An anti-inflammatory, antibacterial and ROS-responsive natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel and preparation method thereof
Through the development of natural polyphenol-coupled polyphosphazene hydrogel, the prevention problem of peritoneal adhesion after tendon injury was solved, and the rapid removal of free radicals and antibacterial effects were achieved, reducing the risk of peritoneal adhesion, and showing in vivo Good injectable and self-healing performance.
Patent Information
- Application Number
- CN202310319220.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-03-29
- Publication Date
- 2024-12-17
- Estimated Expiration
- 2043-03-29
AI Technical Summary
The prior art cannot effectively prevent the formation of peritoneal adhesions after tendon injury, and often lead to a vicious cycle of "adhesion-loosening-readhesion". It lacks effective anti-inflammatory and antibacterial materials, which affects the healing process.
Develop a natural polyphenol-coupled polyphosphazene hydrogel with anti-inflammatory, antibacterial and multi-stage ROS responsiveness, by coupling the phenylborate group with quaternary ammonium salts to natural polyphenols. A hydrogel with multi-stage ROS responsive borate bond was formed and combined with guar gum was prepared.
The hydrogel can quickly remove free radicals, has good antibacterial properties, inhibit bacterial growth, promote healing, reduce inflammation, reduce perinvolvular adhesion risks, and exhibit good injectable and self-healing properties in the body.
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Abstract
Description
Technical Field
[0001] The invention relates to a polyphosphazene-based anti-peritendon adhesion hydrogel belonging to the field of polymer materials, and specifically relates to a natural polyphenol-coupled polyphosphazene-based anti-peritendon adhesion hydrogel with anti-inflammatory, antibacterial and ROS responsive properties and a preparation method thereof. Background Art
[0002] After the tendon is injured or repaired, adhesion tissue is often formed. Peritubular adhesion is the most common complication after tendon injury. About 30% to 40% of patients with tendon injury will have adhesion between the tendon and surrounding tissues after treatment, causing pain and motor dysfunction, which brings a huge burden to the patient's life. At the same time, due to the lack of effective preventive measures in clinical practice, patients often fall into a vicious cycle of "adhesion-loosening-re-adhesion". Inflammation-related cytokines produced in the early acute inflammatory response of Achilles tendon injury are crucial to the formation of peritendinous adhesions. Relieving the level of inflammation in the early inflammatory stage is of great significance for preventing peritendinous adhesions. In addition, infection at the site of injury will further aggravate the inflammatory response. At present, the prevention and treatment methods for peritendinous adhesion mainly include drug therapy, application of physical barriers and rehabilitation training. Although these methods have certain effects, they cannot effectively prevent the formation of adhesions and even inhibit the healing of tendons to a certain extent. Therefore, reducing the level of inflammation in the injured area and effectively removing microorganisms are of great significance for preventing peritendinous adhesions.
[0003] The ideal anti-peritendon adhesion material should have the following characteristics: 1) have good ROS scavenging performance, reduce local inflammation of the damaged Achilles tendon, and shorten the inflammatory stage; 2) have good anti-infection properties; 3) have good compatibility with human tissues and be biodegradable; 4) promote Achilles tendon healing. Summary of the invention
[0004] In order to solve the deficiencies of the prior art, the present invention provides a method for preparing a natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel with anti-inflammatory, antibacterial and multi-level ROS response properties. The hydrogel has the ability to quickly remove 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and ·OH free radicals, good injectability and self-healing properties, and has good contact antibacterial effects on Gram-negative bacteria (E. coli) and Gram-positive bacteria (S. aureus).
[0005] The technical solution adopted by the present invention is:
[0006] 1. A natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel with anti-inflammatory, antibacterial and ROS-responsive properties
[0007] The reactive oxygen species (ROS)-responsive drug-coupled polymer formed between polyphosphazene PZBA functionalized with phenylboronic acid groups and quaternary ammonium salt groups and natural polyphenols was used as an anti-inflammatory and antibacterial component. The reactive oxygen species-responsive drug-coupled polymer was then reacted with biodegradable guar gum (GG) to form a ROS-responsive borate ester bond to obtain a biodegradable polyphosphazene-based anti-tendon adhesion hydrogel with multi-level ROS responsiveness.
