A pro-repairing self-adhering tissue patch and its preparation method and application

Abstract

The present application relates to a kind of self-adhesion tissue patch of promoting repair, the tissue patch includes substrate layer and tissue adhesion layer, wherein the tissue adhesion layer includes acryl RGD.The tissue patch of the present application has specific functional group, can be adhered to tissue surface while maintaining the functionality of artificial patch, without suturing;At the same time, the introduction of RGD short peptide can reduce the damage to the injured tissue again while accelerating the repair speed.

Description

Technical Field

[0001] This invention relates to the field of medical technology, and in particular to a self-adhesive tissue patch that promotes tissue repair, its preparation method, and its application. Background Technology

[0002] In clinical practice, soft tissue defects or injuries often require surgical repair or resection of the affected area (such as the dura mater, lungs, pancreas, and digestive system). To further promote repair or prevent leakage of tissue fluid / blood, artificial patches are used for reinforcement or closure during surgery. Currently, various materials are used to prepare artificial patches in clinical settings, mainly categorized as biological / bio-derived materials and polymeric synthetic materials. Biological / bio-derived materials primarily utilize xenogeneic animal-derived materials, such as porcine / bovine pericardium, dermal matrix, and collagen-based biomembranes. Polymeric materials are mainly biodegradable polyesters, such as polylactic acid, polycaprolactone, polyglycolic acid, and their derivatives and copolymers, as well as non-biodegradable materials, such as expanded polytetrafluoroethylene (ePTFE), polyurethane, and polyethylene terephthalate (PET). However, these types of patches require sutures for fixation or specialized tissue adhesives, which undoubtedly introduces additional secondary damage and prolongs surgical time.

[0003] Currently, the design of self-adhesive patches is primarily achieved through hydrogel technology. Existing technologies mainly promote adhesion between the material and tissue surface by modifying the hydrogel's structure, morphology, chemical modification, or physical mixing. However, these materials have not yet achieved commercial application. The reason for this is that many properties still cannot meet the functional requirements of commercially available products. Hydrogels have the property of absorbing water and swelling, which poses a risk of nerve compression in some enclosed nerves. Furthermore, hydrogels lose their mechanical properties once they excessively absorb water and swell. Therefore, the effectiveness of these gel materials is limited.

[0004] Adhesive tissue patches, such as those mentioned in CN110448727A and CN115462853A, are all based on hydrogel preparation methods. While hydrogel tissue patches exhibit good biocompatibility, the swelling properties of hydrogels result in poor dimensional stability within the body. Furthermore, current techniques typically use catechol as the adhesive functional group, leading to hydrogels often having an opaque, dark appearance, which is detrimental to immediate wound observation. Therefore, an ideal tissue patch should be transparent, possess good dimensional stability, good tissue adhesion, and promote the regeneration of damaged organs and tissues. Summary of the Invention

[0005] The problem the invention aims to solve

[0006] Based on the aforementioned problems in the existing technology, the purpose of this invention is to provide a transparent tissue patch with self-adhesive function that can promote the regeneration of damaged organs and tissues, and a method for preparing the patch thereof.

[0007] Solution for solving the problem

[0008] The present invention provides a self-adhesive tissue patch that promotes repair, the tissue patch comprising a base layer and a tissue adhesion layer, wherein the tissue adhesion layer comprises acryloyl RGD.

[0009] Preferably, the tissue adhesion layer further comprises one or more of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, maleimide acrylate, and isocyanate; more preferably, the tissue adhesion layer is composed of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, maleimide acrylate, and acryloyl RGD.

[0010] Preferably, the molar ratio of N-vinylpyrrolidone to acrylic acid is 1:4-4:1, more preferably 2:1;

[0011] Preferably, the molar ratio of succinimide acrylate to maleimide acrylate is 1:3-3:1, and more preferably 1:1;

[0012] Preferably, the molar ratio of acrylic acid to the sum of succinimide acrylate and maleimide acrylate is 1:3-3:1, preferably 1:1;

[0013] Preferably, the acryloyl RGD is 0.1%-0.9% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate and maleimide acrylate, more preferably 0.3%-0.7%, and even more preferably 0.5%.

[0014] Preferably, the base layer is one or more of biological / biologically derived materials, synthetic polymer materials, or non-degradable materials; more preferably, the base layer is a synthetic polymer material; even more preferably, the base layer is a lactide-glycolic acid copolymer.

