CN110694102A - A 3D printed hydrogel wound dressing with long-lasting antibacterial effect - Google Patents

Abstract

The invention discloses a 3D printing hydrogel wound dressing with long-term antibacterial effect. The preparation materials include: raw materials for reducing nano-silver: sodium alginate and silver nitrate; raw materials for constructing hydrogel: polyvinyl alcohol, carboxymethyl base chitosan/chitosan, sodium alginate, deionized water; raw material of cross-linked hydrogel: calcium chloride. Preparation process: (1) preparing nano-silver-sodium alginate solution solution; (2) preparing polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution; (3) preparing solution to be printed; (4) preparing non-woven 3D printing the hydrogel on the cloth; (5) cross-linking the sample prepared in step 4 (freezing-thawing and soaking in calcium chloride); thereby obtaining a sodium alginate antibacterial hydrogel wound dressing. The prepared sodium alginate hydrogel wound dressing meets the requirements of an ideal dressing.

Description

A 3D printed hydrogel wound dressing with long-lasting antibacterial effect

technical field

The invention belongs to the technical field of wound dressings for the human body, and in particular relates to a preparation method of a 3D printed hydrogel wound dressing with long-acting antibacterial effect.

Background technique

The skin is the largest organ of the human body and plays an important physical, chemical and biological barrier protection role for the human body. When the skin is damaged in a large area or cannot be healed for a long time, it will cause many local or even systemic problems, such as increased metabolism, excessive flow of water and protein, and immune system disorders, which can seriously endanger life.

When the skin is damaged, wound dressings are usually used to replace the damaged skin to temporarily protect the wound, avoid or control wound infection, prevent severe dehydration of the wound, and provide a suitable healing environment. Traditional dressings are currently the most widely used dressings in clinical practice. Traditional dressings have the advantages of low price, simple production process, can prevent the accumulation of wound exudate, and have a certain degree of protective effect on wound healing. However, traditional dressings still have unavoidable shortcomings such as being easy to form adhesion with the wound surface, causing secondary damage to the wound, easily causing exogenous infection, and poor hemostatic effect. In addition, a large number of experiments have proved that moderately moist wounds are more conducive to wound healing, and the moist wound theory is widely accepted.

An ideal wound dressing should: have good biocompatibility; absorb excess wound exudate and blood; promote tissue regeneration; allow gas exchange; be easy to replace without causing secondary damage to the wound; protect the wound , to avoid wound infection.

Hydrogel dressings are a new type of wound dressing that is closest to the ideal dressing requirements. Its high water content (70%-90%) and excellent water retention can keep the wound moist and promote the growth of granulation and epithelial tissue; its soft elastic properties can bring convenience to wound treatment, and the wound will not cause secondary damage; Soothes the wound by lowering the temperature of the wound and relieves pain.

To avoid wound infection, wound dressings often need to be antimicrobial. It is generally divided into two ways: self-antibacterial and loaded antibacterial agent. For example, chitosan (CS) is considered to be one of the most promising wound dressing materials due to its excellent antibacterial, adhesive, oxygen permeability, and connective regeneration properties. However, the antibacterial effect of self-antibacterial hydrogels has great limitations. The most commonly loaded antibacterial agent in hydrogel dressings is antibiotics, but the misuse of antibiotics makes antibiotics less effective in treating infections. Nano-silver has become the most promising inorganic antibacterial agent because of its excellent antibacterial properties and no cytotoxicity.

At present, there are two main methods for loading nano-silver particles: direct addition and in-situ reduction. The direct addition method is simple to operate, and the concentration of nano-silver is easy to control, but the nano-silver is easy to agglomerate, which affects the antibacterial effect. The in situ reduction method can control the particle size and shape of silver nanoparticles by changing the experimental parameters, and at the same time distribute more uniformly in the hydrogel and prevent agglomeration. However, the traditional in-situ reduction method usually uses reducing agents and stabilizers with potential safety hazards. Therefore, it is necessary to find a green and safe method for in-situ reduction of silver nanoparticles.

