Microwave-responsive hydrogel dressing and use thereof in preparation of anti-diabetic chronic infected wound preparation

Abstract

The application discloses a microwave-responsive hydrogel dressing and application thereof in preparation of an anti-diabetic chronic infection wound preparation. The raw material of the hydrogel dressing disclosed by the application comprises: (A) a hydrogel matrix; (B) glucose oxidase; (C) a nano-enzyme composition, wherein the nano-enzyme composition at least comprises a luteolin-manganese dioxide composite; wherein the luteolin-manganese dioxide composite is a solid-phase product obtained by wet blending of luteolin and nano-manganese dioxide. Under microwave irradiation, the heat effect generated by the microwave causes the hydrogel dressing to heat up, the heat-enhanced glucose oxidase consumes glucose to generate hydrogen peroxide, and at the same time, the heat-enhanced luteolin-manganese dioxide composite decomposes the hydrogen peroxide to generate oxygen, thereby simultaneously relieving high glucose and hypoxia, fundamentally breaking the vicious cycle of "high glucose-hypoxia-infection-chronic inflammation" of the diabetic wound, and finally improving the antibacterial effect on the skin wound.

Description

Technical Field

[0001] This application relates to the technical field of biological antimicrobial drugs, and more particularly to microwave-responsive hydrogel dressings and their application in the preparation of antidiabetic chronic infection wound formulations. Background Technology

[0002] Diabetic chronic wounds are a serious complication of diabetes, characterized by a vicious cycle of hyperglycemia, hypoxia, bacterial infection, and chronic inflammation, leading to stagnation of wound healing. In particular, infections with multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) pose a significant challenge to traditional antibiotic treatment.

[0003] Currently, commonly used wound dressings in clinical practice include gauze, foam dressings, and hydrocolloid dressings. These traditional dressings mainly act as physical barriers and are difficult to actively intervene in the wound microenvironment. In recent years, functional hydrogel dressings have received widespread attention due to their advantages such as good moisturizing properties, drug loading capacity, and adjustable structure.

[0004] However, the antibacterial effect of existing hydrogel dressings on skin wounds is relatively limited. Summary of the Invention

[0005] The problem to be solved This application aims to address at least one of the technical problems existing in the prior art. Therefore, one objective of this application is to provide a microwave-responsive hydrogel dressing and its application in the preparation of anti-diabetic chronic infection wound formulations, to better improve the antibacterial effect on skin wounds.

[0006] Problem-solving methods In recent years, hydrogel dressings have attracted widespread attention due to their advantages such as good moisturizing properties, drug loading capacity, and adjustable structure. However, when facing the technical need to improve the antibacterial effect on skin wounds, related technologies usually focus on the destruction or killing effect of hydrogel dressings on bacteria themselves, resulting in relatively limited antibacterial efficacy.

[0007] The inventors of this invention abandoned the improvement approach of "focusing on destroying the bacteria themselves" used in related technologies. Through repeated and in-depth research to solve the aforementioned problems, they realized that under microwave irradiation, the thermal effect of microwaves causes the hydrogel dressing to heat up. This thermally enhanced glucose oxidase consumes glucose to produce hydrogen peroxide, while the thermally enhanced luteolin-manganese dioxide complex decomposes the hydrogen peroxide to produce oxygen. This simultaneously alleviates both high blood sugar and hypoxia, thereby fundamentally breaking the vicious cycle of "high blood sugar-hypoxia-infection-chronic inflammation" in diabetic wounds. This led to the creation of this invention.

[0008] This application provides a microwave-responsive hydrogel dressing, the raw materials of which include: (A) Hydrogel matrix; (B) Glucose oxidase; (C) A nanozyme composition comprising at least a luteolin-manganese dioxide complex; wherein the luteolin-manganese dioxide complex is a solid-phase product obtained by wet blending luteolin and nano-manganese dioxide.

[0009] In any embodiment, the specific process of obtaining a solid product through wet blending includes the following steps: Luteolin and nano-manganese dioxide were fully dispersed in a dispersion medium with a pH of 7-8 to form a dispersion. The dispersion was dried and the solid phase was collected.

[0010] In any embodiment, the dispersion medium is a buffer solution.

[0011] In any embodiment, the drying is freeze-drying.

[0012] In any embodiment, the hydrogel matrix comprises methacrylamide gelatin, methacrylamide hyaluronic acid, and a photoinitiator.

[0013] This application also provides a method for preparing a microwave-responsive hydrogel dressing, comprising the following steps: Provide hydrogel matrix; The glucose oxidase and nanozyme composition are fully dispersed with the hydrogel matrix to form a precursor solution; The precursor solution is fully cured to form a crosslinked compound, resulting in a hydrogel dressing. The nanoenzyme composition contains at least a luteolin-manganese dioxide complex; wherein the luteolin-manganese dioxide complex is a solid-phase product obtained by wet blending luteolin and nano-manganese dioxide.

[0014] In any embodiment, the curing method is irradiation with 405nm blue light.

[0015] In any embodiment, during the formation of the precursor solution, the added mass concentration of glucose oxidase is 2-8 wt%, the added mass concentration of methacrylamide hyaluronic acid is 0.5-2 wt%, and the added mass concentration of photoinitiator is 0.05-0.2 wt%.

[0016] This application also provides the use of the microwave-responsive hydrogel dressing described above in the preparation of anti-diabetic chronic infection wound formulations.

[0017] In another aspect, this application provides a method for caring for skin wounds, in which a microwave-responsive hydrogel dressing as described above is applied to a skin wound caused at least by a chronic infection due to diabetes, and microwave action is applied to the skin wound to which the hydrogel dressing is applied.

[0018] Invention Effects This hydrogel dressing, when irradiated with microwaves, experiences a temperature rise due to the thermal effect. Thermo-enhanced glucose oxidase consumes glucose to produce hydrogen peroxide, while the thermo-enhanced luteolin-manganese dioxide complex decomposes the hydrogen peroxide to generate oxygen. This simultaneously alleviates both hyperglycemia and hypoxia, fundamentally breaking the vicious cycle of "hyperglycemia-hypoxia-infection-chronic inflammation" in diabetic wounds, ultimately improving the antibacterial effect on skin wounds. Microwaves, as a non-invasive physical energy source, offer excellent tissue penetration and controllability, providing convenience for clinical applications.

