CN110755678A

CN110755678A - 3D printing antibacterial hydrogel wound dressing based on green in-situ reduction

Info

Publication number: CN110755678A
Application number: CN201911104667.5A
Authority: CN
Inventors: 陈凯; 王丰艳; 吴晓芳; 刘思雨; 许林敏; 张德坤
Original assignee: China University of Mining and Technology CUMT
Current assignee: China University of Mining and Technology CUMT
Priority date: 2019-11-13
Filing date: 2019-11-13
Publication date: 2020-02-07
Anticipated expiration: 2039-11-13
Also published as: CN110755678B

Abstract

The invention discloses a 3D printing antibacterial hydrogel wound dressing based on green in-situ reduction, which is prepared from the following materials: reducing the raw material of nano silver: gelatin, silver nitrate; raw materials for constructing hydrogel: polyvinyl alcohol, chitosan, gelatin and deionized water; raw materials for crosslinked hydrogel: and (3) sodium citrate. The preparation process comprises the following steps: (1) preparing a nano silver-gelatin solution; (2) preparing polyvinyl alcohol/chitosan/gelatin; (3) preparing a solution to be printed; (4) 3D printing hydrogel on the non-woven fabric; (5) crosslinking (freezing-thawing and soaking in sodium citrate) the sample prepared in step 4; thereby obtaining the gelatin antibacterial hydrogel wound dressing. The prepared hydrogel wound dressing meets the requirements of an ideal dressing.

Description

3D printing antibacterial hydrogel wound dressing based on green in-situ reduction

Technical Field

The invention belongs to the technical field of wound dressings for human bodies, and particularly relates to a preparation method of a 3D printing antibacterial hydrogel wound dressing based on green in-situ reduction.

Background

The skin is the largest organ of the human body, can protect the internal environment of the organism to be stable, resists the invasion of the external environment and has important physical, chemical and biological barrier protection effects. When the skin is wounded, a series of problems are caused to the body. If not healed in time, a large amount of body fluid is lost through the wound, resulting in tissue necrosis and, in severe cases, life-threatening complications. Therefore, after the skin is damaged, its integrity must be restored in time to reestablish homeostasis.

The wound dressing can replace damaged skin to obtain temporary protection effect in the process of wound healing and treatment, avoid or control wound infection and provide a proper healing environment for the wounded surface. Common wound dressings mainly comprise gauze, absorbent cotton and the like, but the traditional wound dressings have a plurality of inevitable defects, for example, secondary injury is easily caused by wound adhesion, the wound is easily dehydrated due to poor moisture retention, wound infection is easily caused due to poor barrier effect, and the like, and the complex and changeable requirements in clinic cannot be met. Meanwhile, people put into question the theory of dry wound healing, and the idea that a properly humid environment can accelerate wound healing is gradually accepted.

Therefore, new wound dressings are gradually emerging in order to cope with the complex and diverse needs and to improve the drawbacks of the conventional wound dressings. The hydrogel is a high polymer material with a net structure, is soft and skin-friendly, has hydrophilic groups inside, can absorb a large amount of water, is firmly combined with the water, and is applied to wound dressings. Compared with the traditional dressing, the hydrogel wound dressing can absorb exudates, maintain the moist environment around the wound, allow gas to permeate, promote the wound healing, relieve pain, improve the microenvironment of the wound surface and inhibit the growth of bacteria. In addition, the hydrogel wound dressing is easy to remove and replace, and cannot cause secondary damage to healed wounds.

Chitosan (CS) has good adsorptivity, permeability, film-forming property, fiber-forming property, moisture absorption and retention property, and better biocompatibility, antibacterial property and biodegradability, and is considered to be one of the wound dressings with the most research prospects. However, chitosan can only dissolve and exert antibacterial action under acidic conditions, and the antibacterial action is limited, so that antibacterial agents are sometimes required to be loaded. As the problem of abuse of antibiotics becomes more serious, non-antibiotic antibacterial agents such as nano silver and the like are widely concerned. However, nano silver particles are easy to agglomerate, the antibacterial effect is influenced, a reducing agent and a stabilizing agent used in the process of reducing the nano silver have potential toxicity, and the preparation method has potential safety hazards. Besides, the nano silver burst release easily influences the activity of cells.

