Hydrogel dressing with functions of resisting bacteria, absorbing endotoxin and promoting healing as well as preparation method and application of hydrogel dressing

Abstract

The invention discloses a hydrogel dressing with antibacterial, endotoxin absorbing and healing promoting functions as well as a preparation method and application thereof, and belongs to the technical field of medical dressings. The hydrogel dressing with the antibacterial, endotoxin absorbing and healing promoting functions comprises a hydrogel layer and a flexible pseudocapacitance electrode layer compounded on the hydrogel layer, the flexible pseudocapacitance electrode layer comprises carbon cloth, a nano electrode material is loaded on the surface of the carbon cloth, and the nano electrode material has pseudocapacitance activity. According to the application, the flexible pseudocapacitance electrode layer with pseudocapacitance activity is compounded on the hydrogel layer for the first time, broad-spectrum and efficient sterilization can be realized and migration and proliferation of cells such as fibroblasts and keratinocytes can be promoted based on electric field energy of the pseudocapacitance, and meanwhile, endotoxin is adsorbed based on positive charges generated by energy released by the pseudocapacitance; chronic wound healing is accelerated by combining antibiosis, endotoxin absorption and tissue healing promotion.

Description

Technical Field

[0001] The present application belongs to the technical field of medical dressings, and in particular relates to a hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions, and a preparation method and application thereof. Background Art

[0002] Diabetic foot ulcer (DFU) is a chronic wound developed from diabetes, characterized by slow healing and recurring attacks, and has become the main cause of non-invasive amputation. In the clinical treatment of diabetic foot, dressings are usually required to provide a moist environment conducive to wound healing, which is particularly important for local wound healing. However, traditional dressings (cotton / gauze) do not have the ability to control exudate, resulting in continuous exudate from diabetic wounds, aggravating bacterial infection and inflammatory response, causing the wound to persist. Therefore, it is of great significance to develop chronic wound dressings with efficient exudate management and broad-spectrum antibacterial properties.

[0003] At present, functional drug-modified hydrogel dressings are commonly used clinically for chronic wound treatment. For example, the prior art with publication number CN 110917391 A discloses a polypeptide-modified sodium alginate / PVA double-network interpenetrating hydrogel dressing, which is prepared by introducing polypeptides and using polypeptide-modified sodium alginate and PVA to form a hydrogel dressing with broad-spectrum antibacterial, wound exudate absorption and wound healing promotion effects, and can be used for chronic wound care.

[0004] However, there are the following problems in the clinical application of functional drug-modified hydrogel dressings: first, its exudate management function is mainly reflected in the absorption / exudate exudate, and the absorption / exudate exudate will cause the loss of antibacterial and / or pro-healing functional drugs, affecting the antibacterial effect and wound healing process; second, the exudate absorption / exudate direction is contrary to the diffusion direction of the functional drug, which reduces the utilization rate of the functional drug, resulting in unsatisfactory actual antibacterial effect and wound healing process. Summary of the invention

[0005] The present application discloses a hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions, as well as a preparation method and application thereof, in order to solve the technical problems of the actual antibacterial effect of functional drug modified hydrogel dressings and the unsatisfactory wound healing process.

[0006] In order to achieve the above-mentioned purpose, the first aspect of the present application provides a hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions, the hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions comprises a hydrogel layer and a flexible pseudocapacitive electrode layer composited on the hydrogel layer;

[0007] Wherein, the flexible pseudocapacitive electrode layer comprises carbon cloth, the surface of the carbon cloth is loaded with nano-electrode material, and the nano-electrode material has pseudo-capacitive activity.

[0008] In some embodiments, the raw material of the hydrogel layer includes polyvinyl alcohol hydrogel and polyacrylamide / sodium alginate hydrogel.

[0009] In some embodiments, the nano-electrode material includes nano-manganese oxide and cobalt disulfide modified superstructure carbon nano-network.

[0010] The second aspect of the present application provides a method for preparing the hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions as described above, the preparation method comprising:

[0011] preparing a carbon cloth-supported nanoelectrode layer;

[0012] The pre-gel solution is injected into the open mold, and after the carbon cloth-supported nano-electrode layer covers the interface of the pre-gel solution, the pre-gel solution undergoes a gelation reaction, and the gelled product is sequentially washed and dried to obtain a pseudocapacitive dressing precursor;

[0013] In a three-electrode system, the pseudocapacitive dressing precursor is used as a working electrode, a platinum electrode is used as a counter electrode, and a saturated Ag / AgCl electrode is used as a reference electrode. A PBS aqueous solution is added as an electrolyte, and the pseudocapacitive dressing precursor is made to undergo a pseudocapacitive reaction on an electrochemical workstation to obtain a hydrogel dressing having antibacterial, endotoxin-absorbing and healing-promoting functions.

[0014] In some embodiments, the carbon cloth-supported nano-electrode layer includes a carbon cloth-supported nano-manganese oxide electrode layer and a carbon cloth-supported cobalt disulfide-modified superstructure carbon nano-network electrode layer.

