A fast asymmetric tissue seal patch, its preparation method and application

Abstract

The application belongs to the technical field of biomedical tissue adhesive materials, and relates to a rapid asymmetric tissue sealing patch as well as a preparation method and application thereof. The rapid asymmetric tissue sealing patch is composed of a strong water-absorbing biological adhesion layer and a hydrophobic biological anti-adhesion layer which is spin-coated on the strong water-absorbing biological adhesion layer. The rapid asymmetric tissue sealing patch provided by the application can realize strong adhesion between a wet dynamic tissue and an engineering solid within 5 seconds, can seal the tissue, and can improve the prevention effect of anastomotic leakage. Meanwhile, the rapid asymmetric tissue sealing patch has excellent anti-adhesion performance, can achieve the effect of preventing tissue adhesion after operation, and can be used in the repair of gastrointestinal defects.

Description

Technical Field

[0001] This invention belongs to the field of biomedical tissue adhesive materials technology, and relates to a rapid asymmetric tissue sealing patch, its preparation method and application, for the repair of gastrointestinal defects. Background Technology

[0002] Anastomotic leakage (AL) is one of the most serious and life-threatening complications of gastrointestinal (GI) defect repair surgery. AL repair failure is one of the most frightening and life-threatening complications after gastrointestinal (GI) surgery, increasing the mortality rate by more than 30%. Therefore, improving the success rate of AL repair surgery is a key focus.

[0003] Manual suturing is commonly used in the surgical repair of anastomotic leaks (AL), but leakage from gastrointestinal anastomoses presents a significant technical challenge that manual suturing cannot address. Bioadhesive patches, due to their strong and immediate adhesion advantages, are gradually replacing surgical suturing. However, while various commercially available bioadhesive patches can manage gastrointestinal anastomotic leaks, they have the following drawbacks:

[0004] (1) Most existing bioadhesive patches are made of materials such as fibrin glue, cyanoacrylate, and hydrogel. In actual use, they have problems such as insufficient adhesion and chemical instability on tissue surfaces covered by blood / body fluids. This results in poor ability to inhibit leakage of digestive fluid at the anastomosis site, failure to achieve good tissue sealing, and poor prevention of anastomotic leakage.

[0005] (2) Many existing biological adhesives do not meet the functional requirements of current surgical procedures and interventions. Most adhesives have double-sided adhesive properties, which may lead to adhesion of surrounding tissues after surgery.

[0006] Existing research indicates that poor anastomotic leakage prevention and postoperative adhesions are serious complications following GI surgery, posing a significant threat to patients' lives and health. For example, approximately 90% of patients undergoing abdominal surgery develop varying degrees of abdominal adhesions, which not only lead to chronic pelvic pain and intestinal obstruction—long-term symptoms—but may also cause organ dysfunction and various acute complications, further exacerbating patient suffering and increasing medical burden. Therefore, effective prevention, early diagnosis, and aggressive treatment of poor anastomotic leakage prevention and postoperative adhesions are crucial for improving the survival rate and quality of life of GI surgery patients. Summary of the Invention

[0007] To address the technical problems of poor anastomotic leakage prevention and postoperative adhesion of surrounding tissues in existing anastomotic leakage (AL) surgical repair, this invention provides a rapid asymmetric tissue sealing patch, its preparation method, and its application.

[0008] This invention comprises a rapid asymmetric tissue sealing patch consisting of a highly absorbent bioadhesive layer and a hydrophobic bio-anti-adhesion coating layer. It can quickly achieve strong adhesion between moist dynamic tissue and engineered solid within 5 seconds, sealing the tissue and improving the prevention of anastomotic leakage. At the same time, it has excellent anti-adhesion properties, achieving the effect of preventing tissue adhesion after surgery.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0010] A rapid asymmetric tissue sealing patch consists of a highly absorbent bioadhesive layer and a hydrophobic bio-anti-adhesion layer spin-coated onto the highly absorbent bioadhesive layer.

[0011] The highly absorbent bioadhesive layer is composed of the following raw materials in the indicated weight percentages: 25%–35% hydrophilic polymer, 0.5%–2.0% adhesive polymer matrix, 1.5%–3.5% biodegradable polymer, 0.1%–0.3% biodegradable crosslinking agent, 0.2%–0.4% nanocarrier, and 0.1%–0.25% photoinitiator, with the balance being water.

[0012] The hydrophobic bio-anti-adhesion layer is composed of anti-adhesion materials and water. The anti-adhesion materials include multiple types of hydrophobic hyperbranched polyethylene, polyurethane, acrylate-modified polyurethane, polylactic acid-glycolic acid copolymer, and gelatin. The mass percentage of the anti-adhesion materials is: 5%–8% hydrophobic hyperbranched polyethylene, 8%–10% polyurethane, 1%–5% acrylate-modified polyurethane, 1%–5% polylactic acid-glycolic acid copolymer, and 1%–5% gelatin.

[0013] The nanocarrier is formed by in-situ deposition of ZIF-8@X and polydopamine in a mass ratio of 2:(0.1-0.5), and ZIF-8@X is made of zinc acetate dihydrate, 2-methylimidazole and active ingredient X in a mass ratio of 4:5:(0.01-0.05).

[0014] Further specified, the thickness of the hydrophobic bio-anti-adhesion layer is 50μm to 200μm; the thickness of the highly absorbent bio-adhesion layer is 100μm to 1000μm.

[0015] Further specifying, the hydrophilic polymer is one or more of acrylic acid, acrylamide, tannic acid, and polyvinyl alcohol.

[0016] Further specifying, the adhesive polymer matrix is ​​one or more selected from acrylic acid grafted N-hydroxysuccinimide ester, polyacrylate grafted N-hydroxysuccinimide ester, poly(ε-lysine) and polyethylene glycol succinimide hexanoate.

[0017] Further specifying, the biodegradable polymer is one or more of tannic acid-modified gelatin, chitosan, and quaternized chitosan.

[0018] Further specifying, the biodegradable crosslinking agent is selected from one or more of N,N-methylenebisacrylamide, N,N-cystamine bisacrylamide, ethylene glycol dimethacrylate, ethylene glycol methacrylate, and methacrylamide gelatin.

[0019] Further specifying, the active ingredient X is one or more of an anti-inflammatory component, a growth factor, or a polypeptide bioactive substance; the anti-inflammatory component is one or more of curcumin (Cur), methylprednisolone sodium succinate (MPSS), vancomycin (VAN), and nimesulide (NIM).

