Preparation method of three-dimensional hydrogel dressing for diabetic foot ulcer

Abstract

The invention relates to the technical field of medical dressings, and discloses a preparation method of a three-dimensional structure hydrogel dressing for diabetic foot ulcers, the hydrogel dressing is prepared from polyvinyl alcohol, polyacrylic acid, hyaluronic acid, chitosan, poly (N-isopropylacrylamide), manganese dioxide and other materials, and through formula optimization and a 3D printing technology, the three-dimensional structure hydrogel dressing for diabetic foot ulcers is prepared. High-precision structure control is realized, and the preparation requirements of hydrogel dressings in complex shapes are met; strong electrostatic interaction and hydrogen-bond interaction occur between the interface of the grid structure hydrogel and the interface of the low-viscosity colloid, so that a stable three-dimensional flexible network structure is formed; the dressing has excellent flexibility, biocompatibility, antibacterial property and a function of promoting wound healing, and can be naturally gelated and participate in treatment of a wound microenvironment.

Description

Technical Field

[0001] This invention relates to the field of medical dressing technology, specifically to a method for preparing a three-dimensional hydrogel dressing for diabetic foot ulcers. Background Technology

[0002] Diabetic foot ulcers are a common complication of diabetes, characterized by being difficult to cure, prone to infection, and prone to recurrence. In severe cases, they can lead to gangrene, amputation, or even death. Traditional wound dressings are difficult to adapt to the complex shape and depth of diabetic foot ulcers, and changing dressings can easily cause secondary damage to the wound, affecting the healing effect.

[0003] In existing technologies, hydrogel dressings combined with drugs, growth factors, or cells have shown some efficacy in the treatment of chronic wounds, but the following problems still exist: high cost and complex manufacturing processes limit their widespread application; added antibiotics, anti-inflammatory drugs, and growth factors are prone to inactivation, drug resistance, and toxic side effects; single components and / or single structures cannot comprehensively address the problems of inflammation, reactive oxygen species, and excessive protease in chronic wounds.

[0004] 3D printing technology offers new possibilities for the preparation of hydrogel dressings, but while meeting functional requirements, it still needs to address challenges in material design and molding fidelity. Summary of the Invention

[0005] To address the technical problems of existing diabetic foot ulcer dressings being costly, having limited components, and having simple structures, this invention provides a method for preparing a three-dimensional hydrogel dressing for diabetic foot ulcers.

[0006] This invention is achieved using the following technical solution: a method for preparing a three-dimensional hydrogel dressing for diabetic foot ulcers, comprising the following steps: S1. Preparation of a pre-hydrogel composed of polyvinyl alcohol, polyacrylic acid and hyaluronic acid; S2. The pre-hydrogel is prepared into a grid structure hydrogel using 3D printing technology; S3. Chitosan, poly(N-isopropylacrylamide), and manganese dioxide low-viscosity colloid are kept at a constant temperature of 30°C and filled into a 3D printed grid structure to form a composite colloid. S4. Apply commercial release paper to the top and bottom of the combined colloid to obtain the initial hydrogel dressing; S5. Place the initial hydrogel dressing in a flat vulcanizing machine and press it without a mold for 30 seconds under a pressure of 2MPa. The hydrogel dressing is then removed.

[0007] Preferably, the pre-hydrogel forming step is as follows: polyvinyl alcohol and hyaluronic acid are dissolved in deionized water, polyacrylic acid is dissolved in sodium citrate, and the solid content ratio of polyvinyl alcohol, hyaluronic acid and polyacrylic acid is 2-2.5:2-1.5:1.8.

[0008] Preferably, the printing conditions are related to the apparent viscosity value, and the apparent viscosity value divided by the printing speed multiplied by the printing nozzle diameter unit ranges from 1.5 to 2.2 (10). 2 ).

[0009] Preferably, the ratio of chitosan to poly(N-isopropylacrylamide) is 40-45:20; manganese dioxide is first mixed with medium-viscosity carboxymethyl cellulose and then added to the chitosan / poly(N-isopropylacrylamide) mixture to enhance dispersibility.

[0010] Preferably, the release paper is placed directly below the 3D printed grid after it is formed, and the upper release paper is placed after the combined colloid is generated.

[0011] Compared with the prior art, the beneficial effects of the present invention are: When used, this invention achieves high-precision structural control through optimized formulation and 3D printing technology, meeting the preparation requirements of complex-shaped hydrogel dressings; strong electrostatic interactions and hydrogen bonding occur between the grid structure hydrogel and the low-viscosity colloid interface, forming a stable three-dimensional flexible network structure; the dressing has excellent flexibility, biocompatibility, antibacterial properties and wound healing promotion functions, and can naturally gel and participate in the treatment of the wound microenvironment. Attached Figure Description

[0012] Figure 1 This is a schematic diagram of the dressing preparation process of the present invention. Detailed Implementation

[0013] The technical solution of the present invention will be further described in detail below through specific embodiments. It should be understood that the implementation of the present invention is not limited to the following embodiments, and any modifications and / or alterations made to the present invention will fall within the protection scope of the present invention.

