CN115337448A - Tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS (reactive oxygen species) response performances and preparation method thereof - Google Patents

Tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS (reactive oxygen species) response performances and preparation method thereof Download PDF

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CN115337448A
CN115337448A CN202211013349.XA CN202211013349A CN115337448A CN 115337448 A CN115337448 A CN 115337448A CN 202211013349 A CN202211013349 A CN 202211013349A CN 115337448 A CN115337448 A CN 115337448A
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polyphosphazene
ros
inflammatory
ppba
antibacterial
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CN115337448B (en
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俞豪杰
倪志鹏
王立
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Zhejiang University ZJU
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    • AHUMAN NECESSITIES
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    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/008Hydrogels or hydrocolloids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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    • A61L2300/41Anti-inflammatory agents, e.g. NSAIDs
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Abstract

The invention discloses tannin-coupled polyphosphazene-based hydrogel with anti-inflammatory, antibacterial and ROS (reactive oxygen species) response performances and a preparation method thereof. The polyphosphazene-based hydrogel wound dressing is obtained by reacting polyphosphazene with tannin and polyvinyl alcohol solution in sequence. The obtained PPBA-TA-PVA hydrogel can effectively inhibit the growth of escherichia coli within 4h, and shows degradation behavior while effectively eliminating 1, 1-diphenyl-2-trinitrophenylhydrazine (DPPH) free radicals and OH free radicals. The anti-inflammatory micromolecules of the tannic acid are covalently combined by ROS responsive borate bonds, and the anti-inflammatory micromolecules have the characteristics of safe and low-toxicity ROS response and release. The invention has good anti-inflammatory, antibacterial and ROS response performance, can effectively shorten the inflammatory stage of the diabetic wound and accelerate the wound healing by reducing proinflammatory cytokines (IL-6 and IL-1 beta), and has wide application prospect in the field of biomedical materials.

Description

Tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS (reactive oxygen species) response performances and preparation method thereof
Technical Field
The invention belongs to the technical field of high polymer materials, and relates to a polyacrylonitrile-based hydrogel wound dressing, in particular to a tannin-coupled polyacrylonitrile-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS (reactive oxygen species) response performances and a preparation method thereof.
Technical Field
Diabetic wounds are a serious and common complication of diabetes, and current treatment regimens remain nonspecific. By 2035, patients with diabetic wounds are expected to reach 9000 tens of thousands to 1.5 billion people, with about 20% of moderately severe diabetic wound patients facing amputations. There is a large body of evidence that in diabetic wounds, long-term low-level inflammation accumulates excess Reactive Oxygen Species (ROS) in the wound, disrupting key processes of wound repair, such as angiogenesis, ECM remodeling and re-epithelialization, thereby preventing the development of the wound from the inflammatory phase to the healing increase phase. In addition, the hyperglycemic microenvironment of the diabetic wound is more easily infected by microorganisms than other wounds, bacterial infection often causes additional accumulation of ROS, which causes insufficient oxygenation, not only further slows down the healing of the diabetic wound, but also causes abnormal pathological changes (neuropathy, vasculopathy and other complex systemic effects), and causes difficult healing. Therefore, reducing ROS levels and effectively eliminating microorganisms from the wound is critical for diabetic wound healing.
An ideal diabetic wound dressing should have the following characteristics: 1) Has good ROS eliminating performance, relieves the inflammation of the diabetic wound, and shortens the inflammation stage; 2) Has good anti-infection performance; 3) The compatibility to human tissues is good, and no tissue injury or infection risk exists; 4) The use is simple and convenient, and the use is convenient for the wounded; 5) Can be effectively stored for a long time, and the property is kept stable in a wider temperature range.
Disclosure of Invention
In order to solve the defects of the prior art, the invention aims to provide the tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS (reactive oxygen species) response performances and the preparation method thereof.
The invention is realized by the following technical scheme:
1. tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS (reactive oxygen species) response performances
The PPBA-TA nano conjugate containing phenylboronic acid group and quaternary ammonium salt group functionalized polyphosphazene PPBA and tannic acid TA is used as an anti-inflammatory and antibacterial component; the PPBA-TA nano conjugate and polyvinyl alcohol react to form ROS responsive borate bond to obtain the polyphosphazene-based hydrogel wound dressing (PPBA-TA-PVA) with ROS responsive degradation performance.