[0020] Further specifying, the photoinitiator is one or more of lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (LAP), 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (photoinitiator 2959), α-ketoglutaric acid (AKG), and trimethylbenzoyl-diphenylphosphine oxide (TPO).

[0021] The present invention provides a method for preparing a rapid asymmetric tissue sealing patch, comprising the following steps:

[0022] S1. Preparation of a highly absorbent bioadhesive layer

[0023] S1.1. The hydrophilic polymer, adhesive polymer matrix, biodegradable polymer, biodegradable crosslinking agent, nanocarrier and photoinitiator are uniformly dispersed in water according to the mass percentages described above to prepare a hydrogel precursor solution.

[0024] S1.2 Pour the hydrogel precursor solution from step S1.1 into a glass mold and irradiate it with 345nm ultraviolet light for 1 min to 5 min. The free radicals in the hydrogel precursor solution will polymerize until the mold is formed. Then demold to obtain a highly absorbent bioadhesive layer.

[0025] S2. Disperse the anti-blocking material in water according to the stated mass percentage, and mix evenly to form a spin-coating solution;

[0026] S3. Spin-coating the spin-coating solution from step S2 onto the highly absorbent bioadhesive layer prepared in step S1. The spin-coating solution forms a hydrophobic bioadhesive layer on the highly absorbent bioadhesive layer. After spin-coating is completed, a rapid asymmetric tissue sealing patch is obtained.

[0027] In this invention, a rapid asymmetric tissue sealing patch is used in the repair of gastrointestinal defects. When applied, the rapid asymmetric tissue sealing patch effectively seals, repairs, and prevents adhesion of tissue.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0029] 1. The rapid asymmetric tissue sealing patch provided by this invention comprises a highly absorbent bioadhesive layer and a hydrophobic bio-anti-adhesion layer spin-coated onto the highly absorbent bioadhesive layer. The highly absorbent bioadhesive layer achieves rapid tissue sealing by rapidly adsorbing body fluids, strengthening the transient hydrogen bonding between carboxyl and hydroxyl groups on the surface of moist tissue, and the covalent synergistic effect of the strong covalent bonds formed between the -NHS groups and the tissue. Simultaneously, the continuous release of anti-inflammatory drugs and other substances from the nanocarrier provides long-lasting anti-inflammatory, healing-promoting, and growth-enhancing functions. The hydrophobic bio-anti-adhesion layer possesses highly efficient anti-protein and anti-cell adhesion properties, thereby achieving anti-bioadhesion properties. The rapid asymmetric tissue sealing patch can rapidly achieve strong adhesion between moist dynamic tissue and engineered solids under different pH values ​​and air or hydraulic pressure, improving the prevention of anastomotic leakage; it also has excellent adhesion and anti-adhesion effects; it is suitable for anti-adhesion treatment in defect repair, especially for anti-adhesion after gastrointestinal defect repair.

[0030] 2. In this invention, the hydrophobic bio-anti-adhesion spin coating utilizes hydrophobic spin coating film-forming technology to achieve its loading on a highly absorbent bio-adhesive layer, possessing high biocompatibility and excellent adhesion and anti-adhesion effects, and has broad application prospects in the field of biomedical materials.

[0031] 3. Through experimental research, this invention has found that under a certain pressure (10kPa), the rapid asymmetric tissue sealing patch can achieve strong adhesion between moist dynamic tissue and engineered solid in less than 5 seconds. It has the characteristics of rapid hemostasis, good cell biocompatibility, biodegradability and tissue compatibility, meeting the needs of different tissue adhesion. It has wide applicability to tissue adhesion and provides a new biomaterial design idea and strategy for tissue adhesion repair and prevention of postoperative adhesion.

[0032] 4. The rapid asymmetric tissue sealing patch provided by this invention has excellent seamless suturing and tissue defect healing properties, making it of great potential in the fields of wound treatment and tissue defect repair. It also provides reference and inspiration for the research and development of a new generation of biomedical tissue adhesives and dressings, such as non-invasive, rapid, strong, repairing, anti-adhesion, and controllable degradation biological tissue patches, which may also become a new platform for biological scaffolds, drug delivery systems, and wearable and implantable devices. Attached Figure Description

[0033] Figure 1 The SEM images show the interface and surface of the asymmetric adhesive patch prepared in Example 1.

[0034] Figure 2 Water contact angle diagram of the anti-adhesion layer of the asymmetric adhesive patch prepared in Example 1;

[0035] Figure 3 Water contact angle diagram of the asymmetric adhesive patch adhesive layer prepared in Example 1;

[0036] Figure 4 The stress-strain curves for Examples 1, 2, and 3 are shown below.

[0037] Figure 5 This is a weighing diagram of the PVC and stainless steel adhered in Example 1;

[0038] Figure 6 Images of bent and twisted pigskin used for tissue patch adhesion;

[0039] Figure 7 Bursting resistance maps of Examples 1, 2, and 3 compared to commercial tissue patches on the surface of a pig stomach;

[0040] Figure 8 The diagram shows the L929 cell compatibility of Examples 1 and 2.

[0041] Figure 9 This is an ultrasound image taken 7 days after the skin of a rat was implanted in Example 1.

[0042] Figure 10 The image shows the sealing and repair process at 2 weeks in a rat intestinal defect model, as shown in Example 1.

[0043] Figure 11 Immunofluorescence images of rats with colonic defects repaired 2 weeks prior to Example 1. Detailed Implementation

[0044] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. However, the embodiments described are only some embodiments of the present invention, and not all embodiments.

[0045] This invention provides a rapid asymmetric tissue sealing patch, which consists of a highly absorbent bioadhesive layer and a hydrophobic bio-anti-adhesion layer spin-coated on the highly absorbent bioadhesive layer.

[0046] In this invention, the thickness of the hydrophobic bio-anti-adhesion layer is preferably 50μm, 80μm, 100μm, 120μm, 150μm, 180μm or 200μm; the thickness of the highly absorbent bio-adhesion layer is preferably 100μm, 200μm, 300μm, 400μm, 500μm, 600μm, 700μm, 800μm, 900μm or 1000μm.

[0047] In this invention, the highly absorbent bioadhesive layer is composed of the following raw materials in the indicated mass percentages: 25%–35% hydrophilic polymer, 0.5%–2.0% adhesive polymer matrix, 1.5%–3.5% biodegradable polymer, 0.1%–0.3% biodegradable crosslinking agent, 0.2%–0.4% nanocarrier, and 0.1%–0.25% photoinitiator, with the balance being water.

