A drug electrically controlled release hydrogel patch for wound healing

Abstract

The invention discloses a hydrogel patch for wound healing, belonging to the technical field of biomedical materials. The hydrogel patch includes a sheet electrode, a conductive hydrogel, a reservoir and a flexible circuit. Two sheet electrodes are respectively attached to the two side surfaces of the conductive hydrogel to form a sandwich structure, wherein a sheet electrode has a hole in the middle; the two sheet electrodes are connected to the flexible circuit through a wire, and the flexible circuit controls the voltage difference between the two sheet electrodes; the reservoir is used for storing drug solutions, including a reservoir cavity and a reservoir hole, and the conductive hydrogel forms a closed space with the reservoir cavity through the reservoir hole, and a part of the conductive hydrogel is exposed to the outside and a part is in the reservoir cavity; the conductive hydrogel is exposed to the outside and the surface of the sheet electrode with the middle hole attached is the treatment surface facing the wound. The hydrogel patch can realize the long-term continuous supplementation of drugs in the hydrogel and the program-controlled drug release, and promote wound healing through electrical stimulation and drug release.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a drug electrically controlled-release hydrogel patch for wound healing. Background Art

[0002] Wound healing is a complex and orderly biological process, involving activation of the coagulation system, inflammatory response, proliferation of granulation tissue, re-epithelialization of skin defects, and other processes. Diabetic wounds are more difficult to heal than ordinary wounds, which is mainly related to the microcirculation problems in diabetic patients, high blood sugar environment, immune function problems, chronic inflammatory state, etc. Nowadays, there are many products on the market that can accelerate wound healing, including drugs to prevent infection, antibiotics, hydrogel dressings, cytokines, etc. Among them, hydrogel dressings are easy to apply, customizable, biosafe, green and economical, and have high patient compliance, which has attracted widespread attention.

[0003] The Chinese patent document with publication number CN116199910A discloses a conductive hydrogel dressing and a preparation method and its application in the field of diabetic wound repair. The conductive hydrogel dressing in the invention includes conductive molecules and hydrogels. The conductive molecules are doped in the hydrogel cross-linked network, and the hydrogel can react with glucose. The invention uses the reaction between hydrogel and glucose to change its conductive parameters, and then monitors the changes in blood sugar levels in the wound area of ​​diabetic patients in real time. According to the differences in blood sugar levels, targeted treatment of chronic diabetic wounds can be carried out.

[0004] A Chinese patent document with publication number CN111617306A discloses an ion-conductive hydrogel composite dressing and a preparation method thereof. The ion-conductive hydrogel composite dressing comprises a base layer, a water-absorbing layer and a hydrogel layer stacked in sequence. The water-absorbing layer is composed of carboxymethyl cellulose grafted with polyacrylic acid. The raw materials of the hydrogel layer include sodium alginate, tunicate cellulose and CaCl2. The ion-conductive hydrogel composite dressing has excellent conductivity and moisturizing properties, and can effectively promote wound healing.

[0005] The application mode of the hydrogel dressings in the above inventions is to directly apply them on the wound to play the role of anti-inflammatory and antibacterial to promote the healing of chronic wounds. Although it has certain application prospects in the field of wound healing, it has certain limitations, mainly including: (1) The fixed volume of hydrogel has a very limited drug loading capacity, which makes it difficult to achieve the effect of long-term treatment at one time, and frequent dressing changes are not conducive to wound healing, which may cause secondary damage and reduce compliance; (2) Most hydrogel dressings rely on passive diffusion as a drug release mechanism, and the drug release rate is determined by the drug concentration. The efficacy of the dressing on the wound will gradually deteriorate as the drug concentration decreases; (3) For diabetic wounds, the blood sugar at the wound changes with the patient's daily diet rhythm, so the medication rhythm at the wound also needs to be adjusted accordingly, and conventional dressings cannot meet this change demand. In summary, how to make the drug in the hydrogel continuously replenished and the release controlled is the main problem currently faced by dressings that promote the recovery of chronic wounds. Summary of the invention

[0006] In view of the deficiencies in the prior art, the present invention provides a hydrogel patch for wound healing with electrically controlled drug release. The hydrogel patch can achieve long-term continuous replenishment of drugs in the hydrogel and programmed drug release, and synergistically promotes wound healing through electrical stimulation and drug release. It has great application potential in the fields of drug controlled release and wound dressings.