2. Preparation method of tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS (reactive oxygen species) response performances
The functionalized polyphosphazene PPBA containing phenylboronic acid groups and quaternary ammonium salt groups is poly [ N, N-dimethyl-aminoethyl-p-methyl phenylboronic acid ammonium bromide) (N, N-dimethyl ethylenediamine) ] phosphazene; the boric acid group grafting rate of the polyphosphazene is 15-30%.
Firstly, respectively and fully dissolving functional polyphosphazene PPBA containing phenylboronic acid groups and quaternary ammonium salt groups, tannic acid TA and polyvinyl alcohol PVA in deionized water to respectively obtain polyphosphazene PPBA solution, tannic acid TA solution and polyvinyl alcohol PVA solution; and then adding the polyphosphazene PPBA solution into the tannic acid TA solution, mixing and stirring to obtain a PPBA-TA nano conjugate, finally adding the PPBA-TA nano conjugate into a polyvinyl alcohol PVA solution, and mixing and stirring to obtain the tannic acid coupled polyphosphazene based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances.
The functional polyphosphazene PPBA containing the phenylboronic acid group and the quaternary ammonium salt group is 10-30 parts by mass, the tannic acid TA is 1-3 parts by mass, the polyvinyl alcohol PVA is 10-30 parts by mass, the sum of the deionized water of the three solutions is 1000-2000 parts by mass, and the proportion of the deionized water in the three solutions is equal to the mass part ratio of the three solutions.
The mixing and stirring time is 10-30 minutes.
The mixing and stirring speed is 500-1000 rpm.
The particle size of the PPBA-TA nano conjugate is 50-200 nm.
The hydrogel wound dressing has good contact bacteriostasis performance, gram-negative bacteria escherichia coli suspension is coated on the surface of the hydrogel obtained in the step 3) and cultured at 37 ℃, the 4-hour growth inhibition rate of the hydrogel on escherichia coli reaches 93.1 +/-1.1%, and the 8-hour growth inhibition rate reaches 99.4 +/-0.6%.
The hydrogel wound dressing can effectively remove 1, 1-diphenyl-2-trinitrophenylhydrazine (DPPH) free radicals and OH free radicals. Each part of hydrogel was able to scavenge 100 parts DPPH free radical (0.1 mM) and 100 parts OH free radical (1 mM) in 20h, calculated as parts by mass.
The hydrogel wound dressing has an ROS response function, can be degraded in OH free radical solution (1 mM), has a positive correlation between the degradation rate and the coupling concentration of TA, and is immersed in the OH free radical solution, so that the 96-hour hydrogel degradation rate is 40% -98%.
The hydrogel wound dressing is capable of reducing proinflammatory cytokines (IL-6, IL-1 beta).
The invention has the following beneficial effects:
1. the tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances provided by the invention has good antibacterial performance, rich quaternary ammonium salt groups and protonatable tertiary amine groups provided by poly [ N, N-dimethyl-aminoethyl-p-methylphenylboronic acid ammonium bromide) (N, N-dimethylethylenediamine) ] phosphazene (PPBA) in a hydrogel framework can be contacted with thalli and then adsorbed to the surface of the thalli, penetrate cell walls, disturb the composition of cell membranes through the change of osmotic pressure and the decomposition of organic matters, promote the leakage of intracellular substances (DNA and RNA), further die the thalli, avoid the use of antibiotics, slow down the occurrence of multidrug resistant bacteria, and has long-term and effective antibacterial performance.
2. The tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances provided by the invention has good anti-inflammatory performance. The hydrogel is coupled with natural polyphenol tannic acid with anti-inflammatory effect, and phenolic hydroxyl in the tannic acid can be combined with free radicals to form an o-benzoquinone structure, so that the effect of removing the free radicals is exerted.
3. The tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances provided by the invention has good ROS response performance, ROS can attack a single bond between boron and a benzene ring to form an unstable peroxide intermediate, and then hydrolysis is carried out to remove a boric acid group, so that the separation of the boric acid group and the benzene ring is caused. The hydrogel can release the attached TA as needed when ROS levels are high, thereby maintaining the ROS concentration in the wound at a reasonable level.
4. The tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances, provided by the invention, can reduce proinflammatory cytokines (IL-6 and IL-1 beta) and greatly shorten the inflammation stage in a rat diabetic wound model.
Drawings
FIG. 1 shows the contact inhibition rate of the hydrogel prepared in example 1 against E.coli.
FIG. 2 is a graph showing the DPPH radical scavenging rate of the hydrogel prepared in example 1.