[0048] In this invention, the hydrophobic bio-anti-adhesion layer is composed of anti-adhesion materials and water. The anti-adhesion materials include multiple types of hydrophobic hyperbranched polyethylene, polyurethane, acrylate-modified polyurethane, polylactic acid-glycolic acid copolymer, and gelatin. The mass percentages of the anti-adhesion materials are: 5%–8% hydrophobic hyperbranched polyethylene, 8%–10% polyurethane, 1%–5% acrylate-modified polyurethane, 1%–5% polylactic acid-glycolic acid copolymer, and 1%–5% gelatin.

[0049] Preferably, the hydrophobic bio-anti-adhesion layer can be understood as follows: the hydrophobic bio-anti-adhesion layer is composed of the following mass percentage of anti-adhesion raw materials: 5% to 8% hydrophobic hyperbranched polyethylene, with the balance being water.

[0050] Preferably, the hydrophobic bio-anti-adhesion layer can also be understood as: the hydrophobic bio-anti-adhesion layer is composed of the following mass percentages of anti-adhesion raw materials: 5% to 8% hydrophobic hyperbranched polyethylene and 8% to 10% polyurethane, with the balance being water.

[0051] Preferably, the hydrophobic bio-anti-adhesion layer can also be understood as follows: the hydrophobic bio-anti-adhesion layer is composed of the following anti-adhesion raw materials in the following mass percentages: 5% to 8% hydrophobic hyperbranched polyethylene, 1% to 5% polylactic acid-glycolic acid copolymer (PLGA) and 1% to 5% gelatin, with the balance being water.

[0052] Preferably, the hydrophobic bio-anti-adhesion layer can also be understood as follows: the hydrophobic bio-anti-adhesion layer is composed of the following anti-adhesion raw materials in the following mass percentages: 5% to 8% hydrophobic hyperbranched polyethylene, 8% to 10% polyurethane, 1% to 5% acrylate-modified polyurethane, 1% to 5% PLGA and 1% to 5% gelatin, with the balance being water.

[0053] In this invention, the nanocarrier is formed by in-situ deposition of ZIF-8@X and polydopamine (PDA) at a mass ratio of 2:(0.1-0.5). In practice, the mass ratio of ZIF-8@X to polydopamine (PDA) is (2:0.1), (2:0.2), (2:0.3), (2:0.4), or (2:0.5).

[0054] Preferably, ZIF-8@X is prepared from zinc acetate dihydrate, 2-methylimidazole, and active ingredient X in a mass ratio of 4:5:(0.01 to 0.05). In practice, the mass ratio of zinc acetate dihydrate, 2-methylimidazole, and active ingredient X is (4:5:0.01), (4:5:0.02), (4:5:0.03), (4:5:0.04), or (4:5:0.05).

[0055] In this invention, the hydrophilic polymer is one or more of acrylic acid (AAc), acrylamide (AAm), tannic acid (TA), and polyvinyl alcohol (PVA). When multiple polymers are selected, they are mixed in any mass ratio.

[0056] In this invention, the adhesive polymer matrix is ​​one or more of the following: acrylic acid-grafted N-hydroxysuccinimide ester (AAc-NHS ester), polyacrylate-grafted N-hydroxysuccinimide ester (PAAc-NHS ester), poly(ε-lysine) (ε-PL), and polyethylene glycol succinimide hexanoate (PEG-SS). When multiple are selected, they are mixed in any mass ratio.

[0057] The biodegradable polymer is one or more of tannic acid-modified gelatin (TA-Gel), chitosan (CS), and quaternized chitosan (QCS). When multiple types are selected, they are mixed in any mass ratio. Tannic acid-modified gelatin (TA-Gel) is a compound produced by the reaction of gelatin and tannic acid; quaternized chitosan (QCS) is also known as chitosan quaternary ammonium salt.

[0058] The biodegradable crosslinking agent is selected from one or more of N,N-methylenebisacrylamide (MBA), N,N-cystaminebisacrylamide (BACA), ethylene glycol dimethacrylate (PEGDMA), ethylene glycol methacrylate (PEGMA), and methacrylamide gelatin (GelMA). When multiple agents are selected, they are mixed in any mass ratio.

[0059] In this invention, the active ingredient is one or more of anti-inflammatory components, growth factors, or polypeptide bioactive substances.

[0060] Preferably, the anti-inflammatory component is one or more of curcumin (Cur), methylprednisolone sodium succinate (MPSS), vancomycin (VAN), and nimesulide (NIM). When multiple components are selected, they are mixed in any mass ratio.

[0061] Preferably, the growth factor is one or more of acidic fibroblast growth factor and basic fibroblast growth factor; when multiple factors are selected, they are mixed in any mass ratio.

[0062] In this invention, the photoinitiator is one or more of lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (LAP), 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (Irgacure 2959), α-ketoglutaric acid (AKG), and trimethylbenzoyl-diphenylphosphine oxide (TPO). When multiple photoinitiators are selected, they are mixed in any mass ratio.

[0063] This invention also provides a method for preparing a rapid asymmetric tissue sealing patch, comprising the following steps:

[0064] S1. Preparation of a highly absorbent bioadhesive layer

[0065] S1.1. The hydrophilic polymer, adhesive polymer matrix, biodegradable polymer, biodegradable crosslinking agent, nanocarrier and photoinitiator are uniformly dispersed in water according to the above mass percentages to prepare a hydrogel precursor solution.

[0066] S1.2 Pour the hydrogel precursor solution from step S1.1 into a glass mold and irradiate it with 345nm ultraviolet light for 1 min to 5 min. The free radicals in the hydrogel precursor solution will polymerize until the mold is formed. After demolding, a highly absorbent bioadhesive layer is obtained.

[0067] In step S1 of this invention, the specific preparation process of the nanocarrier is as follows:

[0068] (1) Dissolve zinc acetate dihydrate in methanol solution to obtain a methanol solution of zinc acetate dihydrate;

[0069] (2) Dissolve both active ingredient X and 2-methylimidazole in methanol solution to obtain a mixed solution;

[0070] (3) The methanol solution of zinc acetate dihydrate is slowly added to the mixed solution, and ZIF-8@X is obtained by stirring, centrifugation, washing and drying in sequence; preferably, the precipitate is separated by stirring at 800 r / min for 6 h and centrifuging at 8000 r / min for 5 min; the precipitate is washed with methanol 3 times and dried at 60℃ for 12 h.