[0015] In some embodiments, the carbon cloth-supported nano manganese oxide electrode layer is prepared by a potassium permanganate hydrothermal method, wherein the concentration of the potassium permanganate aqueous solution is 6 to 15 mmol / L.

[0016] In some embodiments, the method for preparing the carbon cloth-supported cobalt disulfide-modified superstructured carbon nanonetwork electrode layer comprises:

[0017] The blend of polyacrylonitrile grafted carbon nanotubes and cobalt chloride is added to an alcohol solvent, dispersed by ultrasonication, ground and evaporated to dryness, and then the obtained product is subjected to a sulfurization reaction in a sulfur-containing atmosphere to obtain a superstructured carbon nanonetwork modified with cobalt disulfide;

[0018] The cobalt disulfide modified superstructure carbon nanonetwork is dispersed in an alcohol solvent, and then dropped on a carbon cloth and vacuum dried to obtain a carbon cloth-supported cobalt disulfide modified superstructure carbon nanonetwork electrode layer.

[0019] In some embodiments, when the product is subjected to a sulfurization reaction in a sulfur-containing atmosphere, the heating rate is 5 to 10° C. / min, the insulation temperature is 280 to 350° C., and the insulation time is 6 to 12 hours.

[0020] In some embodiments, the concentration of the cobalt disulfide modified superstructured carbon nanonetwork dispersed in the alcohol solvent is 0.5-5 mg / mL.

[0021] In some embodiments, the loading amount of the cobalt disulfide modified superstructure carbon nanonetwork on the carbon cloth is 1 to 5 mg / cm 2 .

[0022] In some embodiments, the vacuum drying is carried out at a temperature of 40 to 80° C. and for a time of 6 to 12 hours.

[0023] In some embodiments, the pre-gel solution includes polyvinyl alcohol aqueous dispersion or polyacrylamide / sodium alginate mixed aqueous dispersion.

[0024] In some embodiments, when the pseudocapacitive dressing precursor undergoes a pseudocapacitive reaction on an electrochemical workstation, the charging voltage is less than or equal to 1 V, and the charging time is 10 to 60 minutes.

[0025] The third aspect of the present application provides the use of the hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions in chronic wound dressing.

[0026] Compared with the prior art, the advantages or beneficial effects of the embodiments of the present application include at least:

[0027] The hydrogel dressing provided in the present application is compounded with a flexible pseudocapacitive electrode layer having pseudocapacitive activity, so that the prepared hydrogel dressing has pseudocapacitive activity. On the one hand, the electric field energy released by the pseudocapacitor can destroy the bacterial membrane and the bacterial respiratory chain protein, and play a synergistic bactericidal effect, so that the prepared hydrogel dressing has a broad-spectrum and efficient bactericidal effect; on the other hand, the positive charge generated by the energy released by the pseudocapacitor can produce a strong electrostatic interaction with the bacterial metabolites (endotoxins), so that the endotoxins produced by the bacterial metabolism at the wound surface can be selectively absorbed, which plays a role in preventing inflammatory reactions and accelerating wound healing; thirdly, the electric field energy released by the pseudocapacitor can exert an electrical stimulation effect on the wound tissue, which is beneficial to promote the migration and proliferation of cells such as fibroblasts and keratinocytes, and accelerate wound healing, thereby giving the prepared hydrogel dressing multiple functions such as antibacterial, endotoxin absorption and healing promotion, and is suitable for chronic wound care; fourthly, the hydrogel dressing of the present application no longer introduces functional drugs, so that the corresponding defects of functional drug-modified hydrogel dressings can be effectively avoided, and a new direction is provided for the development of functional hydrogel dressings. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments recorded in the present application, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0029] Figure 1 Photos of MO-12@PVA-C in different shapes and sizes provided in the embodiments of the present application;

[0030] Figure 2 Photos of MO-12@PVA-C at different folding / twisting angles provided in the embodiments of the present application;

[0031] Figure 3 The antibacterial performance test results of MO-12@PVA-U, MO-12@PVA-C and MO-12@PVA-C_24 provided in the embodiments of the present application, wherein a is the antibacterial graph of MO-12@PVA-U and MO-12@PVA-C; b is the antibacterial rate bar graph of MO-12@PVA-U and MO-12@PVA-C;

[0032] Figure 4 The open circuit voltage-time curve of MO@PVA-C provided in the embodiment of the present application in a 0.01M PBS solution containing Escherichia coli, Staphylococcus aureus, and endotoxin and a pure 0.01M PBS solution, wherein: Figure 4 The open circuit voltage-time curves of MO@PVA-C in 0.01 M PBS solution containing Escherichia coli, Staphylococcus aureus, endotoxin and pure 0.01 M PBS solution;

[0033] Figure 5 A bar graph showing the endotoxin absorption rate of MO@PVA-U and MO@PVA-C provided in the examples of the present application;

