Electroactive wound dressing system based on magnetoelectric technology and preparation method and application thereof

Abstract

The invention discloses an electroactive wound dressing system based on a magnetoelectric technology and a preparation method and application thereof, and belongs to the technical field of wound healing medical instruments, and the electroactive wound dressing system based on the magnetoelectric technology comprises a magnetoelectric composite electroactive wound dressing, a portable medical backpack and a mobile application program. The magnetoelectric composite electroactive wound dressing is high in biocompatibility, the current output level is in the microampere level, the biological regulation and control requirement can be met, a user can achieve sequential implementation of a programmed time sequence regulation and control strategy through a mobile application program on electronic equipment, and the application range is wide. Current output of the magnetoelectric composite electroactive wound dressing is adjusted wirelessly, quickly and accurately, so that on-demand electrical stimulation treatment is realized, and ultra-fast early wound healing is realized.

Description

Technical Field

[0001] The present invention relates to the technical field of wound healing medical instruments, and in particular to an electroactive wound dressing system based on magnetoelectric technology, and a preparation method and application thereof. Background Art

[0002] Wounds that exceed a critical size will take a long time to heal, and delayed healing may hinder functional recovery and increase the risk of complications. Wound healing is a dynamic and complex process, which is mainly mediated by two complex biological phases, namely the inflammatory phase and the proliferative phase. During the inflammatory phase, the recruitment and regulation of immune cells, especially macrophages, are key steps in the initial formation of the regenerative environment; while during the proliferative phase, the migration and proliferation of fibroblasts make an important contribution to tissue repair. Long-term or insufficient inflammation may lead to chronic damage or abnormal regenerative environment formation, while improper activity of fibroblasts may lead to insufficient healing quality or scar formation. Therefore, programmed temporal regulation of the inflammatory and proliferative phases plays a vital role in tissue regeneration.

[0003] Traditional tissue repair methods mainly include drug-controlled delivery systems and multi-component complex material systems. However, due to the difficulty in accurately controlling the release of drugs or functional substances at a specific time point, these strategies cannot effectively act on target cells at a specific time, thus hindering the programmed timing regulation of wound healing. Compared with traditional methods, electrotherapy has significant advantages, with a wide range of biological effects and good biosafety. However, most current clinical electrotherapy delivery methods mainly rely on direct contact between wires and patient tissues, which brings risks such as inconvenient user experience, local contact infection, and unstable transcutaneous current input. Therefore, achieving wireless power output is of great significance in medical applications.

[0004] Previous studies have shown that an appropriate and stable current output level is an indispensable factor for the effectiveness of electrical stimulation therapy, and microampere-level currents are believed to have significant biological effects in promoting stem cell differentiation, immune regulation, metabolic reprogramming, etc. Piezoelectric or triboelectric technology has been applied in the biomedical field, including wireless regulation of tissue repair, energy supply, and information transmission. However, the current values ​​generated by the above methods fail to meet the microampere level requirements, and their output levels are limited to the nanoampere level. Therefore, there is an urgent need to develop new electroactive wound dressings with efficient and stable electrical stimulation outputs to accelerate wound healing. Summary of the invention

[0005] The purpose of the present invention is to provide an electroactive wound dressing system based on magnetoelectric technology, and a preparation method and application thereof. The electroactive wound dressing system based on magnetoelectric technology provided by the present invention can achieve efficient and stable microampere-level current stimulation output, and realize ultra-fast early wound healing.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides an electroactive wound dressing system based on magnetoelectric technology, including a magnetoelectric composite electroactive wound dressing, a portable medical backpack and a mobile application;

[0008] The portable medical backpack is integrated with a transmitting terminal device to programmatically control the current output of the magneto-electric composite electro-active wound dressing;

[0009] The magnetoelectric composite electroactive wound dressing comprises a three-layer structure, wherein the outer layer is a PVA insulating packaging layer, the middle layer is a LM receiving coil, and the inner layer is a GelMA-BP conductive hydrogel layer;

[0010] The mobile application is installed on the user's electronic device.