[0007] The specific technical solutions adopted are as follows:

[0008] A hydrogel patch for electrically controlled drug release for wound healing, comprising a sheet electrode, a conductive hydrogel, a liquid reservoir and a flexible circuit;

[0009] Two sheet electrodes are respectively attached to the two side surfaces of the conductive hydrogel to form a sandwich structure; one of the sheet electrodes has a hole in the middle; the two sheet electrodes are connected to a flexible circuit through wires, and the flexible circuit can control the voltage difference between the two sheet electrodes;

[0010] The liquid reservoir comprises a liquid reservoir cavity and a liquid reservoir hole, the conductive hydrogel forms a closed space with the liquid reservoir cavity through the liquid reservoir hole, a part of the conductive hydrogel is exposed to the outside, and a part is in the liquid reservoir cavity; the liquid reservoir is used to store drug solution, when the liquid reservoir is filled with drug solution, the conductive hydrogel is immersed in the drug solution to supplement the drug;

[0011] The surface of the conductive hydrogel exposed to the outside and attached with a sheet electrode with a middle opening is the treatment surface facing the wound surface, and the conductive hydrogel can be in direct contact with the wound surface; the conductive hydrogel includes a conductive filler and a drug, wherein the conductive filler and the drug are doped in the hydrogel cross-linked network.

[0012] The electrically controlled drug release hydrogel patch for wound healing provided by the present invention accelerates wound healing through the synergistic effect of electrical stimulation and controlled drug release. On the one hand, when the hydrogel patch is in direct contact with the wound, the electrical circuit formed by the hydrogel patch and the wound will generate electrical stimulation to the wound. On the other hand, when a voltage difference is generated between two sheet electrodes, the release rate of the drug in the conductive hydrogel is accelerated. The greater the voltage difference, the faster the release rate. The rate at which the drug reaches the wound can be adjusted by adjusting the flexible circuit, thereby achieving control of the drug release rate.

[0013] The sheet electrode is a metal mesh electrode or a carbon mesh electrode, and the material of the metal mesh electrode is selected from titanium, nickel, aluminum, zinc, copper, iron, silver, gold or alloy.

[0014] Optionally, the conductive filler is graphene oxide, carbon nanotubes, polypyrrole, polythiophene, nanometal particles or metal nanowires, the drugs include but are not limited to metformin and curcumin, and the hydrogel material forming the hydrogel cross-linked network includes chitosan, polyvinyl alcohol, polyacrylamide or carboxymethyl chitosan.

[0015] Preferably, the mass ratio of the conductive filler to the hydrogel material forming the hydrogel cross-linked network is 0.018-0.054:1. If the mass ratio is lower than the above range, the hydrogel has poor conductivity and slow electric-controlled release response. If the mass ratio is higher than the above range, the hydrogel conductivity is too strong and electrolysis may occur on the electrode. The mass ratio of the drug to the hydrogel material forming the hydrogel cross-linked network is 0.054-0.09:1. The selection of this range refers to clinical treatment requirements.

[0016] The preparation method of the conductive hydrogel is as follows: a mixed solution containing conductive fillers, drugs and a hydrogel material forming a hydrogel cross-linking network is frozen and thawed to obtain the conductive hydrogel.

[0017] Preferably, the preparation method of the conductive hydrogel is as follows: dissolving the conductive filler and the first hydrogel material in water, heating and stirring at 90-100°C for 4-5 hours to obtain a first precursor solution; mixing the drug and the second hydrogel material and dissolving them in water, stirring evenly to obtain a second precursor solution; and mixing the first precursor solution and the second precursor solution and cooling them to obtain the conductive hydrogel.

[0018] Further preferably, in the first precursor solution, the mass concentration of the first hydrogel material is 8-10%; and in the second precursor solution, the mass concentration of the second hydrogel material is 1-3%.

[0019] The flexible circuit includes a power supply, a voltage regulating circuit, a potentiometer and a main controller arranged on a flexible substrate; the power supply supplies power to the electrically controlled drug release hydrogel patch for wound healing; the voltage regulating circuit provides a voltage difference between two sheet electrodes; the potentiometer acts as a current limiting resistor; the main controller controls the opening and closing of the voltage regulating circuit, and can set the potentiometer resistance value according to the drug administration process instructions, thereby adjusting the voltage difference between the two sheet electrodes, and continuously performs analog-to-digital conversion, acquisition and monitoring of the voltage difference between the two sheet electrodes.