[0034] Figure 6 The wound healing performance test results of MO@PVA-U and MO@PVA-C provided in the embodiments of the present application, wherein a is the fibroblast migration diagram of the control group, MO@PVA-U group and MO@PVA-C group at 0h, 12h and 24h; b is the corresponding cell migration rate, and the results are plotted as SD±mean value (n=4); c is the staining image of live cells and dead cells in each group; d is the corresponding CCK-8 value of fibroblasts in each group, and the results are plotted as SD±mean value (n=6), scale bar: 200μm, *P<0.05, **P<0.01, ***P<0.001. DETAILED DESCRIPTION

[0035] The technical solutions in the embodiments of the present application will be described clearly and completely below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0036] In the following description of this embodiment, the term "and / or" is used to describe the association relationship of associated objects, indicating that there may be three relationships. For example, A and / or B can represent: A exists alone, B exists alone, and A and B exist at the same time. A and B can be singular or plural. The character " / " generally indicates that the associated objects before and after are in an "or" relationship.

[0037] In the following description of this embodiment, the term "at least one" refers to one or more, and "plurality" refers to two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single items or plural items. For example, "at least one of a, b or c", or "at least one of a, b and c", can all represent: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, c can be single or multiple, respectively.

[0038] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit the present application. The singular forms "a", "an" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings.

[0039] Those skilled in the art should understand that in the following description of the embodiments of the present application, the order of serial numbers does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0040] Those skilled in the art will appreciate that the numerical ranges in the embodiments of the present application are to be understood as each intermediate value between the upper and lower limits of the scope also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded in the scope.

[0041] Unless otherwise specified, the technical / scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which this application belongs. Although this application only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of this application. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0042] In a first aspect, an embodiment of the present application provides a hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions. The hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions comprises a hydrogel layer and a flexible pseudocapacitive electrode layer composited on the hydrogel layer;

[0043] The flexible pseudocapacitive electrode layer comprises carbon cloth, the surface of which is loaded with nano-electrode material, and the nano-electrode material has pseudocapacitive activity, wherein pseudocapacitive activity refers to the property of being able to undergo Faradaic redox process on the surface and near the surface of the electrode material.

[0044] In the embodiment of the present application, the hydrogel layer is compounded with a flexible pseudocapacitive electrode layer having pseudocapacitive activity, so that the prepared hydrogel dressing has pseudocapacitive activity. On the one hand, the electric field energy released by the pseudocapacitor can destroy the bacterial membrane and the bacterial respiratory chain protein, play a synergistic bactericidal effect, thereby giving the prepared hydrogel dressing a broad-spectrum and efficient bactericidal effect; on the other hand, the positive charge generated by the pseudocapacitor release energy can produce a strong electrostatic interaction with the bacterial metabolites (endotoxins), thereby selectively removing the endotoxins produced by bacterial metabolism at the wound surface, playing a role in preventing inflammatory reactions and accelerating wound healing; thirdly, the electric field energy released by the pseudocapacitor can exert an electrical stimulation effect on the wound tissue, which is beneficial to promote the migration and proliferation of cells such as fibroblasts and keratinocytes, accelerate wound healing, thereby giving the prepared hydrogel dressing multiple functions such as antibacterial, endotoxin absorption and healing promotion, and can be suitable for chronic wound care; at the same time, the hydrogel dressing of the present application no longer introduces functional drugs, thereby effectively avoiding the corresponding defects of functional drug-modified hydrogel dressings, and providing a new direction for the development of functional hydrogel dressings.

[0045] In an exemplary embodiment, the raw material of the hydrogel layer is preferably polyvinyl alcohol hydrogel or polyacrylamide / sodium alginate hydrogel.

[0046] Among them, the polyvinyl alcohol hydrogel or polyacrylamide / sodium alginate hydrogel selected in the embodiment of the present application has good biocompatibility, can provide a favorable moist environment for wound healing, and play a role in promoting wound healing. The hydrogen bonding force between the polyvinyl alcohol chains or the chemical bonds or electrostatic forces between the polyacrylamide / sodium alginate molecular chains can form a network skeleton structure, and the network skeleton structure can form a entangled structure with the carbon cloth, so that the prepared hydrogel dressing has good mechanical properties and interlayer bonding strength, effectively avoiding the shedding and peeling between the hydrogel layer and the flexible pseudocapacitor electrode layer.

[0047] In an exemplary embodiment, the nano-electrode material is preferably a superstructured carbon nano-network modified by nano-manganese oxide and cobalt disulfide.

[0048] Among them, the superstructured carbon nanonetwork modified with nano manganese oxide or cobalt disulfide selected in the embodiments of the present application has good electrochemical properties and flexibility. Even in a bent state, its electrochemical properties will not change significantly, and can well meet the flexibility requirements of wound dressings.

