An intelligent multimodal bionic interactive wound repair device and preparation method thereof

Abstract

The present invention discloses an intelligent multi-modal bionic interactive wound repair device and a preparation method thereof, and relates to the technical field of medical devices. The device includes a highly adaptable flexible structure, a multi-level gel dressing layer, and a tearable anti-adhesive layer. The highly adaptable flexible structure is made of a flexible material, and is designed with a cross-groove structure on both sides, which is ergonomic, laser-engraved on the surface, and can connect, fix and protect the device architecture; the multi-level gel dressing layer is composed of a bionic three-layer hydrogel embedded with different sensors and indicators, wherein the top layer achieves antibacterial while forming a micromagnetic field to promote absorption and synergistic repair; the middle layer is embedded with drug-loaded microspheres, and the drug is released on demand, and the ultrasonic magnetic field interaction is used for the acute phase, and the sustained release is used for the middle and late phases when there is no intervention; the bottom layer is dual antibacterial, and can be seamlessly adhered to and non-invasively separated from the wound skin; the early infection alarm of the wound can identify, integrate and feedback wound information to achieve functional treatment.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to an intelligent multi-modal bionic interactive wound repair device and a preparation method thereof. Background Art

[0002] Skin wound healing is a complex and delicate pathophysiological process, among which the healing process of chronic wounds is particularly complex. It not only seriously affects the quality of life of patients, but also generates huge medical expenses during the treatment process. It has become a major problem in the 21st century. Therefore, it is very important to find an effective treatment method. The main systemic factors affecting wound healing are ultimately manifested as local factors of the wound, such as wound temperature, humidity, pH, bacterial infection, etc.

[0003] At present, clinical judgment of wound healing usually relies on directly removing the dressing for observation. However, this practice may increase the risk of wound infection, lead to scars that are difficult to remove, and thus affect the normal healing speed of the wound. In addition, the drug release in the dressing is unstable, and it is impossible to effectively guide when to change the dressing. This depends on clinical experience, which is prone to misjudgment and waste of resources; the mismatch between the wound and the dressing size will also lead to waste of resources. At the same time, traditional dressings cannot provide the best growth microenvironment, lack antibacterial function, and are susceptible to environmental pollution, thereby increasing the risk of infection. In addition, adhesive injury is a huge threat to extensive full-thickness skin trauma, because adhesion can cause unbearable pain, aggravate the trauma after the dressing is removed, and even cause permanent secondary damage. Finally, the patient's slight movement will cause the traditional dressing to separate from the wound, prolong the treatment process, and changing the dressing will increase the pain. Therefore, it is necessary to improve the dressing design to reduce the frequency of dressing changes, relieve patient pain, and promote wound re-epithelialization and healing.

[0004] In order to solve the above problems, various improvement methods have been proposed. For example, the existing patent CN 109431688 B provides a pH-sensitive smart dressing, which is composed of a pH sensor, a single-chip microcomputer, algae sponge and a piezoelectric film. It changes in pH to produce deformation, thereby achieving drug release. It has good biocompatibility and can provide a microenvironment for cell growth. However, this design has only a single sensor, which is prone to misjudgment or untimely response, delaying the healing speed of the wound; secondly, the design cannot meet the patient's activity needs, especially at the joints. When the patient moves a little, the design may shift, thereby prolonging the healing time; thirdly, the design cannot meet the patient's early wound infection and drug replacement prompts; finally, when changing the dressing, the design may adhere to the skin wound, causing secondary skin damage.

[0005] In addition, CN 110960352 B discloses a smart dressing and its preparation method. The patent provides a smart dressing, including a transparent dressing patch, a pH sensor unit fixed on the transparent dressing patch, and a wound contact dressing covering the pH sensor unit; the invention can monitor the pH changes of the wound in real time and feedback the infection information of the wound on the basis of meeting the requirements of wound care, which is helpful to take rapid and timely treatment, thereby avoiding serious infection of the wound. However, the invention also has only one sensor, and wound infection is easy to misjudge; secondly, there is only a single-layer dressing, and there is no drug release to promote wound healing. The dressing needs to be changed frequently and has no long-term treatment function; thirdly, because it cannot be customized, it will shift when it does not match or when it moves; finally, when changing the dressing, it may also cause secondary skin damage.