[0020] Optionally, the flexible circuit also includes a wireless communication circuit, which is used to receive wireless communication instructions (medication process instructions, etc.) sent from the control terminal and transmit them to the main controller; the wireless communication instructions can also be preset in the main controller.

[0021] The liquid reservoir cavity comprises a liquid reservoir body and a liquid reservoir membrane, the liquid reservoir body and the liquid reservoir membrane are connected by adhesive to form the liquid reservoir cavity, the liquid reservoir body and the liquid reservoir membrane are both made of flexible polymer materials, and the flexible polymer materials include polydimethylsiloxane (PDMS), thermoplastic polyurethane (TPU), polybutylene terephthalate-adipate (PBAT) or linear triblock copolymer (SEBS) and other materials with an elastic modulus of less than 5MPa after molding.

[0022] The drug solution in the reservoir can be updated using a pipetting device. The concentration of the drug solution in the reservoir can be selected to be 3-5 mg / mL. The specific concentration range is selected based on clinical treatment requirements.

[0023] Preferably, the thickness of the hydrogel patch for wound healing with electrically controlled drug release is 2-6 mm, and further 3-5 mm. The hydrogel patch is thin, flexible, can fit the curvature of the skin, and is easy to use.

[0024] The present invention also provides the application of the hydrogel patch for wound healing with electrically controlled drug release in the field of biomedical materials. Specifically, the hydrogel patch can be used to prepare a therapeutic patch for promoting wound healing.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] (1) The replenishability of the drug solution in the reservoir of the hydrogel patch for wound healing provided by the present invention overcomes the defect of limited drug loading capacity of conventional hydrogel dressings and avoids secondary damage to the wound during the dressing change process.

[0027] (2) For diabetic wounds, the blood sugar level at the wound site changes rhythmically with the patient's lifestyle and diet. The conductive hydrogel in the electrically controlled drug release hydrogel patch for wound healing provided by the present invention releases drugs under program control to meet the rhythmic changes in medication for diabetic patients' wounds.

[0028] (3) The drug electrically controlled release hydrogel patch for wound healing provided by the present invention accelerates wound healing through the synergistic effect of electrical stimulation and drug controlled release. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 It is a structural diagram of the hydrogel patch for electrically controlled drug release for wound healing.

[0030] Figure 2 The present invention is a block diagram of the flexible circuit system in the hydrogel patch for electrically controlled drug release for wound healing.

[0031] Figure 3 It is a drug release curve diagram of the wound healing drug electrically controlled release hydrogel patch under different voltages.

[0032] Figure 4 It is a drug release curve diagram of the wound healing drug electrically controlled release hydrogel patch after multiple drug supplements.

[0033] Figure 5 This is a picture of the wound healing effect in animal experiments.

[0034] Reference numerals: 1 flexible circuit, 11 power supply, 12 main controller, 13 voltage regulating circuit, 14 wireless communication circuit, 15 potentiometer, 21 liquid reservoir membrane, 22 liquid reservoir body, 31 first sheet electrode, 32 second sheet electrode, 4 conductive hydrogel. DETAILED DESCRIPTION

[0035] The present invention will be further described below in conjunction with the examples and drawings. It should be understood that these examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention. The operating methods in the following examples that do not specify specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturer. Contents not described in detail in this specification belong to prior art known to professionals and technicians in the field.

[0036] Example 1

[0037] Figure 1 Schematic diagram of the structure of the hydrogel patch for wound healing, which includes sheet electrodes, conductive hydrogel, a liquid reservoir and a flexible circuit, with a thickness of 5 mm; wherein the sheet electrodes are titanium mesh electrodes, the first sheet electrode 31 and the second sheet electrode 32 are both 80 mesh, 0.1 mm in wire diameter, and 20 mm × 20 mm in size, and the second sheet electrode 32 is provided with a hole with a diameter of 18 mm.

[0038] The first sheet electrode 31 and the second sheet electrode 32 are respectively attached to the two side surfaces of the conductive hydrogel 4 to form a sandwich structure, and are connected to the flexible circuit 1 through wires.