[0071] (4) Add dopamine hydrochloride to Tris buffer containing ZIF-8@X, and then sequentially stir, centrifuge, wash and dry to obtain the nanocarrier ZIF-8@X@PDA. Preferably, the Tris buffer pH is 8.5, the mixture is stirred at 800 r / min for 12 h, centrifuged at 8000 r / min for 5 min to separate, washed 3 times with ethanol, and dried at 60 °C for 12 h.

[0072] S2. Disperse the anti-blocking material in water according to the above mass percentages, and mix evenly to form a spin-coating solution;

[0073] S3. Spin-coating the spin-coating solution from step S2 onto the highly absorbent bioadhesive layer prepared in step S1. The spin-coating solution forms a hydrophobic bioadhesive layer on the highly absorbent bioadhesive layer. After spin-coating is completed, a rapid asymmetric tissue sealing patch is obtained.

[0074] In this step, the spin coating is carried out in a spin coater at a speed of 500 rpm for 10 to 30 seconds, and the spin coating is repeated 3 to 5 times.

[0075] This invention also provides an application of a rapid asymmetric tissue sealing patch in the repair of gastrointestinal defects. The rapid asymmetric tissue sealing patch applies 10 kPa pressure to the surface of wet tissue, achieving durable tissue adhesion and sealing within 5 seconds through tissue fluid absorption and expansion, and chemical cross-linking of the tissue surface.

[0076] The above-mentioned technical solutions of the present invention will be described in detail below with several specific embodiments.

[0077] It should be noted that, unless otherwise specified, the chemical reagents and raw materials used in the following examples are all existing known products purchased from the market.

[0078] It should be noted that, unless otherwise specified, the operations or conditions used in the following embodiments are conventional operations in the art. For example, unless the operating temperature is specified, it refers to room temperature operation.

[0079] Examples 1 to 6

[0080] The rapid asymmetric tissue sealing patch provided in this embodiment consists of a highly absorbent bioadhesive layer and a hydrophobic bio-anti-adhesion layer spin-coated onto the highly absorbent bioadhesive layer.

[0081] In this embodiment, the highly absorbent bioadhesive layer is composed of the following raw materials by mass percentage: 30.0% hydrophilic polymer, 1.0% adhesive polymer matrix, 2.0% biodegradable polymer, 0.2% biodegradable crosslinking agent, 0.25% nanocarrier, and 0.15% photoinitiator, with the balance being water.

[0082] In this embodiment, the specific selection of hydrophilic polymer, adhesive polymer matrix, biodegradable polymer, biodegradable crosslinking agent and photoinitiator is shown in Table 1.

[0083] In this embodiment, the nanocarrier is formed by in-situ deposition of ZIF-8@X and PDA at a mass ratio of 2:0.2. ZIF-8@X is prepared by zinc acetate dihydrate, 2-methylimidazole, and active ingredient X at a mass ratio of 4:5:0.05. The specific selection of active ingredient X is shown in Table 1.

[0084] In this embodiment, the hydrophobic bio-anti-adhesion layer is composed of anti-adhesion raw materials and water. The specific selection of anti-adhesion raw materials and their corresponding mass percentages, as well as the mass percentage of water, are shown in Table 2.

[0085] In this embodiment, a hydrophobic bio-anti-adhesion layer is spin-coated onto the surface of a highly absorbent bio-adhesive layer using a spin coater, thereby constructing an asymmetric multifunctional tissue sealing patch with a highly absorbent bio-adhesive layer at the bottom and a hydrophobic bio-anti-adhesion layer at the top.

[0086] Specifically, the method for preparing the rapid asymmetric tissue sealing patch provided in this embodiment includes the following steps:

[0087] S1. Preparation of a highly absorbent bioadhesive layer

[0088] S1.1 According to the mass percentages in Table 1, the hydrophilic polymer, adhesive polymer matrix, biodegradable polymer, biodegradable crosslinking agent, nanocarrier ZIF-8@X@PDA and photoinitiator are uniformly dispersed in deionized water to prepare a hydrogel precursor solution.

[0089] In this embodiment, the preparation method of the nanocarrier ZIF-8@X@PDA is as follows:

[0090] Step 1: Prepare ZIF-8@X according to the mass ratio of zinc acetate dihydrate, 2-methylimidazole, and active ingredient X of 4:5:0.05; the specific process is as follows:

[0091] (1) At 25℃, 4g of zinc acetate dihydrate was dissolved in 100mL of methanol solution to obtain a methanol solution of zinc acetate dihydrate.

[0092] (2) Dissolve 0.05g of active ingredient X and 5g of 2-methylimidazole in 100mL of methanol solution to obtain a mixed solution;

[0093] (3) The methanol solution of zinc acetate dihydrate was slowly added to the mixed solution. After stirring magnetically at 800 r / min for 6 h, the precipitate was separated by centrifugation at 8000 r / min for 5 min. The precipitate was then washed three times with methanol and dried at 60 °C for 12 h to obtain the nanocarrier ZIF-8@X loaded with active ingredients.

[0094] Step 2: Nanocarriers are formed through in-situ deposition of ZIF-8@X and PDA at a mass ratio of 2:0.2. The specific process is as follows:

[0095] 2 g ZIF-8@X was added to 100 mL of Tris buffer at pH 8.5, and then 0.2 g of dopamine hydrochloride was added at 25 °C. After magnetic stirring at 800 r / min for 12 h, in-situ deposition of polydopamine was completed. The precipitate was then separated by centrifugation at 8000 r / min for 5 min and washed three times with ethanol. Finally, the precipitate was dried at 60 °C for 12 h to obtain the PDA-coated nanocarrier ZIF-8@X@PDA.

[0096] S1.2 Pour the precursor solution into a glass mold and induce free radical polymerization at room temperature using 345nm ultraviolet light. Irradiate with ultraviolet light for 1–5 min. After molding, demold to obtain a highly absorbent bioadhesive layer with a thickness of 200 μm.

[0097] S2. Disperse the anti-blocking material in water according to the mass percentage in Table 2, and mix evenly to form a spin-coating solution;

[0098] S3. Preparation of rapid asymmetric tissue sealing patches

[0099] The spin-coating solution in step S2 is spin-coated onto the highly absorbent bioadhesive layer prepared in S1. The spin-coating solution forms a hydrophobic bioadhesive layer on the highly absorbent bioadhesive layer. After spin-coating is completed, a rapid asymmetric tissue sealing patch is obtained.

