An injectable wound dressing with antibacterial and near-infrared response and a preparation method thereof

By disrupting bacterial cell membranes and utilizing near-infrared response to increase temperature through liquid dendritic macromolecular wound dressings, the problem of insufficient antibacterial properties of traditional dressings is solved, achieving efficient adhesion and antibacterial effect, suitable for rapid healing of pathological wounds.

CN116999611BActive Publication Date: 2025-12-26TSINGHUA SHENZHEN INTERNATIONAL GRADUATE SCHOOL +1
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Patent Information

Application Number
CN202310803007.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-07-03
Publication Date
2025-12-26
Estimated Expiration
2043-07-03

AI Technical Summary

Technical Problem

Existing wound dressings lack effective antibacterial properties and are difficult to adhere completely to the skin, affecting the treatment effect, especially when dealing with pathological wounds, making it difficult to control infection.

Method used

This liquid dendritic macromolecular wound dressing disrupts bacterial cell membranes by grafting trimethylammonium chloride and utilizes dopa-iron metal chelates to respond to near-infrared light and raise the local temperature. Combined with a cross-linking agent, it forms an injectable hydrogel with excellent antibacterial and near-infrared responsive properties.

Benefits of technology

It enables convenient use of wound dressings, ensures complete skin adhesion, possesses highly effective antibacterial properties, reduces the risk of reinfection, and has good biocompatibility and adjustable mechanical strength, making it suitable for near-infrared responsive materials and antibacterial coatings for surgical instruments.

✦ Generated by Eureka AI based on patent content.

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Abstract

The application discloses an injectable wound dressing with antibacterial and near-infrared response and a preparation method thereof, and belongs to the biomedical field.The wound dressing is made of components including the following raw materials: dendritic macromolecules, a biomacromolecule solution, a trivalent iron ion solution and a crosslinking agent solution.The wound dressing can be quickly prepared by mixing the biomacromolecule solution, the trivalent iron ion solution, the dendritic macromolecules and EDC / NHS to generate metal chelation and amide reaction, and has antibacterial and near-infrared response;the wound dressing is in a liquid state before gelation, has injectability and good adhesion, and can completely adhere to damaged skin to realize the function of protecting the skin;the wound dressing also has the advantages of high biocompatibility, simple preparation method, easy availability of raw materials and easy scale production.
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Description

TECHNICAL FIELD

[0001] The present application relates to the biomedical field, in particular to an injectable wound dressing with antibacterial and near-infrared response and a preparation method thereof. BACKGROUND

[0002] Penicillin antibiotics invented in the early 20th century is the greatest invention of mankind against infectious diseases. Today, mankind has been completely dependent on various kinds of antibiotics including quinolone antibiotics, beta-lactam antibiotics, macrolides, aminoglycosides, etc. However, the abuse of antibiotics has seriously threatened human health and thus led to the production of many drug-resistant bacteria. The number of deaths caused by infectious diseases worldwide each year has exceeded 7 million, but there is no effective method to alleviate this problem. Using non-antibiotics to solve the bacterial infections encountered in clinical practice has gradually become a research hotspot. Especially in the face of pathological wound infection (diabetic foot, varicose veins of lower extremities, etc.), the use of antibacterial wound dressings on the basis of disease control is the latest therapy to solve this problem.

[0003] At present, most of the wound dressings used in clinical practice use hydrogels to maintain the wet state of the wound to promote healing and repair, and do not have effective antibacterial function. In addition, most wound dressings are in the form of sheets or bandages, which are difficult to completely adhere to the skin and affect the final therapeutic effect. Therefore, it is urgent to develop a wound dressing with excellent antibacterial performance and convenient use to solve this clinical problem. SUMMARY

[0004] The present application aims to overcome the shortcomings of traditional wound dressings that do not have excellent antibacterial performance and are difficult to use, and provides an injectable wound dressing with antibacterial and near-infrared response and a preparation method thereof. The wound dressing of the present application is a liquid dendritic macromolecule grafted with a large number of trimethylammonium chloride, which can penetrate into the cell membrane of bacteria and destroy its structure to achieve excellent antibacterial performance. In addition, the wound dressing contains a dopa-iron metal chelate bond, which has excellent near-infrared response performance, and can enhance the local antibacterial ability of the wound dressing by external irradiation of near-infrared light to improve the local temperature.