In conclusion, aiming at the problems of the traditional wound dressing carrying nano silver, the silver-carrying hydrogel wound dressing which is more green and safe in preparation method, meets the requirements of ideal wound dressings and has more stable antibacterial effect of nano silver particles has important significance.

Disclosure of Invention

The existing wound dressing also has the following disadvantages: (1) the moisture retention capability is poor, and the wound surface is easy to adhere; (2) the single-component antibacterial hydrogel has weak antibacterial performance and cannot meet the clinically complex antibacterial requirement; (3) the nano silver has potential cytotoxicity, and the preparation method has potential safety hazards; (4) potential safety hazards exist in the raw materials for preparing the hydrogel and the use of reagents in the preparation process; (5) the mechanical properties are generally poor.

The purpose of the invention is as follows: aiming at the problems of the existing wound dressing, the green in-situ reduction-based 3D printing antibacterial hydrogel wound dressing which is more in line with the requirements of ideal wound dressings and has a safer preparation method and the preparation method thereof are provided.

The technical scheme is as follows: in order to achieve the purpose, the invention adopts the technical scheme that:

the invention relates to a green in-situ reduction-based 3D printing antibacterial hydrogel wound dressing which comprises the following raw materials: polyvinyl alcohol, chitosan, gelatin, silver nitrate and deionized water.

The preparation method of the green in-situ reduction-based 3D printing antibacterial hydrogel wound dressing comprises the following specific steps:

1) reducing nano silver: dissolving gelatin in deionized water, heating in 50 deg.C water bath, and stirring to obtain gelatin solution; preparing 1% silver nitrate solution. Dropwise adding the silver nitrate solution into the gelatin solution according to the mass ratio of 1-5:100, reacting for more than 10 hours at 90 ℃ in a dark place, and violently stirring to obtain a yellow nano silver-gelatin solution.

2) Preparation of polyethylene-out/chitosan/gelatin solution: dissolving polyvinyl alcohol in deionized water, fully swelling, heating in a water bath at 95 ℃, stirring, and fully dissolving; adding acetic acid to make the pH value of the solution tend to weak acidity (chitosan can only be dissolved under weak acid condition), adding chitosan and gelatin, and stirring at 50 deg.C to obtain polyvinyl alcohol/chitosan/gelatin solution. Wherein, the mass fraction is 10 percent of polyvinyl alcohol, 3 percent of added acetic acid, 6 percent to 14 percent of chitosan and 4 percent to 12 percent of gelatin.

3) Preparation of a solution to be printed: mixing the nano silver-gelatin solution and the polyvinyl alcohol/chitosan/gelatin solution according to the volume ratio of 1:1, uniformly stirring, and ultrasonically removing bubbles.

4)3D printing to prepare the hydrogel dressing: and pouring the prepared solution to be printed into a special 3D printing material cylinder. The nonwoven fabric was used as a substrate, and the hydrogel sample was printed on the nonwoven fabric to bond the hydrogel to the nonwoven fabric. 3D printing technical parameters: the temperature of the charging barrel is 20-60 ℃, the printing pressure is 0.1-0.3 MPa, the platform temperature is-4 ℃, the printing speed is 2-5mm/s, and the diameter of the needle is 0.16-0.31 mm.

5) Crosslinking of the hydrogel dressing: the samples were freeze-thawed 4 times (-6 hours at 20 ℃ C., 2 hours at room temperature). After the final thawing, soaking in 0.3mol/L sodium citrate solution for crosslinking for 12 hours. Taking out, soaking in deionized water, and changing water every 6 hr to remove non-crosslinked part.