[0019] In addition, the hydrogel dressing of this application regulates key pro-inflammatory pathways such as IL-17 and TNF, downregulates the expression of pro-inflammatory factors, upregulates the expression of anti-inflammatory factors, and upregulates VEGF to promote angiogenesis, thereby achieving high-quality wound healing.

[0020] The hydrogel dressing of this application is sprayable, which can be evenly covered on irregular wounds by a spraying device to achieve coverage without dead corners; its rapid light curing characteristics facilitate clinical operation; its good adhesion ensures that the dressing remains stable on dynamic wound sites; its porous structure is conducive to gas exchange and cell migration; and its excellent swelling and water retention properties can effectively manage wound exudate and maintain a moist healing environment.

[0021] The hydrogel dressing of this application has good cell compatibility and blood compatibility, and has not shown systemic toxicity when used in vivo, showing good prospects for clinical application. Attached Figure Description

[0022] Figure 1 The images shown are scanning electron microscope (SEM) images of the hydrogel dressing (LMG@GH-MA) of this application, along with magnified images of a portion thereof.

[0023] Figure 2 This image demonstrates the sprayability of the LMG@GH-MA precursor solution for the hydrogel dressing of this application. Figure a shows the spraying process, and Figure b shows the hydrogel dressing formed by rapid cross-linking after irradiation with 405 nm blue light for 20 seconds.

[0024] Figure 3 Photographs showing the formation of hydrogel on pigskin after different number of sprays (3, 5, and 7) of the hydrogel dressing of this application.

[0025] Figure 4Figure a shows the microwave response of the hydrogel dressings of this application. Figure a is an infrared thermographic image of GH-MA and LMG@GH-MA hydrogels after microwave irradiation (4 W) for 20 min. Scale bar: 15-55 o Figures C and b are the temperature rise curves.

[0026] Figure 5 In the figure, Figure a shows the activity data of glucose oxidase as a function of temperature, and Figure b shows the real-time oxygen content of LMG@GH-MA consuming H2O2 to generate O2.

[0027] Figure 6 The antibacterial properties of hydrogel dressings are shown in Figure a, where LMG@GH-MA and pure hydrogel GH-MA are actual antibacterial plates after microwave treatment, and Figure b is the quantitative antibacterial rate.

[0028] Figure 7 Cell fluorescence image after 24 h of co-culture of hydrogel dressing and cells. Scale bar: 200 μm.

[0029] Figure 8 Images showing cell migration of NIH-3T3 fibroblasts at 0, 24, 48, and 72 h after scratching in the hydrogel dressing control group and the LMG@GH-MA group. Scale bar: 200 μm.

[0030] Figure 9 The cell survival rate of NIH-3T3 fibroblasts after co-culturing with GH-MA and LMG@GH-MA for 1, 3, and 5 days.

[0031] Figure 10 Figure 1 shows the effect of hydrogel dressing in actual application. Figure 2a is a representative photograph of the wound healing process of the control group, 3M group and LMG@GH-MA group on days 0, 1, 3, 5, 7 and 12 after treatment. Scale bar: 0.5 cm. Figure 3b is the curve of wound healing rate change of each group within 12 days.

[0032] Figure 11 To illustrate the in vivo antibacterial effect of hydrogel dressings, Figure a shows bacterial agar plate images of wound tissue homogenates from each group on day 3 post-treatment, and Figure b shows the antibacterial rate.

[0033] Figure 12 To perform transcriptomic analysis on the skin tissue after treatment, a KEGG enrichment analysis of downregulated genes in the LMG@GH-MA group compared to the control group was obtained.

[0034] Figure 13 The results of RT-qPCR analysis of Raw264.7 macrophages co-cultured with LMG@GH-MA for 24 h were... TNF-α, IL- 17A, IL-10, VEGF The relative mRNA expression level.

[0035] Figure 14 Immunohistochemical staining images of TNF-α, IL-6, and IL-10 in wound tissues of the control group, 3M group, and LMG@GH-MA group.

[0036] Figure 15 Immunofluorescence staining for TNF-α and IL-17A.

[0037] Figure 16 The quantitative wound healing effect of the LMG@GH-MA+LPS group on day 12 after treatment is shown in Figure a. Figure a is a picture of the healed tissue, Figure b is the healing rate, and Figure c is an immunofluorescence staining image of TNF-α and IL-17A in the wound tissue of the LMG@GH-MA+LPS group.

[0038] Figure 17 The antibacterial effects of Lut-Mn / MnO2 in Comparative Example 1, Comparative Example 2, and Comparative Example 3 were compared. Detailed Implementation

[0039] The embodiments of this application are hereby disclosed in detail with appropriate reference to the accompanying drawings. However, unnecessary detailed descriptions may be omitted. For example, detailed descriptions of well-known matters and repetitive descriptions of actually identical structures may be omitted. This is to avoid making the following description unnecessarily lengthy and to facilitate understanding by those skilled in the art. Furthermore, the accompanying drawings and the following description are provided to enable those skilled in the art to fully understand this application and are not intended to limit the subject matter of the claims.

[0040] The "range" disclosed in this application is defined by a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, which define the boundaries of a particular range. Ranges defined in this way can include or exclude endpoints and can be arbitrarily combined; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for a specific parameter, it is expected that ranges of 60-110 and 80-120 are also included. Furthermore, if minimum range values ​​of 1 and 2 are listed, and if maximum range values ​​of 3, 4, and 5 are listed, then the following ranges are all expected: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5. In this application, unless otherwise stated, the numerical range "ab" represents a shortened representation of any combination of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0-5" indicates that all real numbers between "0-5" have been listed in this article; "0-5" is simply a shortened representation of these numerical combinations. Furthermore, when a parameter is stated as an integer ≥2, it is equivalent to disclosing that the parameter is, for example, an integer such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0041] Unless otherwise specified, all embodiments and optional embodiments of this application can be combined to form new technical solutions.

[0042] Unless otherwise specified, all technical features and optional technical features of this application may be combined to form new technical solutions.

[0043] Unless otherwise specified, all steps in this application may be performed sequentially or randomly, preferably sequentially. For example, the method includes steps (a) and (b), indicating that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, the mention that the method may also include step (c) indicates that step (c) may be added to the method in any order. For example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc.