[0049] In a second aspect, the present application provides a method for preparing the hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions according to the first aspect, and the preparation method preferably comprises:

[0050] preparing a carbon cloth-supported nanoelectrode layer;

[0051] The pre-gel solution is injected into the open mold, and after the carbon cloth-supported nano-electrode layer covers the interface of the pre-gel solution, the pre-gel solution undergoes a gelation reaction, and the gelled product is sequentially washed and dried to obtain a pseudocapacitive dressing precursor;

[0052] In a three-electrode system, the pseudocapacitive dressing precursor is used as a working electrode, a platinum electrode is used as a counter electrode, and a saturated Ag / AgCl electrode is used as a reference electrode. A PBS aqueous solution is added as an electrolyte, and the pseudocapacitive dressing precursor is made to undergo a pseudocapacitive reaction on an electrochemical workstation to obtain a hydrogel dressing having antibacterial, endotoxin-absorbing and healing-promoting functions.

[0053] It should be noted that the opening mold can use homemade molds of various shapes, such as an open rectangular mold, an open special-shaped mold, etc. The embodiment of the present application does not impose any special restrictions on this. However, in order to ensure that the prepared hydrogel dressing has good wettability, sealing and exudate absorption effects, the depth of the opening mold (hydrogel thickness) is preferably 50 to 200 μm, for example, 50 μm, 150 μm, 200 μm or any one within the depth range.

[0054] In an exemplary embodiment, the carbon cloth-supported nano-electrode layer is preferably a carbon cloth-supported nano-manganese oxide electrode layer or a carbon cloth-supported cobalt disulfide-modified superstructure carbon nano-network electrode layer.

[0055] Among them, the carbon cloth-loaded nano-manganese oxide electrode layer or the carbon cloth-loaded cobalt disulfide-modified superstructured carbon nanonetwork electrode layer selected in the embodiments of the present application have good flexibility and electrochemical properties, which can well meet the flexibility requirements of wound dressings, and the entangled structure generated by the hydrogel layer and the carbon cloth substrate can effectively improve the mechanical properties and interlayer stability of the layered hydrogel dressing, and has a good effect on chronic wound coverage and care.

[0056] It should be noted that the carbon cloth-loaded nano-manganese oxide electrode layer or the carbon cloth-loaded cobalt disulfide-modified superstructured carbon nanonetwork electrode layer refers to a carbon cloth electrode with surface growth / loaded nano-manganese oxide or cobalt disulfide-modified superstructured carbon nanonetwork material formed by in situ growth / loading of nano-manganese oxide or cobalt disulfide-modified superstructured carbon nanonetwork material on the surface of the carbon cloth substrate.

[0057] In an exemplary embodiment, the carbon cloth-supported nano manganese oxide electrode layer is preferably prepared by potassium permanganate hydrothermal method. The method for preparing the carbon cloth-supported nano manganese oxide electrode layer by potassium permanganate hydrothermal method specifically includes:

[0058] The carbon cloth is immersed in a potassium permanganate aqueous solution for hydrothermal reaction at 150°C for 12 hours, cooled naturally to room temperature, rinsed with pure water and dried overnight in a vacuum environment at 60°C. The concentration of the potassium permanganate aqueous solution is preferably 6 to 15 mmol / L, for example 6 mmol / L, 9 mmol / L, 12 mmol / L, 15 mmol / L or any one within the concentration range.

[0059] In an exemplary embodiment, the method for preparing the carbon cloth-supported cobalt disulfide-modified superstructured carbon nanonetwork electrode layer preferably comprises:

[0060] The blend of polyacrylonitrile grafted carbon nanotubes (CNT-PAN molecular brushes) and cobalt chloride (CoCl2) is added to an alcohol solvent, ultrasonically dispersed and ground and evaporated to dryness, and then the resulting product is subjected to a sulfurization reaction in a sulfur-containing atmosphere to obtain a superstructured carbon nanonetwork modified with cobalt disulfide;

[0061] The cobalt disulfide modified superstructure carbon nanonetwork is dispersed in an alcohol solvent, and then dropped on a carbon cloth and vacuum dried to obtain a carbon cloth-supported cobalt disulfide modified superstructure carbon nanonetwork electrode layer.

[0062] Wherein, when the obtained product is subjected to a sulfurization reaction in a sulfur-containing atmosphere, the heating rate is preferably 5 to 10°C / min, such as 5°C / min, 8°C / min and 10°C / min, the holding temperature is preferably 280 to 350°C, such as 280°C, 300°C, 320°C and 350°C, and the holding time is preferably 6 to 12h, such as 6h, 7h, 8h, 9h, 10h, 11h, 12h, etc.; the concentration of the cobalt disulfide modified superstructure carbon nanonetwork dispersed in the alcohol solvent is 0.5 to 5mg / mL, such as 0.5mg / mL, 1mg / mL, 2mg / mL and 5mg / mL, etc.; the loading amount of the cobalt disulfide modified superstructure carbon nanonetwork on the carbon cloth is preferably 1 to 5mg / cm 2 , for example 1mg / cm 2 , 2mg / cm 2 、3mg / cm 2 , 4mg / cm 2 and 5mg / cm 2 The vacuum drying temperature is 40 to 80°C, such as 40°C, 50°C, 60°C, 70°C and 80°C, etc., and the time is preferably 6 to 12 hours, such as 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, etc. The specific values ​​within the process parameter range are not particularly limited in the present application examples, and those skilled in the art can reasonably select according to the reaction conditions.