[0008] The natural polyphenol is one of tannic acid (TA), epigallocatechin gallate (EGC) and epigallocatechin gallate (EGCG).
[0009] The polyphosphazene PZBA containing phenylboronic acid groups and quaternary ammonium salt functionalization is specifically poly[N,N-dimethyl-aminoethyl-p-methylphenylboronic acid ammonium bromide)(N,N-dimethylethylenediamine-ethyl acetate ammonium bromide)]phosphazene.
[0010] The grafting rate of the boric acid groups of the polyphosphazene PZBA functionalized with phenylboronic acid groups and quaternary ammonium salt is 15-30%.
[0011] 2. Preparation method of natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel with anti-inflammatory, antibacterial and ROS-responsive properties
[0012] After polyphosphazene PZBA functionalized with phenylboronic acid groups and quaternary ammonium salt groups, natural polyphenols and guar gum are fully dissolved in deionized water, PZBA solution, natural polyphenol solution and guar gum solution are obtained respectively; then the natural polyphenol solution is added to the PZBA solution and mixed and stirred to obtain a reactive oxygen species responsive drug-coupled polymer; then the reactive oxygen species responsive drug-coupled polymer is added to the guar gum solution and mixed and stirred to obtain a multi-level ROS responsive and biodegradable polyphosphazene-based anti-tendon periadhesion hydrogel.
[0013] The natural polyphenol is one of tannic acid, epigallocatechin gallate and epigallocatechin gallate.
[0014] In terms of mass fractions, the polyphosphazene PZBA functionalized with phenylboronic acid groups and quaternary ammonium salt groups is 10 to 30 parts, the natural polyphenol is 1 to 3 parts, the guar gum is 10 to 30 parts, the sum of the deionized water of the PZBA solution, the natural polyphenol solution and the guar gum solution is 1000 to 2000 parts, and the ratio of the deionized water in the PZBA solution, the natural polyphenol solution and the guar gum solution is equal to the mass ratio of the polyphosphazene PZBA functionalized with phenylboronic acid groups and quaternary ammonium salt groups, the natural polyphenol and the guar gum.
[0015] The mixing and stirring time is 10 to 30 minutes.
[0016] The shape of the multi-level ROS responsive and biodegradable polyphosphazene-based anti-peritendon adhesion hydrogel is arbitrary.
[0017] The hydrogel provided by the present invention has a good contact antibacterial effect on both Gram-negative and Gram-positive bacteria, and can basically inhibit the growth of all bacteria in a short period of time.
[0018] In the hydrogel provided by the present invention, the active oxygen-responsive borate bonds serve as cross-linking chemical bonds of the hydrogel network and as coupling chemical bonds between natural polyphenols (TA, EGC or EGCG) and PZBA, so that the hydrogel has multi-level ROS response performance.
[0019] The hydrogel provided by the present invention can quickly remove 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and ·OH free radicals.
[0020] The network skeleton of the hydrogel provided by the present invention contains high-density quaternary ammonium salt groups, which enables the hydrogel to adsorb negatively charged bacteria through electrostatic interaction, hydrogen bonding force, and hydrophobic binding between surfactant molecules and protein molecules, resulting in inhibition of bacterial growth and death, thereby providing efficient passive contact antibacterial ability.
[0021] The hydrogel provided by the present invention uses dynamic borate bonds as cross-linking chemical bonds of the hydrogel, so that the hydrogel has good injectability and self-healing properties.