[0015] The present invention also provides a method for preparing the tissue patch, the method comprising the following steps:

[0016] (1) Preparation of the base layer;

[0017] (2) Preparation of tissue adhesion layer solution;

[0018] (3) Prepare the self-adhesive tissue patch;

[0019] Step 2 includes:

[0020] (2c) Prepare tissue adhesion layer solution using maleimide acrylate and acryloyl RGD.

[0021] Preferably, step 2c includes purifying N-vinylpyrrolidone and acrylic acid, then adding N-vinylpyrrolidone, acrylic acid, succinimide acrylate, maleimide acrylate and acryloyl RGD to purified water, adding a photoinitiator and stirring to obtain a tissue adhesion layer solution.

[0022] Preferably, the molar ratio of N-vinylpyrrolidone to acrylic acid is 1:4-4:1, more preferably 2:1;

[0023] Preferably, the molar ratio of succinimide acrylate to maleimide acrylate is 1:3-3:1, and more preferably 1:1;

[0024] Preferably, the molar ratio of acrylic acid to the sum of succinimide acrylate and maleimide acrylate is 1:3-3:1, preferably 1:1;

[0025] Preferably, the acryloyl RGD is 0.1%-0.9% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate and maleimide acrylate, more preferably 0.3%-0.7%, and even more preferably 0.5%.

[0026] Preferably, step 2 further includes:

[0027] (2a) Preparation of maleimide acrylate;

[0028] (2b) Preparation of acryloyl RGD;

[0029] Preferably, step 2a includes adding acrylic monomer to tetrahydrofuran, adding a dicyclohexylcarbodiimide solution dissolved in tetrahydrofuran while stirring, mixing, adding a hydroxyethylmaleimide solution dissolved in tetrahydrofuran, filtering under reduced pressure after the reaction is complete, rotary evaporating, adding diethyl ether, filtering again, rotary evaporating, and drying to obtain maleimide acrylate.

[0030] Preferably, step 2b includes adding RGD short peptide and acrylic monomer to MES buffer, dissolving them, adding MES buffer containing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, reacting at room temperature, dialyzing the product, and drying to obtain acryloyl RGD.

[0031] Preferably, step 1 includes:

[0032] (1a) Dissolve the film-forming polymer in an organic solvent to obtain a film-forming polymer solution;

[0033] (1b) The film-forming polymer solution obtained in step 1a is coated as a base layer using a coating machine.

[0034] Preferably, step 3 includes:

[0035] The tissue adhesion layer solution prepared in step 2 was coated onto the base layer prepared in step 1, and then dried after being irradiated with ultraviolet light.

[0036] The present invention also provides the application of the self-adhesive tissue patch or the method thereof in the preparation of tissue and organ repair products for humans or animals.

[0037] The effects of the invention

[0038] The transparent self-adhesive tissue patch of the present invention has specific functional groups, such as covalent bonds and ionic bonds, which can adhere to the tissue surface without sutures while maintaining the functionality of artificial patches; at the same time, the introduction of RGD short peptides can accelerate the repair speed while reducing further damage to the injured tissue. Attached Figure Description

[0039] Figure 1 This is a schematic diagram of the molecular structure of the polymer in the tissue patch of Example 1.

[0040] Figure 2 The image shows the infrared spectrum of the polymer in the tissue patch of Example 1.

[0041] Figure 3 This is a schematic diagram of cell proliferation after co-culturing tissue patches and cells in Examples 1 to 8. Detailed Implementation

[0042] To make the technical solution and beneficial effects of the present invention more apparent and understandable, a detailed description is provided below by listing specific embodiments. The accompanying drawings are not necessarily drawn to scale, and local features may be enlarged or reduced to more clearly show the details of the local features; unless otherwise defined, the technical and scientific terms used herein have the same meanings as those in the technical field to which this application pertains.

[0043] The present invention provides a self-adhesive tissue patch that promotes repair, the tissue patch comprising a base layer and a tissue adhesion layer, wherein the tissue adhesion layer comprises acryloyl RGD.

[0044] In some embodiments, the tissue adhesion layer further comprises one or more of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, maleimide acrylate, and isocyanate.

[0045] In some embodiments, the tissue adhesion layer is composed of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, maleimide acrylate, and acryloyl RGD.

[0046] In some embodiments, the molar ratio of N-vinylpyrrolidone to acrylic acid is 1:4 to 4:1.