[0005] The present application first provides a wound dressing made of components including the following raw materials: dendritic macromolecule, biological macromolecule solution, trivalent iron ion solution and crosslinking agent solution;

[0006] The volume fraction of the dendritic macromolecule is 0.01% to 20% based on the total volume of the wound dressing; the volume fraction of the biological macromolecule solution is 1% to 60%; the volume fraction of the trivalent iron ion solution is 0.01% to 20%; the volume fraction of the crosslinking agent solution is 0.1% to 50%; and the balance is water or buffer;

[0007] The concentration of the biological macromolecule solution is 0.005-0.5 g / mL;

[0008] The concentration of the ferric ion solution is 10-500 mM; specifically, 50 mM;

[0009] The concentration of the crosslinking agent solution is 10-100 mg / mL; specifically, 100 mg / mL.

[0010] Preferably, the volume of the dendritic macromolecule is 1%-10% of the total volume of the wound dressing, more preferably 2.5%-5%; the volume fraction of the biological macromolecule solution is 30%-60%, more preferably 50%; the volume fraction of the ferric ion solution is 1%-20%, preferably 5%-15%, more preferably 10%; and the volume fraction of the crosslinking agent solution is 20%-40%, more preferably 30%.

[0011] In the above wound dressing, the buffer is dilute hydrochloric acid buffer, phosphate buffer, phosphate buffered saline, Tris-hydrochloric acid buffer, glycine-hydrochloric acid buffer, disodium hydrogen phosphate-sodium citrate buffer, citric acid-sodium hydroxide-hydrochloric acid buffer, citric acid-sodium citrate buffer, disodium hydrogen phosphate-potassium dihydrogen phosphate buffer, potassium dihydrogen phosphate-sodium hydroxide buffer, boric acid-borax buffer, borax-sodium hydroxide buffer, or sodium carbonate-sodium bicarbonate buffer.

[0012] In the above wound dressing, the biological macromolecule is any one of gelatin, chitosan, silk fibroin, heparin, sodium alginate, albumin, cellulose, dextran, chondroitin sulfate, polypeptide, and a macromolecule formed by modification of these biological macromolecules; specifically, gelatin and chitosan; more specifically, the mass ratio of the gelatin and chitosan is 10:1; and the gelatin is specifically pigskin gelatin.

[0013] The solvent of the biological macromolecule solution is water.

[0014] The biological macromolecule solution further includes an auxiliary solvent for assisting the dissolution of the biological macromolecule; specifically, the auxiliary solvent is an acid; more specifically, hydrochloric acid or aqueous glacial acetic acid.

[0015] In the above wound dressing, the biological macromolecule is gelatin and chitosan; and in the biological macromolecule solution, the concentration of the gelatin is 0.2 g / mL, and the concentration of the chitosan is 0.02 g / mL.

[0016] The crosslinking agent is any one of the following:

[0017] 1) 1-ethyl-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide ester (NHS);

[0018] Specifically, the mass ratio of the 1-ethyl-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide ester (NHS) is 1:1;

[0019] 2) macromolecules modified by 1-ethyl-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide ester; the macromolecules are biological macromolecules with active amino groups, such as chitosan, gelatin, hyaluronic acid, and chondroitin sulfate, etc.;

[0020] The solvent of the ferric ion solution and the crosslinking agent solution is water.

[0021] The ferric ion solution is a ferric chloride solution.

[0022] The above-mentioned wound dressing is any one of the following:

[0023] (1) the volume fraction of the dendritic macromolecule is 2.5 or 5% based on the total volume of the wound dressing; the volume fraction of the biological macromolecule solution is 50%; the volume fraction of the ferric ion solution is 10%; the volume fraction of the crosslinking agent solution is 30%; the balance is water or buffer; the biological macromolecule solution is a mixed solution containing 0.2 g / mL of gelatin and 0.02 g / mL of chitosan; the ferric ion solution is a ferric chloride solution with a concentration of 50 mM; the crosslinking agent solution is a mixed solution of 1-ethyl-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide ester (NHS) with a concentration of 50 mg / mL respectively;

[0024] (2) the volume fraction of the dendritic macromolecule is 2.5 or 5% based on the total volume of the wound dressing; the volume fraction of the gelatin solution is 25%; the concentration of the chitosan solution is 25%; the volume fraction of the ferric ion solution is 10%; the volume fraction of the crosslinking agent solution is 30%; the balance is water or buffer; the concentration of the gelatin solution is 0.2 g / mL; the concentration of the chitosan solution is 0.02 g / mL; the ferric ion solution is a ferric chloride solution with a concentration of 50 mM; the crosslinking agent solution is a mixed solution of 1-ethyl-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide ester (NHS) with a concentration of 50 mg / mL respectively.