[0044] Unless otherwise specified, the terms "comprising" and "including" as used in this application can be open-ended or closed-ended. For example, "comprising" and "including" can mean that other components not listed may also be included, or that only the listed components may be included.

[0045] Unless otherwise specified, the term "or" is inclusive in this application. For example, the phrase "A or B" means "A, B, or both A and B". More specifically, the condition "A or B" is satisfied by any of the following conditions: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0046] Microwave-responsive hydrogel dressing The microwave-responsive hydrogel dressing of this application contains the following raw materials: (A) Hydrogel matrix; (B) Glucose oxidase; (C) A nanozyme composition comprising at least a luteolin-manganese dioxide complex; wherein the luteolin-manganese dioxide complex is a solid-phase product obtained by wet blending luteolin and nano-manganese dioxide.

[0047] As used in this text, the term "microwave-responsive hydrogel dressing" refers to the fact that external microwave stimulation can trigger the interaction of glucose oxidase and luteolin-manganese dioxide complex contained in the hydrogel dressing, thereby improving its performance. Specifically, the thermal effect of microwaves raises the temperature of the hydrogel dressing. This thermally enhanced glucose oxidase consumes glucose to produce hydrogen peroxide, while the thermally enhanced luteolin-manganese dioxide complex decomposes the hydrogen peroxide to produce oxygen. This simultaneously alleviates both hyperglycemia and hypoxia, thus fundamentally breaking the vicious cycle of "hyperglycemia-hypoxia-infection-chronic inflammation" in diabetic wounds, ultimately improving the antibacterial effect on skin wounds. In short, microwaves can trigger a cascade catalytic effect in hydrogel dressings.

[0048] The microwave conditions involved in the above microwave response type can be demonstrated as irradiation at a microwave intensity of 4 W for 20 minutes. Of course, different combinations of this intensity and irradiation time can be used to achieve controllable temperature rise, such as stabilizing the temperature at 40-45℃.

[0049] As used herein, the term "hydrogel matrix" refers to the material used in hydrogel excipients to participate in the formation of the gel product. Here, the gel product has an interconnected and uniformly distributed three-dimensional porous network structure, as is well known to those skilled in the art.

[0050] As a specific example of a hydrogel matrix, it may contain methacrylamide gelatin, methacrylamide hyaluronic acid, and a photoinitiator.

[0051] The preceding text mentioned that "the luteolin-manganese dioxide complex is a solid product obtained by wet blending luteolin and nano-manganese dioxide." As used in this text, "wet blending" refers to a process technology that uniformly mixes two or more components (such as polymers, fillers, drugs, active materials, etc.) in a liquid medium, and determines whether to separate the solid from the mixed liquid system based on the desired product form (solid or liquid phase). Its core lies in using solvents or dispersion media (such as water, NMP, DMF, etc.) to assist in achieving a more uniform and stable dispersion effect.

[0052] As a specific example of wet blending, the specific process for obtaining a solid product by wet blending includes the following steps: Luteolin and nano-manganese dioxide were fully dispersed in a dispersion medium with a pH of 7-8 to form a dispersion. The dispersion was dried and the solid phase was collected.

[0053] Here, the dispersion medium is preferably a buffer solution, such as phosphate buffer solution (PBS).

[0054] Here, drying can preferably be freeze-dried, for example, freeze-drying at -55 to -45°C for 12 to 36 hours, and particularly preferably drying at -50°C for 24 hours.

[0055] Preparation method of microwave-responsive hydrogel dressing The hydrogel dressing of this application includes the following steps: Provide hydrogel matrix; The glucose oxidase and nanozyme composition are fully dispersed with the hydrogel matrix to form a precursor solution; The precursor solution is fully cured to form a crosslinked compound, resulting in a hydrogel dressing. The nanoenzyme composition contains at least a luteolin-manganese dioxide complex; wherein the luteolin-manganese dioxide complex is a solid-phase product obtained by wet blending luteolin and nano-manganese dioxide.

[0056] Here, the implementation methods of hydrogel matrix, luteolin-manganese dioxide complex, etc. are the same as those described above, and will be briefly described here.

[0057] Here, a curing method can be demonstrated as irradiation with 405 nm blue light for 20 seconds, etc.

[0058] Here, the hydrogel matrix can be added in the process of forming the precursor solution as follows: the mass concentration of methacryloyl hyaluronic acid is 0.5-2wt%, and the mass concentration of photoinitiator is 0.05-0.2wt%.

[0059] Here, the method of adding glucose oxidase during the formation of the precursor solution can be demonstrated as follows: the mass concentration of added glucose oxidase is 2-8 wt%.

[0060] Application of microwave-responsive hydrogel dressings The above-mentioned microwave-responsive hydrogel dressing is used in the preparation of anti-diabetic chronic infection wound formulations.

[0061] As a specific example, a diabetic chronic infection wound is a diabetic wound infected with MRSA.

[0062] Here, the application of microwave-responsive hydrogel dressings in anti-diabetic chronic infection wound preparations has effects on wounds including, but not limited to, promoting wound healing and having antibacterial effects against bacteria causing the wound. Because the hydrogel dressings possess a porous structure of hydrogel cross-linking products, this facilitates gas exchange and cell migration; excellent swelling and water-retention properties effectively manage wound exudate and maintain a moist healing environment.

[0063] Here, wound healing is promoted through the following mechanisms to promote the healing of chronic infections caused by diabetes: (1) Microwave-triggered cascade catalysis: Under microwave irradiation, the hydrogel dressing is heated to 40-45℃. The heat-enhanced glucose oxidase consumes glucose to produce hydrogen peroxide, while the heat-enhanced luteolin-manganese dioxide complex decomposes hydrogen peroxide to produce oxygen, thus simultaneously alleviating high sugar and hypoxia. (2) Excellent antibacterial properties: It achieves nearly 100% clearance of MRSA by physically destroying the bacterial cell membrane; (3) Immune microenvironment remodeling: downregulates the expression of pro-inflammatory factors TNF-α, IL-6, and IL-17A, upregulates the expression of anti-inflammatory factor IL-10, and upregulates the expression of vascular endothelial growth factor VEGF; (4) Promotes cell migration: Promotes fibroblast migration and accelerates wound re-epithelialization.