[0047] In some embodiments, the molar ratio of N-vinylpyrrolidone to acrylic acid is 2:1.

[0048] In some embodiments, the molar ratio of succinimide acrylate to maleimide acrylate is 1:3 to 3:1.

[0049] In some embodiments, the molar ratio of succinimide acrylate to maleimide acrylate is 1:1.

[0050] In some embodiments, the molar ratio of the acrylic acid to the sum of succinimide acrylate and maleimide acrylate is 1:3 to 3:1.

[0051] In some embodiments, the molar ratio of the acrylic acid to the sum of succinimide acrylate and maleimide acrylate is 1:1.

[0052] In some embodiments, the acryloyl RGD is 0.1% to 0.9% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, and maleimide acrylate.

[0053] In some embodiments, the acryloyl RGD is 0.3% to 0.7% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, and maleimide acrylate.

[0054] In some embodiments, the acryloyl RGD is 0.5% of the sum of the masses of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, and maleimide acrylate.

[0055] In some embodiments, the base layer is one or more of a biological / bio-derived material, a synthetic polymer material, or a non-degradable material.

[0056] In some embodiments, the base layer is a synthetic polymer material.

[0057] In some embodiments, the base layer is a lactide-glycolic acid copolymer.

[0058] In some implementations, the thickness of the substrate layer is 5 μm.

[0059] In some embodiments, the tissue patch is 30 μm thick.

[0060] The present invention also provides a method for preparing the tissue patch, the method comprising the following steps:

[0061] (1) Preparation of the base layer;

[0062] (2) Preparation of tissue adhesion layer solution;

[0063] (3) Prepare the self-adhesive tissue patch;

[0064] Step 2 includes:

[0065] (2c) Prepare tissue adhesion layer solution using maleimide acrylate and acryloyl RGD.

[0066] In some embodiments, step 2c includes purifying N-vinylpyrrolidone and acrylic acid, then adding N-vinylpyrrolidone, acrylic acid, succinimide acrylate, maleimide acrylate and acryloyl RGD to purified water, adding a photoinitiator and stirring to obtain a tissue adhesion layer solution.

[0067] In some embodiments, the molar ratio of N-vinylpyrrolidone to acrylic acid is 1:4 to 4:1.

[0068] In some embodiments, the molar ratio of N-vinylpyrrolidone to acrylic acid is 2:1.

[0069] In some embodiments, the molar ratio of succinimide acrylate to maleimide acrylate is 1:3 to 3:1.

[0070] In some embodiments, the molar ratio of succinimide acrylate to maleimide acrylate is 1:1.

[0071] In some embodiments, the molar ratio of the acrylic acid to the sum of succinimide acrylate and maleimide acrylate is 1:3 to 3:1.

[0072] In some embodiments, the molar ratio of the acrylic acid to the sum of succinimide acrylate and maleimide acrylate is 1:1.

[0073] In some embodiments, the acryloyl RGD is 0.1% to 0.9% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, and maleimide acrylate.

[0074] In some embodiments, the acryloyl RGD is 0.3% to 0.7% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, and maleimide acrylate.

[0075] In some embodiments, the acryloyl RGD is 0.5% of the sum of the masses of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, and maleimide acrylate.

[0076] In some embodiments, the photoinitiator is photoinitiator 2959.

[0077] In some embodiments, step 2c involves purifying N-vinylpyrrolidone and acrylic acid by vacuum distillation, then adding 4.48 g of N-vinylpyrrolidone, 1.45 g of acrylic acid, 1.88 g of succinimide acrylate, 2.15 g of maleimide acrylate, and 0.05 g of acryloyl RGD to 20 mL of purified water, stirring evenly at room temperature, and then adding 0.21 g of photoinitiator, stirring evenly in the dark to obtain a tissue adhesion layer solution.

[0078] In some implementations, step 2 further includes:

[0079] (2a) Preparation of maleimide acrylate;

[0080] (2b) Preparation of acryloyl RGD.

[0081] In some embodiments, step 2a includes adding acrylic monomer to tetrahydrofuran, adding a solution of dicyclohexylcarbodiimide dissolved in tetrahydrofuran while stirring, mixing, adding a solution of hydroxyethylmaleimide dissolved in tetrahydrofuran, filtering under reduced pressure after the reaction is complete, rotary evaporating, adding diethyl ether, filtering again, rotary evaporating, and drying to obtain maleimide acrylate.