FIG. 3 shows the OH radical scavenging ratio of the hydrogel prepared in example 1.
FIG. 4 shows the degradation rate of the hydrogel prepared in example 1 in OH radical solution.
FIG. 5 is a graph showing the healing rate of the hydrogel prepared in example 1 on diabetic wounds of rats.
FIG. 6 shows the contact bacteriostatic rate of the hydrogel prepared in example 2 against E.coli.
FIG. 7 is a graph showing the DPPH radical scavenging rate of the hydrogel prepared in example 2.
FIG. 8 shows the OH radical scavenging ratio of the hydrogel prepared in example 2.
FIG. 9 shows the degradation rate of the hydrogel prepared in example 2 in OH radical solution.
FIG. 10 is a graph showing the rate of healing of diabetic wounds in rats by the hydrogel prepared in example 2.
FIG. 11 shows the contact inhibition rate of the hydrogel prepared in example 3 against E.coli.
FIG. 12 is a graph of DPPH radical scavenging efficiency for the hydrogel prepared in example 3.
FIG. 13 shows the OH radical scavenging ratio of the hydrogel prepared in example 3.
FIG. 14 is a graph of the degradation rate of the hydrogel prepared in example 3 in OH radical solution.
FIG. 15 is a graph showing the rate of healing of diabetic wounds in rats by the hydrogel prepared in example 3.
Detailed Description
The present invention will be described in more detail with reference to specific examples, but the embodiments of the present invention are not limited thereto.
The examples of the invention are as follows:
the functional polyphosphazene PPBA containing the phenylboronic acid group and the quaternary ammonium salt group is specifically poly [ N, N-dimethyl-aminoethyl-p-methyl phenylboronic acid ammonium bromide) (N, N-dimethyl ethylenediamine) ] phosphazene.
Example 1
Polyphosphazene (PPBA) 30mg, tannic Acid (TA) 1mg and polyvinyl alcohol (PVA) 30mg were dissolved in 900. Mu.l, 100. Mu.l and 1000. Mu.l of deionized water, respectively, until completely dissolved.
Firstly, respectively and fully dissolving functional polyphosphazene PPBA containing phenylboronic acid groups and quaternary ammonium salt groups, tannic acid TA and polyvinyl alcohol PVA in deionized water to respectively obtain polyphosphazene PPBA solution, tannic acid TA solution and polyvinyl alcohol PVA solution; and then adding the polyphosphazene PPBA solution into the tannic acid TA solution, mixing and stirring to obtain the PPBA-TA nano conjugate, wherein the particle size of the PPBA-TA nano conjugate is 50-200 nm. And finally, adding the PPBA-TA nano conjugate into a polyvinyl alcohol PVA solution, and mixing and stirring to obtain the tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances. Wherein the mixing and stirring time is 10 minutes and the rotation speed is 1000rpm.
Will be in logarithmic growth phase at a 10. Mu.l concentration of 10 6 A suspension of CFU of Escherichia coli ATCC 25922 bacteria was dispersed on the hydrogel surface and cultured in a 37 ℃ incubator for 1h, 2h, 4h and 8h. After co-incubation, 1ml of PBS solution was added to the hydrogel surface and sonication was performed for 30 minutes. LB solid medium was spread with 100. Mu.l of the solution, and cultured overnight in a 37 ℃ incubator, and the number of colonies on the medium was counted.
0.4ml of the hydrogel provided by the invention and 30ml of DPPH free radical solution (0.1 mM) are incubated together at 37 ℃ in a dark place, and the DPPH free radical scavenging capacity of the PPBA-TA-PVA hydrogel at different times is measured through ultraviolet absorption intensity of 517 nm. 0.4ml of the hydrogel provided by the invention was incubated with 25ml of OH free radical solution (1 mM) at 37 ℃ in the absence of light, and a certain amount of the solution was mixed with an equal volume of TMB (10 mM, DMSO) for 10min at different times. And (3) determining the scavenging capacity of the PPBA-TA-PVA hydrogel to hydroxyl free radicals at different times by using 904nm ultraviolet absorption intensity.
1ml of the hydrogel provided by the invention and 50ml of OH free radical solution (1 mM) are incubated together at 37 ℃ in the dark, and the consumption of the hydrogel is observed at different times to determine the ROS response degradation capability of the hydrogel wound dressing.
The hydrogel provided by the invention is filled in the wound by taking a streptomycin-induced rat diabetic wound model as an object, the dressing is replaced periodically, and the healing condition of the wound is observed to determine the performance of the hydrogel wound dressing in promoting the healing of the diabetic wound.
