are as follows: 20% polyacrylic acid (PAA) is added to the coacervate solution, and 0.03% N,N′-bis(acryloyl)cysteine ​​(BAC) and 0.15% N-hydroxysuccinimide are added. The mixture is stirred at 70°C for 1 hour to allow the polyacrylic acid (PAA) to be evenly dispersed in the coacervate solution and initiate polymerization. Step 3: Prepare underwater adhesion-on-demand debonding wet tissue adhesive 5% chitosan was introduced into the tissue adhesive and mixed, stirring at 70°C and 300 rpm for 3 hours until the chitosan was completely dissolved and a homogeneous solution was formed. Subsequently, 0.15 mol / l CaCl2 was added and stirred for 30 minutes to ensure sufficient cross-linking.

[0038] Apply the cross-linked adhesive solution to the surface to be adhered, or pour it into a mold to form it. When debonding is required, soak the adhesive part in EDTA solution (0.4M) for 2 minutes to remove Ca 2+ , leading to network disintegration.

[0039] Example 3 Step 1: Preparation of foot silk protein aggregate solution Specific steps: Polyethylene glycol (PEG) (3% w / v) was dissolved in deionized water (DI) and stirred at 70°C and 300 rpm for 2.5 hours until completely dissolved to form a homogeneous solution. Subsequently, polyglutamic acid (3% w / v) was added to the above polymer solution and stirred at 25°C and 300 rpm for 2.5 hours to form a viscous coacervate solution. Step 2: Prepare a strong wet tissue adhesive The specific steps are as follows: 20% polyacrylic acid (PAA) is added to the coacervate solution, and 0.03% N,N′-bis(acryloyl)cysteine ​​(BAC) and 0.15% ammonium persulfate (APS) are added. The mixture is stirred at 80°C for 3 hours to allow the polyacrylic acid (PAA) to be evenly dispersed in the coacervate solution and initiate polymerization. Step 3: Prepare underwater adhesion-on-demand debonding wet tissue adhesive 3% hyaluronic acid was introduced into the tissue adhesive and mixed, stirring at 80°C and 300 rpm for 2.5 hours until the hyaluronic acid was completely dissolved and a homogeneous solution was formed. Subsequently, 0.05% M CaCl2 was added and stirred for 20 minutes to ensure sufficient cross-linking.

[0040] Apply the cross-linked adhesive solution to the surface to be adhered, or pour it into a mold to form it. When debonding is required, soak the adhesive part in EDTA solution (0.6M) for 1 minute to remove Ca 2+ , leading to network dissociation; Example 4 Step 1: Preparation of foot silk protein aggregate solution Polyethylene glycol (PEG) (2.5% w / v) was dissolved in deionized water (DI) and stirred at 70°C and 300 rpm for 2 hours until it was completely dissolved to form a homogeneous solution. Subsequently, dopamine (2.5% w / v) was added to the above polymer solution and stirred at 25°C and 300 rpm for 2 hours to form a viscous coacervate solution. Step 2: Prepare a strong wet tissue adhesive 30% polymethacrylic acid (PMA) was added to the coacervate solution, and 0.02% 4,4′-dimercaptodibenzamide (DMPA) and 0.1% N-hydroxysuccinimide were added, and stirred at 75°C for 2 hours to allow the polymethacrylic acid (PMA) to be uniformly dispersed in the coacervate solution and initiate polymerization; Step 3: Prepare underwater adhesion-on-demand debonding wet tissue adhesive 5% sodium alginate was introduced into the tissue adhesive and stirred at 70°C and 310 rpm for 2 hours until the natural polysaccharide was completely dissolved and a homogeneous solution was formed. Subsequently, 0.12 M CaCl2 was added and stirred for 20 minutes to ensure sufficient cross-linking.

