Moist tissue surface adhesive material and method of making and use thereof

Abstract

This invention discloses a wet tissue surface adhesive material, its preparation method, and its application, relating to the field of biomedical materials technology. The wet tissue surface adhesive material comprises: (1) dopamine-modified methacryloyl hyaluronic acid (HAMA-DOPA); (2) Pluronic F127-diacrylate (F127DA); (3) aldehyde-modified polyether F127 (F127CHO); (4) oxidized methacryloyl hyaluronic acid (OHAMA); and (5) a photoinitiator for initiating a photopolymerization reaction of the methacryloyl groups and acrylate groups in the above components under visible light irradiation. The photoinitiator comprises at least one of: lithium phenyl (2,4,6-trimethylbenzoyl) phosphate or a photoinitiator composition, wherein the photoinitiator composition comprises: eosin Y at a concentration of 0.05 to 0.25 mmol / L; triethanolamine at a mass-volume ratio of 1.5% to 3%; and N-vinylcaprolactam at a mass-volume ratio of 1% to 2%. This invention enables rapid, strong, and safe tissue adhesion.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to a wet tissue surface adhesive material, its preparation method, and its application. Background Technology

[0002] Achieving rapid, strong, and durable adhesion to moist tissue surfaces has been a long-standing challenge in clinical surgery, wound management, and tissue engineering. Traditional suture methods are not only cumbersome and time-consuming, but can also cause secondary tissue damage, trigger inflammatory responses, and potentially leave scars. Therefore, biological tissue adhesives have received widespread attention as an ideal alternative or supplementary solution. Currently, in the field of biological tissue adhesion, especially in applications on moist tissue surfaces, existing technologies mainly revolve around the following typical approaches.

[0003] 1. Cyanoacrylates are primarily composed of cyanoacrylate monomers, typically containing small amounts of plasticizers and stabilizers. Upon contact with moisture or nucleophilic substances such as amino acids on tissue surfaces, the monomers undergo anionic polymerization to form long polycyanoacrylate chains, resulting in mechanical interlocking and covalent bonding between the tissue and the material. These materials exhibit rapid curing and high adhesive strength, and have been used clinically for skin incision closure. However, their polymer products are relatively brittle and prone to detachment from soft or dynamic tissues; the degradation process may produce cytotoxic substances such as formaldehyde, and their adhesive effect is significantly reduced in humid environments, thus limiting their application in internally humid environments.

[0004] 2. Fibrin glue's main components are fibrinogen and thrombin, and it is usually a two-component system that is mixed immediately before use. It mimics the final stage of human blood clotting, where fibrinogen is converted into fibrin monomers under the action of thrombin, which then polymerize into a fibrin network, providing hemostasis and sealing. Although it has good biocompatibility and is biodegradable, fibrin glue generally has low adhesive strength and is prone to failure in areas under tension; its cured products are easily and rapidly absorbed by bodily fluids, resulting in a short adhesive duration and a potential risk of pathogen transmission.

[0005] 3. Photocurable natural polymer hydrogels are typically composed of methacrylamide-modified natural polymers (such as methacrylamide gelatin (GelMA) and methacrylamide hyaluronic acid (HAMA)) and photoinitiators. Under irradiation with a specific wavelength of light (ultraviolet or visible light), the photoinitiator decomposes to generate free radicals, initiating a copolymerization reaction of the carbon-carbon double bonds between the methacrylamide groups, forming a covalently cross-linked three-dimensional network structure. These materials retain the good biocompatibility of natural polymers, and the curing process has the advantage of spatiotemporal controllability. Visible light curing systems are becoming a development trend due to their better tissue penetration and lower risk of cell damage. However, their application on moist tissue surfaces faces challenges: the prepolymer is easily diluted and washed away by tissue fluid, making it difficult to effectively accumulate at the target site; and the adhesion strength and stability of a single photocrosslinked network are often insufficient in a moist environment.

[0006] 4. Polysaccharide-based adhesives, such as systems composed of oxidized dextran and gelatin, achieve adhesion through a Schiff base reaction between aldehyde and amino groups. These materials exhibit good biocompatibility, but their reaction rate, mechanical strength, and stability under dynamic humid conditions still require improvement.

[0007] 5. Temperature-responsive implantable materials are represented by thermosensitive block copolymers such as polyether F127. These polymers form micelles in water and undergo a sol-gel transition with temperature changes. Utilizing the reverse thermogel property of polyether F127, it exists as a flowable sol at room temperature, facilitating injection; upon reaching body temperature, it rapidly transforms into a non-flowing hydrogel, thereby fixing the encapsulated drug or cells at the application site. Its thermosensitive properties help resist initial dilution and flushing by tissue fluid. However, simple physical gels lack chemical groups that actively and firmly bind to tissues; their adhesion mainly relies on weak physical adsorption, resulting in very limited adhesive strength. When used in dynamic or load-bearing tissues, interfacial delamination or overall displacement is prone to occur.

[0008] These existing technologies generally face two major challenges when dealing with wet surfaces infiltrated by tissue fluid and washed by blood: first, the adhesive precursor solution is easily diluted or washed away by tissue fluid, making it impossible to effectively accumulate at the target site and form a stable adhesive interface; second, it is difficult to quickly form a high-strength and high-stability chemical bond with the tissue surface in a wet environment.

[0009] To address these challenges, researchers have begun developing multifunctional adhesive systems with temperature-responsive properties. One such approach involves introducing polyether F127 into bioadhesive systems. Polyether F127 possesses unique reverse thermogel properties: it exists as an injectable solution at room temperature, but rapidly transforms into a non-flowing hydrogel near body temperature. This property helps to "lock" the adhesive components at the application site, effectively resisting dilution and erosion by tissue fluid, creating favorable conditions for subsequent adhesive reactions. However, this closest existing approach has significant limitations. First, a pure polyether F127 physical gel lacks the ability to actively bond with tissues and chemicals; its adhesion relies primarily on physical blocking and weak physical adsorption, resulting in limited adhesive strength. Second, although some studies have attempted to simply blend polyether F127 with other adhesive components (such as oxidized polysaccharides), such physical mixing struggles to achieve deep functional synergy. The inert segments of polyether F127 cannot participate in building a robust, unified cross-linked network, potentially leading to insufficient interfacial bonding and poor long-term stability. Therefore, in the field of wet tissue adhesion, there is an urgent need for an innovative material that can deeply integrate "dilution-resistant temperature-sensitive properties" with "efficient and active chemical bonding function" at the molecular level. An ideal adhesive should be able to rapidly gel after application to resist erosion, while simultaneously establishing a strong and durable bond with the wet tissue surface through multiple stable chemical bonding mechanisms.

[0010] In summary, although existing technologies offer a variety of tissue adhesion solutions, they all face significant technical bottlenecks that urgently need to be addressed when dealing with moist, dynamic, and complex physiological environments.