[0011] The present invention also provides a method for preparing the magnetoelectric composite electroactive wound dressing system of the above technical solution, wherein the magnetoelectric composite electroactive wound dressing and the portable medical backpack are connected by a conductive material; the method for preparing the magnetoelectric composite electroactive wound dressing comprises the following steps:

[0012] (1) mixing polyvinyl alcohol and deionized water, and heating and stirring to obtain a polyvinyl alcohol solution;

[0013] Pour the polyvinyl alcohol solution into a mold, perform freeze-thaw cycle treatment, repeat the freeze-thaw cycle treatment 2 to 4 times, and obtain a PVA insulating packaging layer;

[0014] The freeze-thaw cycle process includes sequentially cooling, freezing and thawing;

[0015] (2) using a multifunctional flexible electronic printing device to print an LM receiving coil on the surface of the PVA insulating packaging layer obtained in step (1);

[0016] The material of the LM receiving coil is gallium-indium alloy;

[0017] (3) after mixing the methacrylated gelatin (abbreviated as GeMA) foam and the initiator solution, heating them in a water bath and adding black phosphorus (abbreviated as BP) solution in a light-proof and shaking condition, a GelMA-BP mixed solution is obtained;

[0018] The GelMA-BP mixed solution is dripped onto the LM receiving coil obtained in step (2), and subjected to photocuring treatment to form a GelMA-BP conductive hydrogel layer, thereby obtaining a magnetoelectric composite electroactive wound dressing.

[0019] Preferably, the concentration of polyvinyl alcohol in the polyvinyl alcohol solution in step (1) is 7wt% to 15wt%; and the molecular weight of the polyvinyl alcohol is 75,000 to 80,000.

[0020] Preferably, the freeze-thaw cycle treatment in step (1) comprises sequentially cooling at room temperature, freezing at -25°C to -15°C for 10 to 14 hours, and thawing at 20 to 28°C for 4 to 8 hours.

[0021] Preferably, the printing parameters in step (2) include: line width of 150-300 μm, line spacing of 100-180 μm, and number of coils of 8-14 turns.

[0022] Preferably, the water bath heating temperature in step (2) is 50 to 80° C., and the water bath heating time is 15 to 40 minutes.

[0023] Preferably, the light used for the photocuring treatment in step (3) is UV light, and the time of the photocuring treatment is 30 to 60 seconds.

[0024] Preferably, the portable medical backpack is designed by 3ds Max software and then 3D printed by a light-curing 3D printer;

[0025] The portable medical backpack also includes a transmitting coil, a microcontroller unit, a Bluetooth module and an inverter;

[0026] The transmitting coil is placed at the lowest end to minimize the distance to the magneto-electric composite electro-active wound dressing;

[0027] The inverter is used to convert the DC voltage input by the microcontroller unit into a high-frequency current. After the high-frequency current passes through the transmitting coil, a high-frequency magnetic field is generated around the backpack. Through the principle of electromagnetic induction, an induced high-frequency current is generated in the LM receiving coil in the magnetoelectric composite electroactive wound dressing, thereby acting on the wound.

[0028] The user can wirelessly control the input voltage of the transmitter through the mobile application on the electronic device and the Bluetooth module, thereby realizing programmed regulation of the current output of the magnetoelectric composite electroactive wound dressing.

[0029] Preferably, the dimensions of the transmitting coil are: made of silk-covered wire, with an inner diameter of 15 to 30 mm, an outer diameter of 30 to 50 mm, and a thickness of 1.5 to 3.5 mm.

[0030] The present invention also provides the application of the electroactive wound dressing system based on magnetoelectric technology described in the above technical solution in an electroactive wound healing medical instrument.

[0031] The present invention provides an electroactive wound dressing system based on magnetoelectric technology, including a magnetoelectric composite electroactive wound dressing, a portable medical backpack and a mobile application; the portable medical backpack integrates a transmitting terminal device to programmatically control the current output of the magnetoelectric composite electroactive wound dressing; the magnetoelectric composite electroactive wound dressing includes a three-layer structure, the outer layer is a PVA insulating packaging layer, the middle layer is a LM receiving coil, and the inner layer is a GelMA-BP conductive hydrogel layer; the mobile application is installed on the user's electronic device. Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0032] (1) The magnetoelectric composite electroactive wound dressing described in the present invention has the advantages of simple structure, low cost, good softness, strong conductivity and strong biocompatibility. The LM receiving coil printed by the multifunctional flexible electronic device can adapt to wounds of different sizes and shapes and has strong adaptability; (2) The magnetoelectric composite electroactive wound dressing described in the present invention is not limited by surface charge, and can respond to the magnetic field changes of the transmitting terminal to generate a high level of current. The current output level is at the microampere level, which can meet the needs of biological regulation; (3) For the current output parameters of the magnetoelectric composite electroactive wound dressing described in the present invention, the user can adjust it wirelessly, quickly and accurately through the mobile application on the electronic device, thereby realizing on-demand electrical stimulation treatment and accurately regulating the various stages of wound regeneration; (4) The programmed timing control strategy of the user through the mobile application on the electronic device described in the present invention has a good regulatory effect on the polarization conversion of macrophages in the inflammatory phase and the proliferation and migration ability of fibroblasts in the proliferative phase, and finally realizes ultra-fast early wound healing. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is a schematic diagram of the structure of the magnetoelectric composite electroactive wound dressing prepared in Example 1 of the present invention;

