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CN-121971685-A - Preparation method and application of hydrogel patch with Janus asymmetric adhesion

CN121971685ACN 121971685 ACN121971685 ACN 121971685ACN-121971685-A

Abstract

The invention discloses a preparation method and application of a hydrogel patch with Janus asymmetric adhesion, which is characterized by comprising the following steps of uniformly mixing GelMA-T, OHA, a photoinitiator LAP, AAc and AAc-NHS, injecting the solution into a glass plate die under the protection of nitrogen, performing ultraviolet irradiation crosslinking to form gel, drying to obtain an adhesion layer, adding SBMA, gelMA, MBAA and ammonium persulfate APS into water, fully stirring and mixing to obtain a mixed solution, immersing one side of the adhesion layer obtained in the step 1 into the mixed solution for thermal crosslinking to obtain the hydrogel patch with Janus asymmetric adhesion characteristics.

Inventors

  • CAO CHAO
  • QI RONGBIN
  • LI HONG
  • WU XIANG
  • HUANG CHUNLIAN
  • SHAO HANJIE

Assignees

  • 宁波大学附属第一医院

Dates

Publication Date
20260505
Application Date
20251124

Claims (7)

  1. 1. A method for preparing a hydrogel patch with Janus asymmetric adhesion, which is characterized by comprising the following steps: step 1, preparation of an adhesive layer Uniformly mixing GelMA-T, oxidized hyaluronic acid OHA, a photoinitiator LAP, acrylic acid AAc and acrylic acid N-hydroxysuccinimide ester AAc-NHS, injecting the solution into a glass plate mold under the protection of nitrogen, and performing ultraviolet irradiation crosslinking to form gel and drying to obtain an adhesive layer; Step 2, preparation of hydrogel patch Adding [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide SBMA, methacrylic gelatin GelMA, N' -methylene bisacrylamide MBAA and ammonium persulfate APS into water, fully stirring and mixing to obtain a mixed solution, immersing one side of the adhesive layer obtained in the step 1 into the mixed solution, and thermally crosslinking to obtain the hydrogel patch with Janus asymmetric adhesive characteristics.
  2. 2. The method for preparing the hydrogel patch with Janus asymmetric adhesion according to claim 1, wherein the method comprises the following steps: step 1, preparation of an adhesive layer Adding 0.05-0.2g GelMA-T, 0.1-0.3g OHA and 0.01-0.03 g LAP into 5-20 g water, completely dissolving at 40 ℃ and fully stirring, adding 1-5g AAc and 0.01-0.03 g AAc-NHS, continuously stirring uniformly, introducing nitrogen into the mixed solution to deoxidize, injecting the solution into a glass plate mold under the protection of nitrogen, irradiating and crosslinking for 20-40 minutes by 365-nm ultraviolet light to form gel, soaking the gel into deionized water to remove biotoxic monomer molecules, and drying at 30-50 ℃ for 10-30 minutes to obtain an adhesive layer; Step 2, preparation of hydrogel patch Adding 1-3 g SBMA, 0.1-0.3 g GelMA, 0.04-0.08 g MBAA and 0.05-0.2 g APS into 5-20 g water, fully stirring and mixing to obtain a mixed solution, placing the adhesive layer obtained in the step 1 into a mold, mixing the solution for 20-40 minutes on one side, and then thermally crosslinking for 50-70 minutes at 50-70 ℃ to obtain the hydrogel patch with Janus asymmetric adhesive characteristics.
  3. 3. The method for preparing the hydrogel patch with Janus asymmetric adhesion according to claim 2, wherein the method comprises the following steps: step 1, preparation of an adhesive layer Adding 0.1g GelMA-T, 0.2g OHA and 0.02g LAP into 10 g water, completely dissolving at 40 ℃ and fully stirring, adding 3g AAc and 0.02g AAc-NHS, continuously stirring uniformly, introducing nitrogen into the mixed solution to deoxidize, injecting the solution into a glass plate mold under the protection of nitrogen, performing irradiation crosslinking for 30 minutes by 365 nm ultraviolet light to form gel, soaking the gel into deionized water to remove biotoxic monomer molecules, and drying at 40 ℃ for 20 minutes to obtain an adhesive layer; Step 2, preparation of hydrogel patch Adding 2g SBMA, 0.2 g GelMA, 0.06 g MBAA and 0.1 g APS into 10 g water, fully stirring and mixing to obtain a mixed solution, placing the adhesive layer obtained in the step 1 into a mold, mixing the solution for 30 minutes on one side, and thermally crosslinking at 60 ℃ for 60 minutes to obtain the hydrogel patch with Janus asymmetric adhesion characteristics.
  4. 4. The preparation method of the hydrogel patch with Janus asymmetric adhesion according to any one of claims 1 to 3, which is characterized in that the GelMA is synthesized by dissolving 8 to 12g m in 100 mL phosphate buffer, slowly and uniformly dropwise adding 1 to 3 mL methacrylic anhydride after complete dissolution at 60 ℃, adjusting the temperature to 50 ℃, reacting for 3 hours, adding 400mL of phosphate buffer, stopping the reaction, dialyzing in deionized water by using a dialysis bag with a cut-off molecular weight of 8KD to 14KD after the reaction is finished, and freeze-drying after the dialysis to obtain the methacrylic gelatin.
  5. 5. The method for preparing a hydrogel patch with Janus asymmetric adhesion according to claim 4, wherein the GelMA-T is prepared by dissolving 3-5g GelMA in 200 mL deionized water, continuously stirring at 60deg.C until completely dissolving, adding 1.63g EDC and 1.35g NHS to the solution, reacting for 20-40 min, adding 2.54 g Tris, continuing to react at 25deg.C for 48 hr, dialyzing in deionized water for 4 days by using dialysis bag with molecular weight cutoff of 8KD-14KD, and lyophilizing to obtain GelMA-T product.
  6. 6. The preparation method of the hydrogel patch with Janus asymmetric adhesion according to any one of claims 1 to 3, which is characterized in that the oxidized hyaluronic acid is prepared by a periodate oxidation method, wherein the steps are that 0.2 to 0.4 mol/L of sodium periodate solution is dropwise added into 8 to 12 mg/mL of hyaluronic acid solution, a reaction system is preserved for 4 to 8 hours in a dark place, then ethylene glycol is added to terminate the reaction, after stirring, dialysis is carried out in deionized water for 4 days by using a dialysis bag with a molecular weight cutoff of 3500D, and then an OHA product is obtained through freeze drying.
  7. 7. Use of a hydrogel patch prepared by the method of any one of claims 1-3 in the preparation of a lung-leakage repair agent.