[0011] (1) Poor initial anchoring ability on moist tissue surfaces. When existing adhesive precursor solutions (including photocurable prepolymers) are applied to moist tissue surfaces, they are easily diluted or washed away by tissue fluid and blood, resulting in the loss of effective ingredients and the inability to form a high-concentration adhesive transition layer at the target interface. This not only reduces the bonding efficiency but also significantly reduces the final adhesive strength.

[0012] (2) It is difficult to achieve both interfacial adhesion strength and cohesive strength. Cyanoacrylates have high cohesive strength but are brittle; fibrin glue and simple physical thermosensitive gels have weak interfacial adhesion. Although photocurable natural polymer hydrogels can provide cohesive strength through cross-linking, their chemical bonding mechanism with the surface of moist tissue is simple (mainly relying on limited Schiff base reactions or physical adsorption), which often results in interfacial adhesion strength that is lower than the strength of the tissue itself, becoming a weak link in failure.

[0013] (3) Limited functional integration and lack of synergistic enhancement mechanisms. Many existing technologies focus on solving only one aspect of the problem. For example, the introduction of polyether F127 only provides temperature-sensitive and dilution-resistant properties, but does not endow it with the ability to participate in chemical bonding. Similarly, most photocrosslinking systems focus on building the material's bulk network and lack designs specifically for strong chemical bonding at wetted interfaces. This functional fragmentation makes it difficult for materials to cope with complex application scenarios.

[0014] (4) Long-term stability and biosafety face challenges. Residues of chemical crosslinking agents (such as divinyl sulfone used for HA crosslinking) may induce inflammation. Some photoinitiators may damage cells under ultraviolet light irradiation. In addition, dynamic Schiff base bonds may hydrolyze under physiological conditions, affecting the long-term stability of the adhesive.

[0015] Currently, the core technological bottleneck in the field of wet tissue adhesion lies in the fact that existing material systems struggle to simultaneously achieve both the physical properties of "dilution resistance" and "highly efficient and stable" chemical adhesion at the molecular design level. Most solutions either emphasize one aspect or involve simple physical blending, failing to achieve deep functional synergy and a significant leap in performance. Therefore, there is an urgent need to develop a novel intelligent adhesive material that can integrate temperature-responsive anti-dilution properties with strong, multi-mechanism synergistic chemical adhesion at the molecular level, thereby achieving reliable, durable, and safe tissue adhesion even under harsh physiological conditions. Summary of the Invention

[0016] To address the technical problems existing in the prior art, embodiments of the present invention provide a wet tissue surface adhesive material, its preparation method, and its application. The technical solution is as follows:

[0017] A wet tissue surface adhesive material, the wet tissue surface adhesive material comprising:

[0018] (1) Dopamine-modified methacryloyl hyaluronic acid (HAMA-DOPA);

[0019] (2) Prönnicke F127-diacrylate (F127DA);

[0020] (3) Aldehyde-modified polyether F127 (F127CHO);

[0021] (4) Oxymethylacrylamide hyaluronic acid (OHAMA); and

[0022] (5) A photoinitiator for initiating a photopolymerization reaction of the methacryloyl groups and acrylate groups in the above components under visible light irradiation, wherein the photoinitiator comprises at least one of lithium phenyl (2,4,6-trimethylbenzoyl) phosphate or a photoinitiator composition, wherein the photoinitiator composition comprises: eosin Y at a concentration of 0.05 to 0.25 mmol / L; triethanolamine at a mass-volume ratio of 1.5% to 3%; and N-vinylcaprolactam at a mass-volume ratio of 1% to 2%.

[0023] Optionally, the adhesive material for the moist tissue surface further includes:

[0024] (6) A solvent, the solvent comprising at least one of phosphate buffer (PBS) and carbonate-bicarbonate buffer (CBS).

[0025] Optionally, in the dopamine-modified methacrylamide hyaluronic acid, the grafting rate of dopamine is 5%-15%, and / or the grafting rate of methacrylamide groups is 10%-50%;

[0026] And / or, in the aldehyde-modified polyether F127, the degree of substitution of the aldehyde group is 50%-95%;

[0027] And / or, in the oxidized methacryloyl hyaluronic acid, the grafting rate of methacrylic anhydride is 10%-60%, and / or, the degree of aldehyde oxidization is 10%-50%.

[0028] Optionally, the weight-volume ratio of HAMA-DOPA to the solvent is 1% to 8%;

[0029] And / or, the weight-volume ratio of the F127DA to the solvent is 5% to 20%;

[0030] And / or, the weight-volume ratio of the F127CHO to the solvent is 5% to 20%;

[0031] And / or, the weight-volume ratio of the OHAMA to the solvent is 1% to 8%;

[0032] And / or, the weight-volume ratio of the photoinitiator to the solvent is 0.05% to 0.3%;

[0033] Furthermore, the weight-volume ratio of the sum of F127DA and F127CHO to the solvent is ≤35% (20% ≤ 35%); and the weight-volume ratio of the sum of HAMA-DOPA and OHAMA to the solvent is ≤10%.

[0034] The method for preparing the adhesive material for the moist tissue surface includes:

[0035] (1) Dissolve the HAMA-DOPA, F127DA, F127CHO, OHAMA and the photoinitiator in a solvent at low temperature to obtain a prepolymer that can flow at low temperature;

[0036] (2) The prepolymer solution is applied to the surface of a moist tissue and the prepolymer solution is converted into a hydrogel at 35℃-40℃;

[0037] (3) Irradiate the hydrogel with visible light to solidify it and obtain the wet tissue surface adhesive material.

[0038] Optionally, in step (1), the weight-volume ratio of HAMA-DOPA to the solvent is 1% to 8%;

[0039] And / or, the weight-volume ratio of the F127DA to the solvent is 5% to 20%;

[0040] And / or, the weight-volume ratio of the F127CHO to the solvent is 5% to 20%;

[0041] And / or, the weight-volume ratio of the OHAMA to the solvent is 1% to 8%;

[0042] And / or, the weight-volume ratio of the photoinitiator to the solvent is 0.05% to 0.3%;

[0043] And / or, the weight-volume ratio of the sum of F127DA and F127CHO to the solvent is ≤35% (20% ≤ 35%).

[0044] And / or, the weight-volume ratio of the sum of HAMA-DOPA and OHAMA to the solvent is ≤10%;

[0045] And / or, in step (1), the low temperature is 0°C to 10°C;

[0046] And / or, in step (2), the conversion of the prepolymer into a non-flowing hydrogel is carried out at a temperature of 35-37°C.

[0047] Optionally, in step (2), the polyether F127 segments of F127DA and F127CHO self-assemble under temperature stimulation of 35-40°C to form a micelle physical cross-linking network, thereby transforming the solution into a hydrogel.

[0048] And / or, in step (3), the photoinitiator initiates a copolymerization reaction of the methacryloyl groups and acrylate groups in the HAMA-DOPA, the F127DA and the OHAMA to form a second covalent crosslinking network;

[0049] And / or, in step (3), the aldehyde group of F127CHO reacts with the amino group on the tissue surface to form a Schiff base reaction, and the aldehyde group of OHAMA reacts with the amino group on the tissue surface to form a third adhesive network.