[0034] Figure 2 This is a SEM image of the GelMA-BP conductive hydrogel layer prepared in Example 1 of the present invention;

[0035] Figure 3 A schematic diagram of the magnetoelectric composite electroactive wound dressing prepared in Example 1 of the present invention receiving the high-frequency magnetic field generated by the transmitting end device in the portable medical backpack;

[0036] Figure 4 This is a graph showing the variation trend of ACRMS generated by the LM receiving coil in the magnetoelectric composite electroactive wound dressing according to Example 1 of the present invention with respect to voltage and distance;

[0037] Figure 5 This is a trend diagram of the ACRMS generated by the LM receiving coil in the magnetoelectric composite electroactive wound dressing in Example 1 of the present invention as a function of angle;

[0038] Figure 6 This is a schematic diagram of the working principle of the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention;

[0039] Figure 7 A schematic diagram of a portable medical backpack prepared in Example 1 of the present invention;

[0040] Figure 8 This is a live / dead cell staining image after macrophages and fibroblasts are electrically stimulated by the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention;

[0041] Fig. 9 Schematic diagram of the programmed timing control strategy of the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention;

[0042] Fig.10 This is a physical picture of the electroactive wound dressing system based on magnetoelectric technology used in Example 1 of the present invention for treating critical-sized full-thickness skin defects on the back of rats;

[0043] Fig.11 The actual pictures of the back wounds of rats on days 0, 3, 7 and 14 after being treated with the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention;

[0044] Fig.12 The wound healing trajectory simulation and wound healing rate statistics of rat back wounds on days 0, 3, 7 and 14 after treatment with the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention. DETAILED DESCRIPTION

[0045] The present invention provides an electroactive wound dressing system based on magnetoelectric technology, including a magnetoelectric composite electroactive wound dressing, a portable medical backpack and a mobile application;

[0046] The portable medical backpack is integrated with a transmitting terminal device to programmatically control the current output of the magneto-electric composite electro-active wound dressing;

[0047] The magnetoelectric composite electroactive wound dressing comprises a three-layer structure, wherein the outer layer is a PVA insulating packaging layer, the middle layer is a LM receiving coil, and the inner layer is a GelMA-BP conductive hydrogel layer;

[0048] The mobile application is installed on the user's electronic device.

[0049] The present invention also provides a method for preparing the magnetoelectric composite electroactive wound dressing system of the above technical solution, wherein the magnetoelectric composite electroactive wound dressing and the portable medical backpack are connected by a conductive material; the method for preparing the magnetoelectric composite electroactive wound dressing comprises the following steps:

[0050] (1) mixing polyvinyl alcohol and deionized water, and heating and stirring to obtain a polyvinyl alcohol solution;

[0051] Pour the polyvinyl alcohol solution into a mold, perform freeze-thaw cycle treatment, repeat the freeze-thaw cycle treatment 2 to 4 times, and obtain a PVA insulating packaging layer;

[0052] The freeze-thaw cycle process includes sequentially cooling, freezing and thawing;

[0053] (2) using a multifunctional flexible electronic printing device to print an LM receiving coil on the surface of the PVA insulating packaging layer obtained in step (1);

[0054] The material of the LM receiving coil is gallium-indium alloy;

[0055] (3) After mixing the methacrylated gelatin and the initiator solution, heating in a water bath and adding the black phosphorus solution in a light-proof and shaking condition to obtain a GelMA-BP mixed solution;

[0056] The GelMA-BP mixed solution is dripped onto the LM receiving coil obtained in step (2), and subjected to photocuring treatment to form a GelMA-BP conductive hydrogel layer, thereby obtaining a magnetoelectric composite electroactive wound dressing.