[0006] Therefore, it is urgent to develop a new design and preparation method that can comprehensively solve existing clinical problems in order to improve the effectiveness and safety of dressings in wound repair. The new dressing should be able to provide appropriate wound adhesion and adaptability, reduce the risk of falling off and wrinkling, and avoid adhesion damage when replacing auxiliary materials to reduce pain; at the same time, it should prevent the adhesion of bacteria and dirt, as well as multiple antibacterial properties to reduce the risk of cross-infection; it should also include a structure to ensure the stable release of drugs, optimize the continuous effect of drugs on the wound surface, and preferably be able to coordinate treatment and repair in multiple aspects; in addition, it should have an intelligent design that can communicate effectively with patients and doctors, and transmit wound conditions, drug release status and other important information in real time. In summary, it is necessary not only to improve the treatment effect, but also to enhance the comfort and safety of patients, and to meet the growing and diversified needs of modern clinical treatment dressings, thereby promoting the progress of medical practice. Summary of the invention

[0007] One of the purposes of the present invention is to provide an intelligent multimodal bionic interactive wound repair device to solve the above technical problems. The main body of the wound repair device is a multi-level sandwich structure, which is divided into a highly adaptable flexible structure, a multi-level gel dressing layer and a tearable anti-sticking layer from the far skin end to the near skin end; the highly adaptable flexible structure is made of flexible material through 3D technology, with a double-sided cross-groove structure, and a surface laser engraving to form a self-cleaning micro-nano structure, with a processor, a battery, a micro-magnet, and a positioning column embedded inside, a micro-hook at the edge, and a high-elastic fixing rope net; the self-cleaning micro-nano structure is composed of a series of micro-nano columnar or conical structures, the height of which is 50 nm-100 µm, the diameter is 50 nm-100µm, and the structure spacing is 10 nm-10 µm; the multi-level gel dressing layer is composed of a bionic three-layer hydrogel embedded with an interactive module; the bionic three-layer hydrogel is divided into a top layer, a middle layer and a bottom layer from the far skin end to the near skin end, and the layers are embedded together by a quasi-sine structure layer; the interactive module is composed of a dressing body contamination indicator, a dressing change reminder and an early wound infection alarm, which are fixed by a positioning column; the dressing body contamination indicator is located at the edge of the multi-level gel dressing layer and runs through the entire multi-level gel dressing layer; the dressing change reminder is located at 2 / 3 of the height of the middle layer; the early wound infection alarm is an integrated sensor that can receive and transmit a variety of information, located in the center of the bottom layer close to the skin, and the size is 5-30% of the total area of ​​the bottom layer near the skin;

[0008] To better implement the present invention, further, the flexible material is PVC;

[0009] To better implement the present invention, further, the cross-groove structure is a structure composed of multiple grooves that cross each other horizontally and vertically;

[0010] To better implement the present invention, further, the quasi-sinusoidal structure layer is a mesh tray structure for fixing the multi-level gel dressing layer;

[0011] To better implement the present invention, further, the early infection warning device for wounds is an integrated sensor composed of any two or more of a pH sensor, a uric acid sensor, a temperature sensor, a humidity sensor, a nitric oxide sensor, a pressure sensor, and a bacterial metabolite sensor;

[0012] To better implement the present invention, further, the processor, the interaction module and the battery are electrically connected by wires;

[0013] The processor can receive and analyze the data monitored by the sensor and feed it back to the medical staff through the communication module, and coordinate the operation of other modules;

[0014] The interactive module is used to feed back information to the doctor through vision (light), touch (motor), and hearing (speaker), that is, it will vibrate when indicating the early infection of the wound, will flash the flash light when prompting to change the medicine, and will make a sound when the dressing device body is contaminated.

[0015] The second object of the present invention is to provide a method for preparing an intelligent multi-modal bionic interactive wound repair device, which is carried out according to the following operating steps:

[0016] (1) Preparation of highly adaptable flexible structures: Scan the geometric contours of the patient's wound, combine the scanning results with the design requirements of the processor, micro hooks, positioning columns, micro magnets, batteries, and quasi-sinusoidal structure layers to perform computer modeling and 3D printing, and then perform three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving on the surface to obtain a highly adaptable flexible structure;

[0017] To better realize the present invention, further, the three-dimensional ultrasonic nitrogen jet combines an ultrasonic system, a nitrogen emission system and a three-dimensional motion system to reduce the fallback and adhesion of laser ablation products generated by femtosecond laser in the laser working area on the surface of the highly adaptable flexible structure, so as to improve the laser processing efficiency and microstructure quality;

[0018] To better implement the present invention, further, the femtosecond laser engraving parameters are as follows: the diameter of the focused laser beam is 25 µm, the laser energy density is 0.5-1.5 J / cm 2 , pulse width is 250-350fs, pulse frequency is 50-250kHz, wavelength is 100-500nm;

[0019] (2) Preparation of the top layer: dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding a photoinitiator 2-hydroxy-2-methylacetophenone and magnetic nanoparticles, and stirring and mixing under ultrasound to obtain a solution A; injecting solution A into a mold matching the highly adaptable flexible structure, and polymerizing the solution under 254 nm ultraviolet light at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 24-48 h to obtain a top layer;