[0025] In the above-mentioned wound dressing, the dendritic macromolecule is prepared by a method comprising the following steps:

[0026] (1) synthesizing a primary dendrimer by polymerization reaction of a multi-armed olefin ester and / or ether, polyethylene glycol diacrylate and dopamine;

[0027] (2) synthesizing a dendrimer by reacting the primary dendrimer with allyl ammonium again.

[0028] In the above wound dressing, the multi-armed olefin ester and / or ether is at least one of pentaerythritol triacrylate, pentaerythritol tetraacrylate, polydipentaerythritol hexaacrylate and pentaerythritol triallyl ether;

[0029] The structural formulae of the pentaerythritol triacrylate, pentaerythritol tetraacrylate, polydipentaerythritol hexaacrylate and pentaerythritol triallyl ether are respectively shown in formula I, formula II, formula III and formula IV;

[0030]

[0031] The polyethylene glycol diacrylate can be of different molecular weights, and its structural formula is shown in formula V, wherein n is 50-1,000,000;

[0032]

[0033] The dopamine is at least one of hydrochloric acid dopamine, carbidopa, droxidopa, levodopa, levodopa D3, L-methyldopa hydrate, levodopa methyl hydrochloride, 6-hydroxydopamine hydrobromide, 6-hydroxy-DL-dopa, 5-hydroxydopamine hydrochloride and 6-hydroxydopamine hydrochloride;

[0034] The allyl ammonium is at least one of acryloyloxyethyl trimethyl ammonium chloride, 2-methacryloyloxyethyl phosphocholine, [2-(methacryloyloxy)ethyl] trimethyl ammonium chloride, [2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide and (3-acrylamidopropyl) trimethyl ammonium chloride.

[0035] In the above wound dressing, the molar ratio of the multi-armed olefin ester and / or ether, polyethylene glycol diacrylate, dopamine and allyl ammonium is 1:1-10:1-10:1-10.

[0036] In the above method for preparing the dendrimer, in step (1), the polymerization reaction is carried out in an inert atmosphere;

[0037] The polymerization reaction is carried out in an organic solvent; specifically, the organic solvent is dimethyl sulfoxide;

[0038] The temperature of the polymerization reaction is 40-90°C; the time is 0.5-2h; and the polymerization reaction is carried out in the dark;

[0039] In step (2), the reaction between the first dendrimer and allyl ammonium is carried out in an inert atmosphere; the reaction temperature is 40-90 DEG C; the reaction time is 0.5-2 h; and the reaction is carried out in the dark.

[0040] The application also provides a preparation method of the wound dressing, comprising the following steps:

[0041] The biomacromolecule, the ferric ion and the crosslinking agent are respectively prepared into solutions, which are then mixed with the dendrimer and stirred to obtain the wound dressing.

[0042] Finally, the application provides a wound dressing kit comprising the wound dressing and the near-infrared device.

[0043] The application of the above-mentioned wound dressing or the wound dressing and the near-infrared device in the preparation of a product for treating wound healing also belongs to the protection scope of the application.

[0044] The emission wavelength of the above-mentioned near-infrared device is 808-1064 nm; and specifically, the emission wavelength can be 808 nm.

[0045] The wound dressing has antibacterial property; and the bacteria are at least one of Escherichia coli, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.

[0046] The wound dressing has near-infrared response, and the wavelength of the near-infrared response is 808-1064 nm; and specifically, the wavelength can be 808 nm.

[0047] The wound dressing has near-infrared response performance and injectability, and the near-infrared response can realize synergistic antibacterial effect of near-infrared, and the injectability can realize convenient use of the dressing.