[0057] In one embodiment, the heating and stirring temperature is 80-95° C.; the heating and stirring time is 0.5-2 h.

[0058] In one embodiment, the concentration of polyvinyl alcohol in the polyvinyl alcohol solution is 7wt% to 15wt%; the molecular weight of the polyvinyl alcohol is 75,000 to 80,000; and the polyvinyl alcohol is in powder form.

[0059] In one embodiment, the thickness of the polyvinyl alcohol solution in the mold is 1 to 3 mm.

[0060] In one embodiment, the freeze-thaw cycle treatment includes sequentially cooling at room temperature, freezing at -25°C to -15°C for 10 to 14 hours, and thawing at 20 to 28°C for 4 to 8 hours.

[0061] In one embodiment, the thickness of the PVA insulating packaging layer is 1 to 3 mm.

[0062] In one embodiment, the multifunctional flexible electronic printing device is DB100 produced by Shanghai Mifang Company.

[0063] In one embodiment, the printing parameters include: line width of 150-300 μm, line spacing of 100-180 μm, and number of coils of 8-14 turns.

[0064] In one embodiment, the gallium-indium alloy was purchased from Dongguan Huatai Metal Material Technology Co., Ltd., with a melting point of 16°C and an electrical conductivity of 3.40×10 6 S / m (at 20°C).

[0065] In one embodiment, the water bath heating temperature is 50-80° C., and the water bath heating time is 15-40 min.

[0066] In one embodiment, the initiator in the initiator standard solution is LAP; the concentration of the initiator in the initiator standard solution is 0.001-0.004 g / mL. In one embodiment, the concentration of the initiator in the initiator standard solution is 0.0025 g / mL.

[0067] In one embodiment, the concentration of GelMA in the GelMA-BP mixed solution is 5-30 g / mL, and the concentration of BP is 100 μg / mL.

[0068] In one embodiment, the BP solution is added at a temperature of 35-39°C.

[0069] In one embodiment, the light used in the light curing process is UV light, and the time of the light curing process is 30 to 60 seconds.

[0070] In one embodiment, the GelMA-BP conductive hydrogel layer has a thickness of 3 to 5 mm.

[0071] In one embodiment, the portable medical backpack is designed by 3ds Max software and then 3D printed by a light-curing 3D printer;

[0072] The portable medical backpack also includes a transmitting coil, a microcontroller unit, a Bluetooth module and an inverter; the transmitting coil is placed at the bottom to minimize the distance from the magnetoelectric composite electroactive wound dressing. The Bluetooth module is used to wirelessly control the magnitude of the input voltage of the transmitting end by a mobile application on the electronic device. Afterwards, the DC voltage input by the microcontroller unit is converted into a high-frequency current after passing through the inverter. The high-frequency current generates a high-frequency magnetic field around the backpack after passing through the transmitting coil, and an induced high-frequency current is induced in the LM coil in the magnetoelectric composite electroactive wound dressing through the principle of electromagnetic induction.

[0073] The inverter is used to convert the DC voltage input by the microcontroller unit into a high-frequency current, and the high-frequency current generates a high-frequency magnetic field through the transmitting coil;

[0074] The user controls the input voltage of the transmitter through the mobile application on the electronic device and the Bluetooth module, thereby realizing programmed regulation of the current output of the magnetoelectric composite electroactive wound dressing.

[0075] The slight movement of the medical backpack in the present invention will not affect the continuous electrical stimulation, and more importantly, will not affect the healing of the wound.

[0076] In one embodiment, the raw material used for 3D printing is 405nm white UV sensitive resin.

[0077] In one embodiment, the dimensions of the transmitting coil are: made of silk-covered wire, with an inner diameter of 15 to 30 mm, an outer diameter of 30 to 50 mm, and a thickness of 1.5 to 3.5 mm.

[0078] In one embodiment, the microcontroller unit is MCU, Android.

[0079] In one embodiment, the Bluetooth module is HC-05.

[0080] In one embodiment, the inverter is XKT-412; the operating voltage of the inverter is 4-12V; the operating frequency of the inverter is 75-85kHz.

[0081] The present invention also provides the application of the electroactive wound dressing system based on magnetoelectric technology described in the above technical solution in an electroactive wound healing medical instrument.

[0082] In one embodiment, a user utilizes a mobile application on an electronic device in conjunction with a Bluetooth module to programmatically control the current output of the magnetoelectric composite electroactive wound dressing.