[0050] And / or, in step (3), the dopamine groups in the HAMA-DOPA covalently crosslink with the amino and thiol groups on the tissue surface through the catechol groups, thereby enhancing interfacial interactions.

[0051] Optionally, in step (2), the application is by injection, application, or dripping;

[0052] And / or, in step (3), the wavelength range of the visible light is 400 nm to 550 nm;

[0053] And / or, in step (3), the power of the irradiation is from 10 mW / cm² to 50 mW / cm²;

[0054] And / or, in step (3), the irradiation time is from 10 seconds to 240 seconds.

[0055] The application of the aforementioned wet tissue surface adhesive material in the preparation of wet tissue surface adhesive products.

[0056] A moist tissue surface adhesive product, the product comprising the aforementioned moist tissue surface adhesive material.

[0057] The beneficial effects of the technical solutions provided in the embodiments of the present invention include at least the following:

[0058] This invention provides an adhesive material for moist tissue surfaces, its preparation method, and its applications. By innovatively introducing methacryloyl hyaluronic acid and aldehyde-modified polyether F127, this material successfully combines excellent temperature-responsive anti-dilution properties with a strong chemical adhesive capability through multiple synergistic mechanisms, thereby achieving rapid, firm, stable, and safe tissue adhesion and closure even in harsh, moist physiological environments. This invention innovatively combines four key components to construct a four-fold synergistic system of "physical thermosensitive gel + photocrosslinking network + multiple chemical crosslinking + biomimetic adhesion," significantly improving the material's retention capacity, adhesive strength, and stability on moist tissue surfaces.

[0059] (1) Excellent adaptability to wet tissue surfaces

[0060] The anti-dilution and erosion capabilities are significantly improved. Based on the synergistic thermosensitive effect of F127DA and F127CHO, the prepolymer can rapidly transform from solution to gel upon contact with the tissue surface, forming a stable physical barrier. This characteristic enables the material to effectively resist dilution and erosion by tissue fluid and blood, ensuring a high concentration of active components in the target bonding area. The thermosensitive gel network, acting as a "physical anchor," provides a stable reaction platform for subsequent photocrosslinking and chemical crosslinking, overcoming the technical challenge of traditional adhesives easily leaching from wet surfaces.

[0061] (2) High interfacial adhesion strength

[0062] HAMA-DOPA provides basic wet adhesion through biomimetic catechol chemistry, achieving tight bonding with tissue surfaces at the molecular level. The aldehyde groups of F127CHO and OHAMA form stable Schiff base bonds with the amino groups on the tissue surface, constructing a chemical cross-linking interface. The photocross-linking network ensures that all components form a unified overall structure, avoiding interfacial delamination.

[0063] (3) Excellent mechanical properties and durability

[0064] The hydrophobic microdomains introduced in F127DA serve as physical cross-linking points, significantly enhancing the material's toughness and tear resistance. The photocrosslinking network provides stable skeletal support, ensuring sufficient mechanical strength. The formation of multiple cross-linking networks gives the material excellent stability in physiological environments, maintaining long-term adhesion and meeting the needs of long-term tissue repair.

[0065] (4) Excellent biocompatibility and safety

[0066] Based on hyaluronic acid and Pluronic F127, it exhibits excellent biocompatibility and biodegradability. Utilizing a visible light curing system, it avoids tissue damage caused by ultraviolet radiation. The temperature-sensitive gelation process is a physical change, generating no irritating byproducts.

[0067] (5) Superior operability and ease of clinical application

[0068] It is a free-flowing solution at room temperature, facilitating precise application to complex wounds via syringe. Temperature-sensitive gelation provides an initial operating window, allowing for easy adjustment of material placement. Finally, light curing ensures final shaping and precise adhesion. Furthermore, it adapts to complex anatomical structures and adheres well to irregular tissue surfaces, offering unique advantages in minimally invasive surgery and complex wound repair.

[0069] (6) Broad organizational adaptability

[0070] The material of this invention exhibits excellent adhesion on a variety of moist tissue surfaces. It provides high light transmittance and gentle adhesion in ophthalmic tissues, making it suitable for applications in optical areas. It achieves strong wound closure in skin tissues, avoiding suture trauma. It provides sufficient adhesive strength and flexibility in cartilage tissues. It maintains stable adhesion even in the moist environment of internal organs.

[0071] (7) The preparation process is simple and easy to industrialize.

[0072] Its components are well-compatible, exhibiting good compatibility and stability in aqueous solutions. The preparation process is simple, requiring no complex synthesis steps, and can be completed at room temperature. Quality control is reliable, with widely available raw materials and easy quality control. Attached Figure Description

[0073] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0074] Figure 1 This is a diagram illustrating the reversible temperature-sensitive curing and light-curing properties of Embodiment 1 provided in this invention;

[0075] Figure 2 This is a diagram illustrating that Embodiment 1 of the present invention has high transmittance in the visible light wavelength range;

[0076] Figure 3 This is a diagram illustrating the good degradation resistance of Example 1 provided in Example 1 of the present invention;

[0077] Figure 4 This is a diagram illustrating the good injectability and water resistance of Example 1 provided in this invention;

[0078] Figure 5 This is a diagram illustrating the good cohesion on the tissue surface provided in Embodiment 1 of the present invention;

[0079] Figure 6 This is an illustration of Embodiment 1 of the present invention, which shows that Embodiment 1 has high tissue adhesion and can effectively seal perforations;

[0080] Figure 7 This is a diagram illustrating the good cell compatibility of Example 1 provided in Embodiment 1 of the present invention;

[0081] Figure 8 This is a diagram illustrating that Embodiment 1 of the present invention has a high burst pressure. Detailed Implementation

[0082] The technical solution of the present invention will now be described with reference to the accompanying drawings.

[0083] In embodiments of the present invention, words such as "exemplarily," "for example," etc., are used to indicate that something is an example, illustration, or description. Any embodiment or design described as "exemplary" in the present invention should not be construed as being more preferred or advantageous than other embodiments or designs. Specifically, the use of the word "exemplary" is intended to present the concept in a concrete manner. Furthermore, in embodiments of the present invention, the meaning expressed by "and / or" can be both, or either one.

[0084] Based on an in-depth analysis of existing technologies, this invention aims to overcome the core technological bottlenecks currently faced by wet tissue adhesives, specifically addressing the following technical problems:

[0085] (1) Solving the problem that adhesive precursors are easily diluted and washed away on wet surfaces. In the prior art, adhesive solutions are difficult to retain when they come into contact with wet tissue surfaces, and are easily diluted by tissue fluid or blood and washed away from the target site, resulting in adhesive failure. The primary objective of this invention is to provide a material that can undergo a rapid physical state transformation after application, changing from a solution to a gel, thereby firmly anchoring itself to the wet tissue surface and effectively resisting dilution and washing away.