[0048] Compared with the prior art, the application has the following advantages:

[0049] (1) The gelatin chitosan solution, the ferric ion solution, the dendrimer and EDC / NHS are mixed to realize metal chelation and amide reaction, so that the in-situ crosslinking hydrogel wound dressing with antibacterial property and near-infrared response can be quickly prepared;

[0050] (2) The wound dressing is in a liquid state before gelation, has injectability and good adhesion, and can completely adhere to damaged skin to realize the function of protecting the skin; the wound dressing also has the advantages of high biocompatibility, simple preparation method, easy availability of raw materials and easy scale production;

[0051] (3) The application adopts cation to destroy the bacterial cell membrane structure and synergistic antibacterial of photothermal response to effectively reduce the risk of wound re-infection; the photothermal mechanism of the wound dressing of the application is mainly the metal chelate bond formed by the dopamine group on the dendritic macromolecule and the trivalent iron ion;

[0052] (4) The wound dressing of the application has short gelation time, adjustable mechanical strength and self-healing performance; at the same time, it has injectability and can be used with a clinical syringe; in addition, the wound dressing of the application is a hydrogel, which can also be used for near-infrared responsive materials and surgical instrument antibacterial coating, etc.;

[0053] (5) The wound dressing of the application has good biocompatibility and antibacterial property, and can inhibit the growth of escherichia coli, staphylococcus aureus and methicillin-resistant staphylococcus aureus; it is a non-antibiotic antibacterial material. BRIEF DESCRIPTION OF DRAWINGS

[0054] Figure 1 The nuclear magnetic hydrogen spectrum of the dendritic macromolecule prepared for example 1 of the application;

[0055] Figure 2 The swelling degradation curve of the hydrogel prepared for example 2 of the application;

[0056] Figure 3 The adhesion diagram of the hydrogel prepared for example 3 of the application;

[0057] Figure 4 The injectability diagram of the hydrogel of example 4 of the application;

[0058] Figure 5 The near-infrared response diagram of the hydrogel of example 5 of the application;

[0059] Figure 6 The antibacterial diagram of the hydrogel of example 6 of the application;

[0060] Figure 7 The near-infrared synergistic antibacterial diagram of the hydrogel of example 7 of the application;

[0061] Figure 8 The biocompatibility diagram of the hydrogel of example 8 of the application. DETAILED DESCRIPTION

[0062] The application will be further described in detail below in conjunction with specific embodiments, and the given examples are only for illustrating the application, not for limiting the scope of the application.

[0063] The experimental methods in the following examples are all conventional methods, unless otherwise specified.

[0064] The quantitative test in the following examples is set up with three repeated experiments, and the average value is taken.

[0065] The materials, reagents, etc. used in the following examples can be obtained from commercial channels unless otherwise specified.

[0066] In the following examples, the collagenase is type I collagenase (enzyme activity is ≥125 U / mg), which is purchased from Merck, item number C909787;

[0067] The lysozyme is from chicken egg white (enzyme activity is 40000 U / mg), which is purchased from Merck, item number L812356;

[0068] The pH of the PBS solution is 7.2-7.4.

[0069] The E. coli used in the following examples is a gram-negative E. coli (E. coli), which is described in the literature (Artificial Nonenzymatic Antioxidant MXene Nanosheet-Anchored Injectable Hydrogel as a Mild Photothermal-Controlled Oxygen Release Platform for Diabetic Wound Healing, Yang Li et al., ACS Nano 2022, 16, 7486-7502), which is available to the public from Jiangsu University of Science and Technology, or with the consent of Jiangsu University of Science and Technology, from the applicant, and the above-mentioned biological materials are only used for repeating the relevant experiments of the present application and cannot be used for other purposes.

[0070] The S. aureus is a gram-positive S. aureus (Gram-positive Staphylococcus aureus, S. aureus), which is described in the literature (Artificial Nonenzymatic Antioxidant MXene Nanosheet-Anchored Injectable Hydrogel as a Mild Photothermal-Controlled Oxygen Release Platform for Diabetic Wound Healing, Yang Li et al., ACS Nano 2022, 16, 7486-7502), which is available to the public from Zhejiang University of Technology, or with the consent of Zhejiang University of Technology, from the applicant, and the above-mentioned biological materials are only used for repeating the relevant experiments of the present application and cannot be used for other purposes.