[0083] The electroactive wound dressing system based on magnetoelectric technology provided by the present invention can wirelessly, quickly and accurately adjust the current output parameters of the magnetoelectric composite electroactive wound dressing through applications on electronic devices including smart phones, thereby realizing on-demand electrical stimulation treatment, accurately regulating the various stages of wound regeneration, and realizing ultra-fast early wound healing.

[0084] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0085] Example 1

[0086] An electroactive wound dressing system based on magnetoelectric technology, comprising a magnetoelectric composite electroactive wound dressing and a portable medical backpack;

[0087] The portable medical backpack is integrated with a transmitting terminal device to programmatically control the current output of the magneto-electric composite electro-active wound dressing;

[0088] The magnetoelectric composite electroactive wound dressing comprises a three-layer structure, wherein the outer layer is a PVA insulating packaging layer, the middle layer is a LM receiving coil, and the inner layer is a GelMA-BP conductive hydrogel layer.

[0089] The preparation method of the magnetoelectric composite electroactive wound dressing system comprises the following steps:

[0090] The magnetoelectric composite electroactive wound dressing and the portable medical backpack are connected by a conductive material; the preparation method of the magnetoelectric composite electroactive wound dressing comprises the following steps:

[0091] (1) Powdered PVA with a molecular weight of 75,000 to 80,000 was dissolved in deionized water, heated in a water bath at 90° C. with magnetic stirring for 1 h to obtain a polyvinyl alcohol solution with a polyvinyl alcohol concentration of 10 wt%, and then the polyvinyl alcohol solution was poured into a mold culture dish to control the thickness to be 2 mm, cooled at room temperature and then frozen at -20° C. for 12 h, and then thawed at 25° C. for 6 h, and the freeze-thaw cycle was repeated three times to obtain a PVA insulating packaging layer with a thickness of 2 mm;

[0092] (2) using a multifunctional flexible electronic printing device to print a LM receiving coil on the surface of the PVA insulating packaging layer prepared in step (1);

[0093] The multifunctional flexible electronic printing device is DB100 of Shanghai Mifang Company; the printing parameters include: line width 200 microns, line spacing 150 microns, a total of 10 turns;

[0094] The material of the LM receiving coil used is gallium-indium alloy; the gallium-indium alloy was purchased from Dongguan Huatai Metal Material Technology Co., Ltd., with a melting point of 16°C and a conductivity of 3.40×10 6 S / m (at 20°C);

[0095] (3) Weigh 0.2 g of GelMA into a centrifuge tube, add 2 mL of a 0.0025 g / mL LAP initiator standard solution, shake and mix to ensure that GelMA is completely soaked, place the mixture in a 60-70°C water bath, heat and dissolve for 20-30 minutes in a dark and shaking condition, and continue to add 40 μL of a 5 mg / mL BP solution in a dark and 37°C water bath to avoid low-temperature gelation, to obtain a GelMA-BP mixed solution; the concentration of GelMA in the GelMA-BP mixed solution is 5-30 g / mL, and the concentration of BP is 100 μg / mL;

[0096] The GelMA-BP mixed solution is dripped onto the LM receiving coil obtained in step (2), and exposed to UV light for photocuring for 30-60 seconds to form a GelMA-BP conductive hydrogel layer with a thickness of 3-5 mm, thereby obtaining a magnetoelectric composite electroactive wound dressing; the portable medical backpack is designed using 3ds Max software, and then 405nm white UV sensitive resin is used as a raw material, and 3D printing is performed using a photocuring 3D printer;

[0097] The portable medical backpack also includes a transmitting coil, a microcontroller unit, a Bluetooth module and an inverter;

[0098] The transmitting coil is arranged at the bottom of the portable medical backpack to minimize the distance from the magnetoelectric composite electroactive wound dressing, and is connected to the microcontroller unit to generate a high-frequency magnetic field around the portable medical backpack; the size of the transmitting coil is 22 mm in inner diameter, 44 mm in outer diameter, and 2.4 mm in thickness;

[0099] The microcontroller unit is MCU, Android, and is connected to an inverter and a Bluetooth module, and is used to generate a specified input DC voltage under the control of the Bluetooth module; the input DC voltage is converted into a high-frequency current after passing through the inverter, and the high-frequency current generates a high-frequency magnetic field around the portable medical backpack after passing through the transmitting coil, and generates an induced high-frequency current in the LM receiving coil in the magnetoelectric composite electroactive wound dressing through the principle of electromagnetic induction, thereby acting on the wound