[0086] (2) Solving the problem of insufficient interfacial chemical bonding strength in humid environments. Existing adhesives often rely on single, weak forces (such as physical adsorption or dynamic Schiff base bonds) for chemical bonding with the surface of moist tissues, resulting in weak interfacial bonding strength. The core objective of this invention is to construct a multi-layered and stable chemical cross-linking network within the material and at the material-tissue interface, and to significantly improve initial adhesion and long-term bonding strength by introducing more diverse and stable covalent bonding mechanisms.

[0087] (3) Solving the problem of the difficulty in synergistic integration of "anti-dilution properties" and "active adhesive function". In the prior art, the components that provide temperature-sensitive properties (such as polyether F127) and the components that provide adhesive function (such as oxidized polysaccharides) are often simply physically mixed, resulting in poor functional synergy. The key objective of this invention is to endow the temperature-sensitive component with chemical adhesive activity through molecular design, and to enable it to synergize deeply with other components in the system at the molecular level, so as to achieve the organic unity of physical properties and chemical functions, thereby producing a synergistic enhancement effect of "1+1>2".

[0088] (4) Achieving controllability and ease of operation in the bonding process. While ensuring high performance, this invention also aims to make the material have both injectable construction properties and spatiotemporal controllability of light curing, providing clinicians with ample operating window and precise curing triggering capability, simplifying surgical procedures and improving bonding accuracy.

[0089] In summary, the purpose of this invention is to provide an adhesive material for moist tissue surfaces, its preparation method, and its application. This material, through the innovative introduction of oxymethacrylamide-modified hyaluronic acid and aldehyde-modified polyether F127, successfully combines excellent temperature-responsive anti-dilution properties with a strong chemical adhesive capability through multiple synergistic mechanisms, thereby achieving rapid, firm, stable, and safe tissue adhesion and closure even in harsh, moist physiological environments.

[0090] (1) Core components

[0091] A specific combination of four active components and a synergistic temperature-sensitive system of dual F127 derivatives that is "anti-dilution + enhanced + adhesive";

[0092] Using only a single F127 derivative, or replacing functionalized F127 with ordinary F127, will not achieve the desired multiple functions simultaneously. Temperature sensitivity is only achieved when the combined concentration of F127DA and F127CHO is greater than or equal to 20%, but too high a concentration will affect operation. Oxymethylacrylamide hyaluronic acid (OHAMA) possesses bifunctional properties, providing not only the double bonds required for photocuring crosslinking but also aldehyde functional groups that provide tissue adhesion.

[0093] (2) Network structure and working mechanism

[0094] The construction sequence and synergistic mechanism of the four-fold network (temperature-sensitive gelation followed by photocuring).

[0095] (3) Preparation method and application

[0096] (4) Product form and application field

[0097] In specific applications involving moist tissue surfaces, the technical effects of this invention are more pronounced on moist tissue surfaces.

[0098] To address the technical problems existing in the background art, this invention provides an adhesive material for moist tissue surfaces, its preparation method, and its application. This solution innovatively combines four key components to construct a four-fold synergistic system of "physical thermosensitive gel + photocrosslinking network + multiple chemical crosslinking + biomimetic adhesion," significantly improving the material's retention ability, adhesion strength, and stability on moist tissue surfaces.

[0099] (1) Core components

[0100] The wet tissue surface adhesive material of the present invention comprises the following four key active components:

[0101] Component A: Dopamine-modified methacryloyl hyaluronic acid (HAMA-DOPA). This component is the core of achieving strong adhesion in underwater and humid environments. It is prepared by grafting dopamine onto the methacryloyl hyaluronic acid backbone. The role of the dopamine group is to mimic the catechol chemical structure of mussel adhesive protein, forming various strong interactions with the tissue surface through the catechol group, including hydrogen bonding, π-π stacking, metal coordination, and Michael addition or Schiff base reactions between quinone compounds formed after oxidation and amino and thiol groups on the tissue surface. This unique biomimetic adhesion mechanism enables it to maintain extremely strong adhesion even in humid and underwater environments. The role of the methacryloyl group is to enable it to participate in the formation of a photocrosslinking network, ensuring a stable chemical bond between the biomimetic adhesion component and the material bulk, and preventing interfacial delamination.

[0102] The molecular formula of the dopamine-modified methacrylamide hyaluronic acid is: (C 14 H 21 NO 11 )w(C 19 H 27 NO 12 ) x (C 22 H 30 N2O 12 ) y (C 27 H 36 N2O 13 ) z The preparation method can be found in "Q. Wang, X. Zhao, F. Yu, P.-H. Fang, L. Liu, X. Du, W. Li, D. He, Y. Bai, S. Li, J. Yuan, Photocurable and Temperature-Sensitive Bioadhesive Hydrogels for Sutureless Sealing of Full-Thickness Corneal Wounds, Small Methods (2023) e2300996. https: / / doi.org / 10.1002 / smtd.202300996."

[0103] Component B: Prönnicke F127-diacrylate (F127DA). This component is key to enhanced mechanical properties. The F127 segment provides temperature-responsive characteristics, remaining an injectable solution at room temperature and transforming into a non-flowing hydrogel at body temperature, effectively preventing the pre-adhesion solution from being diluted and washed away by tissue fluid. The diacrylate end groups function by copolymerizing with the methacryloyl groups of other components under visible light irradiation, introducing hydrophobic microdomains as physical crosslinking points, significantly enhancing the toughness, mechanical strength, and creep resistance of the crosslinked network. Prönnicke F127-diacrylate is a triblock copolymer, commercially available, for example, from Suzhou Yongqinquan Intelligent Equipment Co., Ltd.

[0104] Component C: Aldehyde-modified polyether F127 (F127CHO). This component is key to synergistic crosslinking. The role of the F127 segments is to further enhance the temperature response characteristics of the system, ensuring a high concentration of the adhesive active component in the target bonding region. The role of the aldehyde end groups is to transform the temperature-sensitive component into crosslinking points with chemical adhesive activity. These aldehyde groups can undergo Schiff base reactions with amino groups on the surface of biological tissues, tightly integrating the physical temperature-sensitive network with the chemical adhesive network. The aldehyde-modified polyether F127 is commercially available, for example, from Suzhou Yongqinquan Intelligent Equipment Co., Ltd.

[0105] Component D: Oxymethylacrylamide hyaluronic acid (OHAMA). This component is the core of the multiple crosslinking process. The role of the methacrylamide group is to participate in the photopolymerization reaction in the presence of a photoinitiator, contributing to the formation of a stable photocrosslinking network and providing the basic mechanical strength of the material. The role of the aldehyde group is to react with the amino groups on the surface of biological tissues to form a Schiff base, directly participating in and enhancing the chemical adhesion between the material and the tissue interface, and strengthening the internal crosslinking network. The preparation method of the methacrylated hyaluronic acid can be found in "Preparation of Double Crosslinked Injectable Hydrogel from Decellularized Muscle Matrix for Promoting Myoblast Proliferation and Myoblast Differentiation" or H. Zhou, S. Zhang, J. Qiu, M. Jiang, Z. Liu, Z. Zou, J. Zhou, Y. He, X, Yang, Z. Guo, G. Sa. Sustained release of migrasomes from a methacrylate-oxidized hyaluronic acid / methacrylated gelatin compositehydrogel accelerates skin wound healing. International Journal of Biological Macromolecules (2025) 306 part 1. https: / / doi.org / 10.1016 / j.ijbiomac.2025.141355.