[0064] It should be added that hydrogel dressings achieve immune microenvironment remodeling by inhibiting the IL-17 and TNF signaling pathways; the inhibition of the TNF-α / IL-17 pathway by hydrogel dressings is a function-dependent mechanism by which they promote wound healing.

[0065] Skin wound care methods The microwave-responsive hydrogel dressing is applied to a skin wound caused by at least a chronic infection due to diabetes, and microwave action is applied to the skin wound to which the hydrogel dressing is applied.

[0066] Here, as an example, the conditions for microwave action can be controlled heating under 4W microwave irradiation for 20 minutes, for example, the temperature stabilizing at 40-45℃.

[0067] Here, spraying can be used as a demonstrative method for dressing application. Specifically, the dressing can be evenly applied to irregular wound surfaces using a spraying device, and the thickness of the dressing can be adjusted by controlling the number of sprays.

[0068] Implementation process of the embodiments and comparative examples The following describes embodiments of this application. The embodiments described below are exemplary and are only used to explain this application, and should not be construed as limiting this application. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Reagents or instruments used, unless otherwise specified, are all conventional products that can be obtained commercially.

[0069] Example 1

[0070] I. Preparation of luteolin-manganese dioxide complex (Lut-Mn / MnO2) Step 1: Weigh 50 mg of manganese dioxide (MnO2) nanoparticles and add them to 30 mL of phosphate buffer solution (PBS, pH=7.4) containing 50 mg of luteolin (Lut); Step two, transfer the mixture to a 50 mL beaker and heat at 25±1 °C. o C. Stir continuously at 150 rpm for 24 hours in the dark.

[0071] Step 3: After stirring, centrifuge the suspension at 10,000 rpm for 10 minutes, discard the supernatant, and wash the precipitate three times with deionized water.

[0072] Step 4: Place the obtained product in a vacuum freeze dryer and freeze-dry at -50°C for 24 hours to obtain a greenish-brown powdery luteolin-manganese dioxide complex (Lut-Mn / MnO2), which is then sealed and stored at 4°C for later use.

[0073] II. Preparation of LMG@GH-MA hydrogel dressing Step 1: Mix 1 g of methacrylamide gelatin (GelMA), 0.5 g of methacrylamide hyaluronic acid (HAMA), and 20 mg of photoinitiator LAP in a ratio of 5% GelMA, 1% HAMA, and 0.1% LAP. Add the mixture to 20 mL of phosphate buffer solution to obtain the GH-MA precursor solution.

[0074] Step 2: Disperse the Lut-Mn / MnO2 prepared in Part I and glucose oxidase (GOx) in the GH-MA precursor solution at a mass ratio of 1:2, mix well, and obtain the LMG@GH-MA precursor solution.

[0075] Step 3: The LMG@GH-MA precursor solution is sprayed through a spraying device and irradiated with 405 nm blue light for 20 seconds to rapidly crosslink and form an LMG@GH-MA hydrogel dressing.

[0076] Example 2

[0077] I. Preparation of luteolin-manganese dioxide complex (Lut-Mn / MnO2) Step 1: Weigh 40 mg of manganese dioxide (MnO2) nanoparticles and add them to 30 mL of phosphate buffer solution (PBS, pH=7.2) containing 50 mg of luteolin (Lut); Step two, transfer the mixture to a 50 mL beaker and heat at 25±1 °C. o C. Stir continuously at 150 rpm for 24 hours in the dark.

[0078] Step 3: After stirring, centrifuge the suspension at 10,000 rpm for 10 minutes, discard the supernatant, and wash the precipitate three times with deionized water.

[0079] Step four: Place the obtained product in a vacuum freeze dryer at -45°C. o After freeze-drying at C for 20 hours, a greenish-brown powdery luteolin-manganese dioxide complex (Lut-Mn / MnO2) was obtained and stored in a sealed container at 4°C for later use.

[0080] II. Preparation of LMG@GH-MA hydrogel dressing Step 1: Mix 1 g of methacrylamide gelatin (GelMA), 0.5 g of methacrylamide hyaluronic acid (HAMA), and 15 mg of photoinitiator LAP in a ratio of 5% GelMA, 1% HAMA, and 0.1% LAP, and add the mixture to 20 mL of phosphate buffer solution to obtain the GH-MA precursor solution.

[0081] Step 2: Disperse the Lut-Mn / MnO2 prepared in Part I at a concentration of 4 mg / mL and glucose oxidase (GOx) at a concentration of 10 mg / mL in the GH-MA precursor solution, mix well, and obtain the LMG@GH-MA precursor solution.

[0082] Step 3: The LMG@GH-MA precursor solution is sprayed through a spraying device and irradiated with 405 nm blue light for 20 seconds to rapidly crosslink and form an LMG@GH-MA hydrogel dressing.

[0083] Example 3

[0084] I. Preparation of luteolin-manganese dioxide complex (Lut-Mn / MnO2) Step 1: Weigh 60 mg of manganese dioxide (MnO2) nanoparticles and add them to 30 mL of phosphate buffer solution (PBS, pH=7.6) containing 50 mg of luteolin (Lut); Step two, transfer the mixture to a 50 mL beaker and heat at 25±1 °C. o C. Stir continuously at 150 rpm for 24 hours in the dark.

[0085] Step 3: After stirring, centrifuge the suspension at 10,000 rpm for 10 minutes, discard the supernatant, and wash the precipitate three times with deionized water.

[0086] Step 4: Place the obtained product in a vacuum freeze dryer and freeze-dry at -55°C for 30 hours to obtain a greenish-brown powdery luteolin-manganese dioxide complex (Lut-Mn / MnO2), which is then sealed and stored at 4°C for later use.

[0087] II. Preparation of LMG@GH-MA hydrogel dressing Step 1: Mix 1.5 g of methacrylamide gelatin (GelMA), 0.5 g of methacrylamide hyaluronic acid (HAMA), and 24 mg of photoinitiator LAP in a ratio of 5% GelMA, 1% HAMA, and 0.1% LAP. Add the mixture to 20 mL of phosphate buffer solution to obtain the GH-MA precursor solution.