In conclusion, it is of great significance to design a safer preparation method and prepare an antibacterial hydrogel wound dressing that meets the requirements of an ideal wound dressing.

SUMMARY OF THE INVENTION

The existing wound dressings also have the following shortcomings: (1) poor moisturizing ability and easy to adhere to the wound surface; (2) the antibacterial performance of the single-component antibacterial hydrogel is weak and cannot meet the complex clinical antibacterial requirements; (3) nanometer Silver itself has potential cytotoxicity, and the preparation method has potential safety hazards; (4) the use of raw materials for preparing hydrogels and the use of reagents in the preparation process has safety hazards; (5) the mechanical properties are generally poor.

Purpose of the invention: In view of the above problems existing in current wound dressings, to provide a 3D printed hydrogel wound dressing with long-acting antibacterial effect and a preparation method thereof that is more in line with the requirements of ideal wound dressings and has a safer preparation method.

Technical scheme: In order to realize the above-mentioned purpose, the technical scheme adopted in the present invention is:

The raw materials of a 3D printing hydrogel wound dressing with long-acting antibacterial effect of the present invention include polyvinyl alcohol, carboxymethyl chitosan, sodium alginate, silver nitrate, and deionized water.

The preparation method of the 3D printed hydrogel wound dressing with long-acting antibacterial effect includes the following specific steps:

1) Reduction of nano-silver: dissolving sodium alginate in deionized water, heating in a 50° C. water bath and fully stirring to obtain a sodium alginate solution; preparing a 1% silver nitrate solution. The silver nitrate solution is added dropwise to the sodium alginate solution in a mass ratio of 1-5:100, reacted at 90° C. for more than 10 hours in the dark, and vigorously stirred to obtain yellow nano-silver-sodium alginate.

2) Preparation of polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution: dissolve polyvinyl alcohol in deionized water, and after fully swelling, heat and stir in a water bath at 95° C. to fully dissolve. Add carboxymethyl chitosan and sodium alginate, and stir evenly at 50° C. to obtain a polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution.

3) Preparation of the solution to be printed: Mix the nano-silver-sodium alginate solution and the polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution in a volume ratio of 1:1, stir evenly, and ultrasonically remove air bubbles.

4) Preparation of hydrogel dressing by 3D printing: Pour the prepared solution to be printed into a special cartridge for 3D printing. The non-woven fabric was used as the substrate, and the hydrogel sample was printed on the non-woven fabric to combine the hydrogel with the non-woven fabric. 3D printing technical parameters: barrel temperature is 20℃-30℃, printing pressure is 0.1MPa-0.3MPa, platform temperature is -4℃-4℃, printing speed is 2-5mm/s, needle diameter is 0.16-0.31mm .

5) Cross-linking of the hydrogel dressing: freeze-thaw the sample 4 times (freeze at -20°C for 6 hours and thaw at room temperature for 2 hours). Soak in 2% calcium chloride solution for 12 hours after the last thaw. Remove and soak in deionized water with water changes every 6 hours to remove uncrosslinked parts.

A 3D printed hydrogel wound dressing with long-lasting antibacterial effect prepared by the above scheme is closer to the requirements of an ideal wound dressing, and the preparation process is safer, and has the following advantages:

The present invention selects polyvinyl alcohol, carboxymethyl chitosan and sodium alginate as raw materials to construct a hydrogel. Among them, sodium alginate and carboxymethyl chitosan have excellent biocompatibility, and sodium alginate is used as a reducing agent and stabilizer to prepare silver nanoparticles; while carboxymethyl chitosan is very soluble in water, and in medium It also has antibacterial properties in a sexual environment, and it cooperates with nano-silver particles to improve antibacterial properties; polyvinyl alcohol is a highly safe polymer, which can effectively improve mechanical properties when combined with natural polymer materials.

(1) The silver nanoparticles are reduced by the sodium alginate heating method, the preparation method is simple, and other reagents with potential safety hazard are not used. The obtained nano-silver has a small and uniform particle size, and is compounded with other polymer materials to make its performance more stable and avoid agglomeration.