[0106] Component E: Photoinitiator is used to generate free radicals under visible light irradiation, which initiate photopolymerization reactions of the methacryloyl groups and acrylate groups in each component.

[0107] Component F: Solvents for components A, B, C, D, and E, forming a prepolymer solution, including: phosphate buffer and carbonate-bicarbonate buffer (CBS).

[0108] The pH of the phosphate buffer solution is 7.2-7.4.

[0109] The pH of carbonate-bicarbonate buffer (CBS) is 7.2-7.4.

[0110] (2) Synergistic effect and working principle of each component

[0111] The working principle of this invention is based on a four-fold sequential activation and synergistic mechanism of "physical thermosensitive gel + photocrosslinking network + multiple chemical crosslinking + biomimetic adhesion":

[0112] First layer of network: Temperature-triggered physical gel network (dilution resistant)

[0113] When the mixed prepolymer containing the four key components is applied to a moist tissue surface, the F127 polyether segments of F127DA and F127CHO rapidly self-assemble under body temperature stimulation, forming a dense micellar physical cross-linking network. This transforms the solution into a non-flowing hydrogel within seconds to tens of seconds. This preferential process effectively resists dilution and erosion by tissue fluid, providing a stable platform for subsequent chemical reactions.

[0114] Second layer network: Photoinduced covalent cross-linked network (enhancement)

[0115] After the material is initially anchored, it is irradiated with visible light. The photoinitiator decomposes to generate free radicals, which initiate a copolymerization reaction of the active groups (methacryloyl groups and acrylate groups) in HAMA-DOPA, F127DA, and OHAMA, forming a second, more robust covalent cross-linked network. This step significantly enhances the material's bulk mechanical strength and structural stability.

[0116] The third network: interfacial chemical cross-linking network (strong adhesion)

[0117] Throughout the process, multiple chemical cross-linking reactions occur simultaneously and continuously, including the Schiff base reaction between the aldehyde group of F127CHO and the amino group on the tissue surface, and the Schiff base reaction between the aldehyde group of OHAMA and the amino group on the tissue surface. These reactions construct dense chemical cross-linking points at the material-tissue interface, forming a stable third adhesive network.

[0118] The fourth mechanism: biomimetic wet adhesion network (strong underwater adhesion)

[0119] The dopamine groups in HAMA-DOPA form a variety of powerful interactions with tissue surfaces through unique catechol chemistry. The catechol groups of dopamine can bind to the tissue surface via hydrogen bonds, and upon oxidation, form quinone compounds. These compounds then covalently crosslink with amino and thiol groups on the tissue surface, enhancing interfacial interactions through π-π stacking and coordination bonds. These mechanisms ensure reliable adhesion even in the most challenging wet environments.

[0120] These four mechanisms are activated sequentially, interconnected, and synergistically enhanced. Among them, the aldehyde groups of F127CHO and OHAMA react with the Schiff base of amino groups on the tissue surface to construct a stable chemical cross-linking interface, while the biomimetic adhesion mechanism of HAMA-DOPA provides unique adaptability to wet environments. Together, they solve the core problem of "staying, adhering firmly, and having high strength" on wet surfaces.

[0121] (3) Optimal Solution

[0122] In dopamine-modified methacryloyl hyaluronic acid (HAMA-DOPA), the grafting rate of dopamine is preferably 5%-15%, and the grafting rate of methacryloyl groups is 10%-50%.

[0123] In oxidized methacryloyl hyaluronic acid (OHAMA), the grafting rate of methacrylic anhydride is 10%-60%, and the degree of aldehyde oxidization is 10%-50%.

[0124] In aldehyde-modified polyether F127 (F127CHO), the degree of substitution of the aldehyde group is preferably 50%-95%.

[0125] The photoinitiator is preferably lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP) or at least one of a photoinitiator composition comprising: eosin Y at a concentration of 0.05 to 0.25 mmol / L; triethanolamine at a mass-volume ratio of 1.5% to 3%; and N-vinylcaprolactam at a mass-volume ratio of 1% to 2%.

[0126] The preferred concentrations of each component in phosphate-buffered saline (PBS) are:

[0127] HAMA-DOPA: 1% w / v to 8% w / v;

[0128] F127DA: 5% w / v to 20% w / v;

[0129] F127CHO: 5% w / v to 20% w / v;

[0130] OHAMA: 1% w / v to 8% w / v;

[0131] Furthermore, the total concentration of F127DA+F127CHO ≤ 20% w / v and the total concentration of HAMA-DOPA and OHAMA ≤ 10% w / v.

[0132] Photoinitiator: 0.05% w / v to 0.3% w / v;

[0133] (4) Preparation and usage methods

[0134] The preparation method of this invention is simple and suitable for large-scale production and clinical operation, and mainly includes the following steps:

[0135] Solution preparation: Dissolve HAMA-DOPA, F127DA, F127CHO, OHAMA and photoinitiator together in phosphate buffer solution pre-cooled in an ice bath, mix well, and obtain a prepolymer solution that can flow at low temperature.

[0136] Application to tissues: Inject, apply, or drop the prepolymer onto the surface of moist tissue that needs to be bonded or filled.

[0137] Thermosensitive gelation: The prepolymer rapidly transforms into a non-flowing hydrogel at body temperature, achieving initial anchoring.

[0138] Photocuring: Irradiation with visible light in the wavelength range of 400nm to 550nm, with an irradiation power of 10mW / cm². 2 Up to 50mW / cm 2 The irradiation time is from 10 to 240 seconds to complete the final curing.

[0139] Through the above technical solution, the present invention successfully solves the key technical problems of existing technologies, such as easy dilution on the surface of moist tissue, insufficient interfacial adhesion strength, and poor functional synergy, and provides a new generation of moist tissue adhesive material with excellent performance and convenient operation.

[0140] To make the technical problems, technical solutions and advantages of the present invention clearer, a detailed description will be given below in conjunction with the accompanying drawings and specific embodiments.

[0141] Unless otherwise specified, the experimental methods described in the following embodiments are conventional experimental methods well known to those skilled in the art, and are performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Where specific conditions are not specified in the experimental methods, they are generally operated under conventional conditions.

[0142] Unless otherwise specified, all materials and reagents described in the following examples are commercially available.

[0143] Example 1

[0144] (1) Dopamine-modified methacryloyl hyaluronic acid (HAMA-DOPA): 3%.