[0100] Specifically, the spin coating solution is added to the spin coater, the highly absorbent bioadhesive layer is placed on the substrate, and the spin coating is performed at 500 r / min for 20 s. The spin coating solution is then applied to the center of the surface of the highly absorbent bioadhesive layer. This process is repeated 5 times until all the spin coating solution is applied to the highly absorbent bioadhesive layer. A hydrophobic bioadhesive layer with a thickness of 100 μm is formed on the highly absorbent bioadhesive layer, resulting in a rapid asymmetric tissue sealing patch.

[0101] The specific selection of each raw material in Examples 1 to 6 above is shown in Tables 1 and 2.

[0102] Table 1. Raw material list of the highly absorbent bioadhesive layer in each embodiment.

[0103]

[0104] Table 2. List of anti-adhesion materials for the hydrophobic bio-anti-adhesion layer in each embodiment.

[0105] Example Hydrophobic hyperbranched polyethylene polyurethane Acrylic modified polyurethane gelatin PLGA water Example 1 5％ 10％ - - - 85％ Example 2 8％ 10％ 2％ - - 80％ Example 3 5％ 8％ - - 2％ 85％ Example 4 5％ 8％ - - 2％ 85％ Example 5 5％ 8％ - 2％ - 85％ Example 6 5％ 8％ - 2％ - 85％

[0106] In the above embodiments, in addition to the material selections given, the hydrophilic polymer can be replaced with one or more of acrylic acid (AAc), acrylamide (AAm), tannic acid (TA), and polyvinyl alcohol (PVA); the adhesive polymer matrix can be replaced with one or more of acrylic acid grafted N-hydroxysuccinimide ester (AAc-NHS ester), polyacrylate grafted N-hydroxysuccinimide ester (PAAc-NHS ester), poly(ε-lysine) (ε-PL), and polyethylene glycol succinimide hexanoate (PEG-SS); the biodegradable polymer can be replaced with one or more of tannic acid modified gelatin (TA-Gel), chitosan (CS), and quaternized chitosan (QCS); and the biodegradable crosslinking agent can be replaced with one or more of N,N-methylenebisacrylamide (MBA), N,N-cystamine bisacrylamide (BACA), ethylene glycol dimethacrylate (PEGDMA), ethylene glycol methacrylate (PEGMA), and methacrylamide gelatin (GelMA). The active ingredient can also be replaced with one or more of the following: anti-inflammatory components, growth factors, or polypeptide bioactive substances. The photoinitiator can also be replaced with one or more of the following: lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (LAP), 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (Irgacure 2959), α-ketoglutaric acid (AKG), and trimethylbenzoyl-diphenylphosphine oxide (TPO). The thickness of the hydrophobic bio-anti-adhesion layer can be arbitrarily selected within the range of 50 μm to 200 μm; the thickness of the highly absorbent bio-adhesive layer can be arbitrarily selected within the range of 100 μm to 1000 μm. Through the above selections and replacements, an asymmetric multifunctional tissue sealing patch with the same or similar properties as in Examples 1 to 6 is formed.

[0107] The following tests were conducted to evaluate the performance of the asymmetric multifunctional tissue sealing patch in order to verify the beneficial effects of the present invention.

[0108] Specifically, the rapid asymmetric tissue sealing patches (hereinafter referred to as tissue sealing patches) from Examples 1 to 6 were used as test samples for performance testing. The performance testing included the following aspects:

[0109] 1. Microstructure

[0110] Scanning electron microscope images of the rapid asymmetric tissue sealing patch of Test Example 1, such as... Figure 1 As shown.

[0111] from Figure 1 As can be seen, the rapid asymmetric tissue sealing patch of Example 1 exhibits an asymmetric microstructure, with a distinct interface layer between the highly absorbent bioadhesive layer and the hydrophobic bio-anti-adhesion layer, and presents a porous and nearly circular network structure. Simultaneously, a uniformly interconnected porous network structure can be observed in the highly absorbent bioadhesive layer (adhesion layer) of the test sample, which is conducive to cell adsorption and growth and promotes wound healing; while the hydrophobic bio-anti-adhesion layer (non-adhesion side) shows a denser structure, which is unfavorable to cell adhesion and growth.

[0112] 2. Asymmetric hydrophilicity / hydrophobicity

[0113] To investigate the hydrophilic-hydrophobic asymmetric properties of the tissue patch of this invention, a contact angle meter was used to measure the contact angles of the hydrophobic bio-anti-adhesion layer (see [reference]). Figure 2 ) and the contact angle of the highly absorbent bioadhesive layer (see Figure 3 ).

[0114] Depend on Figure 2 It can be seen that the contact angle of the hydrophobic bio-anti-adhesion layer is 108.3° (>90° is hydrophobic); from Figure 3 It is known that the contact angle of the highly absorbent bioadhesive layer is 66.4° (<90° indicates hydrophilicity). This indicates that the hydrophobic bio-anti-adhesion layer is hydrophobic, while the highly absorbent bioadhesive layer is hydrophilic. Therefore, the rapid asymmetric tissue sealing patch provided by this invention exhibits asymmetry in its hydrophilic-hydrophobic interface.

[0115] 3. Adhesion performance

[0116] Overlap shear strength and interfacial toughness are important evaluation indicators for assessing the adhesion ability of rapid asymmetric tissue sealing patches. This study conducted tests using the overlap-shear test (ASTM F2255) and the T-peel tensile strength test (ASTM F2256).

[0117] The tissue sealing patches from Examples 1 to 6 were tested using an electronic universal testing machine (Model: Instron 5967). All tests were conducted at 50 mm / min. -1 The peeling speed was measured. Meanwhile, commercially available clinical tissue patches (Coseal and Tisseel) served as a control group.

[0118] Figure 4The stress-strain curves for Examples 1-3 are shown. It can be seen that the fracture stresses of the tissue patches provided in Examples 1, 2, and 3 are 228 kPa, 198 kPa, and 103 kPa, respectively, and their fracture deformation rates are as high as 800%, 860%, and 1030%, respectively. This indicates that the tissue patch provided by the present invention has excellent plastic deformation capacity and flexibility, and can meet the mechanical performance requirements in the repair of gastrointestinal defects.

[0119] The adhesion test results of the tissue sealing patches of Examples 1 to 6 and the commercial tissue patches are shown in Table 3.