[0039] The flexible circuit 1 includes a power supply 11, a voltage regulating circuit 13, a wireless communication circuit 14, a potentiometer 15 and a main controller 12 arranged on a flexible substrate; the flexible substrate adopts a polyimide substrate with a thickness of 0.12 mm, the power supply 11 uses a button battery to power the drug controlled release hydrogel patch, the main controller 12 is specifically a microcontroller (MCU) with Bluetooth function, the voltage regulating circuit 13 is a DC-DC voltage regulating circuit, which provides a voltage difference between the first sheet electrode 31 and the second sheet electrode 32, the potentiometer 15 plays the role of a current limiting resistor, the wireless communication circuit 14 is used to receive wireless communication instructions (drug administration process instructions, voltage change process instructions, etc.) sent from the control terminal, and transmit them to the main controller 12, and the wireless communication instructions can also be preset in the main controller 12; the main controller 12 controls the opening and closing of the voltage regulating circuit 13, and can set the resistance value of the potentiometer 15 according to the drug administration process instructions, thereby adjusting the voltage difference between the first sheet electrode 31 and the second sheet electrode 32, and continuously performs analog-to-digital conversion and acquisition monitoring on the voltage difference between the two sheet electrodes to maintain a stable voltage supply. The block diagram of the flexible circuit system is shown in FIG. Figure 2 shown.

[0040] The liquid reservoir comprises a liquid reservoir cavity and a liquid reservoir hole. The liquid reservoir cavity comprises a liquid reservoir body 22 and a liquid reservoir membrane 21. The liquid reservoir body 22 is 50 mm long, 20 mm wide and 4 mm deep. The diameter of the liquid reservoir hole is 20 mm. The liquid reservoir body 22 and the liquid reservoir membrane 21 are connected by adhesive to form the liquid reservoir cavity. The liquid reservoir body 22 and the liquid reservoir membrane 21 are both made of polydimethylsiloxane (PDMS), which has good flexibility and can be bent, twisted or stretched. The conductive hydrogel 4 forms a closed space with the liquid reservoir cavity through the liquid reservoir hole. A part of the conductive hydrogel 4 is exposed to the outside and a part is in the liquid reservoir cavity. The liquid reservoir is used for storing drug solutions. When the liquid reservoir is filled with drug solutions, the conductive hydrogel is immersed in the drug solution to replenish the drugs.

[0041] The conductive hydrogel is preferably 20 mm in diameter and 5 mm in thickness. The invention discloses a conductive hydrogel having a cylindrical shape of mm, comprising graphene oxide and metformin, wherein the graphene oxide and metformin are doped in a hydrogel cross-linked network, and the hydrogel cross-linked network is formed by hydrogel materials chitosan and polyvinyl alcohol; specifically, the preparation method of the conductive hydrogel is as follows: dissolving graphene oxide and polyvinyl alcohol in water, heating and stirring at 95°C for 5 hours to obtain a first precursor solution (in the first precursor solution, the mass concentration of polyvinyl alcohol is 9%); dissolving metformin and chitosan in water, stirring and mixing at room temperature to obtain a second precursor solution (in the second precursor solution, the mass concentration of chitosan is 2%); mixing the first precursor solution and the second precursor solution in a volume ratio of 1:1 and stirring (in the mixed solution, the ratio of the mass of graphene oxide to the mass sum of polyvinyl alcohol and chitosan is 0.036:1, and the ratio of the mass of metformin to the mass sum of polyvinyl alcohol and chitosan is 0.054:1), and performing three cycles of freezing and thawing at -20°C to form a conductive hydrogel.

[0042] The surface of the conductive hydrogel 4 exposed to the outside and attached with the second sheet electrode 32 is the treatment surface facing the wound surface, and the conductive hydrogel 4 can be in direct contact with the wound surface. When a voltage is applied to the first sheet electrode 31 and the second sheet electrode 32, the conductive hydrogel is energized to accelerate the release of the drug, and the skin wound is electrically stimulated at the same time, accelerating the healing of the wound.

[0043] Example 2

[0044] In this embodiment, the structure of the wound healing drug electrically controlled release hydrogel patch is the same as that of Embodiment 1, except that a different conductive hydrogel is used;

[0045] In this embodiment, the preparation method of the conductive hydrogel is as follows: carbon nanotubes and polyvinyl alcohol are dissolved in water, heated and stirred at 95°C for 5 hours to obtain a first precursor solution; metformin and chitosan are mixed and dissolved in water, and stirred and mixed evenly at room temperature to obtain a second precursor solution; the first precursor solution and the second precursor solution are mixed in a volume ratio of 1:1 and then stirred (in the mixed solution, the ratio of the mass of the carbon nanotubes to the sum of the mass of polyvinyl alcohol and chitosan is 0.018:1, and the ratio of the mass of metformin to the sum of the mass of polyvinyl alcohol and chitosan is 0.054:1), and three cycles of freeze-thaw are performed at -20°C to form a conductive hydrogel.