[0145] (2) Pronnic F127-diacrylate (F127DA): 15%, available from, for example, Suzhou Yongqinquan Intelligent Equipment Co., Ltd., model EFL-F127DA-001.

[0146] (3) Aldehyde polyether F127 (F127CHO): 5%, which can be purchased from, for example, Suzhou Yongqinquan Intelligent Equipment Co., Ltd., model EFL-F127-CHO-001.

[0147] (4) Oxymethylacrylamide hyaluronic acid (OHAMA): 2%.

[0148] (5) Photoinitiator: Lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP) 0.25%.

[0149] The percentages above are weight-volume ratios, specifically in g / ml. For example, 3% is 0.03 g / ml.

[0150] In the dopamine-modified methacryloyl hyaluronic acid, the grafting rate of dopamine is 10%, and the grafting rate of methacryloyl groups is 40%.

[0151] And / or, in the aldehyde-modified polyether F127, the degree of substitution of the aldehyde group is 50%;

[0152] And / or, in the oxidized methacryloyl hyaluronic acid, the grafting rate of methacrylic anhydride is 40% and the degree of aldehyde oxidization is 30%.

[0153] (6) Solvent: Phosphate buffer (PBS), pH 7.4.

[0154] The above components were dissolved together in a phosphate buffer solution pre-cooled in an ice bath and mixed thoroughly to obtain a prepolymer that can flow at low temperature.

[0155] Application to tissues: Inject, apply, or drop the prepolymer onto the surface of moist tissue that needs to be bonded or filled.

[0156] Thermosensitive gelation: The prepolymer rapidly transforms into a non-flowing hydrogel at body temperature, achieving initial anchoring.

[0157] Photocuring: Irradiation with visible light at a wavelength of 500nm and an irradiation power of 30mW / cm². 2 The irradiation time is 240 seconds to complete the final curing.

[0158] Example 2

[0159] (1) Dopamine-modified methacryloyl hyaluronic acid (HAMA-DOPA): 1%;

[0160] (2) Pronic F127-diacrylate (F127DA): 5%;

[0161] (3) Aldehyde-modified polyether F127 (F127CHO): 15%;

[0162] (4) Oxymethylacrylamide hyaluronic acid (OHAMA): 1%;

[0163] (5) Photoinitiator: Lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP) 0.05%;

[0164] In the dopamine-modified methacryloyl hyaluronic acid, the grafting rate of dopamine is 5%, and the grafting rate of methacryloyl groups is 10%.

[0165] And / or, in the aldehyde-modified polyether F127, the degree of substitution of the aldehyde group is 50%;

[0166] And / or, in the oxidized methacrylamide hyaluronic acid, the grafting rate of methacrylic anhydride is 10%, and the degree of aldehyde oxidization is 10%.

[0167] (6) Solvent: Phosphate buffer (PBS), pH 7.4.

[0168] The above components were dissolved together in a phosphate buffer solution pre-cooled in an ice bath and mixed thoroughly to obtain a prepolymer that can flow at low temperature.

[0169] Application to tissues: Inject, apply, or drop the prepolymer onto the surface of moist tissue that needs to be bonded or filled.

[0170] Thermosensitive gelation: The prepolymer rapidly transforms into a non-flowing hydrogel at body temperature, achieving initial anchoring.

[0171] Photocuring: Irradiation with visible light at a wavelength of 400nm and an irradiation power of 10mW / cm². 2 The irradiation time is 240 seconds to complete the final curing.

[0172] Example 3

[0173] (1) Dopamine-modified methacryloyl hyaluronic acid (HAMA-DOPA): 8%;

[0174] (2) Pronic F127-diacrylate (F127DA): 20%;

[0175] (3) Aldehyde-modified polyether F127 (F127CHO): 15%;

[0176] (4) Oxymethylacrylamide hyaluronic acid (OHAMA): 8%;

[0177] (5) Photoinitiator: Lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP) 0.3%;

[0178] In the dopamine-modified methacryloyl hyaluronic acid, the grafting rate of dopamine is 15%, and the grafting rate of methacryloyl groups is 50%.

[0179] And / or, in the aldehyde-modified polyether F127, the degree of substitution of the aldehyde group is 95%;

[0180] And / or, in the oxidized methacrylamide hyaluronic acid, the grafting rate of methacrylic anhydride is 60% and the degree of aldehyde oxidization is 50%.

[0181] (6) Solvent: Phosphate buffer (PBS), pH 7.3.

[0182] The above components were dissolved together in a phosphate buffer solution pre-cooled in an ice bath and mixed thoroughly to obtain a prepolymer that can flow at low temperature.

[0183] Application to tissues: Inject, apply, or drop the prepolymer onto the surface of moist tissue that needs to be bonded or filled.

[0184] Thermosensitive gelation: The prepolymer rapidly transforms into a non-flowing hydrogel at body temperature, achieving initial anchoring.

[0185] Photocuring: Irradiation with visible light at a wavelength of 550nm and an irradiation power of 50mW / cm². 2 The irradiation time is 10 seconds to complete the final curing.

[0186] Example 4

[0187] (1) Dopamine-modified methacryloyl hyaluronic acid (HAMA-DOPA): 5%;

[0188] (2) Pronic F127-diacrylate (F127DA): 10%;

[0189] (3) Aldehyde-modified polyether F127 (F127CHO): 20%;

[0190] (4) Oxymethylacrylamide hyaluronic acid (OHAMA): 5%;

[0191] (5) Photoinitiator: Lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP) 0.15%;

[0192] In the dopamine-modified methacrylamide hyaluronic acid, the grafting rate of dopamine is 10%, and the grafting rate of methacrylamide groups is 30%.

[0193] And / or, in the aldehyde-modified polyether F127, the degree of substitution of the aldehyde group is 75%;

[0194] And / or, in the oxidized methacryloyl hyaluronic acid, the grafting rate of methacrylic anhydride is 35%, and the degree of aldehyde oxidization is 30%.

[0195] (6) Solvent: Carbonate-bicarbonate buffer (CBS), pH 7.2.

[0196] The above components were dissolved together in a phosphate buffer solution pre-cooled in an ice bath and mixed thoroughly to obtain a prepolymer that can flow at low temperature.

[0197] Application to tissues: Inject, apply, or drop the prepolymer onto the surface of moist tissue that needs to be bonded or filled.

[0198] Thermosensitive gelation: The prepolymer rapidly transforms into a non-flowing hydrogel at body temperature, achieving initial anchoring.

[0199] Photocuring: Irradiation with visible light at a wavelength of 500nm and an irradiation power of 30mW / cm². 2 The irradiation time is 175 seconds to complete the final curing.

[0200] Performance testing:

[0201] The following uses Example 1 as an example to measure various properties of the adhesive material on the surface of moist tissue. Those skilled in the art will understand or will find through experiments that other embodiments within the scope of this invention or the results of Examples 2-4 are similar to those of Example 1, and will not be described in detail here.