[0022] The beneficial effects of the present invention are as follows:
[0023] 1. The hydrogel provided by the present invention has inherent antibacterial properties and has a highly effective inhibitory effect on both Escherichia coli and Staphylococcus aureus. The hydrogel skeleton with cationic quaternary ammonium salt functional groups does not have the problem of failure, so that the hydrogel will not have the time-effectiveness problem caused by the release time limit of the antibacterial component during use, avoiding the use of antibiotics, slowing down the emergence of multidrug-resistant bacteria, and the antibacterial performance is effective for a long time.
[0024] 2. The hydrogel provided by the present invention has good injectability, has in-situ formability during surgery, is convenient for minimally invasive surgery in vivo, and has small scars, etc. It can reduce the pain of patients and improve their compliance.
[0025] 3. The anti-inflammatory drug coupled hydrogel provided by the present invention can not only prevent the problem of drug burst release, but also release natural polyphenols (TA, EGC and EGCG) on demand according to the ROS level. The phenolic hydroxyl groups in TA, EGC and EGCG can combine with free radicals to form an o-benzoquinone structure, thereby playing the role of free radical scavenging. Thus, the ROS around the Achilles tendon is maintained at a reasonable concentration. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] Figure 1 This is the 4-hour contact inhibition rate of the hydrogel prepared in Example 1 against Escherichia coli and Staphylococcus aureus.
[0027] Figure 2 The scavenging efficiency of the hydrogel prepared in Example 1 on DPPH free radicals.
[0028] Figure 3 The scavenging efficiency of the hydrogel prepared in Example 1 on OH free radicals.
[0029] Figure 4 The hydrogel prepared in Example 1 was used to treat the peritendinous adhesion level of Achilles tendon contusion 7 and 14 days after injury.
[0030] Figure 5 The hydrogel prepared in Example 1 was used to treat the adhesion level around the tendon 7 and 14 days after Achilles tendon rupture.
[0031] Figure 6 This is the 4-hour contact inhibition rate of the hydrogel prepared in Example 2 against Escherichia coli and Staphylococcus aureus.
[0032] Figure 7 The scavenging efficiency of the hydrogel prepared in Example 2 on DPPH free radicals.
[0033] Figure 8 This is the scavenging efficiency of the hydrogel prepared in Example 2 on OH free radicals.
[0034] Fig. 9 The hydrogel prepared in Example 2 was used to treat the peritendinous adhesion level of Achilles tendon contusion 7 and 14 days after injury.
[0035] Fig.10 The hydrogel prepared in Example 2 was used to treat the adhesion level around the tendon 7 and 14 days after Achilles tendon rupture.
[0036] Fig.11 This is the 4-hour contact inhibition rate of the hydrogel prepared in Example 3 against Escherichia coli and Staphylococcus aureus.
[0037] Fig.12 The scavenging efficiency of the hydrogel prepared in Example 3 on DPPH free radicals.
[0038] Fig.13 This is the scavenging efficiency of the hydrogel prepared in Example 3 on OH free radicals.
[0039] Fig.14 The hydrogel prepared in Example 3 was used to treat the peritendinous adhesion level of Achilles tendon contusion 7 and 14 days after injury.
[0040] Fig.15 The hydrogel prepared in Example 3 was used to treat the adhesion level around the tendon 7 and 14 days after Achilles tendon rupture. DETAILED DESCRIPTION
[0041] The present invention is described in more detail below in conjunction with specific embodiments, but the embodiments of the present invention are not limited thereto.
[0042] Embodiments of the present invention are as follows:
[0043] The polyphosphazene PZBA containing phenylboronic acid groups functionalized with quaternary ammonium salts is specifically poly[N,N-dimethyl-aminoethyl-p-methylphenylboronic acid ammonium bromide)(N,N-dimethylethylenediamine-ethyl acetate ammonium bromide)]phosphazene. Tannic acid (TA), epigallocatechin gallate (EGC) and epigallocatechin gallate (EGCG).
[0044] Example 1
[0045] Dissolve 30 mg of polyphosphazene PZBA, 1 mg of tannic acid (TA) and 30 mg of guar gum (GG) in 900 μl, 100 μl and 1000 μl of deionized water respectively until they are completely dissolved.