[0120] Table 3 Comparison of adhesion test results for various embodiments and commercial tissue patches

[0121]

[0122] Table 3 shows that the lap shear strength of commercial tissue patches Coseal and Tisseel were 3.8 kPa and 9.1 kPa, respectively, and their tensile strengths were 6.4 kPa and 10.6 kPa, respectively. The corresponding shear strengths for Examples 1 to 6 were 86 kPa, 72 kPa, 56 kPa, 45 kPa, 68 kPa, and 59 kPa, respectively. This indicates that the lap shear strength of the tissue sealing patches in Examples 1 to 6 was significantly higher than that of the commercial tissue patches (Coseal and Tisseel). This suggests that the addition of the adhesive polymer matrix in these examples has a synergistic effect, thereby helping to improve the lap shear strength and tensile strength of the tissue sealing patches. The interfacial toughness of Examples 1 to 6 showed similar results to the lap shear strength, at 425 J·m. -2 370J·m -2 321 J·m -2 309 J·m -2 406 J·m -2 With 401 J·m -2 This indicates that the test sample of the present invention needs to absorb more energy during structural failure in order to maintain the structural integrity of the sample and has better adhesion.

[0123] In addition, the adhesion characteristics of the highly absorbent bioadhesive layer interface in each test sample were investigated. One side of the highly absorbent bioadhesive layer from Example 1 was attached to the substrate for 5 minutes, and then a load was applied to the other side, such as... Figure 5 As shown; where: load is the load, hydrogel is the hydrogel, which here refers to a highly absorbent bioadhesive layer.

[0124] from Figure 5 As can be clearly seen, the highly absorbent bio-adhesive layer of this invention can lift a 1350g weight. Figure 5(First and second images from left to right); When adhered to a stainless steel surface, it can be stretched under external force (adhesive). Figure 5 (Third image from left to right); Furthermore, the rapid asymmetric tissue sealing patch adhered to PVC can adhere to a 500g weight. Figure 5 (The two figures on the far right). As can be seen, the highly absorbent bioadhesive layer in Example 1 has excellent adhesion properties.

[0125] To further evaluate the wet tissue adhesion properties of the tissue sealing patch of the present invention, the hydrophobic bio-anti-adhesion layer side of the sealing tissue patch of Example 1, stained with edible dye, was adhered to the back of pigskin fat sprayed with PBS. After adhesion for 2 minutes, the pigskin was then subjected to various stretching and bending (see...). Figure 6 The sealing tissue patch was found to adhere stably to the pigskin fat layer under both tensile and bending conditions. This indicates that the sealing tissue patch of the present invention has good hydrophobic adhesion properties.

[0126] 4. Adhesion of wet tissue

[0127] The Burst Pressure method was used to evaluate the wet tissue sealing performance of the tissue sealing patches (test samples) provided in Examples 1 to 6 on porcine intestines, stomach and skin, while commonly used commercial tissue patches (Coseal, Histoacryl and Tisseel) were used as controls.

[0128] This study designed an experimental apparatus for measuring rupture pressure, including an N2 inlet valve, an inlet pipe, a digital pressure gauge, and a pressure chamber. The specific testing procedure involved fixing porcine stomach tissue with a pre-cut (5 mm diameter) wound onto the cylinder of the pressure chamber and connecting it to the N2 inlet pipe and pressure monitor. Then, test samples were adhered to the wound surface, and after pressing for 10 seconds, pressure was applied at a rate of 10 mL / min. -1 N2 was introduced at a constant rate to pressurize the system. The pressure within the system was continuously monitored using a pressure gauge. The maximum pressure at which the sealant ruptured at the defect was determined as the rupture pressure. The sealing performance under cyclic loading was evaluated. Each test was repeated at least three times. Figure 7 As shown.

[0129] from Figure 7It can be seen that the adhesion forces of the test samples in Examples 1 to 6 to moist porcine gastric tissue were 174 mmHg, 162 mmHg, 83 mmHg, 65 mmHg, 162 mmHg, and 173 mmHg, respectively, which were significantly higher than those of commercial tissue patches such as Coseal (≈24 mmHg), Histoacryl (≈37.5 mmHg), and Tisseel (≈37.5 mmHg). This indicates that the rapid asymmetric tissue sealing patch prepared in this example has excellent sealing performance for moist tissues in various locations. Furthermore, the changes in adhesion forces in Examples 1 to 6 also show that selecting different adhesive and hydrophilic matrices helps to adjust the adhesion and mechanical properties of the moist tissue interface.

[0130] In summary, compared with commercial tissue patches, the samples of this invention all exhibit excellent tissue adhesion ability and have great potential for transformation and application in the field of medical tissue sealing patches.

[0131] 5. Hemostatic effect

[0132] The hemostatic properties of Examples 1 to 3 were tested using a rat liver hemorrhage model.

[0133] The testing procedure was as follows: After anesthetizing the rats, they were placed in a supine position. The skin was prepared, and a 5cm incision was made in the abdominal cavity. The liver was pulled out and placed on filter paper. A 5mm diameter and 3mm deep defect was created in the left lobe of the liver using a punch. Test samples from Examples 1 to 3 were then adhered to the wound until complete hemostasis was achieved. The weight of the filter paper was immediately measured, and the amount of bleeding was recorded (n=3). The time when the area of ​​the filter paper no longer expanded was defined as the hemostasis time. A blank control group was also set up. The results are shown in Table 4.

[0134] Table 4 Comparison of rat liver hemorrhage performance in each example

[0135]

[0136]

[0137] The tests revealed that the blood area on the filter paper was larger in the blank control group, while the bleeding area in the experimental groups was significantly reduced, with Example 1 showing the smallest amount of bleeding. Further analysis of the bleeding volume in Table 4 shows that the bleeding volume in the blank control group was 325 mg, while the bleeding volumes in the experimental groups (Examples 1, 2, and 3) were 96 mg, 112 mg, and 105 mg, respectively. The corresponding hemostasis time also showed a similar trend. The hemostasis time in the blank control group was 264 s, while the hemostasis times in Examples 1, 2, and 3 were 146 s, 183 s, and 165 s, respectively. Compared to the blank control group, the tissue sealing patches provided in Examples 1, 2, and 3 significantly reduced bleeding and shortened hemostasis time. Therefore, the rapid asymmetric tissue sealing patch provided by this invention exhibits excellent hemostatic performance. Further analysis of the technical solution of the present invention reveals that its excellent hemostatic effect mainly depends on: (1) the hydrophilic polymer and its interconnected uniform porous network structure in the highly absorbent bioadhesive layer, which facilitates rapid adsorption of bleeding and concentration of clotting factors in the blood; (2) the adhesive polymer matrix adheres quickly and firmly to the tissue wound surface, achieving the purpose of sealing and hemostasis. Example 1, as a preferred rapid asymmetric tissue sealing patch, uses hydrophilic polymer polyacrylic acid to easily absorb body fluids at the tissue interface, achieving rapid tissue adhesion at the wet tissue interface.