[0202] 1. The thermo-curing and photocuring properties of the adhesive material for the moist tissue surface of Example 1 were determined. The determination method is as follows: The prepolymer solution of Example 1 before photocuring was placed in a water bath at 20°C, a water bath at 37°C (photocuring or non-photocuring), and a water bath at 20°C for 10 minutes each. Before each switch, the container was tilted and the flow of the prepolymer solution inside was observed.

[0203] Experimental results are as follows Figure 1 As shown.

[0204] Figure 1 This is a diagram illustrating the reversible temperature-sensitive curing and photocuring characteristics of Example 1 provided by the present invention. As can be seen from the diagram, the prepolymer of Example 1 exhibits excellent temperature-sensitive properties, capable of transitioning between flow, solidification, and flow again at temperatures below body temperature, body temperature, and below body temperature. This temperature-sensitive transition effect disappears after photocuring.

[0205] 2. The transmittance of the adhesive material on the moist tissue surface in Example 1 was determined. The determination method is as follows: A rectangular hydrogel (3 cm long, 1 cm wide, and 100 μm thick) was prepared. Before testing, the sample was soaked in PBS solution (pH=7.4) for 1 hour to allow it to fully absorb water. The transmittance in the wavelength range of 400 to 800 nm was measured using a UV-Vis spectrophotometer at 37°C.

[0206] Experimental results are as follows Figure 2 As shown.

[0207] Figure 2 This is a diagram illustrating the high transmittance of Example 1 within the visible light wavelength range, as provided in Example 1 of the present invention. As can be seen from the diagram, Example 1 exhibits high transparency after curing, with a transmittance exceeding 90%, which does not affect its use in tissues requiring high transmittance.

[0208] Compared with the prior art, the wet tissue surface adhesive material of the present invention has a very high light transmittance, with a light transmittance of more than 90% in the visible light range.

[0209] 3. The degradation resistance of the wet tissue surface adhesive material of Example 1 was determined as follows: Approximately 200 mg of sample was placed in 5 mL of 0.1 M Tris-HCl buffer (pH 7.4) containing 5 mM CaCl2 and equilibrated at 37°C for 1 hour. Subsequently, it was transferred to pure water, PBS buffer, or collagenase solution (concentration 1 mg / mL). To maintain enzyme activity, the collagenase solution was changed every 8 hours. Samples were removed at different time points, and the surface liquid was gently blotted dry with filter paper before weighing. The residual weight percentage was calculated using the following formula: Residual weight % = Wt / W0 × 100%, where W0 is the initial weight of the hydrogel, and Wt is the weight of the hydrogel at each time point.

[0210] Experimental results are as follows Figure 3 As shown.

[0211] Figure 3 This is a diagram illustrating the good degradation resistance of Example 1 provided in Example 1 of the present invention. As can be seen from the diagram, Example 1 exhibits good degradation resistance in different degradation solution environments.

[0212] Compared with the prior art, the wet tissue surface adhesive material of the present invention has good degradation resistance and can meet the requirements of long-term stability in the in vivo enzymatic hydrolysis environment before tissue repair.

[0213] 4. The injectability and water resistance of the wet tissue surface adhesive material of Example 1 were determined by the following method: The prepolymer solution of Example 1 was loaded into a syringe and injected through needles of different sizes (25G, 33G) or pipette tips. After injection into warm water at 37°C, the solution was observed. Two minutes after injection, the injection area was rinsed with water to observe its solubility in water.

[0214] Experimental results are as follows Figure 4 As shown.

[0215] Figure 4 This is a diagram illustrating the good injectability and water resistance of Example 1 provided by the present invention. As can be seen from the diagram, the prepolymer of Example 1 can be injected through a fine needle, which is beneficial for precise control of the injection volume and injection site. Moreover, it can solidify at near body temperature through temperature sensitivity, reducing the dilution effect on the adhesive in the liquid environment, and remains in place to exert its adhesive effect.

[0216] Compared with the prior art, the wet tissue surface adhesive material of the present invention has good injectability and water resistance, can be injected into a liquid environment near body temperature and maintain its shape after injection, and can withstand the erosion of a certain liquid flow without spreading.

[0217] 5. The cohesive force of the wet tissue surface adhesive material of Example 1 on the tissue surface was determined as follows: The sample or fibrin glue used as a control was dropped onto the surface of an upright pig eyeball fixed on a scaffold (maintaining a temperature of approximately 37°C). The change in solution position of the sample was recorded from the time of application (0 seconds) to 1 minute later (60 seconds).

[0218] Experimental results are as follows Figure 5 As shown.

[0219] Figure 5 This is a diagram illustrating the good cohesiveness of Example 1 on the tissue surface provided by Example 1 of the present invention. As can be seen from the diagram, after the sample is dropped onto the ocular surface, it can quickly solidify in the dropping area and does not flow to other areas due to gravity.

[0220] Compared with the prior art, the wet tissue surface adhesive material of the present invention has good cohesion on the tissue surface, which again demonstrates the temperature sensitivity and tissue adhesion of Example 1.

[0221] 6. The tissue adhesion of the moist tissue surface adhesive material of Example 1 was determined as follows: A full-thickness corneal and corneal-scleral incision was made on a pig eyeball, including a corneal T-shaped incision and a corneal-scleral linear incision. A 3 mm long T-shaped incision was made in the center of the cornea using a 15° surgical puncture knife; similarly, a 3 mm long linear incision was made at the limbus. Then, Example 1 was applied to the wound using a 25-gauge blunt needle and cured by light irradiation for 4 minutes. Finally, the sealed cornea was evaluated by optical coherence tomography (OCT).

[0222] Experimental results are as follows Figure 6 As shown.

[0223] Figure 6 This is a diagram illustrating the high tissue adhesion of Embodiment 1 provided by the present invention. As can be seen from the diagram, Embodiment 1 has high tissue adhesion and can effectively seal perforations.

[0224] Compared with the prior art, the tissue adhesive material of the present invention has good tissue adhesion, which can seal the moist tissue surface (such as the cornea in the state of aqueous humor leakage) and complete the curing and bonding. After the operation, the anterior chamber can be restored and aqueous humor can no longer leak out through the wound.

[0225] 7. The cytotoxicity of cells in Example 1 was determined as follows: Corneal epithelial, stromal, and endothelial cells were seeded at a density of 5000 cells / cm² in 24 / 96-well tissue culture plates (BD Biosciences), and cultured using complete culture medium and extraction buffer, respectively. The extraction buffer was prepared by immersing the sample in complete culture medium and soaking at 37°C for 48 hours. Cell viability was assessed using a fluorescence live / dead staining method: calcein AM (0.5 μL / mL) and ethinyl bromophenazine dimer 1 (2 μL / mL) were diluted with PBS to prepare a staining solution, which was then added to the wells after replacing the culture medium. Cells were then incubated in the dark at 37°C for 30 minutes. Images of live and dead cells were acquired using an inverted fluorescence microscope on days 1, 3, and 5 of culture. Cell proliferation was further quantitatively detected using the CCK-8 assay; absorbance was measured at 450 nm using a microplate reader on days 1, 3, and 5 of culture.