[0046] Example 3

[0047] In this embodiment, the structure of the hydrogel patch for wound healing drug electrical controlled release is the same as that of embodiment 1, except that a different conductive hydrogel is used;

[0048] In this embodiment, the preparation method of the conductive hydrogel is as follows: graphene oxide and polyvinyl alcohol are dissolved in water, heated and stirred at 95°C for 5 hours to obtain a first precursor solution; metformin and chitosan are mixed and dissolved in water, and stirred and mixed evenly at room temperature to obtain a second precursor solution; the first precursor solution and the second precursor solution are mixed in a volume ratio of 1:1 and then stirred (in the mixed solution, the ratio of the mass of carbon nanotubes to the sum of the mass of polyvinyl alcohol and chitosan is 0.054:1, and the ratio of the mass of metformin to the sum of the mass of polyvinyl alcohol and chitosan is 0.09:1), and three cycles of freeze-thaw are performed at -20°C to form a conductive hydrogel.

[0049] Sample analysis

[0050] Taking the hydrogel patch for wound healing with electrically controlled drug release in Example 1 as an example, the function of the hydrogel patch was verified;

[0051] A uniform voltage was applied to the conductive hydrogel in the wound healing drug controlled release hydrogel patch, and the voltage value was changed. The drug release concentration under the applied voltage of 0V, 1V, and 2V was measured by UV spectrophotometer to verify the relationship between voltage and drug release. Figure 3 As shown in Figure 3, the drug release increases with increasing voltage. At 0V, the drug passively diffuses from the hydrogel at a steady and slow rate, which is about half of the rate at 1V and a quarter of the rate at 2V.

[0052] A fixed voltage of 1V was applied to the wound healing drug controlled release hydrogel patch, and the drug release was measured at the same time interval. When the measured initial drug release curve tended to be flat, it meant that the initial drug loading in the conductive hydrogel was about to be released. At this time, 2 ml of drug solution (3 mg / ml metformin solution) was injected into the reservoir, and the drug curve measurement was continued. It was observed that the drug was released again. The above steps were repeated later, and the results showed that ( Figure 4 ), within 15 days, a single replenishment of drug solution can enable the hydrogel to meet 5 days of release requirements, significantly extending the treatment time of the hydrogel patch.

[0053] Thirty male Sprague-Dawley (SD) rats aged 6 weeks (200-250 g) were used. After fasting for 16 hours, a single intraperitoneal injection of 65 mg / Kg of streptozotocin (STZ) was used to establish a diabetic disease model. The blood glucose level of the rats was monitored three days later, and the blood glucose and body weight were tested twice within a week for a total of two weeks. If the blood glucose level was >16.7mmol / L and accompanied by polyphagia, polydipsia, polyuria and weight loss, the diabetic rat model was considered successful, and the wound model was further established. The rats were anesthetized by intraperitoneal injection of pentobarbital (35 mg / kg). After anesthesia, the diabetic rats were shaved and a circular wound with a diameter of 1.8 cm was made in the center of the dorsal side of each rat. The rats were then divided into three experimental groups, with blank hydrogel (no metformin was added during the synthesis process in Example 1), drug-loaded hydrogel dressing (conductive hydrogel in Example 1), and wound healing drug electrically controlled release hydrogel patch in Example 1 covering the wound (applying electrical stimulation and supplementing drugs), and an additional blank control group was set up. Wound images were collected and wound size measurements were taken at 0, 3, 7, 10, 14, 17, and 21 days. The results are shown in Figure 2. Figure 5 As shown, it can be seen that during the treatment, the overall wound area tends to decrease. During the first 10 days of treatment, the wounds of the rats in the control group did not show obvious healing effects. Compared with the blank group, the blank hydrogel showed a slight therapeutic effect, indicating that the hydrogel itself also has a certain effect in promoting wound healing. Compared with the blank hydrogel, the therapeutic effect of the drug-loaded hydrogel dressing was further enhanced, proving that the selected model drug metformin has the effect of promoting wound healing. The wound healing drug electro-controlled release hydrogel patch group showed a more obvious therapeutic effect and faster healing rate than the other three groups, and obvious wound closure was observed on the 14th day.