[0100] The Bluetooth module is HC-05;

[0101] The inverter is XKT-412, with an operating voltage range of 4-12V and an operating frequency of 79kHz, and is used to convert the DC voltage input by the microcontroller unit into a high-frequency current, and the high-frequency current generates a high-frequency magnetic field through the transmitting coil;

[0102] The user controls the input voltage of the transmitter through the mobile application on the electronic device and the Bluetooth module, thereby realizing programmed regulation of the current output of the magnetoelectric composite electroactive wound dressing.

[0103] 1. Structural Characterization

[0104] The structural schematic diagram of the magnetoelectric composite electroactive wound dressing prepared in Example 1 is as follows Figure 1 As shown, the magnetoelectric composite electroactive wound dressing consists of three layers: an outer layer is a PVA insulating encapsulation layer, a middle layer is a LM receiving coil composed of liquid metal, and an inner layer is a GelMA-BP conductive hydrogel layer.

[0105] The SEM image of the GelMA-BP conductive hydrogel layer prepared in Example 1 is as follows: Figure 2As shown by Figure 2 As shown, the GelMA-BP conductive hydrogel prepared in Example 1 has a rich porous structure.

[0106] The schematic diagram of the magnetoelectric composite electroactive wound dressing prepared in Example 1 receiving the high-frequency magnetic field generated by the transmitting end device in the portable medical backpack is as follows: Figure 3 As shown by Figure 3 It can be seen that the transmitting end device of the portable medical backpack described in Example 1 will generate a changing high-frequency magnetic field in the surrounding space. When the magnetoelectric composite electroactive wound dressing enters the magnetic field range, an alternating voltage will be induced in the LM receiving coil, and then a current will be generated in the LM receiving coil. This current is transmitted through the GelMA-BP conductive hydrogel, applying electrical stimulation to the wound area to promote wound healing.

[0107] 2. Electrical output performance test

[0108] The influence of different input voltages (DC) and distances (h) on the AC voltage effective value (ACRMS) generated by the LM receiving coil in the magnetoelectric composite electroactive wound dressing in Example 1 of the present invention was investigated, and the ACRMS generated by the LM receiving coil in the magnetoelectric composite electroactive wound dressing in Example 1 was obtained as the following diagram shows: Figure 4 As shown by Figure 4 It can be seen that the increase in input voltage will lead to a corresponding increase in the power of the transmitting coil in the portable medical backpack in Example 1, thereby generating a stronger high-frequency magnetic field. Therefore, the alternating voltage induced in the LM receiving coil in Example 1 will also increase, resulting in an increase in the ACRMS in the LM receiving coil. Obviously, there is a certain linear relationship between the input voltage and the ACRMS, indicating that adjusting the input voltage can be used as a method to control the induced alternating current in the LM receiving coil.

[0109] The influence of different angles (θ) between the receiving coil and the transmitting coil on the ACRMS generated by the LM receiving coil in the magnetoelectric composite electroactive wound dressing in Example 1 of the present invention was investigated, and the ACRMS generated by the LM receiving coil in the magnetoelectric composite electroactive wound dressing in Example 1 was obtained as shown in the following figure: Figure 5 As shown by Figure 5 It can be seen that the angle (θ) between the LM receiving coil and the transmitting coil in Example 1 also affects the transmission efficiency. When the LM receiving coil is aligned parallel to the transmitting coil, the magnetic field can pass through the LM receiving coil to the greatest extent, so that the induced ACRMS reaches the maximum value. When θ is 90°, ACRMS is the minimum value.

[0110] 3. Principle of Wireless Stimulation Output

[0111] The schematic diagram of the working principle of the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention is as follows: Figure 6 The schematic diagram of the portable medical backpack prepared in Example 1 of the present invention is as follows Figure 7 As shown by Figure 6 It can be seen that the mobile application (i.e. Figure 6 The "Health" APP on the electronic device in the middle) wirelessly controls the input voltage of the transmitter through the Bluetooth module to meet the electrical stimulation requirements of different treatment stages. The transmitter device and the wireless control Bluetooth module are integrated in Figure 7 In the 3D printed medical backpack shown, the changing DC voltage is converted into a high-frequency current through an inverter, and the high-frequency current generates a high-frequency magnetic field through the transmitting coil. According to the principle of electromagnetic induction, the magnetic field induces a high-frequency current in the LM receiving coil of the dressing. It is worth noting that the slight movement of the portable medical backpack will not affect the continuous electrical stimulation and will not interfere with the healing of the wound.