[0082] In some embodiments, step 2a involves adding 10g of purified acrylic acid monomer obtained by vacuum distillation to a flask containing 100mL of tetrahydrofuran, adding 43g of a dicyclohexylcarbodiimide solution dissolved in 100mL of tetrahydrofuran under magnetic stirring, stirring for 30min to ensure thorough mixing, and finally slowly adding 23.5g of a hydroxyethylmaleimide solution dissolved in 200mL of tetrahydrofuran. The reaction is carried out at room temperature for 24 hours. After the reaction is complete, the reaction byproduct dicyclohexylurea is removed by vacuum filtration, and the filtrate is then rotary evaporated to dryness. An appropriate amount of diethyl ether is added, and the mixture is filtered again to remove insoluble matter. The filtrate is then rotary evaporated to dryness, and the final product is dried in a vacuum drying oven for 24 hours to obtain maleimide acrylate.

[0083] In some embodiments, step 2b includes adding RGD short peptide and acrylic monomer to MES buffer, dissolving them, adding MES buffer containing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, reacting at room temperature, dialyzing the product, and drying to obtain acryloyl RGD.

[0084] In some embodiments, step 2b involves adding 26.6 g of RGD short peptide and 5 g of purified acrylic acid monomer to a flask containing 20 mL of MES buffer. After complete dissolution, MES buffer containing 13.3 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride is added, and the reaction is carried out at room temperature for 24 hours. After the reaction is complete, the product is dialyzed with purified water for 5 days, with the water being changed every 8-16 hours. After drying, acryloyl RGD is obtained.

[0085] In some implementations, step 1 includes:

[0086] (1a) Dissolve the film-forming polymer in an organic solvent to obtain a film-forming polymer solution;

[0087] (1b) The film-forming polymer solution obtained in step 1a is coated as a base layer using a coating machine.

[0088] In some embodiments, the film-forming polymer is a lactide-glycolic acid copolymer.

[0089] In some embodiments, the molar ratio of lactic acid to glycolic acid in the lactide-glycolic acid copolymer is 50:50, and Mw = 100000 Da.

[0090] In some embodiments, the organic solvent is a dichloromethane / acetone solution.

[0091] In some embodiments, the dichloromethane / acetone solution v / v = 8:2.

[0092] In some embodiments, the film-forming polymer solution is a 10% w / v solution.

[0093] In some embodiments, step 1a involves dissolving 10g of lactide-glycolic acid copolymer in 100ml of dichloromethane / acetone to prepare a 10% w / v solution.

[0094] In some embodiments, step 1b involves using a scraper to coat the release paper with a base layer of a certain thickness, and then placing the release paper and the base layer together in a vacuum oven to dry for later use.

[0095] In some embodiments, the release paper is a silicone-coated release paper.

[0096] In some embodiments, the drying is performed at 40°C for 30 minutes.

[0097] In some implementations, the thickness of the substrate layer is 5 μm.

[0098] In some embodiments, step 1b involves using a scraper to coat a 5μm thick base layer onto the silicone oil-coated release paper, then placing the base layer and release paper together in a vacuum oven and treating it at 40°C for 30 minutes before use.

[0099] In some implementations, step 3 includes:

[0100] The tissue adhesion layer solution prepared in step 2 was coated onto the base layer prepared in step 1, and then dried after being irradiated with ultraviolet light.

[0101] In some implementations, the ultraviolet irradiation is performed under an ultraviolet lamp for 180 seconds.

[0102] In some embodiments, the drying is performed in a vacuum drying oven at 60°C for 72 hours.

[0103] In some embodiments, step 3 involves applying the tissue adhesion layer solution prepared in step 2 onto the substrate layer prepared in step 1 using a laboratory coater, irradiating it under a UV lamp for 180 seconds, and then placing it in a vacuum drying oven to dry at 60°C for 72 hours.

[0104] The present invention also provides the application of the self-adhesive tissue patch or the method thereof in the preparation of tissue and organ repair products for humans or animals.

[0105] Example 1: Preparation of self-adhesive tissue patch #1

[0106] 1. Preparation of the base layer:

[0107] (a) Dissolve 10g of lactide-glycolic acid copolymer (PLGA, with a molar ratio of lactic acid to glycolic acid of 50:50, Mw = 100000Da) particles in 100ml of dichloromethane / acetone (v / v = 8:2) to prepare a 10% w / v solution.