In the healing process of diabetic wounds, tissues around the wounds are taken at the 10 th day respectively, and fluorescence quantification pcr is carried out on genes related to inflammatory factors IL-6 and IL-1 beta, and the performance of the hydrogel wound dressing in reducing the level of wound inflammation is determined.
The results of this example are shown in fig. 1 to 5, fig. 1 shows the contact bacteriostasis performance of the obtained hydrogel on escherichia coli, and it can be seen from the figure that the gel material has excellent contact bacteriostasis performance. The bacteriostatic rate of the antibacterial agent can reach 46.7 +/-5.2% in 1 hour, and the bacteriostatic rate can reach 98.3 +/-1.1% in 8 hours, so that the bacteria can be basically killed. FIGS. 2 and 3 show the scavenging performance of the obtained hydrogel for DPPH free radicals and OH free radicals, and it can be seen that the gel material has good ROS scavenging performance. It can eliminate 94.7 +/-1.9% of DPPH free radicals in 70h and 93.6 +/-0.3% of OH free radicals in 8h. FIG. 4 shows the ROS response degradation performance of the hydrogel, and it can be seen that about 27.8 + -2.0% of the hydrogel degrades in OH free radical solution for 96 h. FIG. 5 shows the healing of diabetic wounds treated by the gel material, and it can be seen from the figure that the wound healing rate of the hydrogel group is 65.0 + -3.2% on the 6 th day of wound healing, compared with the healing rate of the blank control group (44.0 + -4.4%), the invention is more capable of promoting the healing of diabetic wounds. In the healing process of diabetic wounds, the expression levels of the inflammatory factors IL-6 and IL-1 beta in the group of the invention were 0.53 times and 0.59 times of those in the blank control group at day 10, respectively.
Example 2
Polyphosphazene (PPBA) 30mg, tannic Acid (TA) 2mg and polyvinyl alcohol (PVA) 30mg were dissolved in deionized water 800. Mu.l, 200. Mu.l and 1000. Mu.l, respectively, to be completely dissolved.
Firstly, respectively and fully dissolving functional polyphosphazene PPBA containing phenylboronic acid groups and quaternary ammonium salt groups, tannic acid TA and polyvinyl alcohol PVA in deionized water to respectively obtain polyphosphazene PPBA solution, tannic acid TA solution and polyvinyl alcohol PVA solution; and then adding the polyphosphazene PPBA solution into the tannic acid TA solution, mixing and stirring to obtain the PPBA-TA nano conjugate, wherein the particle size of the PPBA-TA nano conjugate is 50-200 nm. And finally, adding the PPBA-TA nano conjugate into a polyvinyl alcohol PVA solution, and mixing and stirring to obtain the tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances. Wherein the mixing and stirring time is 30 minutes and the rotation speed is 500rpm.
Will be in logarithmic growth phase at a 10. Mu.l concentration of 10 6 A suspension of CFU of Escherichia coli ATCC 25922 bacteria was dispersed on the hydrogel surface and cultured in a 37 ℃ incubator for 1h, 2h, 4h and 8h. After co-incubation, 1ml of PBS solution was added to the hydrogel surface and sonication was performed for 30 minutes. LB solid medium was spread with 100. Mu.l of the solution, and cultured overnight in a 37 ℃ incubator, and the number of colonies on the medium was counted.
0.4ml of the hydrogel provided by the invention and 30ml of DPPH free radical solution (0.1 mM) are incubated together at 37 ℃ in a dark place, and the DPPH free radical scavenging capacity of the PPBA-TA-PVA hydrogel at different times is measured through ultraviolet absorption intensity of 517 nm. 0.4ml of the hydrogel provided by the invention was incubated with 25ml of OH free radical solution (1 mM) at 37 ℃ in the absence of light, and a certain amount of the solution was mixed with an equal volume of TMB (10 mM, DMSO) for 10min at different times. And (3) determining the scavenging capacity of the PPBA-TA-PVA hydrogel to hydroxyl free radicals at different times by using 904nm ultraviolet absorption intensity.
1ml of the hydrogel provided by the invention and 50ml of OH free radical solution (1 mM) are incubated together at 37 ℃ in the dark, and the ROS response degradation capability of the hydrogel wound dressing is measured by observing the consumption condition of the hydrogel at different times.