[0063] It should be noted that the mass ratio of CNT-PAN molecular brush to CoCl2 is preferably 5:1 to 7:10, such as 5:1, 4:1, 7:10, etc. The embodiments of the present application do not impose any particular restrictions on this, so long as a superstructured carbon nanonetwork modified with cobalt disulfide can be prepared.

[0064] It should be understood by those skilled in the art that causing the pseudocapacitive dressing precursor to undergo a pseudocapacitive reaction specifically refers to charging treatment on an electrochemical workstation. Among them, in the embodiments of the present application, the preferred charging voltage is less than or equal to 1V, such as 0.1V, 0.2V, 0.4V, 0.8V and 1V, etc., and the charging time is 10 to 60min, such as 10min, 20min, 30min, 40min, 50min and 60min, etc. The embodiments of the present application do not impose any particular restrictions on the specific values ​​within the parameter range, and those skilled in the art can reasonably choose according to the actual performance of the flexible pseudocapacitive electrode layer.

[0065] In the third aspect, the embodiment of the present application provides the application of the hydrogel dressing with antibacterial, endotoxin absorption and healing promotion functions according to the embodiment of the present application for use in chronic wound care materials. Among them, the hydrogel dressing with antibacterial, endotoxin absorption and healing promotion functions according to the embodiment of the present application can achieve synergistic sterilization, selective absorption of endotoxins and promotion of migration and proliferation of cells such as fibroblasts and keratinocytes based on pseudocapacitive activity. Therefore, when the hydrogel dressing with antibacterial, endotoxin absorption and healing promotion functions is used for chronic wound care, it can play a role in broad-spectrum and efficient sterilization, anti-inflammatory and wound healing promotion, and has a good effect on chronic wound closure care.

[0066] The technical solution of the present application will be further described below in conjunction with specific embodiments.

[0067] Example 1

[0068] This embodiment provides a method for preparing a hydrogel dressing (MO-12@PVA-C) having antibacterial, endotoxin absorbing and healing promoting functions, comprising the following steps:

[0069] S11: soaking the commercial carbon cloth in a potassium permanganate aqueous solution with a concentration of 12 mmol / L, hydrothermally reacting at 150° C. for 12 h, naturally cooling to room temperature, rinsing with pure water, and drying in a vacuum environment at 60° C. overnight to obtain a carbon cloth-supported nano-manganese oxide electrode layer (MO-12);

[0070] S12: Filling the pre-dissolved 20% PVA aqueous dispersion into an open mold with different structural shapes with a depth of 200 μm, and covering the opening of the open mold with the carbon cloth-supported nano-manganese oxide electrode layer MO-12, placing it in a refrigerator at a temperature of -20°C, and performing 3 freeze-thaw cycles (freezing for 18 hours and thawing for 4 hours in each cycle) to complete gelation, and then placing the gelled product in deionized water for washing for 1-2 days and freeze-drying for 2 days in turn to obtain a pseudocapacitive dressing precursor (MO-12@PVA);

[0071] S13: In a three-electrode system, the pseudocapacitive dressing precursor MO-12@PVA was used as the working electrode, the platinum electrode was used as the counter electrode, and the saturated Ag / AgCl electrode was used as the reference electrode. A 0.01 M PBS aqueous solution was added as the electrolyte. A voltage of 0.8 V was applied to the pseudocapacitive dressing precursor MO-12@PVA on a CHI660E electrochemical workstation for a total of 10 min to obtain the hydrogel dressing MO-12@PVA-C with antibacterial, endotoxin absorption and healing-promoting functions.

[0072] Among them, the concentration of the potassium permanganate aqueous solution can be changed (for example, 6 mmol / L, 9 mmol / L and 15 mmol / L), and according to the method of Example 1, hydrogel dressings MO-6@PVA-C, MO-9@PVA-C and MO-15@PVA-C with antibacterial, endotoxin absorption and healing promotion functions are respectively prepared.

[0073] Example 2

[0074] This embodiment provides a method for preparing a hydrogel dressing (MO-12@PAAM / Alg-C) having antibacterial, endotoxin absorbing and healing promoting functions, comprising the following steps:

[0075] S21: soaking the commercial carbon cloth in a potassium permanganate aqueous solution with a concentration of 12 mmol / L, hydrothermally reacting at 150° C. for 12 h, naturally cooling to room temperature, rinsing with pure water, and drying in a vacuum environment at 60° C. overnight to obtain a carbon cloth-supported nano-manganese oxide electrode layer (MO-12);

[0076] S22: preparing a sodium alginate aqueous solution with a mass concentration of 4%, adding acrylamide monomer with a mass concentration of 40%, stirring evenly, and sequentially adding 1% N,N-methylenebisacrylamide, 5% ammonium persulfate and 5% tetramethylethylenediamine aqueous solution, stirring evenly, to obtain a polyacrylamide / sodium alginate pregel solution;