[0138] 6. In vitro cell compatibility

[0139] To evaluate the in vitro biocompatibility and cytotoxicity of the rapid asymmetric tissue sealing patch, mouse fibroblasts (L929) were evaluated using CCK-8.

[0140] 500 mg of samples from Examples 1, 2, and 3 were used as experimental groups, and were placed in 10 mL of Dulbecco modified Eagle medium (DMEM) supplemented with 10 v / v% fetal bovine serum and penicillin-streptomycin, respectively, and incubated at 37°C for 24 hours. DMEM without tissue gel incubation served as the control group. Caco-2 cells were cultured at 0.5 × 10⁻⁶ cells / mL. 5 Cells were seeded at a density of 4 cells per group (n=4) in confocal dishes with a diameter of 20 mm; then treated with control and conditioned media and incubated at 37°C for 24 hours in a 5% CO2 atmosphere. The absorbance at 450 nm was measured using a microplate reader. Cell viability was calculated.

[0141]

[0142] Among them, A s : Absorbance of the experimental group's aperture; A c : Control group well absorbance; A b : Absorbance of the blank group wells.

[0143] Figure 8The cell survival curves of Caco-2 cells co-cultured with the control group and Examples 1 and 2 at 1 day, 3 days and 5 days, respectively, show that the survival rate of Caco-2 cells in this invention is comparable to that of the control group, indicating that the rapid asymmetric tissue sealing patch of this invention exhibits biocompatibility and cell non-toxicity.

[0144] 7. Biodegradability

[0145] Twenty-eight healthy SD rats were selected and anesthetized by intraperitoneal injection. An incision was made along the midline of the rat's back down to the deep fascia layer. Subcutaneous tissue was dissected laterally along the incision to fully expose the dorsal muscle layer. The fascia tissue on the surface of the muscle was then dissected. The control group was the suture group, while the experimental groups were implanted with test samples from Examples 1 to 6 (n=3). The test samples were observed using small animal ultrasound at 1, 2, 3, and 4 weeks of the experimental period. Subsequently, the tissue was removed and sectioned to observe the immune response.

[0146] Figure 9 The image shows an ultrasound image of the defect site 7 days after subcutaneous implantation of the rapid asymmetric tissue sealing patch of Example 1. The morphology of the rapid asymmetric tissue sealing patch and the edema of the surrounding tissue are clearly visible after implantation, indicating that the rapid asymmetric tissue sealing patch has good biodegradability.

[0147] Meanwhile, in Example 1, the tissue patch completely degraded after 2 weeks of subcutaneous implantation in rats, while in Example 3, the degradation time was 4 weeks. Analysis showed that the cross-linking agent in Example 1 was short-chain biodegradable BACA, resulting in fewer cross-linking points and a relatively loose network structure in the hydrogel. Furthermore, the ester bonds of BACA are easily hydrolyzed in body fluids, leading to a degradation time of 2 weeks. In Example 3, the cross-linking agent was BACA:PEGDMA (1:1). The long-chain structure of PEGDMA provided more cross-linking sites, resulting in a denser cross-linking network, higher mechanical strength of the tissue patch, and slower penetration by hydrolytic enzymes or water molecules, thus reducing the degradation rate. Its degradation time was 4 weeks. In summary, the optimal selection of cross-linking agent types and ratios in this invention helps to achieve synergistic optimization of the tissue patch's degradation rate, mechanical strength, and biocompatibility, thereby matching the regenerative and repair capabilities of different sites.

[0148] 8. In vivo repair of colonic defects in a rat model

[0149] The animal studies in this test were approved by the Ethics Committee of the Air Force Medical University (IACUC).

[0150] Establishment of a rat colonic defect model: Male rats (SP, 40–55 kg, 200–230 g) were fasted for 24 hours preoperatively to reduce the contents of the descending colon. Rats were placed in a dorsal recumbent position with fur covering their backs and prepared aseptically. An incision was made along the midline of the abdomen with a scalpel, cutting through the white line to directly access the peritoneum, extending the incision to match the skin incision. The spiral colon was externalized and dissected using a moist sponge. Ingested colonic contents were expelled from the predetermined surgical site, and a portion of the colonic wall was isolated using a lateral biting forceps. Two lesions were created on the colonic wall using a 5 mm diameter biopsy perforation to simulate anastomotic leakage. A suture control group, a commercial control group (commercial tissue patches Coseal, Tisseel, and Suture), and an experimental group (tissue sealing patch from Example 1) were then set up, adhered to the biopsy area to create a seal, and pressed for 10 seconds (n=5). The colon was thoroughly cleaned and returned to the abdomen, then the entire abdominal cavity was cleaned and aspirated before closing the open incision. Two weeks after repair, the rats were euthanized, and the wound area sealed with the GI patch was excised and fixed with 10% formalin for 24 hours for histological and immunofluorescence analysis. Under routine monitoring, two rats in the control suture group died, with a mortality rate of 40%; all rats in the commercial control group and Example 1 survived and maintained normal health. The results are shown in Table 5.

[0151] Table 5. Results of colonic defect repair in each group

[0152]

[0153]

[0154] Figure 10 The images show photographs of the tissue sealing patch used in Example 1 in a rat colonic defect model, illustrating tissue sealing and postoperative adhesions. The first three images from left to right show adhesions at the colonic defect site during surgery, while the fourth image from the far right shows the adhesion effect at the colonic defect site two weeks post-surgery. It can be seen that using the tissue sealing patch of Example 1, there was no significant adhesion or connective tissue at the colonic defect site. Furthermore, Table 5 shows that the mortality rate in the rats in Example 1 was 0, and no significant adhesions or inflammatory reactions were observed. Therefore, the tissue sealing patch provided in Example 1 can effectively repair colonic defects, not only eliminating abdominal wall adhesions and connective tissue, but also promoting faster colonic defect repair.