[0041] Apply the cross-linked adhesive solution to the surface to be adhered, or pour it into a mold to form it. When debonding is required, soak the adhesive part in EDTA solution (0.5M) for 2 minutes to remove Ca 2+ , leading to network dissociation; Example 5 Step 1: Preparation of foot silk protein aggregate solution Polyvinyl alcohol (PVA) (2.5% w / v) was dissolved in deionized water (DI) and stirred at 80°C and 300 rpm for 2 hours until it was completely dissolved to form a homogeneous solution. Subsequently, polyglutamic acid (2.5% w / v) was added to the above polymer solution and stirred at 25°C and 300 rpm for 2 hours to form a viscous coacervate solution. Step 2: Prepare a strong wet tissue adhesive 10% polyacrylic acid (PAA) was added to the coacervate solution, and 0.04% 3,3′-dimercaptodipropionic acid and 0.15% 2,2′-azobis(2-methylpropionamide) dihydrochloride (AIBN) were added. The mixture was stirred at 70°C for 2 h to allow the polyacrylic acid (PAA) to be uniformly dispersed in the coacervate solution and to initiate polymerization. Step 3: Prepare underwater adhesion-on-demand debonding wet tissue adhesive 4% chitosan was introduced into the tissue adhesive and stirred at 80°C and 290 rpm for 2 hours until the chitosan was completely dissolved and a homogeneous solution was formed. Subsequently, 0.1 M CaCl2 was added and stirred for 10 minutes to ensure sufficient cross-linking.

[0042] Apply the cross-linked adhesive solution to the surface to be adhered, or pour it into a mold to form it. When debonding is required, soak the adhesive part in EDTA solution (0.5M) for 2 minutes to remove Ca 2+ , leading to network disintegration.

[0043] Example 6 Step 1: Preparation of foot silk protein aggregate solution Polyethylene glycol (PEG) (2.5% w / v) was dissolved in deionized water (DI) and stirred at 60°C and 300 rpm for 2 hours until it was completely dissolved to form a homogeneous solution. Subsequently, tannic acid (2.5% w / v) was added to the polymer solution and stirred at 40°C and 300 rpm for 2 hours to form a viscous coacervate solution. Step 2: Prepare a strong wet tissue adhesive 20% polyacrylic acid (PAA) was added to the coacervate solution, and 0.03% 3,3′-dimercaptodipropionic acid (DMPA) and 0.05% ammonium persulfate (APS) were added. The mixture was stirred at 75°C for 2 h to allow the polyacrylic acid (PAA) to be uniformly dispersed in the coacervate solution and to initiate polymerization. Step 3: Prepare underwater adhesion-on-demand debonding wet tissue adhesive 4% hyaluronic acid was introduced into the tissue adhesive and mixed, stirring at 80°C and 300 rpm for 2 hours until the natural polysaccharide was completely dissolved and a homogeneous solution was formed. Subsequently, 0.1 M CaCl2 was added and stirred for 30 minutes to ensure sufficient cross-linking.

[0044] Apply the cross-linked adhesive solution to the surface to be adhered, or pour it into a mold to form it. When debonding is required, soak the adhesive part in EDTA solution (0.5M) for 1 minute to remove Ca 2+ , leading to network disintegration.

[0045] A comparison table of experimental performance test results of the tissue adhesive materials prepared in Examples 1 to 6 of the present invention and commercial fibrin adhesives and cyanoacrylate adhesives is shown in Table 1. The tested properties include: adhesion strength in a dry environment, adhesion strength in a wet environment, and its debonding time.

[0046] Table 1 Performance test results of tissue adhesive materials obtained in Examples 1 to 6 and traditional materials

[0047] The data listed in Table 1 demonstrates that, compared to commercially available fibrin adhesives and cyanoacrylate adhesives, the novel tissue adhesive prepared by the present invention, designed for emergency hemostasis in marine environments and capable of triggering instant debonding on demand, achieves strong adhesion through both covalent and non-covalent bonds. This allows the invented material to maintain an adhesion strength of approximately 160 kPa even in humid environments, demonstrating excellent adhesion properties. Furthermore, when the injured person is transferred to a rear area for further treatment and the dressing needs to be changed, instant debonding can be achieved to prevent secondary injury, thus achieving on-demand instant debonding.