[0077] S23: Filling the polyacrylamide / sodium alginate pregel solution into an open mold with a depth of 200 μm, and covering the opening of the open mold with the carbon cloth-supported nano-manganese oxide electrode layer MO-12, placing it in a constant temperature box at 37°C overnight to complete gelation, and then placing the gelled product in deionized water for washing for 1-2 days and freeze-drying for 2 days to obtain a pseudocapacitive dressing precursor (MO-12@PAAM / Alg);

[0078] S24: In a three-electrode system, the pseudocapacitive dressing precursor MO-12@PAAM / Alg was used as the working electrode, the platinum electrode was used as the counter electrode, and the saturated Ag / AgCl electrode was used as the reference electrode. A 0.01M PBS aqueous solution was added as the electrolyte. A voltage of 0.7V was applied to the pseudocapacitive dressing precursor MO-12@PAAM / Alg on a CHI660E electrochemical workstation for a total of 10 minutes to obtain the hydrogel dressing MO-12@PAAM / Alg-C with antibacterial, endotoxin absorption and healing-promoting functions.

[0079] The concentration of the sodium alginate aqueous solution can be changed (eg, 3.5% and 4.5%), and a hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions can be prepared according to the method of Example 2.

[0080] Example 3

[0081] This embodiment provides a method for preparing a hydrogel dressing (SN-CoS2@PVA-C) having antibacterial, endotoxin absorbing and healing promoting functions, comprising the following steps:

[0082] S31: Add a blend of CNT-PAN molecular brush and CoCl2 (4:1) into 50% ethanol and ultrasonically disperse for 30 minutes, grind and evaporate to dryness and place in a porcelain boat, place the porcelain boat downstream of a tube furnace, and place a porcelain boat filled with sulfur powder upstream of the tube furnace, then heat up to 300°C at a heating rate of 10°C / min, keep warm for 6 hours, and cool to room temperature with the furnace to obtain a cobalt disulfide-modified superstructure carbon nanonetwork material;

[0083] S32: The superstructured carbon nanonetwork material modified with cobalt disulfide was dispersed in ethanol to prepare a 2 mg / mL solution, and then dropped on the carbon cloth so that the loading amount of the superstructured carbon nanonetwork material modified with cobalt disulfide was 2 mg / cm 2 , vacuum drying to obtain a carbon cloth-supported cobalt disulfide-modified superstructured carbon nanonetwork electrode layer (SN-CoS2);

[0084] S33: Filling an open mold with a depth of 200 μm with a pre-dissolved 20% PVA aqueous dispersion, and covering the opening of the open mold with a carbon cloth-supported cobalt disulfide-modified superstructure carbon nanonetwork electrode layer SN-CoS2, placing it in a refrigerator at a temperature of -20°C, and performing 3 freeze-thaw cycles (freezing for 18 h and thawing for 4 h in each cycle) to complete gelation, and then placing the gelled product in deionized water for washing for 1-2 days and freeze-drying for 2 days in turn to obtain a pseudocapacitive dressing precursor (SN-CoS2@PVA);

[0085] S34: In a three-electrode system, the pseudocapacitive dressing precursor SN-CoS2@PVA was used as the working electrode, the platinum electrode was used as the counter electrode, and the saturated Ag / AgCl electrode was used as the reference electrode. A 0.01M PBS aqueous solution was added as the electrolyte. A voltage of 0.8V was applied to the pseudocapacitive dressing precursor SN-CoS2@PVA on a CHI660E electrochemical workstation for a total of 10 minutes to obtain the hydrogel dressing SN-CoS2@PVA-C with antibacterial, endotoxin absorption and healing-promoting functions.

[0086] In order to illustrate the actual performance of the hydrogel dressing prepared in the examples of the present application, MO-12@PVA-U obtained by soaking the MO-12@PVA in Example 1 in a 0.01M PBS aqueous solution for 10 minutes was used as a control sample. The MO-12@PVA-U and the MO-12@PVA-C in Example 1 were used as test samples for structural characterization and performance testing, as follows:

[0087] 1. Physical representation

[0088] Figure 1 Shown are photos of MO-12@PVA-C in different shapes and sizes; Figure 2 Shown are actual photos of MO-12@PVA-C at different folding / twisting angles.

[0089] according to Figure 1 It can be seen that MO-12@PVA-C has customizable size and shape, which can meet the needs of wounds of various sizes and shapes.

[0090] according to Figure 2 It can be seen that MO-12@PVA-C has good flexibility and can be bent or twisted, which can well meet the flexibility requirements of wound dressings.