[0071] Methicillin-resistant Staphylococcus aureus (MRSA) is described in the literature (ECM-mimetic immunomodulatory hydrogel for methicillin-resistant Staphylococcus aureus-infected chronic skin wound healing, Wenshuai Liu et al., Liu et al., Sci. Adv. 8, eabn7006 (2022) 8 July 2022) available to the public from Zhejiang University of Technology, or with the consent of Zhejiang University of Technology from the applicant, the above biomaterials are only used for the relevant experiments of the present application, and cannot be used for other purposes.

[0072] Example 1, Preparation of dendrimer

[0073] Pentaerythritol triacrylate 5.96 g (20 mM), polyethylene glycol diacrylate 700 42 g (60 mM) and dopamine hydrochloride 7.6 g (40 mM) were weighed and dissolved in 80 g of DMSO (dimethyl sulfoxide), the pH of the solution was adjusted to 8.0 with triethylamine, and the reaction was carried out under nitrogen protection at 80°C for 2 h in the dark. After precipitation with methyl tert-butyl ether, an oily product was obtained. The oily product was dissolved again in 80 g of DMSO, and 9.7 g of acryloyloxyethyl trimethylammonium chloride (50 mM) was added, while the pH was adjusted to 8.0 with triethylamine, and the reaction was carried out under nitrogen protection at 80°C for 2 h in the dark. The reaction product was added dropwise to methyl tert-butyl ether to precipitate an oily product, which was dried in a vacuum oven at 37°C for 72 h to remove residual DMSO and methyl tert-butyl ether, and a dendrimer (HBP) was obtained.

[0074] Figure 1 The nuclear magnetic resonance spectrum of the dendrimer prepared above is shown in the figure. From the figure, the chemical shifts of the special functional groups of the dendrimer can be seen, including the trimethylammonium chloride group near 3.5 ppm and the benzene ring hydrogen near 6.9 ppm.

[0075] Example 2

[0076] 1. Preparation of hydrogel

[0077] A mixture solution 1 containing 20% (g / mL) gelatin and 2% (g / mL) chitosan was prepared by weighing 0.4 g of porcine skin gelatin (sigma, WXBD6827V type A, bloom 300) and 0.04 g of chitosan into 2 mL of 0.5% (v / v) glacial acetic acid solution; a mixture solution 2 was prepared by weighing 0.03244 g of ferric chloride into 4 mL of ultrapure water (concentration of 50 mM); a mixture solution 3 was prepared by weighing 50 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide (Macklin, N808856-5g) and 50 mg of N-hydroxysuccinimide ester (Macklin, H6231-25g) into 1 mL of ultrapure water (concentration of each substance was 50 mg / mL); 1 mL of the mixture solution 1, 200 μL of the mixture solution 2, 600 μL of the mixture solution 3, 100 μL of the dendrimer, and 100 μL of ultrapure water were mixed to form a hydrogel.

[0078] 2. Performance test

[0079] (1) The completely cured hydrogel in 1 was cut into small cubes of 300 mg, and then placed in 3 mL of PBS solution or PBS solution containing collagenase (5 U / mL) and lysozyme (200 U / mL), and incubated at 37°C on a shaker at 120 rpm and weighed periodically. The results are shown in Figure 2 , Figure 2 which is a plot of the swelling degradation curve of the hydrogel. It can be seen from Figure 2 that the hydrogel can be quickly degraded under the conditions of lysozyme and collagenase, which indicates that the hydrogel has biocompatibility.

[0080] (2) The mixed uncured hydrogel in 1 was evenly applied to the surface of the object to be adhered, and the adhesion performance was observed after complete curing. The results are shown in Figure 3 , which shows that the hydrogel has certain adhesion performance to various materials including wood, metal and plastic. Figure 3

[0081] (3) The mixed uncured hydrogel in 1 was sucked into a syringe and different black shapes were injected as needed, as shown in Figure 4 .