[0108] (b) Use a scraper to coat a base layer with a thickness of 5 μm onto the silicone oil-coated release paper, and place it together with the release paper into a vacuum oven and treat it at 40°C for 30 min, then set aside for use.

[0109] 2. Preparation of tissue adhesion layer solution:

[0110] (a) Acrylic acid monomer (10 g, 0.139 mol) purified by vacuum distillation was added to a flask containing 100 mL of tetrahydrofuran. A solution of dicyclohexylcarbodiimide (43 g, 0.208 mol) dissolved in 100 mL of tetrahydrofuran was added under magnetic stirring. The mixture was stirred for 30 min to ensure thorough mixing. Finally, a solution of hydroxyethylmaleimide (23.5 g, 0.167 mol) dissolved in 200 mL of tetrahydrofuran was slowly added. The reaction was carried out at room temperature for 24 hours. After the reaction was complete, the byproduct dicyclohexylurea was removed by vacuum filtration. The filtrate was then evaporated to dryness by rotary evaporation. An appropriate amount of diethyl ether was added, and the mixture was filtered again to remove insoluble matter. The filtrate was then evaporated to dryness by rotary evaporation. The final product was dried in a vacuum drying oven for 24 hours to obtain maleimide acrylate.

[0111] (b) Add 26.6 g of RGD short peptide (Arg-Gly-Asp) and 5 g of purified acrylic acid monomer to a flask containing 20 mL of MES buffer. After complete dissolution, add MES buffer containing 13.3 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and react at room temperature for 24 hours. After the reaction, dialyze the product with purified water for 5 days, changing the water every 8-16 hours. After drying, acryloyl RGD is obtained.

[0112] (c) N-vinylpyrrolidone and acrylic acid were purified by vacuum distillation. Then, 4.48 g of N-vinylpyrrolidone, 1.45 g of acrylic acid, 1.88 g of succinimide acrylate, 2.15 g of maleimide acrylate and 0.05 g of acryloyl RGD were added to 20 mL of purified water and stirred evenly at room temperature. Then, 0.21 g of photoinitiator (photoinitiator 2959, i.e., 2-hydroxy-4-(2-hydroxyethoxy)-2-methylphenylacetone) was added and stirred evenly in the dark to obtain a tissue adhesion layer solution.

[0113] 3. Preparation of tissue adhesion layer

[0114] The solution prepared in step (2c) was coated onto the carrier layer dried in step (2a) using a laboratory coating machine, irradiated under a UV lamp for 180s, and then placed in a vacuum drying oven and dried at 60°C for 72h to prepare a self-adhesive tissue patch #1 with a thickness of 30μm.

[0115] Polymer of tissue adhesion layer (structural diagram as shown) Figure 1 (As shown) contains carboxyl, pyrrolidone, RGD segment birthmark, maleimide ester, and succinimide ester groups, with corresponding infrared characteristic absorption peaks ( Figure 2 The following is a sample size: 3382cm -1 (RGD, NH), 2954cm -1 (Acrylic acid, CH), 1812cm -11781cm -1 (Succinimide acrylate, C=O), 1737cm -1 (Pyrrolidone, C=O), 694cm -1 (maleimide acrylate, CH=CH).

[0116] Example 2: Preparation of self-adhesive tissue patch #2

[0117] The preparation method is the same as in Example 1, as shown in Table 1. The difference is that the molar ratio of succinimide acrylate and maleimide acrylate in Example 2 is 3:1, and a self-adhesive tissue patch #2 with a thickness of 30 μm is prepared.

[0118] Table 1. Adhesion strength test results of self-adhesive tissue patches #1 to #8

[0119]

[0120] Example 3: Preparation of self-adhesive tissue patch #3

[0121] The preparation method is the same as in Example 1, as shown in Table 1. The difference is that the molar ratio of succinimide acrylate and maleimide acrylate in Example 3 is 1:3, and a self-adhesive tissue patch #3 with a thickness of 30 μm is prepared.

[0122] Example 4: Preparation of self-adhesive tissue patch #4

[0123] The preparation method is the same as in Example 1, as shown in Table 1. The difference is that the amount of acryloyl RGD added in Example 4 is 0.1% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate and maleimide acrylate, and a self-adhesive tissue patch #4 with a thickness of 30 μm is prepared.

[0124] Example 5: Preparation of self-adhesive tissue patch #5

[0125] The preparation method is the same as in Example 1, as shown in Table 1. The difference is that in Example 5, the amount of acryloyl RGD added is 0.3% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate and maleimide acrylate, and a self-adhesive tissue patch #5 with a thickness of 30 μm is prepared.