The 3D printing antibacterial hydrogel wound dressing prepared by the scheme based on green in-situ reduction is closer to the requirement of ideal wound dressings, the preparation process is safer, and the preparation method mainly has the following advantages:

the invention selects polyvinyl alcohol, chitosan and gelatin as raw materials to construct hydrogel. The gelatin and the chitosan have excellent biocompatibility, and the gelatin is used as a reducing agent and a stabilizing agent to prepare nano silver particles; the chitosan has antibacterial property, and can synergistically resist bacteria with the nano silver particles, so that the antibacterial property is improved; polyvinyl alcohol is a highly safe polymer, and can effectively improve mechanical properties by compounding with natural high molecular materials.

(1) The silver nanoparticles are reduced by adopting a gelatin heating method, the preparation method is simple, and other reagents with potential safety hazards are not used. The obtained nano silver has small and uniform particle size, is compounded with other components to ensure that the performance of the nano silver is more stable, and avoids agglomeration.

(2) According to the invention, the hydrogel is prepared by adopting a 3D printing method, so that the air permeability of the hydrogel is enhanced, and the hydrogel is not easy to adhere to the skin. And the latticed structure increases the contact area with the wound and is beneficial to the release of the silver nanoparticles, so that the wound dressing has higher water absorption and more excellent antibacterial property.

(3) The physical crosslinking method is adopted to replace the chemical crosslinking method, the preparation process is safer, and the potential safety hazard of residual chemical reagents is avoided. The silver nano particles are uniformly distributed in the hydrogel and are slowly released, so that burst release is avoided, and the potential cytotoxicity of the nano silver is reduced.

(4) The mechanical property is excellent, the fabric can be bent into any shape, the fabric is soft and skin-friendly, the tensile strength can reach 0.3MPa, and the compression strength can reach 0.16 MPa.

(5) The combination with the non-woven fabrics solves the problem that the hydrogel can not be fixed with the skin, and the practicability is ensured.

(6) Compared with the traditional preparation method of the hydrogel dressing, the preparation method of the invention has simple preparation process, and meets the requirements of the invention.

Drawings

(1) Fig. 1 is a schematic diagram of a preparation process of the green in-situ reduction-based 3D printing antibacterial hydrogel wound dressing.

(2) Fig. 2 is a schematic view of the green in-situ reduction-based 3D printed antibacterial hydrogel wound dressing of the present invention.

(3) Fig. 3 is a partial performance characterization of a green in situ reduction-based 3D-printed antimicrobial hydrogel wound dressing. (A) Ultraviolet characterization and particle size characterization of nano silver; (B) moisture retention, swelling; (C) compressive and tensile strength; (D) antibacterial property; (E) biocompatibility.

Detailed Description

The invention discloses a preparation method of a 3D printing antibacterial hydrogel wound dressing based on green in-situ reduction. The preparation material comprises the following steps: reducing the raw material of nano silver: gelatin, silver nitrate; raw materials for constructing hydrogel: polyvinyl alcohol, chitosan, gelatin and deionized water; raw materials for crosslinked hydrogel: and (3) sodium citrate.

As shown in fig. 1, the preparation process:

(1) preparing a nano silver-gelatin solution;

(2) preparing a polyvinyl alcohol/chitosan/gelatin solution;

(3) preparing a solution to be printed;

(4) 3D printing hydrogel on the non-woven fabric;

(5) crosslinking (freezing-thawing and soaking in sodium citrate) the sample prepared in step 4; thereby obtaining the silver-loaded polyvinyl alcohol/chitosan/gelatin hydrogel wound dressing.

The prepared hydrogel wound dressing is shown in figure 2 and meets the requirements of an ideal dressing.

The invention is further described with reference to the following figures and examples.