[0046] First, polyphosphazene PZBA, tannic acid (TA) and guar gum (GG) were dissolved in deionized water to obtain polyphosphazene PZBA solution, tannic acid (TA) solution and guar gum (GG) solution respectively; then the tannic acid solution was added dropwise to the polyphosphazene PZBA solution, and the mixture was mixed and stirred to obtain a PZBA-TA drug-coupled polymer. Finally, the PZBA-TA drug-coupled polymer was added to the guar gum (GG) solution, and the mixture was mixed and stirred to obtain a natural polyphenol-coupled polyphosphazene-based anti-tendon peritendon adhesion hydrogel PZBA-TA-GG with anti-inflammatory, antibacterial and multi-level ROS response properties. The mixing and stirring time was 10 minutes and the rotation speed was 500 rpm.
[0047] The growth phase will be logarithmic, and the concentration of 10μl is 10 6 The suspension of CFU of Escherichia coli and Staphylococcus aureus was dispersed on the surface of the hydrogel and cultured in a constant temperature incubator at 37°C for 4 hours. After co-culture, 1 ml of PBS solution was added to the surface of the hydrogel and ultrasonicated for 30 minutes. 100 μl of the solution was applied to LB solid medium and cultured overnight in a constant temperature incubator at 37°C, and the number of colonies on the medium was counted.
[0048] 0.8 ml of the hydrogel provided by the present invention was co-incubated with 30 ml of DPPH free radical solution (0.1 mM) at 37°C in the dark, and the scavenging ability of PPBA-TA-PVA hydrogel on DPPH free radicals at different times was determined by the 517 nm ultraviolet absorption intensity. 0.8 ml of the hydrogel provided by the present invention was co-incubated with 25 ml of OH free radical solution (1 mM) at 37°C in the dark, and a certain amount of the solution was taken at different times and mixed with an equal volume of TMB (10 mM, DMSO) for 10 minutes. The scavenging ability of PPBA-TA-PVA hydrogel on hydroxyl free radicals at different times was determined by the 904 nm ultraviolet absorption intensity.
[0049] The rat Achilles tendon contusion and Achilles tendon rupture model was used as the object. The hydrogel provided by the present invention was used to fill the contused Achilles tendon peritendinous area or the peritendinous area of the ruptured Achilles tendon after suture anastomosis, and then the wound was closed. On the 7th and 14th days, the Achilles tendon peritendinous adhesion was observed and surgically graded to determine the effect of the hydrogel in preventing Achilles tendon peritendinous adhesion.
[0050] The results of this example are as follows Figures 1 to 5 As shown, Figure 1 The PZBA-TA-GG hydrogel has excellent contact antibacterial properties against Escherichia coli and Staphylococcus aureus. The antibacterial rates of the PZBA-TA-GG hydrogel against Escherichia coli and Staphylococcus aureus in 4 hours can reach 99.2±0.7% and 96.4±0.7%. Figure 2 and Figure 3 The scavenging performance of the obtained hydrogel on DPPH free radicals and ·OH free radicals. It can be seen from the figure that the gel material has good ROS scavenging performance. It can scavenged 57.9±2.9% of DPPH free radicals and 51.3±4.2% of ·OH free radicals within 6 hours. Figure 4 The degree of peritendinous adhesion was graded 7 and 14 days after the hydrogel material was used to treat Achilles tendon contusion injury. As can be seen from the figure, the peritendinous adhesion grade was 3 after 7 days of treatment with the hydrogel, and the peritendinous adhesion grade was 2 after 14 days of treatment, which can effectively prevent the occurrence of peritendinous adhesion in Achilles tendon contusion injury. Figure 5 The degree of peritendinous adhesion was graded 7 and 14 days after the hydrogel material was used to treat Achilles tendon rupture injury. As can be seen from the figure, the peritendinous adhesion grade was 4 after 7 days of hydrogel treatment and the peritendinous adhesion grade was 3 after 14 days of treatment, which can effectively prevent the occurrence of peritendinous adhesion in Achilles tendon rupture injury.