[0126] Example 6: Preparation of self-adhesive tissue patch #6

[0127] The preparation method is the same as in Example 1, as shown in Table 1. The difference is that the amount of acryloyl RGD added in Example 6 is 0.7% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate and maleimide acrylate, and a self-adhesive tissue patch #6 with a thickness of 30 μm is prepared.

[0128] Example 7: Preparation of self-adhesive tissue patch #7

[0129] The preparation method is the same as in Example 1, as shown in Table 1. The difference is that the amount of acryloyl RGD added in Example 6 is 0.9% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate and maleimide acrylate, and a self-adhesive tissue patch #7 with a thickness of 30 μm is prepared.

[0130] Example 8: Preparation of self-adhesive tissue patch #8

[0131] The preparation method is the same as in Example 1, as shown in Table 1. The difference is that the amount of acryloyl RGD added in Example 8 is 0, and a self-adhesive tissue patch #8 with a thickness of 30 μm is prepared.

[0132] Example 9: Adhesion Strength Test

[0133] The adhesive strength of the self-adhesive tissue patches prepared in Examples 1-8 was tested according to YY / T 0729.3-2009 "Test Methods for Adhesive Properties of Tissue Adhesives - Part 3: Tensile Strength". The specific steps are as follows:

[0134] Using cyanoacrylate adhesive, tissue patches measuring 2.5cm x 2.5cm and fresh pig liver were bonded to the test substrate. After the cyanoacrylate adhesive cured, the tissue patch and fresh pig liver were bonded together, and a force of 2N was applied to the bonding area. Adhesion tensile strength was tested using a testing machine at a speed of 10mm / min, and the test samples were loaded until failure. The maximum load at which the tissue patch and pig skin failed was the adhesive strength. The results are shown in Table 1.

[0135] The results showed that the adhesive strength was highest when the molar ratio of succinimide acrylate to maleimide acrylate was 1:1; the addition of a small amount of acryloyl RGD had little effect on the adhesive strength.

[0136] Example 10: Adhesion Durability Test

[0137] The adhesion durability of the self-adhesive tissue patch samples prepared in Examples 1-8 was tested using the same test method as in Example 9. The difference was that before testing the adhesion strength between the sample and the pig liver, the adhered sample and the pig liver were immersed in physiological saline and stored for 0-120 hours (simulating a moist wound environment). The adhesion strength was measured at different time points (0h, 24h, 96h, and 120h), and the results are shown in Table 2.

[0138] Table 2. Adhesion durability test results of self-adhesive tissue patches #1 to #8

[0139]

[0140] As a result, the self-adhesive tissue patch of the present invention still exhibits strong adhesion (not less than 1N) to tissue in a humid environment after 120 hours. This demonstrates that the introduction of the RGD short peptide in the present invention did not significantly affect the long-term adhesion strength of the self-adhesive tissue patch in a humid environment.

[0141] Example 11: Cell compatibility evaluation

[0142] The self-adhesive tissue patches #1 to #8 were co-cultured with mouse fibroblasts (L929) and incubated at 37°C and 5% CO2 for 1, 3, and 7 days. Cell proliferation was then assessed using the MTT assay. Results are as follows: Figure 3 As shown, with the extension of culture time, the increase of acryloyl RGD content (from 0% to 0.5%) is significantly beneficial to cell proliferation; while when the acryloyl RGD content increases from 0.5% to 0.9%, the cell proliferation effect shows a slight decreasing trend.

[0143] Combining Examples 10 and 11, the addition of small amounts of acryloyl RGD did not significantly affect the adhesive strength; however, when the content of acryloyl RGD increased from 0.1% to 0.5%, the cell proliferation-promoting effect showed a significant increasing trend with the increase of RGD content, while when the content of acryloyl RGD increased from 0.5% to 0.9%, the cell proliferation-promoting effect showed a decreasing trend. Therefore, the optimal selection of acryloyl RGD is 0.5%.

[0144] In summary, when the molar ratio of succinimide acrylate to maleimide acrylate is 1:1 and the content of acryloyl RGD is 0.5% (i.e., Example 1), the self-adhesive tissue patch prepared exhibits the best adhesive strength and repair-promoting properties.