Description

Preparation method and application of hydrogel patch with Janus asymmetric adhesion Technical Field The invention belongs to the technical field of medical treatment, and particularly relates to a preparation method and application of a hydrogel patch with Janus asymmetric adhesion. Background Persistent lung leakage is a common and troublesome complication after pulmonary surgery (such as pulmonary nodules, pneumothorax, pleural fistulae and the like), and especially for patients with continuous positive airway pressure, the lung leakage can lead to serious complications such as pneumothorax, respiratory insufficiency and the like, and finally can lead to a series of clinical problems such as death, prolonged hospitalization time, increased medical cost, poor postoperative recovery of patients and the like. Thus, prevention of air leakage has been a major clinical goal after lung surgery. The management of lung leakage in current clinical practice relies primarily on conventional surgical sutures, staples and surgical sealing materials, but these methods have significant limitations in that conventional surgical sutures and staples are difficult to provide an effective seal over fragile lung tissue and present the risk of secondary damage to the fragile lung tissue. Lung leakage is a common and troublesome complication following thoracic surgery, and its healing process is often challenged by surgical trauma, mechanical abrasion, and potential bacterial contamination. The dynamic and moist environment of the wound at the position is easy to trigger local inflammatory reaction, generate high-level ROS, prevent proliferation of fibroblasts and collagen deposition, provide conditions for bacterial colonization, further aggravate tissue injury and delay healing process. Therefore, an effective closure and rapid repair of the lung leakage wound are realized, and a multifunctional material which has excellent sealing performance and can actively resist inflammation, oxidization, bacteria and promote tissue regeneration is urgently needed. Hydrogels are widely used in the field of biological tissue engineering due to their excellent three-dimensional network structure and high water content characteristics. Among them, the adhesive hydrogel has been used in medical fields such as tissue wound closure and repair due to its excellent biocompatibility and rapid development of adjustable physicochemical properties. Unfortunately, however, the adhesive hydrogels such as cyanoacrylates and fibrin glues, which are currently used clinically, have limited clinical efficacy due to their limited adhesive strength, poor stability especially in wet environments, and high cost. Therefore, development of a novel sealing material capable of achieving firm wet tissue adhesion, excellent biocompatibility and having an asymmetric adhesion function has become an urgent need in the field of thoracic surgery. Disclosure of Invention The invention aims to provide a preparation method and application of a hydrogel patch with Janus asymmetric adhesion, which have good biocompatibility, mechanical property and sealing property and multiple biological functions of resisting bacteria, resisting oxidation, resisting inflammation, promoting proliferation and the like, and can remarkably reduce the complication risk after lung air leakage repair. The technical scheme adopted for solving the technical problems is that the preparation method of the hydrogel patch with Janus asymmetric adhesion comprises the following steps: step 1, preparation of an adhesive layer Uniformly mixing GelMA-T, oxidized hyaluronic acid OHA, a photoinitiator LAP, acrylic acid AAc and acrylic acid N-hydroxysuccinimide ester AAc-NHS, injecting the solution into a glass plate mold under the protection of nitrogen, and performing ultraviolet irradiation crosslinking to form gel and drying to obtain an adhesive layer; Step 2, preparation of hydrogel patch Adding [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide SBMA, methacrylic gelatin GelMA, N' -methylene bisacrylamide MBAA and ammonium persulfate APS into water, fully stirring and mixing to obtain a mixed solution, immersing one side of the adhesive layer obtained in the step 1 into the mixed solution, and thermally crosslinking to obtain the hydrogel patch with Janus asymmetric adhesive characteristics. Further, step 1, preparation of an adhesive layer Adding 0.05-0.2g GelMA-T, 0.1-0.3g OHA and 0.01-0.03 g LAP into 5-20 g water, completely dissolving at 40 ℃ and fully stirring, adding 1-5g AAc and 0.01-0.03 g AAc-NHS, continuously stirring uniformly, introducing nitrogen into the mixed solution to deoxidize, injecting the solution into a glass plate mold under the protection of nitrogen, irradiating and crosslinking for 20-40 minutes by 365-nm ultraviolet light to form gel, soaking the gel into deionized water to remove biotoxic monomer molecules, and drying at 30-50 ℃ for 10-30 minutes to obta