(2) The present invention adopts the 3D printing method to prepare the hydrogel, so that the hydrogel has a uniform grid structure, enhances the air permeability of the hydrogel, and is not easy to stick to the skin. And the grid-like structure increases the contact area with the wound, and at the same time is conducive to the release of silver nanoparticles, so it has higher water absorption and better antibacterial properties.

(3) Using the physical cross-linking method instead of the chemical cross-linking method, the preparation process is safer, and the safety hazard of residual chemical reagents is avoided. The silver nanoparticles are uniformly distributed in the hydrogel and released slowly to avoid burst release and reduce the potential cytotoxicity of silver nanoparticles.

(4) Excellent mechanical properties, can be bent into any shape, soft and skin-friendly, and the tensile strength can reach 0.3MPa.

(5) The combination with the non-woven fabric solves the problem that the hydrogel cannot be fixed with the skin and ensures the practicability.

Description of drawings

(1) FIG. 1 is a schematic diagram of the preparation process of the 3D printed hydrogel wound dressing with long-acting antibacterial effect of the present invention.

(2) FIG. 2 is a schematic diagram of the 3D printed hydrogel wound dressing with long-acting antibacterial effect of the present invention.

(3) Figure 3 shows the partial performance characterization of the 3D printed hydrogel wound dressing with long-lasting antibacterial effect. (A) water absorption; (B) moisture retention; (C) mechanical properties; (D) antibacterial properties; (E) biocompatibility.

Detailed ways

The invention discloses a preparation method of a 3D printing hydrogel wound dressing with long-acting antibacterial effect. The preparation materials include: raw materials for reducing nano-silver: sodium alginate, silver nitrate; raw materials for building hydrogels: polyvinyl alcohol, carboxymethyl chitosan, sodium alginate, deionized water; raw materials for cross-linked hydrogels : calcium chloride.

As shown in Figure 1, the preparation process:

(1) prepare nano silver-sodium alginate;

(2) prepare polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution;

(3) preparing the solution to be printed;

(4) 3D printing hydrogels on non-woven fabrics;

(5) Crosslinking the sample prepared in step 4 (freezing-thawing and soaking in calcium chloride); thereby obtaining a silver-loaded polyvinyl alcohol/carboxymethyl chitosan/sodium alginate hydrogel wound dressing.

The prepared hydrogel wound dressing is shown in Figure 2, which meets the requirements of an ideal dressing.

The present invention will be further described below with reference to the accompanying drawings and embodiments.

Example 1:

1) Reduction of nano-silver: Dissolve sodium alginate in deionized water, heat it in a 50°C water bath and stir well to obtain a sodium alginate solution with a mass fraction of 0.2%; prepare a silver nitrate solution with a mass fraction of 1%. The silver nitrate solution was added dropwise to the sodium alginate solution at a mass ratio of 1:100, reacted at 90°C in the dark for more than 10 hours, and vigorously stirred to obtain a yellow nano-silver-sodium alginate solution.

2) Preparation of polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution: dissolve polyvinyl alcohol in deionized water, and after fully swelling, heat and stir in a water bath at 95° C. to fully dissolve. Add carboxymethyl chitosan and sodium alginate, and stir evenly at 50° C. to obtain a polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution.

3) Preparation of the solution to be printed: Mix the nano-silver-sodium alginate solution and the polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution in a volume ratio of 1:1, stir evenly, and ultrasonically remove air bubbles. In the final mixed solution, polyvinyl alcohol is 5%, carboxymethyl chitosan is 1%, and sodium alginate is 0.8%.

4) Preparation of hydrogel dressing by 3D printing: Pour the prepared solution to be printed into a special cartridge for 3D printing. The non-woven fabric was used as the substrate, and the hydrogel sample was printed on the non-woven fabric to combine the hydrogel with the non-woven fabric. 3D printing technical parameters: the barrel temperature is 35°C, the printing pressure is 0.22MPa, the platform temperature is -4°C, the printing speed is 4.2mm/s, and the needle diameter is 0.16mm.