[0082] (4) The mixed uncured hydrogel in 1 was added to a glassware with a diameter of 1 cm to form a cylindrical hydrogel block. The hydrogel block was irradiated with near-infrared light (808 nm) of 0.5 W / cm 2 , and the temperature change of the hydrogel was monitored with a thermal imager, and the results are shown in Figure 5 , which shows that the hydrogel has a rapid photothermal heating capacity. Figure 5

[0083] ​​(5) The uncured hydrogel was added to a 48-well plate, then 10 uL of bacteria solution (E. coli, S. aureus or MRSA) with an optical density of 0.5 was added, and incubated at room temperature for 3 h, then 1 mL of PBS solution was added and mixed, 10 uL of the resulting diluted bacteria solution was spread on beef extract peptone solid medium and cultured in an incubator for 24 h (37°C, 5% CO2) to observe the changes in the colonies. The results are shown in Figure 6 It can be seen that HBP has a significant effect on inhibiting the growth of the three microorganisms. Figure 6

[0084] The compositions of the hydrogels in each group are as follows:

[0085] The PBS group is 2 mL of PBS solution;

[0086] The Gel / CS group: 500 uL of 20% gelatin solution + 500 uL of 2% chitosan solution + 600 uL of EDC / NHS + 400 uL of PBS solution;

[0087] The Fe 3+ group: 500 uL of 20% gelatin solution + 500 uL of 2% chitosan solution + 600 uL of EDC / NHS + 200 uL of 50 mM Fe 3+ + 200 uL of PBS;

[0088] The HBP group: 500 uL of 20% gelatin solution + 500 uL of 2% chitosan solution + 50 uL of HBP + 600 uL of EDC / NHS + 350 uL of PBS;

[0089] The HBP / Fe 3+ group-1: 500 uL of 20% gelatin solution + 500 uL of 2% chitosan solution + 50 uL of HBP + 200 uL of 50 mM Fe 3+ + 600 uL of EDC / NHS + 150 uL of PBS;

[0090] The HBP / Fe 3+ group-2: 500 uL of 20% gelatin solution + 500 uL of 2% chitosan solution + 100 uL of HBP + 200 uL of 50 mM Fe 3+ + 600 uL of EDC / NHS + 100 uL of PBS.

[0091] Preparation of 20% gelatin solution: 0.4 g of pigskin gelatin (sigma, WXBD6827V type A, bloom 300) was dissolved in 2 mL of 0.5% (v / v) glacial acetic acid solution to obtain.

[0092] ​Preparation of 2% chitosan solution: 0.04 g of chitosan was dissolved in 2 mL of 0.5% (v / v) glacial acetic acid solution.

[0093] EDC / NHS is a crosslinking agent solution, the same as in 1. Fe 3+ It is a ferric chloride solution, the same as in 1.

[0094] (6) Add the hydrogel to a 48-well plate and cure at room temperature for 3 minutes. Then add 10 μL of bacterial suspension (Escherichia coli, Staphylococcus aureus, or methicillin-resistant Staphylococcus aureus) with an optical density of 0.5. Use 0.5 W / cm². 2 Irradiate the culture with near-infrared light (wavelength 808 nm) for 20 min, then add 1 mL of PBS solution and mix well. Take 10 μL of the diluted bacterial solution and spread it on beef extract peptone solid medium and incubate in an incubator for 24 h (37℃, 5% CO2). Observe the colony changes. Results are shown below. Figure 7 ,Depend on Figure 7 It can be seen that when near-infrared light is introduced, the antibacterial effect of the hydrogel group is significantly improved.

[0095] The various hydrogels are composed of the following:

[0096] PBS group: 2 mL PBS solution;

[0097] Gel / CS group: 500μL 20% gelatin solution + 500μL 2% chitosan solution + 600μL EDC / NHS + 400μL PBS solution;

[0098] HBP / Fe 3+ Group 1: 500 μL 20% gelatin solution + 500 μL 2% chitosan solution + 50 μL HBP + 200 μL 50 mMFe 3+ +600μL EDC / NHS +150μL PBS;

[0099] HBP / Fe 3+ Group 2: 500 μL 20% gelatin solution + 500 μL 2% chitosan solution + 100 μL HBP + 200 μL 50 mM Fe 3+ +600μL EDC / NHS +100μL PBS.

[0100] EDC / NHS is a crosslinking agent solution, the same as in 1. Fe 3+ It is a ferric chloride solution, the same as in 1.