[0112] IV. Cytotoxicity Test

[0113] A cell-dressing co-culture model was established to test the cytotoxicity of the magnetoelectric composite electroactive wound dressing in Example 1 of the present invention, specifically: the magnetoelectric composite electroactive wound dressing was co-cultured with macrophages and fibroblasts, and the current intensity generated inside the magnetoelectric composite electroactive wound dressing was precisely controlled by an external transmitting end device and set to three different levels: no electrical stimulation (Ctrl), low current stimulation (LCS, about 20μA) and high current stimulation (HCS, about 50μA), and the cells were exposed to electrical stimulation of the specified intensity for 15 minutes every day; after 2 days, the macrophages and fibroblasts were stained for live / dead cells to test the cytotoxicity of the dressing.

[0114] The live / dead cell staining images of macrophages and fibroblasts after electrical stimulation by the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention are as follows: Figure 8 As shown by Figure 8 It can be seen that after the magnetoelectric composite electroactive wound dressing in Example 1 of the present invention electrically stimulated macrophages and fibroblasts for 2 days, the macrophages (RAW264.7) and fibroblasts (L929) were both stained green, and no obvious dead cells (red) were observed in all groups, indicating that the magnetoelectric composite electroactive wound dressing in Example 1 of the present invention has no cytotoxicity and has good biocompatibility.

[0115] 5. Rat skin wound healing experiment

[0116] Sprague-Dawley rats (male, 6-8 weeks old) were acclimated for 1 week in a laboratory environment for surgery. Rats were anesthetized by inhalation of isoflurane, and the surgical area on the back of the rats was subsequently shaved and disinfected to create a full-thickness skin wound with a diameter of 12 mm. The rats were randomly divided into four groups, the control group was not treated, and the other three groups were treated with the electroactive wound dressing system of the embodiment of the present invention, and electrical stimulation was applied from the second day (15 minutes per day), and the no electrical stimulation (Ctrl) group was set as the control group, the LCS group received full low-current stimulation (about 20 μA), the HCS group received full high-current stimulation (about 50 μA), and the PES group received programmed electrical stimulation. Use a digital camera to record photos of the wound healing process, and the shooting time is the 0th, 3rd, 7th and 14th days.

[0117] The schematic diagram of the programmed timing control strategy of the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention is as follows Fig. 9 As shown by Fig. 9 It can be seen that the present invention established a programmed timing control strategy (PES) to accelerate wound healing. A low current stimulation (20 μA) to promote macrophage M2 polarization was given during the inflammatory period three days before wound healing, and a high current stimulation (50 μA) to promote fibroblast migration and proliferation was given during the subsequent seven-day proliferation period.

[0118] The above method was used to detect the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention, which was applied to the treatment of critical-size full-thickness skin defects on the back of rats. Fig.10 As shown by Fig.10 It can be seen that when rats are treated with the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention, the electrical stimulation output parameters can be wirelessly controlled through the mobile application on the smartphone.

[0119] The above method was used to detect the actual wounds on the back of rats on days 0, 3, 7 and 14 after treatment with the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention. Fig.11 As shown, the wound healing trajectory simulation and wound healing rate statistics are shown in Fig.12 As shown by Fig.11 and Fig.12 It can be seen that the programmed therapy (PES) group showed the best wound healing effect and significantly accelerated early wound healing, indicating that the use of the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention to achieve the smooth implementation of the programmed timing control strategy can quickly promote wound healing.

[0120] In summary, in the electroactive wound dressing system based on magnetoelectric technology provided by the present invention, the magnetoelectric composite electroactive wound dressing has strong conductivity, no cytotoxicity, high biocompatibility, and a current output level at the microampere level, which can meet the needs of biological regulation; the slight movement of the portable medical backpack will not affect the continuous electrical stimulation and will not interfere with the healing of the wound; the user wirelessly controls the electrical stimulation output parameters of the magnetoelectric composite electroactive wound dressing on the wound through the mobile application on the electronic device, and utilizes the electroactive wound dressing system based on magnetoelectric technology in Example 1 of the present invention to realize the smooth implementation of the programmed timing control strategy, realize on-demand electrical stimulation treatment, and can quickly promote wound healing.