[0051] Example 2
[0052] 30 mg of polyphosphazene (PZBA), 1 mg of epigallocatechin gallate (EGC) and 30 mg of guar gum (GG) were dissolved in 900 μl, 100 μl and 1000 μl of deionized water respectively until they were completely dissolved.
[0053] First, polyphosphazene PZBA, gallic acid (EGC) and guar gum (GG) were dissolved in deionized water to obtain polyphosphazene PZBA solution, gallic acid (EGC) solution and guar gum (GG) solution respectively; then tannic acid solution was added dropwise to the polyphosphazene PZBA solution, mixed and stirred to obtain PZBA-EGC drug-coupled polymer. Finally, the PZBA-EGC drug-coupled polymer was added to the guar gum (GG) solution, mixed and stirred to obtain a natural polyphenol-coupled polyphosphazene-based anti-tendon peritendon adhesion hydrogel PZBA-EGC-GG with anti-inflammatory, antibacterial and multi-level ROS response properties. The mixing and stirring time was 10 minutes and the rotation speed was 500 rpm.
[0054] The growth phase will be logarithmic, and the concentration of 10μl is 10 6 The suspension of CFU of Escherichia coli and Staphylococcus aureus was dispersed on the surface of the hydrogel and cultured in a constant temperature incubator at 37°C for 4 hours. After co-culture, 1 ml of PBS solution was added to the surface of the hydrogel and ultrasonicated for 30 minutes. 100 μl of the solution was applied to LB solid medium and cultured overnight in a constant temperature incubator at 37°C, and the number of colonies on the medium was counted.
[0055] 0.8 ml of the hydrogel provided by the present invention was co-incubated with 30 ml of DPPH free radical solution (0.1 mM) at 37°C in the dark, and the scavenging ability of PPBA-TA-PVA hydrogel on DPPH free radicals at different times was determined by the 517 nm ultraviolet absorption intensity. 0.8 ml of the hydrogel provided by the present invention was co-incubated with 25 ml of OH free radical solution (1 mM) at 37°C in the dark, and a certain amount of the solution was taken at different times and mixed with an equal volume of TMB (10 mM, DMSO) for 10 minutes. The scavenging ability of PPBA-EGC-PVA hydrogel on hydroxyl free radicals at different times was determined by the 904 nm ultraviolet absorption intensity.
[0056] The rat Achilles tendon contusion and Achilles tendon rupture model was used as the object. The hydrogel provided by the present invention was used to fill the contused Achilles tendon peritendinous area or the peritendinous area of the ruptured Achilles tendon after suture anastomosis, and then the wound was closed. On the 7th and 14th days, the Achilles tendon peritendinous adhesion was observed and surgically graded to determine the effect of the hydrogel in preventing Achilles tendon peritendinous adhesion.
[0057] The results of this example are as follows Figures 6 to 10 As shown, Figure 6The PZBA-EGC-GG hydrogel has excellent contact antibacterial properties against Escherichia coli and Staphylococcus aureus. The antibacterial rates of the PZBA-TA-GG hydrogel against Escherichia coli and Staphylococcus aureus in 4 hours can reach 98.9±0.5% and 97.3±1.1%. Figure 7 and Figure 8 The scavenging performance of the obtained hydrogel on DPPH free radicals and ·OH free radicals. It can be seen from the figure that the gel material has good ROS scavenging performance. It can scavenged 95.6±0.7% of DPPH free radicals and 94.8±4.9% of ·OH free radicals within 6 hours. Fig. 9 The degree of peritendinous adhesion was graded 7 and 14 days after the hydrogel material was used to treat Achilles tendon contusion injury. As can be seen from the figure, the peritendinous adhesion grade was 3 after 7 days of treatment with the hydrogel, and the peritendinous adhesion grade was 2 after 14 days of treatment, which can effectively prevent the occurrence of peritendinous adhesion in Achilles tendon contusion injury. Fig.10 The degree of peritendinous adhesion was graded 7 and 14 days after the hydrogel material was used to treat Achilles tendon rupture injury. As can be seen from the figure, the peritendinous adhesion grade was 3 after 7 days of hydrogel treatment and the peritendinous adhesion grade was 3 after 14 days of treatment, which can effectively prevent the occurrence of peritendinous adhesion in Achilles tendon rupture injury.