[0088] Step 2: Disperse the Lut-Mn / MnO2 prepared in Part I at a concentration of 4 mg / mL and glucose oxidase (GOx) at a concentration of 10 mg / mL in the GH-MA precursor solution, mix well, and obtain the LMG@GH-MA precursor solution.

[0089] Step 3: The LMG@GH-MA precursor solution is sprayed through a spraying device and irradiated with 405 nm blue light for 20 seconds to rapidly crosslink and form an LMG@GH-MA hydrogel dressing.

[0090] Example 4

[0091] I. Preparation of luteolin-manganese dioxide complex (Lut-Mn / MnO2) Step 1: Weigh 60 mg of manganese dioxide (MnO2) nanoparticles and add them to 30 mL of phosphate buffer solution (PBS, pH=7.8) containing 50 mg of luteolin (Lut); Step two, transfer the mixture to a 50 mL beaker and heat at 25±1 °C. o C. Stir continuously at 150 rpm for 24 hours in the dark.

[0092] Step 3: After stirring, centrifuge the suspension at 10,000 rpm for 10 minutes, discard the supernatant, and wash the precipitate three times with deionized water.

[0093] Step 4: Place the obtained product in a vacuum freeze dryer and freeze-dry at -50°C for 24 hours to obtain a greenish-brown powdery luteolin-manganese dioxide complex (Lut-Mn / MnO2), which is then sealed and stored at 4°C for later use.

[0094] II. Preparation of LMG@GH-MA hydrogel dressing Step 1: Mix 0.6g of methacrylamide gelatin (GelMA), 0.5g of methacrylamide hyaluronic acid (HAMA), and 14mg of photoinitiator LAP in a ratio of 5% GelMA, 1% HAMA, and 0.1% LAP. Add the mixture to 20 mL of phosphate buffer solution to obtain the GH-MA precursor solution.

[0095] Step 2: Disperse the Lut-Mn / MnO2 prepared in Part I at a concentration of 4 mg / mL and glucose oxidase (GOx) at a concentration of 10 mg / mL in the GH-MA precursor solution, mix well, and obtain the LMG@GH-MA precursor solution.

[0096] Step 3: The LMG@GH-MA precursor solution is sprayed through a spraying device and irradiated with 405 nm blue light for 20 seconds to rapidly crosslink and form an LMG@GH-MA hydrogel dressing.

[0097] Example 5

[0098] I. Preparation of luteolin-manganese dioxide complex (Lut-Mn / MnO2) Step 1: Weigh 50 mg of manganese dioxide (MnO2) nanoparticles and add them to 30 mL of phosphate buffer solution (PBS, pH=7.6) containing 55 mg of luteolin (Lut); Step two, transfer the mixture to a 50 mL beaker and heat at 25±1 °C. o C. Stir continuously at 150 rpm for 24 hours in the dark.

[0099] Step 3: After stirring, centrifuge the suspension at 10,000 rpm for 10 minutes, discard the supernatant, and wash the precipitate three times with deionized water.

[0100] Step 4: Place the obtained product in a vacuum freeze dryer and freeze-dry at -50°C for 24 hours to obtain a greenish-brown powdery luteolin-manganese dioxide complex (Lut-Mn / MnO2), which is then sealed and stored at 4°C for later use.

[0101] II. Preparation of LMG@GH-MA hydrogel dressing Step 1: Mix 1.2 g of methacrylamide gelatin (GelMA), 0.5 g of methacrylamide hyaluronic acid (HAMA), and 18 mg of photoinitiator LAP in a ratio of 5% GelMA, 1% HAMA, and 0.1% LAP. Add the mixture to 20 mL of phosphate buffer solution to obtain the GH-MA precursor solution.

[0102] Step 2: Disperse the Lut-Mn / MnO2 prepared in Part I at a concentration of 4 mg / mL and glucose oxidase (GOx) at a concentration of 10 mg / mL in the GH-MA precursor solution, mix well, and obtain the LMG@GH-MA precursor solution.

[0103] Step 3: The LMG@GH-MA precursor solution is sprayed through a spraying device and irradiated with 405 nm blue light for 20 seconds to rapidly crosslink and form an LMG@GH-MA hydrogel dressing.

[0104] Example 6

[0105] I. Preparation of luteolin-manganese dioxide complex (Lut-Mn / MnO2) Step 1: Weigh 50 mg of manganese dioxide (MnO2) nanoparticles and add them to 30 mL of phosphate buffer solution (PBS, pH=7) containing 44 mg of luteolin (Lut); Step two, transfer the mixture to a 50 mL beaker and heat at 25±1 °C. o C. Stir continuously at 150 rpm for 24 hours in the dark.

[0106] Step 3: After stirring, centrifuge the suspension at 10,000 rpm for 10 minutes, discard the supernatant, and wash the precipitate three times with deionized water.

[0107] Step 4: Place the obtained product in a vacuum freeze dryer and freeze-dry at -50°C for 24 hours to obtain a greenish-brown powdery luteolin-manganese dioxide complex (Lut-Mn / MnO2), which is then sealed and stored at 4°C for later use.

[0108] II. Preparation of LMG@GH-MA hydrogel dressing Step 1: Mix 1 g of methacrylamide gelatin (GelMA), 0.4 g of methacrylamide hyaluronic acid (HAMA), and 17 mg of photoinitiator LAP in a ratio of 5% GelMA, 1% HAMA, and 0.1% LAP. Add the mixture to 20 mL of phosphate buffer solution to obtain the GH-MA precursor solution.

[0109] Step 2: Disperse the Lut-Mn / MnO2 prepared in Part I at a concentration of 4 mg / mL and glucose oxidase (GOx) at a concentration of 10 mg / mL in the GH-MA precursor solution, mix well, and obtain the LMG@GH-MA precursor solution.

[0110] Step 3: The LMG@GH-MA precursor solution is sprayed through a spraying device and irradiated with 405 nm blue light for 20 seconds to rapidly crosslink and form an LMG@GH-MA hydrogel dressing.

[0111] Example 7

[0112] Based on Example 1, the only change is the following process condition: In the preparation process of Part II, in step two, the concentration of Lut-Mn / MnO2 is adjusted to 6 mg / mL.