[0091] 2. Antibacterial performance test

[0092] This example studies the antibacterial activity of MO-12@PVA-U and MO-12@PVA-C against Escherichia coli and Staphylococcus aureus. Before bacterial culture, MO-12@PVA-U and MO-12@PVA-C were irradiated with ultraviolet light for 12 hours. The original bacterial solution of Escherichia coli and Staphylococcus aureus was inoculated into LB medium and cultured in a constant temperature shaker at 37°C for 24 hours. The concentration of the original bacterial solution was determined using a McFarland turbidimeter, and then the bacterial concentration was diluted to 10 6 CFU·mL -1 . Add the diluted bacterial solution to a 48-well plate, 300 μL per well. Immerse MO-12@PVA-U and MO-12@PVA-C in the diluted bacterial solution. The plate count method was used to determine the antibacterial activity of the dressing against bacteria. After co-culturing for a corresponding period of time, the bacterial suspension was diluted 1000 times, 100 μL was spread on the agar culture plate, and cultured at 37°C for another 24 hours. The survival rate was calculated by the following formula:

[0093]

[0094] Where C0 is the concentration of the bacterial solution without any treatment, C t is the residual concentration of bacteria after treatment in the experimental group.

[0095] In addition, we simulated MO-12@PVA-C in a body fluid environment for a long time to investigate its antibacterial properties. Specifically, MO-12@PVA-C was immersed in PBS solution and incubated in a 37°C constant temperature shaker for 24 h to obtain MO-12@PVA-C_24 and conduct antibacterial experiments. The results were Figure 3 As shown. Among them, Figure 3These are the antibacterial performance test results of MO-12@PVA-U, MO-12@PVA-C and MO-12@PVA-C_24. a is the antibacterial graph of MO-12@PVA-U, MO-12@PVA-C and MO-12@PVA-C_24; b is the antibacterial rate bar graph of MO-12@PVA-U, MO-12@PVA-C and MO-12@PVA-C_24.

[0096] according to Figure 3 It can be seen that the antibacterial rate of MO-12@PVA-C against Escherichia coli and Staphylococcus aureus reached 100%, which is much higher than the antibacterial rate of MO-12@PVA-U (39.6% and 32.3%). This proves the important role of the pseudocapacitive activity of MO-12@PVA-C in antibacterial properties. In addition, the antibacterial rate of MO-12@PVA-C_24 against Escherichia coli and Staphylococcus aureus was 100%, proving that the hydrogel dressing prepared by compounding a flexible pseudocapacitive electrode with pseudocapacitive activity on the hydrogel layer in this application has long-lasting antibacterial properties.

[0097] 3. Discharge performance test

[0098] With MO@PVA-C as the working electrode, platinum electrode as the counter electrode, and saturated Ag / AgCl electrode as the reference electrode, the discharge performance of MO@PVA-C in different solutions was studied using voltage-time curves in a three-electrode system. Figure 4 As shown, Figure 4 Open circuit voltage-time curves of MO@PVA-C in 0.01 M PBS solution containing Escherichia coli, Staphylococcus aureus, endotoxin and pure 0.01 M PBS solution.

[0099] according to Figure 4 It can be seen that in 0.01M PBS solution, the potential of MO@PVA-C decreased significantly in the first 1.8h, which is due to the dominant process of the release of cations adsorbed on the surface of MO-C in the form of double-layer capacitance. In the same period of time, the potential of MO@PVA-C in bacterial solution and endotoxin solution decreased more significantly, indicating that in addition to discharging in the form of double-layer capacitance, electron transfer occurred between negatively charged bacteria or endotoxins and electrodes, stimulating the rapid release of pre-embedded cations in the electrodes and the occurrence of electrical neutralization reaction. At 13h, the potential of MO@PVA-C in PBS solution containing Escherichia coli and Staphylococcus aureus decreased again, which may be because a large number of bacteria released negatively charged substances after death, stimulating MO-C to further discharge.

[0100] 4. Endotoxin absorption rate test

[0101] Prepare 10EU mL using endotoxin test water -1endotoxin solution, take 4mL of endotoxin solution and mix with 1cm 2 MO@PVA-C or MO@PVA-U was incubated at 37°C for 3 h in a shaking incubator, and then the endotoxin concentration after treatment was detected using a chromogenic matrix method horseshoe crab kit, and the absorbance was calculated. The results were Figure 5 As shown, Figure 5 This is a bar graph of the endotoxin absorption rate of MO@PVA-U and MO@PVA-C.

[0102] according to Figure 5 It can be seen that the endotoxin absorption rate of MO@PVA-C is 77.4%, which is much higher than the 9.6% of MO@PVA-U. This strong contrast result shows that it is difficult to effectively remove endotoxins by relying solely on the physical adsorption of gel, while under the induction of the electric field, MO@PVA-C can quickly capture most of the endotoxins in a short time.

[0103] 5. Test on wound healing performance

[0104] The result is Figure 6 Among them, a is the migration diagram of fibroblasts in the control group, MO@PVA-U group and MO@PVA-C group at 0h, 12h and 24h; b is the corresponding cell migration rate, and the results are plotted as SD±mean (n=4); c is the staining image of live cells and dead cells in each group; d is the corresponding CCK-8 value of fibroblasts in each group, and the results are plotted as SD±mean (n=6), scale bar: 200μm, *P<0.05, **P<0.01, ***P<0.001.