[0014] In this invention, unless otherwise specified, all parts and percentages are by weight, and the equipment and raw materials used are commercially available or commonly used in the art. Unless otherwise specified, the methods in the following embodiments are conventional methods in the art.

[0015] Unless otherwise specified, the reagents used in the following examples can be purchased from a regular biochemical reagent store.

[0016] Example 1: Please refer to Figure 1This embodiment describes a method for preparing a three-dimensional hydrogel dressing for diabetic foot ulcers. The method involves first fabricating a pre-gel scaffold using 3D printing, then processing it. Next, a low-viscosity colloid is alternately and evenly laid within the scaffold at room temperature, and then flattened under low pressure to form the hydrogel dressing. The method includes the following steps: S1. Preparation of a pre-hydrogel composed of polyvinyl alcohol, polyacrylic acid and hyaluronic acid; S2. The pre-hydrogel is prepared into a grid structure hydrogel using 3D printing technology; S3. Chitosan, poly(N-isopropylacrylamide), and manganese dioxide low-viscosity colloid are kept at a constant temperature of 30°C and filled into a 3D printed grid structure to form a composite colloid. S4. Apply commercial release paper to the top and bottom of the combined colloid to obtain the initial hydrogel dressing; S5. Place the initial hydrogel dressing in a flat vulcanizing machine and press it without a mold for 30 seconds under a pressure of 2MPa. The hydrogel dressing is then removed.

[0017] Further, in step S1, the pre-hydrogel formation step is as follows: polyvinyl alcohol and hyaluronic acid are dissolved in water respectively, and polyacrylic acid is dissolved in sodium citrate. The solid content ratio of polyvinyl alcohol, hyaluronic acid and polyacrylic acid is 2-2.5:2-1.5:1.8. In step S2, the printing conditions are related to the apparent viscosity value. The apparent viscosity (in mPa·s) divided by the printing speed (in mm / min) multiplied by the printing nozzle diameter (in mm) ranges from 1.5 to 2.2 (10). 2 ); In step S3, the ratio of chitosan to poly(N-isopropylacrylamide) is 40-45:20; manganese dioxide is first mixed with medium-viscosity carboxymethyl cellulose and then added to the chitosan / poly(N-isopropylacrylamide) mixture to enhance dispersibility. In step S4, the release paper is placed directly below the 3D printed grid after it is formed, while the upper release paper is placed after the combined colloid is generated.

[0018] Example 2: Based on Example 1, this example describes a method for preparing a three-dimensional hydrogel dressing for diabetic foot ulcers, the preparation steps of which include: S1, polyvinyl alcohol (11g) and hyaluronic acid (9g) were dissolved in deionized water (20ml) respectively, and polyacrylic acid (9g) was dissolved in sodium citrate solution. The three solutions were then thoroughly mixed and stirred. S2. Its apparent viscosity was measured to be approximately 10,000 mPa·S, the printing nozzle diameter was 0.51 mm, and the printing speed was selected as 30 mm / min; S3. Chitosan (11g) and poly(N-isopropylacrylamide) (5.5g) form a solution; manganese dioxide (2g) is first mixed with medium viscosity carboxymethyl cellulose (1wt% solution) and then added to the chitosan / poly(N-isopropylacrylamide) mixture; S4. The release paper is placed directly below the 3D printed grid after it is formed, and the release paper above is placed after the combined colloid is generated. S5. Place the initial hydrogel dressing in a flat vulcanizing machine and press it without a mold for 30 seconds under a pressure of 2MPa. The hydrogel dressing is then removed.

[0019] The final test results showed that the tensile strength was 1.9 MPa and the elongation at break was 658%, indicating good mechanical and elastic deformation capabilities. It also demonstrated strong antibacterial activity against Escherichia coli and Staphylococcus aureus. When applied to the foot ulcers of diabetic patients and replaced with dressings every 12 days, the wounds were essentially healed.