[0145] The adhesive strength test results of the self-adhesive tissue patch of the present invention show that, due to the presence of bifunctional tissue reactive groups in the reactive functional group layer, the two work synergistically to significantly improve the adhesion durability of the tissue closure patch in a moist environment, effectively ensuring that the tissue closure patch maintains durable adhesive strength when used on wounds in a moist environment; at the same time, the addition of RGD short peptides improves the cell compatibility of the material, which is conducive to the adhesion and proliferation of cells on the surface of damaged organs or tissues, thereby promoting their regeneration.

[0146] It should be understood that the above embodiments are exemplary and are not intended to encompass all possible implementations included in the claims. Various modifications and changes can be made to the above embodiments without departing from the scope of this disclosure. Similarly, the various technical features of the above embodiments can be arbitrarily combined to form other embodiments of the present invention that may not be explicitly described. Therefore, the above embodiments only illustrate several implementations of the present invention and do not limit the scope of protection of this patent.

Claims

1. A self-adhesive tissue patch that promotes tissue repair, characterized in that, The tissue patch includes a base layer and a tissue adhesion layer, wherein the tissue adhesion layer comprises acryloyl RGD; The tissue adhesion layer is composed of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, maleimide acrylate, and acryloyl RGD; The molar ratio of N-vinylpyrrolidone to acrylic acid is 1:4-4:1; The molar ratio of succinimide acrylate to maleimide acrylate is 1:1; The molar ratio of acrylic acid to the sum of succinimide acrylate and maleimide acrylate is 1:3-3:1; The acryloyl RGD is 0.1%-0.9% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, and maleimide acrylate; The method for preparing the tissue patch includes the following steps: (1) Preparation of the base layer; (2) Preparation of tissue adhesion layer solution; (3) Prepare the self-adhesive tissue patch; Step 2 includes: (2c) Prepare tissue adhesion layer solution using maleimide acrylate and acryloyl RGD; Step 2c includes purifying N-vinylpyrrolidone and acrylic acid, then adding N-vinylpyrrolidone, acrylic acid, succinimide acrylate, maleimide acrylate and acryloyl RGD to purified water, adding a photoinitiator and stirring to obtain a tissue adhesion layer solution. Step 3 includes: The tissue adhesion layer solution prepared in step 2 was coated onto the base layer prepared in step 1, and then dried after being irradiated with ultraviolet light.

2. The tissue patch according to claim 1, characterized in that, The molar ratio of N-vinylpyrrolidone to acrylic acid is 2:

1.

3. The tissue patch according to claim 1, characterized in that, The molar ratio of acrylic acid to the sum of succinimide acrylate and maleimide acrylate is 1:

1.

4. The tissue patch according to claim 1, characterized in that, The acryloyl RGD is 0.3%-0.7% of the sum of the mass of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, and maleimide acrylate.

5. The tissue patch according to claim 4, characterized in that, The acryloyl RGD is 0.5% of the sum of the masses of N-vinylpyrrolidone, acrylic acid, succinimide acrylate, and maleimide acrylate.

6. The tissue patch according to claim 1, characterized in that, The base layer is a synthetic polymer material.

7. The tissue patch according to claim 6, characterized in that, The base layer is a copolymer of lactide and glycolide.

8. The tissue patch according to claim 1, characterized in that, Step 2 also includes: (2a) Preparation of maleimide acrylate; (2b) Preparation of acryloyl RGD.

9. The tissue patch according to claim 8, characterized in that, Step 2a includes adding acrylic acid monomer to tetrahydrofuran, adding a dicyclohexylcarbodiimide solution dissolved in tetrahydrofuran while stirring, mixing, adding a hydroxyethylmaleimide solution dissolved in tetrahydrofuran, filtering under reduced pressure after the reaction is complete, rotary evaporating, adding diethyl ether, filtering again, rotary evaporating, and drying to obtain maleimide acrylate.

10. The tissue patch according to claim 8, characterized in that, Step 2b includes adding RGD short peptide and acrylic monomer to MES buffer, dissolving them, adding MES buffer containing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, reacting at room temperature, dialyzing the product, and drying to obtain acryloyl RGD.

11. The tissue patch according to claim 1, characterized in that, Step 1 includes: (1a) Dissolve the film-forming polymer in an organic solvent to obtain a film-forming polymer solution; (1b) The film-forming polymer solution obtained in step 1a is coated as a base layer using a coating machine.

12. The use of a self-adhesive tissue patch according to any one of claims 1-11 in the preparation of tissue or organ repair products for humans or animals.

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