Example 1:

1) reducing nano silver: dissolving gelatin in deionized water, heating in a water bath at 50 ℃ and fully stirring to obtain a gelatin solution with the mass fraction of 2%; preparing silver nitrate solution with the mass fraction of 1%. Dropwise adding the silver nitrate solution into the sodium alginate solution according to the mass ratio of 3:100, reacting for more than 10 hours at 90 ℃ in a dark place, and violently stirring to obtain a yellow nano silver-gelatin solution.

2) Preparation of polyvinyl alcohol/chitosan/gelatin solution: dissolving polyvinyl alcohol in deionized water, fully swelling, heating in a water bath at 95 ℃, stirring, and fully dissolving. Adding acetic acid, chitosan and sodium alginate, and stirring at 50 deg.C to obtain polyvinyl alcohol/chitosan/gelatin solution.

3) Preparation of a solution to be printed: mixing the nano silver-gelatin solution and the polyvinyl alcohol/chitosan/gelatin solution according to the volume ratio of 1:1, stirring uniformly, and removing bubbles by ultrasonic. In the final mixed solution, 5% of polyvinyl alcohol, 7% of chitosan and 4% of gelatin were contained.

4)3D printing to prepare the hydrogel dressing: and pouring the prepared solution to be printed into a special 3D printing material cylinder. The nonwoven fabric was used as a substrate, and the hydrogel sample was printed on the nonwoven fabric to bond the hydrogel to the nonwoven fabric. 3D printing technical parameters: the cylinder temperature was 40 ℃, the printing pressure was 0.4MPa, the platform temperature was 4 ℃, the printing speed was 3.5mm/s, and the needle diameter was 0.31 mm.

Example 2:

4)3D printing to prepare the hydrogel dressing: and pouring the prepared solution to be printed into a special 3D printing material cylinder. The nonwoven fabric was used as a substrate, and the hydrogel sample was printed on the nonwoven fabric to bond the hydrogel to the nonwoven fabric. 3D printing technical parameters: the cylinder temperature was 50 ℃, the printing pressure was 0.3MPa, the platform temperature was 4 ℃, the printing speed was 3.5mm/s, and the needle diameter was 0.26 mm.

6) Crosslinking of the hydrogel dressing: the samples were freeze-thawed 4 times (-6 hours at 20 ℃ C., 2 hours at room temperature). After the final thawing, soaking in 0.3mol/L sodium citrate solution for crosslinking for 12 hours. Taking out, soaking in deionized water, and changing water every 6 hr to remove non-crosslinked part.

Example 3:

1) reducing nano silver: dissolving gelatin in deionized water, heating in a water bath at 50 ℃ and fully stirring to obtain a gelatin solution with the mass fraction of 2%; preparing silver nitrate solution with the mass fraction of 1%. Dropwise adding the silver nitrate solution into the sodium alginate solution according to the mass ratio of 5:100, reacting for more than 10 hours at 90 ℃ in a dark place, and violently stirring to obtain a yellow nano silver-gelatin solution.

4)3D printing to prepare the hydrogel dressing: and pouring the prepared solution to be printed into a special 3D printing material cylinder. The nonwoven fabric was used as a substrate, and the hydrogel sample was printed on the nonwoven fabric to bond the hydrogel to the nonwoven fabric. 3D printing technical parameters: the cylinder temperature was 50 ℃, the printing pressure was 0.4MPa, the platform temperature was 4 ℃, the printing speed was 3.5mm/s, and the needle diameter was 0.26 mm.

7) Crosslinking of the hydrogel dressing: the samples were freeze-thawed 4 times (-6 hours at 20 ℃ C., 2 hours at room temperature). After the final thawing, soaking in 0.3mol/L sodium citrate solution for crosslinking for 12 hours. Taking out, soaking in deionized water, and changing water every 6 hr to remove non-crosslinked part.