[0113] Example 8

[0114] Based on Example 1, the only change is the following process condition: in the preparation process of Part II, in step two, the concentration of Lut-Mn / MnO2 is adjusted to 3 mg / mL.

[0115] Comparative Example 1 The antibacterial effect of Lut-Mn / MnO2 was investigated under the condition of omitting glucose oxidase (GOx).

[0116] Comparative Example 2 The study focused solely on the antibacterial effects of luteolin (Lut).

[0117] Comparative Example 3 The antibacterial effect of manganese dioxide (MnO2) nanoparticles was investigated only.

[0118] evaluate The following evaluation items were performed on all of the LMG@GH-MA obtained in Example 1; the following evaluation items were performed on the products obtained in Comparative Examples 1, 2, and 3. For the experimental procedures of the following evaluation items, one-way ANOVA was used for statistical comparison, with ns indicating no significant difference. "*" represents p < 0.05, "**" represents p < 0.01, "***" represents p < 0.001, and "****" represents p < 0.0001. In the figure, "**" represents the conventional marker of statistical significance, corresponding to the corresponding significance level.

[0119] FE-SEM image After freeze-drying, an appropriate amount of the hydrogel sample to be tested was fixed to the sample stage using conductive tape and sputter-coated with gold to enhance conductivity. The microstructure of the sample was observed using a field emission scanning electron microscope (FESEM, model: ZEISS Sigma 500, Zeiss GmbH, Germany), focusing on evaluating the three-dimensional porous structure of the hydrogel and the dispersion of nanoparticles in the matrix.

[0120] Microwave response performance test A TB-1-C type microwave therapy instrument was used as the microwave source, with the output power set to 4 W. The hydrogel sample to be tested was placed in the microwave radiation field and irradiated for 20 minutes. Simultaneously, an infrared thermal imager (model: FLIR E86) was used to monitor and record the temperature changes on the sample surface in real time, recording the temperature value every 2 minutes. The microwave thermal response performance of the hydrogel dressing was evaluated by analyzing the temperature-time curve and thermal image.

[0121] Evaluation of in vitro antibacterial effect The antibacterial efficacy of hydrogel dressings against methicillin-resistant Staphylococcus aureus (MRSA) was evaluated using the plate application method. MRSA bacterial suspensions were diluted to 1×10⁻⁶. 6 CFU / mL, 500 μL was mixed with an equal volume of the test sample. Experimental groups: control group (PBS), GH-MA group, LMG@GH-MA group. Each group was microwaved (4 W, 20 min) and then incubated at 37°C. o Incubate at 37°C for 24 hours. Spread an appropriate amount of the diluted solution onto an LB agar plate and incubate at 37°C. o After culturing at C for 24 h, colonies were counted and the antibacterial rate was calculated.

[0122] Cell compatibility assessment The MTT assay was used to evaluate the cytotoxicity of the hydrogel dressing to fibroblasts (NIH-3T3). Cells were sputtered at a concentration of 1 × 10⁶ cells / cells. 5 Cells were seeded per well in 96-well plates and cultured for 24 h until adherence. Then, they were co-cultured with GH-MA and LMG@GH-MA hydrogels, respectively, with fresh culture medium as a control. After 1, 3, and 5 days of co-culture, MTT solution (0.5 mg / mL) was added and incubated for 4 h. The supernatant was discarded, and DMSO was added to dissolve the crystals. The absorbance was measured at 490 nm, and cell viability was calculated.

[0123] Cell migration ability assessment The effect of hydrogel dressings on the migration ability of NIH-3T3 fibroblasts was evaluated using a scratch assay. Cells were seeded in 12-well plates and cultured to approximately 90% confluence. Straight scratches were made using a 200 μL pipette tip, and detached cells were removed by washing with PBS. LMG@GH-MA extract medium and regular medium were added, and the cells were observed and photographed under an inverted microscope at 0, 24, 48, and 72 h, respectively.

[0124] In vivo treatment efficacy evaluation Establishment of a diabetic MRSA infection rat model: Eight-week-old male SD rats (approximately 220 g) were selected and intraperitoneally injected with streptozotocin (STZ, 40 mg / kg) to induce a diabetic model. Successful model establishment was defined as two consecutive fasting blood glucose levels >16.7 mmol / L. After anesthesia, the backs of the diabetic rats were shaved and disinfected. A full-thickness skin defect was created using a 6 mm biopsy puncture instrument, and 10 μL of MRSA bacterial suspension (1×10⁻⁶) was instilled. 8 (CFU / mL), cover with gauze for 30 min to promote colonization.

[0125] Animal grouping and treatment: The successfully modeled rats were randomly divided into 3 groups (n=6): control group (no treatment), 3M group (covered with 3M medical dressing), and LMG@GH-MA group (sprayed with hydrogel dressing, cured with 405 nm blue light for 20 s, and microwave irradiated for 4 W for 20 min daily).

[0126] Wound healing rate: Wounds were photographed and recorded on days 0, 1, 3, 5, 7, and 12, and the healing rate was calculated.

[0127] In vivo antibacterial effect: On day 3, wound tissue was homogenized, diluted and spread on plates, and colonies were counted after 24 hours.

[0128] Real-time quantitative PCR (RT-qPCR) validation Raw264.7 macrophages were co-cultured with LMG@GH-M for 24 hours, then cells were collected, RNA was extracted using a total RNA extraction kit, and reverse transcribed into cDNA. RT-qPCR was performed using SYBR Green premixed buffer on a Bio-Rad CFXConnect system to detect RNA. TNF-α , IL-17A , IL-10 and VEGF The mRNA expression level of the target gene, etc.

[0129] Functional verification experiment To verify the roles of TNF-α and IL-17 signaling pathways in promoting wound healing with LMG@GH-MA, an additional functional validation group (LMG@GH-MA + LPS group) was established. Rats in this group received the exact same treatment as the LMG@GH-MA group, but received a subcutaneous injection of lipopolysaccharide (LPS, 5 mg / kg) around the wound to activate pro-inflammatory signaling pathways. On day 12 post-treatment, wound healing was assessed in both groups, and the expression levels of TNF-α and IL-17A were detected by immunofluorescence staining.