[0101] (7) Take 1 g of the cured hydrogel prepared in 1 and immerse it in 10 mL of DMEM-H medium (Solarbio, 11995) at 37°C for 24 h to obtain an extraction solution DMEM-H medium, and the control group is DMEM-H medium; add 100 μL of the above-mentioned extraction solution DMEM-H medium or DMEM-H medium to a 96-well plate in which NIH3T3 cells have been planted (10000 cells / well) in advance, and incubate in a carbon dioxide incubator at 37°C for 24 h, then add 10 μL of CCK-8 solution to each well, and continue to incubate for 30 min, and then test the absorbance at 450 nm, as shown in Figure 8 Figure 6, the hydrogel has no cytotoxicity. Each group of experiments is repeated 6 times, and the results are averaged.

Claims

1. A wound dressing, characterized by: The wound dressing is made of components including the following raw materials: dendritic macromolecule, biological macromolecule solution, ferric ion solution and crosslinking agent solution; The volume fraction of the dendritic macromolecule is 0.01%-20% based on the total volume of the wound dressing; the volume fraction of the biological macromolecule solution is 1%-60%; the volume fraction of the ferric ion solution is 0.01%-20%; the volume fraction of the crosslinking agent solution is 0.1%-50%; and the balance is water or buffer; The concentration of the biological macromolecule solution is 0.005-0.5 g / mL; The concentration of the ferric ion solution is 10-500 mM; The concentration of the crosslinking agent solution is 10-100 mg / mL; The biological macromolecule is gelatin and chitosan The crosslinking agent is 1-ethyl-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide ester; The dendritic macromolecule is prepared by a method including the following steps: (1) synthesizing a primary dendritic macromolecule by polymerization reaction of multi-armed olefin ester and / or ether, polyethylene glycol diacrylate and dopamine; (2) reacting the primary dendritic macromolecule with allyl ammonium to synthesize a dendritic macromolecule; The multi-armed olefin ester and / or ether is at least one of pentaerythritol triacrylate, pentaerythritol tetraacrylate, polydipentaerythritol hexaacrylate and pentaerythritol triallyl ether.

2. The wound dressing of claim 1, wherein: The volume fraction of the dendritic macromolecule is 1%-10% based on the total volume of the wound dressing; the volume fraction of the biological macromolecule solution is 30%-60%; the volume fraction of the ferric ion solution is 1%-20%; the volume fraction of the crosslinking agent solution is 20%-40%; and the balance is water or buffer.

3. The wound dressing of claim 1, wherein: The solvent of the biological macromolecule solution is water; The solvents of the ferric ion solution and the crosslinking agent solution are both water.

4. The wound dressing of claim 1, wherein: The dopamine is at least one of hydrochloric acid dopamine, carbidopa, droxidopa, levodopa, levodopa D3, L-methyldopa hydrate, levodopa hydrochloride methyl ester, 6-hydroxydopamine hydrobromide, 6-hydroxy-DL-dopamine, 5-hydroxydopamine hydrochloride and 6-hydroxydopamine hydrochloride; The allyl ammonium is at least one of acryloyloxyethyl trimethyl ammonium chloride, [2-(methacryloyloxy) ethyl] trimethyl ammonium chloride and (3-acrylamidopropyl) trimethyl ammonium chloride.

5. The wound dressing of claim 1, wherein: The molar ratio of the multi-armed olefin ester and / or ether, polyethylene glycol diacrylate, dopamine and allyl ammonium is 1:1-10:1-10:1-10.

6. The wound dressing of claim 1, wherein: In step (1), the polymerization reaction is carried out in an inert atmosphere; The polymerization reaction is carried out in an organic solvent; the organic solvent is dimethyl sulfoxide; The temperature of the polymerization reaction is 40-90 ℃; the time is 0.5-2 h; and the polymerization reaction is carried out in the dark; In step (2), the reaction of the primary dendritic macromolecule with allyl ammonium is carried out in an inert atmosphere; the temperature of the reaction is 40-90 ℃; the time is 0.5-2 h; and the reaction is carried out in the dark.

7. The method for preparing the wound dressing of any one of claims 1-6, comprising the steps of: preparing a solution of the biomacromolecule, the ferric ion and the crosslinking agent respectively, then mixing them with the dendrimer and stirring to obtain the wound dressing.

8. A wound dressing kit comprising the wound dressing of any one of claims 1-6 and a near-infrared device.

9. The use of the wound dressing of any one of claims 1-6 or the wound dressing and the near-infrared device in the preparation of a product for treating wound healing.

Citation Information

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