FIG. 3A illustrates that the gelatin successfully reduces the nano-silver and has small and uniform particle size; FIG. 3B illustrates that the hydrogel has good moisture retention and water absorption properties; FIG. 3C illustrates that the hydrogel has excellent mechanical properties; FIG. 3D illustrates that the antimicrobial properties of the hydrogel are good; FIG. 3E illustrates that the hydrogel has good biocompatibility;

the above description is only of the preferred embodiments of the present invention, and it should be noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the invention and these are intended to be within the scope of the invention.

Claims

1. A preparation method of a 3D printing antibacterial hydrogel wound dressing based on green in-situ reduction is characterized by comprising the following steps: the method comprises the following steps:

(1) preparing a nano silver-gelatin solution with gelatin 2% and silver nitrate 0.01-0.05% by mass;

(2) preparing polyvinyl alcohol/chitosan/gelatin solution with 10% of polyvinyl alcohol, 6-14% of chitosan and 4-12% of gelatin according to mass fraction;

(3) and (3) mixing the solutions obtained in the step 1 and the step 2 according to the ratio of 1:1, preparing a solution to be printed;

(4) 3D printing hydrogel on the non-woven fabric;

(5) crosslinking the sample prepared in step 4: freezing-thawing and soaking sodium citrate to obtain the gelatin antibacterial hydrogel wound dressing.

2. The preparation method of the green in-situ reduction based 3D printing antibacterial hydrogel wound dressing according to claim 1, characterized in that: the method for preparing the nano silver-gelatin solution in the step (1) comprises the following steps:

(1-1) dissolving gelatin in deionized water, heating in a water bath at 50 ℃ and fully stirring to obtain a homogeneous gelatin solution with the mass fraction of 2%;

(1-2) dissolving silver nitrate in deionized water to obtain a silver nitrate solution with the mass fraction of 1%;

(1-3) adding the silver nitrate solution into the gelatin solution according to the mass ratio of 1-5:100, reacting for more than 5 hours at 90 ℃ in a dark place, and violently stirring to obtain a yellow nano silver-gelatin solution.

3. The preparation method of the green in-situ reduction based 3D printing antibacterial hydrogel wound dressing according to claim 1, characterized in that: the method for preparing the polyvinyl alcohol/chitosan/gelatin in the step (2) comprises the following steps:

(2-1) dissolving 10% of polyvinyl alcohol in deionized water according to mass fraction, heating and stirring in a water bath at 95 ℃ after full swelling, and fully dissolving to obtain a polyvinyl alcohol aqueous solution;

(2-2) adding 3% acetic acid to adjust the solution to weak acidity according to mass fraction, adding 6% -14% of chitosan and 3% -12% of gelatin, and uniformly stirring at 50 ℃ to obtain a polyvinyl alcohol/chitosan/gelatin solution.

4. The preparation method of the green in-situ reduction based 3D printing antibacterial hydrogel wound dressing according to claim 1, characterized in that: the method for 3D printing of the hydrogel on the non-woven fabric in the step (4) comprises the following steps:

pouring the prepared solution to be printed into a special 3D printing material cylinder, using the non-woven fabric as a substrate, and printing the hydrogel sample on the non-woven fabric to combine the hydrogel with the non-woven fabric; 3D printing technical parameters: the temperature of the charging barrel is 20-30 ℃, the printing pressure is 0.1-0.5 MPa, the platform temperature is 0-4 ℃, the printing speed is 2.0-5.0mm/s, and the diameter of the needle is 0.16-0.31 mm.

5. The preparation method of the green in-situ reduction based 3D printing antibacterial hydrogel wound dressing according to claim 1, characterized in that: step (5) the method for crosslinking the sample prepared in step 4 comprises the following steps:

freezing the sample at-20 deg.C for 6 hr, thawing at room temperature for 2 hr, and circulating for 4 times; after the final thawing, soaking the mixture in 0.3mol/L sodium citrate solution for crosslinking for 12 hours; taking out, soaking in deionized water, and changing water every 6 hr to remove non-crosslinked part.