[0054] The embodiments described above provide a detailed description of the technical solutions of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, supplements or similar substitutions made within the scope of the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A drug electrically controlled release hydrogel patch for wound healing, characterized in that: Includes sheet electrodes, conductive hydrogels, liquid reservoirs, and flexible circuits; Two sheet electrodes are respectively attached to the two side surfaces of the conductive hydrogel to form a sandwich structure; one of the sheet electrodes has a hole in the middle; the two sheet electrodes are connected to a flexible circuit through wires, and the flexible circuit can control the voltage difference between the two sheet electrodes; The liquid reservoir comprises a liquid reservoir cavity and a liquid reservoir hole, the conductive hydrogel forms a closed space with the liquid reservoir cavity through the liquid reservoir hole, a part of the conductive hydrogel is exposed to the outside, and a part of it is in the liquid reservoir cavity; the liquid reservoir is used to store drug solution, when the liquid reservoir is filled with drug solution, the conductive hydrogel is immersed in the drug solution to replenish the drug; the liquid reservoir cavity comprises a liquid reservoir body and a liquid reservoir membrane, the liquid reservoir body and the liquid reservoir membrane are viscose-connected to form the liquid reservoir cavity, and the materials of the liquid reservoir body and the liquid reservoir membrane are both flexible polymer materials; the drug solution in the liquid reservoir can be updated by using a pipetting device; The surface of the conductive hydrogel exposed to the outside and attached with the sheet electrode with the middle opening is the treatment surface facing the wound surface, and the conductive hydrogel can be in direct contact with the wound surface; the conductive hydrogel includes a conductive filler and a drug, wherein the conductive filler and the drug are doped in the hydrogel cross-linked network; The flexible circuit includes a power supply, a voltage regulating circuit, a potentiometer and a main controller arranged on a flexible substrate; the power supply supplies power to the electrically controlled drug release hydrogel patch for wound healing; the voltage regulating circuit provides a voltage difference between two sheet electrodes; the potentiometer acts as a current limiting resistor; the main controller controls the opening and closing of the voltage regulating circuit, and can set the potentiometer resistance value according to the drug administration process instructions, thereby adjusting the voltage difference between the two sheet electrodes, and continuously performs analog-to-digital conversion, acquisition and monitoring of the voltage difference between the two sheet electrodes.

2. The drug electrically controlled release hydrogel patch for wound healing according to claim 1, characterized in that: The sheet electrode is a metal mesh electrode or a carbon mesh electrode, and the material of the metal mesh electrode is selected from titanium, nickel, aluminum, zinc, copper, iron, silver, gold or alloy.

3. The drug electrically controlled release hydrogel patch for wound healing according to claim 1, characterized in that: The conductive filler includes graphene oxide, carbon nanotubes, polypyrrole, polythiophene, nano-metal particles or metal nanowires; the drug includes metformin or curcumin; and the hydrogel material forming the hydrogel cross-linked network includes chitosan, polyvinyl alcohol, polyacrylamide or carboxymethyl chitosan.

4. The drug electrically controlled release hydrogel patch for wound healing according to claim 1, characterized in that: The mass ratio of the conductive filler to the hydrogel material forming the hydrogel cross-linking network is 0.018-0.054:1, and the mass ratio of the drug to the hydrogel material forming the hydrogel cross-linking network is 0.054-0.09:

1.

5. The drug electrically controlled release hydrogel patch for wound healing according to claim 1, characterized in that: The preparation method of the conductive hydrogel is as follows: a mixed solution containing conductive fillers, drugs and a hydrogel material forming a hydrogel cross-linking network is frozen and thawed to obtain the conductive hydrogel.

6. The drug electrically controlled release hydrogel patch for wound healing according to claim 1, characterized in that: The flexible polymer material includes polydimethylsiloxane, thermoplastic polyurethane, polybutylene terephthalate-adipate or linear triblock copolymer.

7. The drug electrically controlled release hydrogel patch for wound healing according to claim 1, characterized in that: The concentration of the drug solution in the reservoir is 3-5 mg / mL.

8. The wound healing drug electrically controlled release hydrogel patch according to claim 1, characterized in that: The thickness is 2-6mm.

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