[0130] Figure 1 The image shows a scanning electron microscope image of the LMG@GH-MA hydrogel prepared in Example 1. The hydrogel dressing of this application has an interconnected three-dimensional porous structure. The luteolin-manganese dioxide complex nanoparticles (within the red box) are uniformly dispersed in the gel matrix, which is beneficial for gas exchange and cell migration.

[0131] Figure 2 To demonstrate the sprayability of the LMG@GH-MA hydrogel prepared in Example 1: Figure a shows that the precursor solution can be sprayed to form uniform droplets; Figure b shows that after spraying, the hydrogel is rapidly cross-linked after being irradiated with 405 nm blue light for 20 seconds to form a complete hydrogel, which can achieve coverage of irregular wounds without dead angles.

[0132] Figure 3 The LMG@GH-MA hydrogel prepared in Example 1 can be used to construct hydrogel dressings of different thicknesses on pigskin by controlling the number of sprayings (3, 5, 7 times), which facilitates individualized adjustment according to the needs of the wound in clinical practice.

[0133] Figure 4 The microwave responsiveness of the LMG@GH-MA hydrogel prepared in Example 1 is shown in Figure a. Infrared thermal imaging shows that the temperature of LMG@GH-MA increases significantly under microwave irradiation. The heating curve in Figure b shows that its temperature rises steadily to about 40°C, while the temperature rise of pure GH-MA is not significant, demonstrating its excellent microwave responsiveness.

[0134] Figure 5 To illustrate the thermally enhanced cascade catalytic effect of the LMG@GH-MA hydrogel prepared in Example 1, Figure a shows that glucose oxidase activity increases with increasing temperature in the range of 25-45℃; Figure b shows that at 37℃... o At C, LMG@GH-MA can stably produce oxygen, confirming that the microwave thermal effect can simultaneously enhance the cascade catalytic reaction.

[0135] Figure 6 To assess the antibacterial properties of the hydrogel prepared in Example 1, Figure a shows colony photographs. In all groups without microwave treatment, a certain amount of bacteria grew. After microwave treatment, the number of colonies in the GH-MA group decreased slightly, but a large number still survived. In contrast, the number of colonies in the LMG@GH-MA+MW group was extremely low, with almost no colony growth. Figure b shows the quantitative antibacterial rate, indicating that the LMG@GH-MA+MW group had an antibacterial rate of nearly 100% against MRSA, significantly higher than the other groups. This result demonstrates that the hydrogel dressing of this application exhibits excellent antibacterial properties under microwave assistance and can effectively eliminate multidrug-resistant bacteria.

[0136] Figure 7The image shows the cell fluorescence of the hydrogel prepared in Example 1. NIH-3T3 fibroblasts showed good morphology after co-culturing with LMG@GH-MA for 24 h, indicating that the hydrogel dressing has good cell compatibility.

[0137] Figure 8 Cell scratch assays of the hydrogel prepared for Example 1 showed that the scratch widths of the two groups were essentially the same at 0 hours. At 24, 48, and 72 hours, the cell migration distance in the LMG@GH-MA group was significantly greater than that in the control group, and the scratch area was nearly completely closed at 72 hours. This result indicates that the hydrogel dressing of this application can promote fibroblast migration, which is beneficial for accelerating wound re-epithelialization and healing. Figure 9 The hydrogel prepared for this embodiment, as detected by the MTT assay, showed that the cell survival rate remained at a high level after co-culturing with LMG@GH-MA for 1, 3, and 5 days, further confirming its good cell compatibility.

[0138] Figure 10 To illustrate the in vivo therapeutic effect of the hydrogel prepared in Example 1, Figure a shows wound photographs. In a diabetic MRSA-infected rat model, wound healing was slow in the control and 3M groups, with unclosed areas remaining until day 12. In contrast, the LMG@GH-MA group showed significantly faster wound healing, with near-closure by day 7 and almost complete healing by day 12. Figure b shows the quantitative healing rate curves, indicating that the healing rate of the LMG@GH-MA group was significantly higher than that of the control and 3M groups at all time points. This result demonstrates that the hydrogel dressing of this application can significantly accelerate the healing process of infectious diabetic wounds in vivo.

[0139] Figure 11 To illustrate the in vivo antibacterial effect of the hydrogel dressing prepared in Example 1, Figure a shows that after homogenization of wound tissue on day 3, a large number of MRSA colonies were observed on the plates of the control group and the 3M group, while the number of colonies in the LMG@GH-MA group was extremely low. Figure b shows that quantitative analysis revealed that the in vivo antibacterial rate of the LMG@GH-MA group was significantly higher than that of the other groups. This result indicates that the hydrogel dressing of this application can effectively clear MRSA infection in a complex in vivo environment, creating a sterile environment for subsequent tissue regeneration.

[0140] Figure 12 Transcriptomic analysis was performed on skin tissue from the hydrogel synthesized in Example 1 after treatment, yielding a KEGG enrichment analysis map of downregulated genes in the LMG@GH-MA group compared to the control group. The analysis showed that, compared to the control group, the differentially regulated genes in the LMG@GH-MA group were significantly enriched in key pro-inflammatory pathways such as the IL-17 signaling pathway and the TNF signaling pathway. This result indicates that the hydrogel dressing of this application fundamentally alleviates the chronic inflammatory state of diabetic wounds by inhibiting these core pro-inflammatory signaling pathways, revealing its anti-inflammatory mechanism at the transcriptomic level.

[0141] Figure 13 This refers to the relative mRNA expression levels of NF-α, IL-17A, IL-10, and VEGF in Raw264.7 macrophages after co-culturing with LMG@GH-MA for 24 h using the hydrogel synthesized in Example 1, as determined by RT-qPCR. The RT-qPCR results showed that after co-culturing with LMG@GH-MA, pro-inflammatory factors in Raw264.7 macrophages were significantly reduced. TNF-α and IL-17A The mRNA expression level of inflammatory factors was significantly downregulated, while the expression level of anti-inflammatory factors was significantly downregulated. IL-10 and vascular endothelial growth factor VEGF The mRNA expression level was significantly upregulated. This result validates the immunomodulatory effect of the hydrogel dressing in this application at the gene expression level: inhibiting pro-inflammatory responses, promoting anti-inflammatory and angiogenesis, and facilitating the transition of wounds from the inflammatory phase to the proliferative phase.