[0121] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. An electroactive wound dressing system based on magnetoelectric technology, characterized in that: Includes magneto-electric composite electro-active wound dressing, portable medical backpack and mobile application; The portable medical backpack is integrated with a transmitting terminal device to programmatically control the current output of the magneto-electric composite electro-active wound dressing; The magnetoelectric composite electroactive wound dressing comprises a three-layer structure, wherein the outer layer is a PVA insulating packaging layer, the middle layer is a LM receiving coil, and the inner layer is a GelMA-BP conductive hydrogel layer; The mobile application is installed on the user's electronic device.

2. A method for preparing the magnetoelectric composite electroactive wound dressing system according to claim 1, characterized in that: The magnetoelectric composite electroactive wound dressing and the portable medical backpack are connected by a conductive material; the preparation method of the magnetoelectric composite electroactive wound dressing comprises the following steps: (1) mixing polyvinyl alcohol and deionized water, and heating and stirring to obtain a polyvinyl alcohol solution; Pour the polyvinyl alcohol solution into a mold, perform freeze-thaw cycle treatment, repeat the freeze-thaw cycle treatment 2 to 4 times, and obtain a PVA insulating packaging layer; The freeze-thaw cycle process includes sequentially cooling, freezing and thawing; (2) using a multifunctional flexible electronic printing device to print an LM receiving coil on the surface of the PVA insulating packaging layer obtained in step (1); The material of the LM receiving coil is gallium-indium alloy; (3) After mixing the methacrylated gelatin and the initiator solution, heating in a water bath and adding the black phosphorus solution in a light-proof and shaking condition to obtain a GelMA-BP mixed solution; The GelMA-BP mixed solution is dripped onto the LM receiving coil obtained in step (2), and subjected to photocuring treatment to form a GelMA-BP conductive hydrogel layer, thereby obtaining a magnetoelectric composite electroactive wound dressing.

3. The preparation method according to claim 2, characterized in that: The concentration of polyvinyl alcohol in the polyvinyl alcohol solution in step (1) is 7wt% to 15wt%; the molecular weight of the polyvinyl alcohol is 75000 to 80000.

4. The preparation method according to claim 2, characterized in that: The freeze-thaw cycle treatment in step (1) includes sequentially cooling at room temperature, freezing at -25°C to -15°C for 10 to 14 hours, and thawing at 20 to 28°C for 4 to 8 hours.

5. The preparation method according to claim 2, characterized in that: The printing parameters in step (2) include: line width of 150 to 300 μm, line spacing of 100 to 180 μm, and number of coils of 8 to 14 turns.

6. The preparation method according to claim 2, characterized in that: The water bath heating temperature in step (2) is 50 to 80° C., and the water bath heating time is 15 to 40 minutes.

7. The preparation method according to claim 2, characterized in that: The light used for the photocuring treatment in step (3) is UV light, and the time of the photocuring treatment is 30 to 60 seconds.

8. The preparation method according to claim 2, characterized in that: The portable medical backpack is designed by 3ds Max software and then 3D printed by a light-curing 3D printer; The portable medical backpack also includes a transmitting coil, a microcontroller unit, a Bluetooth module and an inverter; The transmitting coil is placed at the lowest end to minimize the distance to the magneto-electric composite electro-active wound dressing; The inverter is used to convert the DC voltage input by the microcontroller unit into a high-frequency current. After the high-frequency current passes through the transmitting coil, a high-frequency magnetic field is generated around the backpack. Through the principle of electromagnetic induction, an induced high-frequency current is generated in the LM receiving coil in the magnetoelectric composite electroactive wound dressing, thereby acting on the wound. The user can wirelessly control the input voltage of the transmitter through the mobile application on the electronic device and the Bluetooth module, thereby realizing programmed regulation of the current output of the magnetoelectric composite electroactive wound dressing.

9. The preparation method according to claim 8, characterized in that: The dimensions of the transmitting coil are as follows: the material is silk-covered wire, the inner diameter is 15-30 mm, the outer diameter is 30-50 mm, and the thickness is 1.5-3.5 mm.

10. Use of the electroactive wound dressing system based on magnetoelectric technology as claimed in claim 1 in electroactive wound healing medical instruments.

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