[0058] Example 3
[0059] Dissolve 30 mg of polyphosphazene (PZBA), 1 mg of epigallocatechin gallate (EGCG), and 30 mg of guar gum (GG) in 900 μl, 100 μl, and 1000 μl of deionized water, respectively, until they are completely dissolved.
[0060] First, polyphosphazene PZBA, epigallocatechin gallate (EGCG) and guar gum (GG) were dissolved in deionized water to obtain polyphosphazene PZBA solution, epigallocatechin gallate (EGC) solution and guar gum (GG) solution respectively; then tannic acid solution was added dropwise to the polyphosphazene PZBA solution, mixed and stirred to obtain PZBA-EGCG drug-coupled polymer. Finally, the PZBA-EGC drug-coupled polymer was added to the guar gum (GG) solution, mixed and stirred to obtain a natural polyphenol-coupled polyphosphazene-based anti-tendon periadhesion hydrogel PZBA-EGCG-GG with anti-inflammatory, antibacterial and multi-level ROS response properties. The mixing and stirring time was 10 minutes and the rotation speed was 500 rpm.
[0061] The growth phase will be logarithmic, and the concentration of 10μl is 10 6The suspension of CFU of Escherichia coli and Staphylococcus aureus was dispersed on the surface of the hydrogel and cultured in a constant temperature incubator at 37°C for 4 hours. After co-culture, 1 ml of PBS solution was added to the surface of the hydrogel and ultrasonicated for 30 minutes. 100 μl of the solution was applied to LB solid medium and cultured overnight in a constant temperature incubator at 37°C, and the number of colonies on the medium was counted.
[0062] 0.8 ml of the hydrogel provided by the present invention was co-incubated with 30 ml of DPPH free radical solution (0.1 mM) at 37°C in the dark, and the scavenging ability of PPBA-EGC-PVA hydrogel on DPPH free radicals at different times was determined by the 517 nm ultraviolet absorption intensity. 0.8 ml of the hydrogel provided by the present invention was co-incubated with 25 ml of OH free radical solution (1 mM) at 37°C in the dark, and a certain amount of the solution was taken at different times and mixed with an equal volume of TMB (10 mM, DMSO) for 10 minutes. The scavenging ability of PPBA-EGCG-PVA hydrogel on hydroxyl free radicals at different times was determined by the 904 nm ultraviolet absorption intensity.
[0063] The rat Achilles tendon contusion and Achilles tendon rupture model was used as the object. The hydrogel provided by the present invention was used to fill the contused Achilles tendon peritendinous area or the peritendinous area of the ruptured Achilles tendon after suture anastomosis, and then the wound was closed. On the 7th and 14th days, the Achilles tendon peritendinous adhesion was observed and surgically graded to determine the effect of the hydrogel in preventing Achilles tendon peritendinous adhesion.