5) Cross-linking of the hydrogel dressing: freeze-thaw the sample 4 times (freeze at -20°C for 6 hours and thaw at room temperature for 2 hours). Soak in 2% calcium chloride solution for 12 hours after the last thaw. Remove and soak in deionized water with water changes every 6 hours to remove uncrosslinked parts.

Example 2:

1) Reduction of nano-silver: Dissolve sodium alginate in deionized water, heat it in a 50°C water bath and stir well to obtain a sodium alginate solution with a mass fraction of 0.2%; prepare a silver nitrate solution with a mass fraction of 1%. The silver nitrate solution was added dropwise to the sodium alginate solution in a mass ratio of 3:100, reacted at 90°C in the dark for more than 10 hours, and vigorously stirred to obtain a yellow nano-silver-sodium alginate solution.

2) Preparation of polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution: dissolve polyvinyl alcohol in deionized water, and after fully swelling, heat and stir in a water bath at 95° C. to fully dissolve. Add carboxymethyl chitosan and sodium alginate, and stir evenly at 50° C. to obtain a polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution.

3) Preparation of the solution to be printed: Mix the nano-silver-sodium alginate solution and the polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution in a volume ratio of 1:1, stir evenly, and ultrasonically remove air bubbles. In the final mixed solution, polyvinyl alcohol is 5%, carboxymethyl chitosan is 1%, and sodium alginate is 0.8%.

4) Preparation of hydrogel dressing by 3D printing: Pour the prepared solution to be printed into a special cartridge for 3D printing. The non-woven fabric was used as the substrate, and the hydrogel sample was printed on the non-woven fabric to combine the hydrogel with the non-woven fabric. 3D printing technical parameters: the barrel temperature is 40°C, the printing pressure is 0.2MPa, the platform temperature is -4°C, the printing speed is 4.2mm/s, and the needle diameter is 0.21mm.

5) Cross-linking of the hydrogel dressing: freeze-thaw the sample 4 times (freeze at -20°C for 6 hours and thaw at room temperature for 2 hours). Soak in 2% calcium chloride solution for 12 hours after the last thaw. Remove and soak in deionized water with water changes every 6 hours to remove uncrosslinked parts.

Example 3:

1) Reduction of nano-silver: Dissolve sodium alginate in deionized water, heat it in a 50°C water bath and stir well to obtain a sodium alginate solution with a mass fraction of 0.2%; prepare a silver nitrate solution with a mass fraction of 1%. The silver nitrate solution was added dropwise to the sodium alginate solution at a mass ratio of 1:100, reacted at 90°C in the dark for more than 10 hours, and vigorously stirred to obtain a yellow nano-silver-sodium alginate solution.

2) Preparation of polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution: dissolve polyvinyl alcohol in deionized water, and after fully swelling, heat and stir in a water bath at 95° C. to fully dissolve. Add carboxymethyl chitosan and sodium alginate, and stir evenly at 50° C. to obtain a polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution.

3) Preparation of the solution to be printed: Mix the nano-silver-sodium alginate solution and the polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution in a volume ratio of 1:1, stir evenly, and ultrasonically remove air bubbles. In the final mixed solution, polyvinyl alcohol is 5%, carboxymethyl chitosan is 1%, and sodium alginate is 0.8%.

4) Preparation of hydrogel dressing by 3D printing: Pour the prepared solution to be printed into a special cartridge for 3D printing. The non-woven fabric was used as the substrate, and the hydrogel sample was printed on the non-woven fabric to combine the hydrogel with the non-woven fabric. 3D printing technical parameters: the barrel temperature is 40°C, the printing pressure is 0.11MPa, the platform temperature is -4°C, the printing speed is 4mm/s, and the needle diameter is 0.21mm.

5) Cross-linking of the hydrogel dressing: freeze-thaw the sample 4 times (freeze at -20°C for 6 hours and thaw at room temperature for 2 hours). Soak in 2% calcium chloride solution for 12 hours after the last thaw. Remove and soak in deionized water with water changes every 6 hours to remove uncrosslinked parts.