The hydrogel provided by the invention is filled in the wound by taking a streptomycin-induced rat diabetic wound model as an object, the dressing is replaced periodically, and the healing condition of the wound is observed to determine the performance of the hydrogel wound dressing for promoting the healing of the diabetic wound.
In the healing process of diabetic wounds, tissues around the wounds are taken at the 10 th day respectively, and fluorescence quantification pcr is carried out on genes related to inflammatory factors IL-6 and IL-1 beta, and the performance of the hydrogel wound dressing in reducing the level of wound inflammation is determined.
The results of this example are shown in fig. 6 to 10, and fig. 6 shows the contact bacteriostatic performance of the obtained hydrogel on escherichia coli, and it can be seen from the figure that the gel material has excellent contact bacteriostatic performance. The bacteriostatic rate of the bacteria in 1 hour can reach 32.2 +/-4.0%, and the bacteriostatic rate in 8 hours can reach 89.5 +/-1.2%, so that the bacteria can be basically killed. FIGS. 7 and 8 show the scavenging properties of the obtained hydrogels for DPPH radical and. OH radical, and it can be seen that the gel materials have good ROS scavenging properties. It can scavenge 99.6 + -1.4% of DPPH free radicals in 70h, and 97.4 + -0.1% of OH free radicals in 8h. FIG. 9 is a graph of the ROS-responsive degradation performance of the hydrogel, from which it can be seen that about 60.5. + -. 2.6% of the hydrogel degrades in OH free radical solution for 96 h. FIG. 10 shows the healing of diabetic wounds treated with the gel material, and it can be seen from the figure that the wound healing rate of the hydrogel group is 83.1 + -2.6% on the 6 th day of wound healing, compared with the healing rate of the blank control group (44.0 + -4.4%), the invention is more capable of promoting the healing of diabetic wounds. In the healing process of diabetic wounds, the expression levels of the inflammatory factors IL-6 and IL-1 beta of the group are 0.53 times and 0.50 times of those of the blank control group at the 10 th day.
Example 3
Polyphosphazene (PPBA) 30mg, tannic Acid (TA) 3mg and polyvinyl alcohol (PVA) 30mg were dissolved in 700. Mu.l, 300. Mu.l and 1000. Mu.l of deionized water, respectively, until completely dissolved.
Firstly, respectively and fully dissolving functional polyphosphazene PPBA containing phenylboronic acid groups and quaternary ammonium salt groups, tannic acid TA and polyvinyl alcohol PVA in deionized water to respectively obtain polyphosphazene PPBA solution, tannic acid TA solution and polyvinyl alcohol PVA solution; and then adding the polyphosphazene PPBA solution into the tannic acid TA solution, mixing and stirring to obtain the PPBA-TA nano conjugate, wherein the particle size of the PPBA-TA nano conjugate is 50-200 nm. And finally, adding the PPBA-TA nano conjugate into a polyvinyl alcohol PVA solution, and mixing and stirring to obtain the tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances. Wherein the mixing and stirring time is 30 minutes and the rotation speed is 1000rpm.
Will be in logarithmic growth phase at a 10. Mu.l concentration of 10 6 CFU of Escherichia coli ATCC 25922 bacterial suspension was dispersed on the hydrogel surface and cultured in a 37 ℃ incubator for 1h, 2h, 4h and 8h. After co-incubation, 1ml of PBS solution was added to the hydrogel surface and sonication was performed for 30 minutes. LB solid medium was spread with 100. Mu.l of the solution, and cultured overnight in a 37 ℃ incubator, and the number of colonies on the medium was counted.
0.4ml of the hydrogel provided by the invention and 30ml of DPPH free radical solution (0.1 mM) are incubated together at 37 ℃ in a dark place, and the DPPH free radical scavenging capacity of the PPBA-TA-PVA hydrogel at different times is measured through ultraviolet absorption intensity of 517 nm. 0.4ml of the hydrogel provided by the invention was co-incubated with 25ml of OH free radical solution (1 mM) at 37 ℃ in the dark, and a certain amount of the solution was mixed with an equal volume of TMB (10 mM, DMSO) for 10min at different times. The scavenging capacity of the PPBA-TA-PVA hydrogel to hydroxyl free radicals at different times is measured by 904nm ultraviolet absorption intensity.
1ml of the hydrogel provided by the invention and 50ml of OH free radical solution (1 mM) are incubated together at 37 ℃ in the dark, and the consumption of the hydrogel is observed at different times to determine the ROS response degradation capability of the hydrogel wound dressing.