[0020] Example 3: Based on Example 1, this example describes a method for preparing a three-dimensional hydrogel dressing for diabetic foot ulcers. Compared to Example 2, the preparation steps do not use 3D printing technology; instead, the pre-hydrogel is directly mixed with a low-viscosity colloid and then pressed into shape. S1, polyvinyl alcohol (11g) and hyaluronic acid (9g) were dissolved in deionized water (20ml) respectively, and polyacrylic acid (9g) was dissolved in sodium citrate solution. The three solutions were then thoroughly mixed and stirred. S2. Chitosan (11g) and poly(N-isopropylacrylamide) (5.5g) form a solution; manganese dioxide (2g) is first mixed with medium viscosity carboxymethyl cellulose (1wt% solution), and then added to the chitosan / poly(N-isopropylacrylamide) mixture; S3. Mix the solutions from step A and step B thoroughly. S4. Place the initial hydrogel dressing in a flat vulcanizing machine, place one sheet of release paper on top and one sheet below it, press without a mold under a pressure of 2MPa for 30 seconds, and then remove to obtain the non-3D printed hydrogel dressing.

[0021] The final test results showed that the tensile strength was 1.9 MPa and the elongation at break was 8%. The dressing had poor elasticity, was not soft, and could not adapt to wounds with complex shapes.

[0022] Example 4: Based on Example 1, this example describes a method for preparing a three-dimensional hydrogel dressing for diabetic foot ulcers. Compared to Example 2, the preparation steps are different except that chitosan and polyacrylic acid are removed. S1. Dissolve 20g of polyvinyl alcohol in 20ml of deionized water, and dissolve 10g of polyacrylic acid in sodium citrate solution. Mix the three solutions thoroughly. S2. Its apparent viscosity was measured to be approximately 10,000 mPa·S, the printing nozzle diameter was 0.51 mm, and the printing speed was selected as 30 mm / min. S3, poly(N-isopropylacrylamide) (8.5g) form a solution; manganese dioxide (2g) is first mixed with medium viscosity carboxymethyl cellulose (1wt% solution), and then added to the poly(N-isopropylacrylamide) mixture; S4. The release paper is placed directly below the 3D printed grid after it is formed, and the release paper above is placed after the combined colloid is generated. S5. Place the initial hydrogel dressing in a flat vulcanizing machine and press it without a mold for 30 seconds under a pressure of 2MPa. The hydrogel dressing is then removed.

[0023] The final test results showed that the tensile strength at break was 0.3 MPa, and the elongation at break was 65%. Both mechanical strength and elastic deformation capacity were reduced, indicating the material was overly soft and pliable. The antibacterial activity against Escherichia coli and Staphylococcus aureus also deteriorated; after 12 days of dressing replacement on a diabetic patient's foot ulcer, the wound did not heal.

[0024] Working principle: Through optimized formulation and 3D printing technology, high-precision structural control is achieved to meet the preparation requirements of complex-shaped hydrogel dressings; strong electrostatic interactions and hydrogen bonding occur between the grid structure hydrogel and the low-viscosity colloid interface, forming a stable three-dimensional flexible network structure; the dressing has excellent flexibility, biocompatibility, antibacterial properties and wound healing promotion functions, and can naturally gel and participate in the treatment of the wound microenvironment.

[0025] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. A method for preparing a stereocomplex hydrogel dressing for diabetic foot ulcers, characterized by, The method comprises the following steps: S1, preparing a pre-hydrogel composed of polyvinyl alcohol, polyacrylic acid and hyaluronic acid; S2, preparing a grid structure hydrogel by 3D printing technology; S3, keeping chitosan, poly-N-isopropyl acrylamide and manganese dioxide low viscosity colloid at a constant temperature of 30°C and filling them into the 3D printed grid structure to form a combined colloid; S4, placing commercial release paper on the top and bottom of the combined colloid to obtain an initial hydrogel dressing; S5, placing the initial hydrogel dressing in a flat plate vulcanizing machine and pressing it under a pressure of 2 MPa for 30 seconds without a mold to obtain the hydrogel dressing.

2. A process for the preparation of a stereocomplex hydrogel dressing for diabetic foot ulcers as claimed in claim 1, wherein, The pre-hydrogel forming step is that polyvinyl alcohol and hyaluronic acid are respectively dissolved in ionized water, polyacrylic acid is dissolved in sodium citrate, and the solid content ratio of polyvinyl alcohol, hyaluronic acid and polyacrylic acid is 2-2.5:2-1.5:1.

8.

3. A process for the preparation of a stereocomplex hydrogel dressing for diabetic foot ulcers as claimed in claim 1, wherein, The printing conditions are related to an apparent viscosity value, the apparent viscosity value divided by the printing speed times the printing nozzle diameter unit is in the range of 1.5-2.2 (10 2 ).

4. The method of claim 1, wherein the method is characterized by: The ratio of chitosan to poly-N-isopropyl acrylamide is 40-45:20; manganese dioxide is first mixed with medium viscosity carboxymethyl cellulose and then added to the chitosan / poly-N-isopropyl acrylamide mixture to enhance dispersibility.

5. The method of claim 1, wherein the method is characterized by: The release paper is directly placed below the 3D printed grid after the grid is formed, and the release paper on the top is placed after the combined colloid is generated.

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