[0226] Experimental results are as follows Figure 7 As shown. Figure 7 This is a diagram illustrating the good cell compatibility of Example 1 provided in Embodiment 1 of the present invention. As can be seen from the diagram, the embodiment does not affect cell proliferation.

[0227] Compared with the prior art, the present invention has good cell compatibility and will not cause cell death or inhibit cell growth after application.

[0228] 8. The burst pressure after tissue adhesion in Example 1 was determined as follows: A corneal-scleral flap was removed from a fresh pig eye and fixed to an artificial anterior chamber. A 4 mm penetrating incision was made in the center of the cornea using a 15-degree ophthalmic scalpel. 15 μL of pre-hydrogel was applied to the corneal incision, followed by in-situ crosslinking for a predetermined time. The artificial anterior chamber was connected to a pressure gauge and an infusion pump, and phosphate-buffered saline was continuously pumped into the artificial anterior chamber at a rate of 5 mL / h. Burst pressure was defined as the highest pressure reached before wound leakage. We compared the burst pressure of Example 1 with that of fibrin glue.

[0229] Experimental results are as follows Figure 8 As shown. By Figure 8 It is evident that Example 1 exhibits a higher burst pressure, significantly exceeding that of fibrin glue, thus providing better resistance to pressure-induced wound dehiscence. Compared to existing technologies, it effectively closes tissue wounds and resists higher intraocular pressure; normal intraocular pressure, pathological intraocular pressure elevation, and intraocular pressure increases caused by eye rubbing do not lead to adhesion failure.

[0230] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A wet tissue surface adhesive material, characterized in that, The adhesive material for the moist tissue surface includes: (1) Dopamine-modified methacryloyl hyaluronic acid (HAMA-DOPA); (2) Prönnicke F127-diacrylate (F127DA); (3) Aldehyde-modified polyether F127 (F127CHO); (4) Oxymethylacrylamide hyaluronic acid (OHAMA); and (5) A photoinitiator for initiating a photopolymerization reaction of the methacryloyl groups and acrylate groups in the above components under visible light irradiation, wherein the photoinitiator comprises at least one of lithium phenyl (2,4,6-trimethylbenzoyl) phosphate or a photoinitiator composition, wherein the photoinitiator composition comprises: eosin Y at a concentration of 0.05 to 0.25 mmol / L; triethanolamine at a mass-volume ratio of 1.5% to 3%; and N-vinylcaprolactam at a mass-volume ratio of 1% to 2%.

2. The adhesive material for wetting tissue surfaces according to claim 1, characterized in that, The adhesive material for the moist tissue surface also includes: (6) A solvent, the solvent comprising at least one of phosphate buffer (PBS) and carbonate-bicarbonate buffer (CBS).

3. The adhesive material for wetting tissue surfaces according to claim 1, characterized in that, In the dopamine-modified methacrylamide hyaluronic acid, the grafting rate of dopamine is 5%-15%, and / or the grafting rate of methacrylamide groups is 10%-50%; And / or, in the aldehyde-modified polyether F127, the degree of substitution of the aldehyde group is 50%-95%; And / or, in the oxidized methacryloyl hyaluronic acid, the grafting rate of methacrylic anhydride is 10%-60%, and / or, the degree of aldehyde oxidization is 10%-50%.

4. The adhesive material for wetting tissue surfaces according to claim 2, characterized in that, The weight-volume ratio of HAMA-DOPA to the solvent is 1% to 8%; And / or, the weight-volume ratio of the F127DA to the solvent is 5% to 20%; And / or, the weight-volume ratio of the F127CHO to the solvent is 5% to 20%; And / or, the weight-volume ratio of the OHAMA to the solvent is 1% to 8%; And / or, the weight-volume ratio of the photoinitiator to the solvent is 0.05% to 0.3%; Furthermore, the weight-volume ratio of the sum of F127DA and F127CHO to the solvent is ≤35% (20% ≤ 35%); and the weight-volume ratio of the sum of HAMA-DOPA and OHAMA to the solvent is ≤10%.

5. The method for preparing the adhesive material for moist tissue surfaces according to any one of claims 1-4, characterized in that, The preparation method includes: (1) Dissolve the HAMA-DOPA, F127DA, F127CHO, OHAMA and the photoinitiator in a solvent at low temperature to obtain a prepolymer that can flow at low temperature; (2) The prepolymer solution is applied to the surface of a moist tissue and the prepolymer solution is converted into a hydrogel at 35℃-40℃; (3) Irradiate the hydrogel with visible light to solidify it and obtain the wet tissue surface adhesive material.

6. The preparation method according to claim 5, characterized in that, In step (1), the weight-volume ratio of HAMA-DOPA to the solvent is 1% to 8%; And / or, the weight-volume ratio of the F127DA to the solvent is 5% to 20%; And / or, the weight-volume ratio of the F127CHO to the solvent is 5% to 20%; And / or, the weight-volume ratio of the OHAMA to the solvent is 1% to 8%; And / or, the weight-volume ratio of the photoinitiator to the solvent is 0.05% to 0.3%; And / or, the weight-volume ratio of the sum of F127DA and F127CHO to the solvent is ≤35% (20% ≤ 35%). And / or, the weight-volume ratio of the sum of HAMA-DOPA and OHAMA to the solvent is ≤10%; And / or, in step (1), the low temperature is 0°C to 10°C; And / or, in step (2), the conversion of the prepolymer into a non-flowing hydrogel is carried out at a temperature of 35-37°C.

7. The preparation method according to claim 5, characterized in that, In step (2), the polyether F127 segments of F127DA and F127CHO self-assemble under temperature stimulation of 35-40°C to form a micelle physical cross-linking network, which transforms the solution into a hydrogel. And / or, in step (3), the photoinitiator initiates a copolymerization reaction of the methacryloyl groups and acrylate groups in the HAMA-DOPA, the F127DA and the OHAMA to form a second covalent crosslinking network; And / or, in step (3), the aldehyde group of F127CHO reacts with the amino group on the tissue surface to form a Schiff base reaction, and the aldehyde group of OHAMA reacts with the amino group on the tissue surface to form a third adhesive network. And / or, in step (3), the dopamine groups in the HAMA-DOPA covalently crosslink with the amino and thiol groups on the tissue surface through the catechol groups, thereby enhancing interfacial interactions.

8. The preparation method according to claim 5, characterized in that, In step (2), the application is by injection, application, or dripping; And / or, in step (3), the wavelength range of the visible light is 400 nm to 550 nm; And / or, in step (3), the power of the irradiation is from 10 mW / cm² to 50 mW / cm²; And / or, in step (3), the irradiation time is from 10 seconds to 240 seconds.

9. The use of the wet tissue surface adhesive material according to any one of claims 1-4 in the preparation of wet tissue surface adhesive products.

10. A surface adhesive product for moist tissues, characterized in that, The product includes a moist tissue surface adhesive material according to any one of claims 1-4.

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