The hydrogel provided by the invention is filled in the wound by taking a streptomycin-induced rat diabetic wound model as an object, the dressing is replaced periodically, and the healing condition of the wound is observed to determine the performance of the hydrogel wound dressing in promoting the healing of the diabetic wound.
In the healing process of the diabetic wound, the tissues around the wound are taken at 3 rd, 6 th and 10 th days respectively, the genes related to inflammatory factors IL-6 and IL-1 beta are subjected to fluorescence quantification pcr, and the performance of the hydrogel wound dressing in reducing the inflammation level of the wound is determined.
The results of this example are shown in fig. 11-15, fig. 11 shows the contact bacteriostatic performance of the obtained hydrogel on escherichia coli, and it can be seen from the figure that the gel material has excellent contact bacteriostatic performance. The bacteriostatic rate of the bacteria in 1 hour can reach 73.1 +/-4.6%, and the bacteriostatic rate in 8 hours can reach 99.4 +/-0.6%, so that the bacteria can be basically killed. FIGS. 12 and 13 show the scavenging performance of the obtained hydrogel for DPPH free radicals and OH free radicals, and it can be seen that the gel material has good ROS scavenging performance. It can scavenge 98.4 + -2.1% of DPPH free radicals in 70h, and can scavenge 81.1 + -4.9% of OH free radicals in 8h. FIG. 14 is a graph showing the ROS response degradation performance of the hydrogel, and it can be seen that the gel material degrades about 60.5. + -. 2.6% of the hydrogel in OH free radical solution for 96 h. FIG. 15 shows the healing of diabetic wounds treated with the gel material, and it can be seen from the figure that the wound healing rate of the hydrogel group is 93.1 + -2.6% on the 6 th day of wound healing, compared with the healing rate of the blank control group (44.0 + -4.4%), the invention is more capable of promoting the healing of diabetic wounds. In the healing process of diabetic wounds, the expression levels of inflammatory factors IL-6 and IL-1 beta of tissues around the wounds are taken on the 10 th day, and the inflammatory factors of the group are obviously less than 0.40 times and 0.76 times of those of the blank control group.

Claims (6)

1. A tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances is characterized in that a PPBA-TA nano conjugate containing phenylboronic acid groups and quaternary ammonium salt groups functionalized polyphosphazene PPBA and tannin TA is adopted as an anti-inflammatory and antibacterial component; the PPBA-TA nano conjugate and polyvinyl alcohol react to form ROS responsive borate bond to obtain the polyphosphazene-based hydrogel wound dressing with ROS responsive degradation performance.
2. The method for preparing the tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS-responsive properties according to claim 1, comprising the following steps:
firstly, respectively and fully dissolving functional polyphosphazene PPBA containing phenylboronic acid groups and quaternary ammonium salt groups, tannic acid TA and polyvinyl alcohol PVA in deionized water to respectively obtain polyphosphazene PPBA solution, tannic acid TA solution and polyvinyl alcohol PVA solution; and adding the polyphosphazene PPBA solution into the tannic acid TA solution, mixing and stirring to obtain a PPBA-TA nano conjugate, finally adding the PPBA-TA nano conjugate into a polyvinyl alcohol PVA solution, and mixing and stirring to obtain the tannic acid coupled polyphosphazene based hydrogel wound dressing with anti-inflammatory, antibacterial and ROS response performances.
3. The method of preparing a tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial, and ROS-responsive properties according to claim 2, wherein the method comprises the steps of: the functional polyphosphazene PPBA solution comprises, by mass, 10-30 parts of phenylboronic acid group and quaternary ammonium salt group-containing functional polyphosphazene PPBA, 1-3 parts of tannic acid TA, 10-30 parts of polyvinyl alcohol PVA, and the sum of deionized water of the three solutions is 1000-2000 parts.
4. The method of preparing a tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial, and ROS-responsive properties according to claim 2, wherein the method comprises the steps of: the mixing and stirring time is 10-30 minutes.
5. The method of preparing a tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial, and ROS-responsive properties according to claim 2, wherein the method comprises the steps of: the mixing and stirring speed is 500-1000 rpm.
6. The method of preparing a tannin-coupled polyphosphazene-based hydrogel wound dressing with anti-inflammatory, antibacterial, and ROS-responsive properties according to claim 2, wherein the method comprises the steps of: the particle size of the PPBA-TA nano conjugate is 50-200 nm.
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