[0142] Figure 14 This is an in vivo immunohistochemical staining image of the hydrogel synthesized in Example 1. Immunohistochemical staining showed that the pro-inflammatory factors TNF-α and IL-6 were strongly positive (brown) in the wound tissue of the control and 3M groups, while the staining of TNF-α and IL-6 was significantly weakened in the LMG@GH-MA group. Conversely, the anti-inflammatory factor IL-10 showed weak staining in the control and 3M groups, but was strongly positive in the LMG@GH-MA group. This result further confirms the immunomodulatory effect of the hydrogel dressing of this application at the protein expression level, consistent with the results of transcriptomics and RT-qPCR.

[0143] Figure 15 This is an immunofluorescence staining of TNF-α and IL-17A after in vivo treatment with the hydrogel synthesized in Example 1. Immunofluorescence staining showed strong and dense fluorescence signals of TNF-α (red) and IL-17A (green) in the wound tissue of the control group and the 3M group, while the fluorescence signals of these two pro-inflammatory factors were significantly weakened in the LMG@GH-MA group. This result further corroborates the inhibitory effect of the hydrogel dressing of this application on key pro-inflammatory pathways, providing intuitive morphological evidence for understanding its immune regulatory mechanism.

[0144] Figure 16The figures show the quantitative wound healing effect on day 12 after treatment with the LMG@GH-MA+LPS hydrogel synthesized in Example 1. Figure a shows the actual healing tissue, figure b shows the healing rate, and figure c shows the immunofluorescence staining images of TNF-α and IL-17A in the wound tissue of the LMG@GH-MA+LPS group. Functional validation experiments showed that subcutaneous injection of lipopolysaccharide (LPS) to activate the TNF-α and IL-17 signaling pathways in addition to LMG@GH-MA treatment significantly weakened the wound healing effect. Figure a shows that the wound healing rate was slower in the LPS intervention group, and figure b quantitatively shows that the healing rate was significantly lower than that in the LMG@GH-MA group alone. Figure c immunofluorescence staining shows that the expression of TNF-α and IL-17A significantly rebounded after LPS intervention. This functional validation experiment provides crucial causal evidence: LPS activation of the TNF-α / IL-17 pathway directly weakens the therapeutic effect of LMG@GH-MA, demonstrating that the healing-promoting effect of the hydrogel dressing in this application functionally depends on the active inhibition of specific pro-inflammatory pathways, rather than merely a correlational observation.

[0145] Figure 17 This section explores the antibacterial effects of Lut-Mn / MnO2 under the condition of omitting glucose oxidase (GOx) in Comparative Example 1, Lut in Comparative Example 2, and MnO2 in Comparative Example 3. The results of plate coating antibacterial activity against MRSA are presented for the control group (Control), luteolin group (Lut), manganese dioxide group (MnO2), and luteolin-manganese dioxide complex group (Lut-Mn / MnO2) under microwave-free (MW-) and microwave-on (MW+) conditions. The figures clearly show that without microwave irradiation, the number of colonies in each group was relatively high, indicating limited antibacterial effect; while under microwave irradiation, the number of colonies in the Lut-Mn / MnO2 group was significantly reduced, with almost no colony growth, demonstrating the best antibacterial effect. Figure b corresponds to the quantitative antibacterial rate statistics. Data shows that, under microwave assistance, the antibacterial rate of the Lut-Mn / MnO2 composite is close to 100%, which is significantly higher than that of the Lut group and the MnO2 group, indicating that the combination of Lut and MnO2 has synergistically enhanced microwave-responsive antibacterial properties.

[0146] The above embodiments are merely illustrative of the technical solutions of this application and are not intended to limit it. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. These modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application, and they should all be covered within the scope of the claims and specification of this application. In particular, as long as there is no structural conflict, the various technical features mentioned in the embodiments can be combined in any way. This application is not limited to the specific embodiments disclosed herein, but includes all technical solutions falling within the scope of the claims.

Claims

1. A microwave-responsive hydrogel dressing, characterized in that, Its raw materials include: (A) Hydrogel matrix; (B) Glucose oxidase; (C) A nanozyme composition comprising at least a luteolin-manganese dioxide complex; wherein the luteolin-manganese dioxide complex is a solid-phase product obtained by wet blending luteolin and nano-manganese dioxide.

2. The microwave-responsive hydrogel dressing according to claim 1, characterized in that, The specific process for obtaining a solid product through wet blending includes the following steps: Luteolin and nano-manganese dioxide were fully dispersed in a dispersion medium with a pH of 7-8 to form a dispersion. The dispersion was dried and the solid phase was collected.

3. The microwave-responsive hydrogel dressing according to claim 2, characterized in that, The dispersion medium is a buffer solution.

4. The microwave-responsive hydrogel dressing according to claim 2, characterized in that, The drying process is freeze-drying.

5. The microwave-responsive hydrogel dressing according to claim 1, characterized in that, The hydrogel matrix comprises methacrylamide gelatin, methacrylamide hyaluronic acid, and a photoinitiator.

6. A method for preparing a microwave-responsive hydrogel dressing, characterized in that, Includes the following steps: Provide hydrogel matrix; The glucose oxidase and nanozyme composition are fully dispersed with the hydrogel matrix to form a precursor solution; The precursor solution is fully cured to form a crosslinked compound, resulting in a hydrogel dressing. The nanoenzyme composition contains at least a luteolin-manganese dioxide complex; wherein the luteolin-manganese dioxide complex is a solid-phase product obtained by wet blending luteolin and nano-manganese dioxide.

7. The preparation method according to claim 6, characterized in that, The curing method is irradiation with 405nm blue light.

8. The preparation method according to claim 6, characterized in that, During the formation of the precursor solution, the added concentration of glucose oxidase is 2-8 wt%, the added concentration of methacrylamide hyaluronic acid is 0.5-2 wt%, and the added concentration of photoinitiator is 0.05-0.2 wt%.

9. The use of the microwave-responsive hydrogel dressing as described in claim 1 in the preparation of anti-diabetic chronic infection wound formulations.

10. A method for caring for skin wounds, characterized in that, Apply the microwave-responsive hydrogel dressing as described in claim 1 to a skin wound caused by at least a chronic infection due to diabetes, and apply microwave action to the skin wound to which the hydrogel dressing is applied.

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