[0155] also, Figure 11 Immunofluorescence images of fibroblasts (αSMA and Col III), macrophages (CD68, M1 type iNOS and Vimentin, M2 type CD206), T cells (CD3), and fibrosis (Col I) markers in rats repaired with colonic defects for 2 weeks, as shown in Example 1.

[0156] Compared with the suture control group, the levels of Col I, Col III, and M1 macrophage markers (iNOS and Vimentin) in Example 1 were significantly reduced. This indicates that the rapid asymmetric tissue sealing patch of Example 1 had lower expression of Col I, Col III, and M1 macrophages, suggesting that the experimental group exhibited lower levels of fibrosis and inflammation during the 2-week defect healing process.

[0157] This experiment demonstrates that in the in vivo repair of a rat colon defect model, the highly absorbent bioadhesive layer of the rapid asymmetric tissue sealing patch can rapidly absorb interfacial moisture and quickly seal the tissue, thus playing a role in tissue sealing. The hydrophobic bio-anti-adhesion layer (non-adhesive layer), as a separating membrane material, enhances anti-protein and anti-cell adhesion properties, preventing adhesion between organs and tissues, thereby achieving asymmetric adhesion. This results in no significant adhesion or connective tissue at the colon defect site, achieving anti-adhesion properties against abdominal wall adhesions. Therefore, the rapid asymmetric tissue sealing patch provided by this invention has significant application value in preventing abdominal adhesions.

[0158] In summary, this invention provides a rapid asymmetric tissue sealing patch with hydrophilic-hydrophobic asymmetry. Under a pressure of 10 kPa, it achieves strong adhesion between moist dynamic tissue and engineered solids in less than 5 seconds. It exhibits good mechanical properties and biocompatibility, as well as excellent tissue adhesion, antibacterial, and hemostatic properties. This multifunctional tissue sealing patch can quickly close damaged wounds, achieving hemostasis, antibacterial effects, and promoting wound healing. It is easy to use and can also be used as a medical tissue adhesive or wound dressing, showing great promise for future applications.

[0159] The above are merely preferred embodiments 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 rapid asymmetric tissue sealing patch, characterized in that, It consists of a highly absorbent bioadhesive layer and a hydrophobic bio-anti-adhesion layer spin-coated onto the highly absorbent bioadhesive layer; The highly absorbent bioadhesive layer is composed of the following raw materials in the indicated weight percentages: 25%–35% hydrophilic polymer, 0.5%–2.0% adhesive polymer matrix, 1.5%–3.5% biodegradable polymer, 0.1%–0.3% biodegradable crosslinking agent, 0.2%–0.4% nanocarrier, and 0.1%–0.25% photoinitiator, with the balance being water; The nanocarrier is formed by in-situ deposition of ZIF-8@X and polydopamine at a mass ratio of 2:(0.1~0.5), and ZIF-8@X is made of zinc acetate dihydrate, 2-methylimidazole and active ingredient X at a mass ratio of 4:5:(0.01~0.05). The hydrophobic bio-anti-adhesion layer is composed of anti-adhesion materials and water. The anti-adhesion materials include multiple types of hydrophobic hyperbranched polyethylene, polyurethane, acrylate-modified polyurethane, polylactic acid-glycolic acid copolymer, and gelatin. The mass percentages of the anti-adhesion materials are: 5%~8% hydrophobic hyperbranched polyethylene, 8%~10% polyurethane, 1%~5% acrylate-modified polyurethane, 1%~5% polylactic acid-glycolic acid copolymer, and 1%~5% gelatin. The hydrophilic polymer is one or more of acrylic acid, acrylamide, tannic acid, or polyvinyl alcohol. The adhesive polymer matrix is ​​one or more of the following: acrylic acid grafted N-hydroxysuccinimide ester, polyacrylate grafted N-hydroxysuccinimide ester, poly(ε-lysine) and polyethylene glycol succinimide hexanoate. The biodegradable polymer is one or more of tannic acid-modified gelatin, chitosan, and quaternized chitosan.

2. The rapid asymmetric tissue sealing patch according to claim 1, characterized in that, The thickness of the hydrophobic bio-anti-adhesion layer is 50 μm to 200 μm; the thickness of the highly absorbent bio-adhesive layer is 100 μm to 1000 μm.

3. The rapid asymmetric tissue sealing patch according to claim 1, characterized in that, The biodegradable crosslinking agent is selected from one or more of N,N-methylenebisacrylamide, N,N-cystaminebisacrylamide, ethylene glycol dimethacrylate, ethylene glycol methacrylate, and methacrylamide gelatin.

4. The rapid asymmetric tissue sealing patch according to claim 1, characterized in that, The active ingredient X is one or more of anti-inflammatory components, growth factors, and polypeptide bioactive substances; the anti-inflammatory components are one or more of curcumin, sodium methylprednisolone succinate, vancomycin, and nimesulide.

5. The rapid asymmetric tissue sealing patch according to claim 1, characterized in that, The photoinitiator is one or more of lithium phenyl (2,4,6-trimethylbenzoyl)phosphate, 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, α-ketoglutaric acid, and trimethylbenzoyl-diphenylphosphine oxide.

6. The method for preparing the rapid asymmetric tissue sealing patch as described in claim 1, characterized in that, The preparation method includes the following steps: S1. Preparation of a highly absorbent bioadhesive layer S1.

1. The hydrophilic polymer, adhesive polymer matrix, biodegradable polymer, biodegradable crosslinking agent, nanocarrier and photoinitiator are uniformly dispersed in water according to the mass percentages described above to prepare a hydrogel precursor solution. S1.2 Pour the hydrogel precursor solution from step S1.1 into a glass mold and irradiate it with 345 nm ultraviolet light for 1 min to 5 min. The free radicals in the hydrogel precursor solution will polymerize until the mold is formed. After demolding, a highly absorbent bioadhesive layer is obtained. S2. Disperse the anti-blocking material in water according to the stated mass percentage, and mix evenly to form a spin-coating solution; S3. Spin-coating the spin-coating solution from step S2 onto the highly absorbent bioadhesive layer prepared in step S1. The spin-coating solution forms a hydrophobic bioadhesive layer on the highly absorbent bioadhesive layer. After spin-coating is completed, a rapid asymmetric tissue sealing patch is obtained.

7. The application of the rapid asymmetric tissue sealing patch as described in claim 1 in the repair of gastrointestinal defects.

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