Figure 3A illustrates that sodium alginate successfully reduced silver nanoparticles with small and uniform particle size; Figure 3B illustrates the good mechanical properties of the hydrogel; Figure 3C illustrates that the hydrogel has excellent water absorption and moisture retention; Figure 3D illustrates The hydrogel has good antibacterial properties and can have a sustained antibacterial effect; Figure 3E shows that the hydrogel has good biocompatibility.

The above is only the preferred embodiment of the present invention, it should be pointed out that: for those skilled in the art, without departing from the principle of the present invention, several improvements and modifications can also be made, and these improvements and modifications are also It should be regarded as the protection scope of the present invention.

Claims (5)

1. a preparation method of 3D printing hydrogel wound dressing with long-acting antibacterial effect is characterized in that: comprise the following steps: (1) by mass fraction, prepare the nano-silver-sodium alginate solution of sodium alginate 0.2% and silver nitrate 0.01-0.05%; (2) In terms of mass fraction, prepare polyvinyl alcohol/carboxymethyl chitosan/sodium alginate with 10% polyvinyl alcohol, 2%-6% carboxymethyl chitosan, and 1.2%-2% sodium alginate solution; (3) Mix the solutions obtained in steps 1 and 2 in a volume ratio of 1:1 to prepare a solution to be printed; (4) 3D printing hydrogels on non-woven fabrics; (5) Cross-linking the sample prepared in step 4: freezing-thawing and soaking in calcium chloride, thereby obtaining a sodium alginate antibacterial hydrogel wound dressing. 2. the preparation method of the 3D printing hydrogel wound dressing with long-acting antibacterial effect according to claim 1, is characterized in that: the method that step (1) prepares nano-silver-sodium alginate solution is: (1-1) Dissolve sodium alginate in deionized water, heat in a water bath at 50°C and fully stir to obtain a homogeneous sodium alginate solution with a mass fraction of 0.2%; (1-2) Dissolve silver nitrate in deionized water to obtain a silver nitrate solution with a mass fraction of 1%; (1-3) The silver nitrate solution is added to the sodium alginate solution in a mass ratio of 1-5:100, and the reaction is performed at 90°C in the dark for more than 10 hours, and vigorously stirred to obtain a yellow nano-silver-sodium alginate solution. 3. The preparation method of the 3D printing hydrogel wound dressing with long-acting antibacterial effect according to claim 1, characterized in that: step (2) preparing polyvinyl alcohol/carboxymethyl chitosan/sodium alginate solution The method is: (2-1) In terms of mass fraction, dissolve 10% of polyvinyl alcohol in deionized water, and after sufficient swelling, heat and stir in a water bath at 95° C. to fully dissolve to obtain an aqueous solution of polyvinyl alcohol; (2-2) In terms of mass fraction, add 2%-6% of carboxymethyl chitosan and 1.2%-2% of sodium alginate, and stir evenly at 50°C to obtain polyvinyl alcohol/carboxymethyl chitosan/ Sodium alginate solution. 4. the preparation method of the 3D printing hydrogel wound dressing with long-acting antibacterial effect according to claim 1, is characterized in that: the method for step (4) 3D printing hydrogel on non-woven fabric is: Pour the prepared solution to be printed into the special barrel for 3D printing, the non-woven fabric is used as the base, and the hydrogel sample is printed on the non-woven fabric to combine the hydrogel and the non-woven fabric; 3D printing technical parameters: material The barrel temperature is 20℃-30℃, the printing pressure is 0.1MPa-0.5MPa, the platform temperature is 0℃-±4℃, the printing speed is 2.0-5.0mm/s, and the needle diameter is 0.16-0.31mm. 5. the preparation method of the 3D printing hydrogel wound dressing with long-acting antibacterial effect according to claim 1, is characterized in that: step (5) the method for cross-linking the sample prepared in step 4 is: Freeze the sample at -20 °C for 6 hours, thaw at room temperature for 2 hours, and cycle 4 times; after the last thawing, soak in 2% calcium chloride solution for cross-linking for 12 hours; take out, soak in deionized water, every 6 hours Change the water once to remove the uncrosslinked parts.

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