Claims

1. A method for preparing an underwater adhesion-on-demand debonding wet tissue adhesive, characterized in that: The specific method is as follows: Step 1, preparing a byssin-mimicking protein aggregate solution: dissolving a short-chain high molecular weight polymer and a natural polyphenol compound in deionized water to obtain a byssin-mimicking protein aggregate solution; Step 2, preparing a strong wet tissue adhesive: adding a long-chain high molecular weight polymer, a cross-linking agent, and a free radical initiator to the byssus protein aggregate solution to obtain a strong wet tissue adhesive; Step 3: preparing an underwater adhesion-on-demand debonding wet tissue adhesive: introducing a natural polysaccharide into a strong wet tissue adhesive and blending them together to obtain an underwater adhesion-on-demand debonding wet tissue adhesive.

2. The method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive according to claim 1, characterized in that: The specific method of step 1 is as follows: The short-chain high molecular polymer is dissolved in deionized water and stirred at 60-80°C and 300 rpm for 2-3 hours to form a first homogeneous solution; then, the natural polyphenol compound is added to the first homogeneous solution and stirred at 25-40°C and 300 rpm for 2-3 hours to form a foot silk protein aggregate solution.

3. The method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive according to claim 2, characterized in that: The concentration of the short-chain high molecular polymer is 2% to 3% w / v, and the concentration of the natural polyphenol compound is 2% to 3% w / v.

4. The method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive according to claim 3, characterized in that: The short-chain high molecular polymer is any one of polyvinyl pyrrolidone, polyethylene glycol or polyvinyl alcohol; The natural polyphenol compound is any one of tannic acid, polyglutamic acid or dopamine.

5. The method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive according to claim 1, characterized in that: The specific method of step 2 is as follows: A long-chain polymer is added to the byssin-like protein coacervate solution, followed by the addition of a cross-linking agent and a free radical initiator, and the mixture is stirred at 70-80°C for 1-3 hours to uniformly disperse the long-chain polymer in the coacervate solution, thereby obtaining a strong wet tissue adhesive.

6. The method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive according to claim 5, characterized in that: The mass ratio of the long-chain high molecular polymer to the byssus protein coagulation solution is 10%-30%, the mass ratio of the crosslinking agent to the byssus protein coagulation solution is 0.02%-0.04%, and the mass ratio of the free radical initiator to the byssus protein coagulation solution is 0.05%-0.15%.

7. The method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive according to claim 5, characterized in that: The long-chain high molecular polymer is any one of polymaleic acid, polymethacrylic acid or polyacrylic acid; The cross-linking agent is any one of N,N′-bis(acryloyl)cysteine, 4,4′-dimercaptodibenzamide or 3,3′-dimercaptodipropionic acid; The free radical initiator is any one of 2,2′-azobis(2-methylpropionamide) dihydrochloride, ammonium persulfate or N-hydroxysuccinimide.

8. The method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive according to claim 1, characterized in that: The specific method of step 3 is as follows: The natural polysaccharide was introduced into a strong wet tissue adhesive and mixed, and stirred at 60-80°C and 290-310 rpm for 2-3 hours to form a second homogeneous solution. Subsequently, a 0.05-0.15 mol / L CaCl2 solution was added and stirred for 10-30 minutes for cross-linking to obtain an underwater adhesion-on-demand debonding wet tissue adhesive. Apply the cross-linked adhesive solution to the surface to be adhered, or pour it into a mold to form it; when debonding is required, soak the adhesive part in ethylenediaminetetraacetic acid solution for 1 to 2 minutes to complete the debonding.

9. The method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive according to claim 8, characterized in that: The natural polysaccharide is any one of sodium alginate, chitosan or hyaluronic acid, the mass ratio of the natural polysaccharide to the strong wet tissue adhesive is 3% to 5%, and the mass ratio of the natural polysaccharide to the CaCl2 solution is 3 to 9.01:1; The concentration of the EDTA solution is 0.4-0.6 mol / L.

10. The underwater adhesion-on-demand debonding wet tissue adhesive prepared according to the method for preparing the underwater adhesion-on-demand debonding wet tissue adhesive according to any one of claims 1 to 9.

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