[0064] The results of this example are as follows Figures 11 to 15 As shown, Fig.11 The PZBA-EGCG-GG hydrogel has excellent contact antibacterial properties against Escherichia coli and Staphylococcus aureus. The antibacterial rates of the PZBA-EGCG-GG hydrogel against Escherichia coli and Staphylococcus aureus in 4 hours can reach 98.9±0.5% and 97.3±1.1%. Fig.12 and Fig.13 The scavenging performance of the obtained hydrogel on DPPH free radicals and ·OH free radicals. It can be seen from the figure that the gel material has good ROS scavenging performance. It can scavenged 94.9±2.2% of DPPH free radicals and 97.3±1.3% of ·OH free radicals within 6 hours. Fig.14 The degree of peritendinous adhesion was graded 7 and 14 days after the hydrogel material was used to treat Achilles tendon contusion injury. As can be seen from the figure, the peritendinous adhesion grade was 3 after 7 days of hydrogel treatment and 1 after 14 days of treatment, which can effectively prevent the occurrence of peritendinous adhesion in Achilles tendon contusion injury. Fig.15The degree of peritendinous adhesion was graded 7 and 14 days after the hydrogel material was used to treat Achilles tendon rupture injury. As can be seen from the figure, the peritendinous adhesion grade was 3 after 7 days of hydrogel treatment and the peritendinous adhesion grade was 2 after 14 days of treatment, which can effectively prevent the occurrence of peritendinous adhesion in Achilles tendon rupture injury.
Claims
1. A natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel with anti-inflammatory, antibacterial and ROS-responsive properties, characterized in that: The reactive oxygen responsive drug-coupled polymer formed between polyphosphazene PZBA functionalized with phenylboronic acid groups and quaternary ammonium salt groups and natural polyphenols was used as an anti-inflammatory and antibacterial component. The reactive oxygen responsive drug-coupled polymer was then combined with biodegradable guar gum to form a ROS-responsive boronate ester bond to obtain a biodegradable polyphosphazene-based anti-tendon adhesion hydrogel with multi-level ROS responsiveness. The natural polyphenol is one of epigallocatechin gallate and epigallocatechin gallate; The polyphosphazene PZBA containing phenylboronic acid groups and quaternary ammonium salt functionalization is specifically poly[(N,N-dimethyl-aminoethyl-p-methylphenylboronic acid ammonium bromide)(N,N-dimethylethylenediamine-ethyl acetate ammonium bromide)]phosphazene.
2. The natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel with anti-inflammatory, antibacterial and ROS-responsive properties according to claim 1, characterized in that: The grafting rate of the boric acid groups of the polyphosphazene PZBA functionalized with phenylboronic acid groups and quaternary ammonium salts is 15-30%.
3. The method for preparing a natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel with anti-inflammatory, antibacterial and ROS-responsive properties according to claim 1, characterized in that: The following steps are involved: After polyphosphazene PZBA functionalized with phenylboronic acid groups and quaternary ammonium salt groups, natural polyphenols and guar gum are fully dissolved in deionized water, PZBA solution, natural polyphenol solution and guar gum solution are obtained respectively; then the natural polyphenol solution is added to the PZBA solution and mixed and stirred to obtain a reactive oxygen species responsive drug-coupled polymer; then the reactive oxygen species responsive drug-coupled polymer is added to the guar gum solution and mixed and stirred to obtain a multi-level ROS responsive and biodegradable polyphosphazene-based anti-tendon periadhesion hydrogel.
4. The method for preparing a natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel with anti-inflammatory, antibacterial and ROS-responsive properties according to claim 3, characterized in that: In parts by mass, the polyphosphazene PZBA functionalized with phenylboronic acid groups and quaternary ammonium salt groups is 10-30 parts, the natural polyphenol is 1-3 parts, the guar gum is 10-30 parts, and the sum of the deionized water of the PZBA solution, the natural polyphenol solution and the guar gum solution is 1000-2000 parts.
5. The method for preparing a natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel with anti-inflammatory, antibacterial and ROS-responsive properties according to claim 3, characterized in that: The mixing and stirring time is 10 to 30 minutes.
6. The method for preparing a natural polyphenol-coupled polyphosphazene-based anti-tendon adhesion hydrogel with anti-inflammatory, antibacterial and ROS-responsive properties according to claim 3, characterized in that: The shape of the multi-level ROS responsive and biodegradable polyphosphazene-based anti-peritendon adhesion hydrogel is arbitrary.