[0105] according to Figure 6 It can be seen that the scratch healing rate of the experimental group with MO@PVA-C as the working electrode was 45.20±4.31% at the 12th hour, and it could reach 90.77±1.34% at 24 hours, while the scratch healing rates of the control group with MO@PVA-U as the working electrode were 12.93±0.98% and 33.01±2.76% at the 12th hour and 24th hour, respectively. Obviously, under the electric field induction provided by MO@PVA-C, the migration rate of fibroblasts was significantly higher than that of the control group. It proves that MO@PVA-C can significantly promote the migration of fibroblasts, which is beneficial to promote wound healing.

[0106] Of course, the clinical effects of Examples 2-3 are comparable to those of Example 1 and will not be described in detail herein.

[0107] The various embodiments in this specification are described in a progressive manner, and the same or similar parts between the various embodiments can be referenced to each other, and each embodiment focuses on the differences from other embodiments.

[0108] The above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit the present application. Although the present application has been described in detail with reference to the aforementioned embodiments, a person of ordinary skill in the art should understand that the technical solutions recorded in the aforementioned embodiments may still be modified, or some or all of the technical features therein may be replaced by equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the present application.

Claims

1. A hydrogel dressing with antibacterial, endotoxin absorbing and healing promoting functions, characterized in that: It comprises a hydrogel layer and a flexible pseudocapacitor electrode layer composited on the hydrogel layer; The flexible pseudocapacitive electrode layer comprises carbon cloth, the surface of the carbon cloth is loaded with nano-electrode material, and the nano-electrode material has pseudo-capacitive activity.

2. The hydrogel dressing according to claim 1, characterized in that The raw materials of the hydrogel layer include polyvinyl alcohol hydrogel and polyacrylamide / sodium alginate hydrogel.

3. The hydrogel dressing according to claim 1, characterized in that The nano-electrode material comprises nano-manganese oxide and a super-structured carbon nano-network modified by cobalt disulfide.

4. A method for preparing a hydrogel dressing having antibacterial, endotoxin absorbing and healing promoting functions according to any one of claims 1 to 3, characterized in that: include: preparing a carbon cloth-supported nanoelectrode layer; The pre-gel solution is injected into the open mold, and after the carbon cloth-supported nano-electrode layer covers the interface of the pre-gel solution, the pre-gel solution undergoes a gelation reaction, and the gelation product is washed and dried to obtain a pseudocapacitive dressing precursor; In a three-electrode system, the pseudocapacitive dressing precursor is used as a working electrode, a platinum electrode is used as a counter electrode, a saturated Ag / AgCl electrode is used as a reference electrode, and a PBS aqueous solution is added as an electrolyte. The pseudocapacitive dressing precursor is subjected to a pseudocapacitive reaction on an electrochemical workstation to obtain a hydrogel dressing having antibacterial, endotoxin-absorbing and healing-promoting functions.

5. The preparation method according to claim 4, characterized in that: The carbon cloth-supported nano-electrode layer comprises a carbon cloth-supported nano-manganese oxide electrode layer and a carbon cloth-supported cobalt disulfide-modified superstructure carbon nano-network electrode layer.

6. The preparation method according to claim 5, characterized in that: The carbon cloth-supported nano manganese oxide electrode layer is prepared by potassium permanganate hydrothermal method; Wherein, the concentration of the potassium permanganate aqueous solution is 6 to 15 mmol / L.

7. The preparation method according to claim 5, characterized in that: The preparation method of the carbon cloth-supported cobalt disulfide-modified superstructure carbon nano-network electrode layer comprises: The blend of carbon nanotubes grafted with polyacrylonitrile and cobalt chloride is added to an alcohol solvent, dispersed by ultrasonication, ground and evaporated to dryness, and then the obtained product is subjected to a sulfurization reaction in a sulfur-containing atmosphere to obtain a superstructured carbon nanonetwork modified with cobalt disulfide; The cobalt disulfide modified superstructure carbon nanonetwork is dispersed in an alcohol solvent, and then dropped on a carbon cloth and vacuum dried to obtain a carbon cloth-supported cobalt disulfide modified superstructure carbon nanonetwork electrode layer.

8. The preparation method according to claim 7, characterized in that: When the product is subjected to a sulfurization reaction in a sulfur-containing atmosphere, the heating rate is 5 to 10°C / min, the insulation temperature is 280 to 350°C, and the insulation time is 6 to 12 hours; and / or, the concentration of the cobalt disulfide modified superstructured carbon nanonetwork dispersed in the alcohol solvent is 0.5 to 5 mg / mL; And / or, the loading amount of the cobalt disulfide modified superstructure carbon nanonetwork on the carbon cloth is 1-5 mg / cm 2 .

9. The preparation method according to any one of claims 4 to 8, characterized in that: When the pseudocapacitive dressing precursor undergoes a pseudocapacitive reaction on the electrochemical workstation, the charging voltage is less than or equal to 1V, and the charging time is 10 to 60 minutes.

10. Use of the hydrogel dressing according to any one of claims 1 to 3 in chronic wound dressing.

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