[0020] To better realize the present invention, further, the amount of the photoinitiator added is 2-3% of the total mass of acryloyl glycinamide and 1-vinyl-1,2,4-triazole;

[0021] To better implement the present invention, further, the pH of the phosphate buffer solution is 7.3-7.5;

[0022] (3) Preparation of drug-loaded microspheres: Pectin, growth-promoting factors, therapeutic drugs and organic solvents are ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount of 20-30 times the volume of solution B is added dropwise under ultrasonic stirring, and then stirring is continued; 10-20% of the volume of the composite oil phase glutaraldehyde ether solution is added under ultrasonic stirring, and then stirring is continued; the precipitate is collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres;

[0023] To better realize the present invention, further, the concentrations of pectin, growth promoting factor and therapeutic drug are 70-80%, 1.0-15.0% and 1.0-15.0% respectively;

[0024] To better implement the present invention, further, the ultrasonic environment has an ultrasonic power of 50-100w;

[0025] (4) Preparation of the middle layer: 2-5% methacrylated hyaluronic acid and 10-20% methacrylated gelatin are dissolved in phosphate buffered saline, and then 0.5-10% drug-loaded microspheres are added. After mixing, 0.1-0.5% photoinitiator is added, and then polymerized under 365 nm ultraviolet light to obtain the middle layer;

[0026] To better implement the present invention, further, the pH of the phosphate buffered saline solution is 7.3-7.5;

[0027] To better realize the present invention, further, the photoinitiator is phenyl-2,4,6-trimethylbenzoyl lithium phosphite;

[0028] (5) Preparation of the bottom layer: β-cyclodextrin, maleic anhydride and N,N-dimethylformamide solution were stirred in an ultrasonic water bath at 78-82°C for 8-12 hours, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 hours to obtain powder C; acrylic acid, aluminum chloride hexahydrate, potassium hydroxide, 1-vinyl-3-butylimidazolium bromide, ammonium persulfate and 2.5-7.5% powder C and antibacterial drugs were dissolved in water, ultrasonically stirred for 10-30 minutes, and then copolymerized in a water bath at 50°C for 15-25 minutes, and then rinsed with running ionized water to obtain the bottom layer;

[0029] To better realize the present invention, further, the concentrations of β-cyclodextrin and maleic anhydride in the N,N-dimethylformamide solution are 17-19% and 15-17% respectively;

[0030] To better realize the present invention, further, the concentrations of acrylic acid, aluminum chloride hexahydrate, potassium hydroxide, 1-vinyl-3-butylimidazolium bromide, ammonium persulfate, powder C, and antibacterial drug are 37-38%, 1.5-2.0%, 0.5-1.0%, 5-10%, 0.2-0.3%, 2.5-7.5%, and 0.5-5%, respectively;

[0031] (6) Preparation of a multimodal bionic interactive intelligent wound repair device: fix the highly adaptable flexible structure, install batteries, micro magnets, dressing body contamination indicators, dressing change reminders, and early wound infection warning devices, then assemble them in the order of top layer, middle layer, and bottom layer, and finally install a tearable anti-sticking layer to obtain a multimodal bionic interactive intelligent wound repair device;

[0032] The components used in the present invention are all commercially available products, and their structures and compositions are known to those skilled in the art.

[0033] Beneficial effects of the present invention:

[0034] (1) Highly adaptable flexible structure: Made of flexible material, with a double-sided cross-groove structure, it is ergonomic and can adapt to the patient's activities without the dressing device coming off the wound. At the same time, the cross-groove structure design can effectively offset the stress generated by the patient's activities and ensure that the dressing device stably fits the wound. The structure is customized for the patient using 3D technology, and its size is precisely matched to the shape of the wound. It not only effectively avoids bacterial infection and waste of resources caused by wound exposure or excessive coverage, but also successfully achieves precise wound treatment by accurately positioning the active ingredients into the wound. The structure can connect, fix and protect the device structure, so that the device can stably exert its therapeutic effect. The surface of the structure is laser engraved to form a self-cleaning micro-nano structure, which can maintain a relatively clean environment and reduce the risk of dirt and grime in the device body. The structure is embedded with magnets to form a micro-magnetic field, which synergizes with the top layer of magnetic nanoparticles in the multi-level gel dressing layer to promote stable drug release and wound healing.

[0035] (2) Multi-level gel dressing layer: It is composed of three layers of bionic hydrogel, each layer is interlocked by a quasi-sinusoidal structure that stabilizes the gel layers and gives full play to the functions of each layer. It can significantly reduce the patient's pain, promote the re-epithelialization process, and provide a good wound microenvironment for the new epithelium;

[0036] (3) The top layer contains magnetic nanoparticles, which are antibacterial and high-strength. They seal the wound surface and prevent microbial infection. At the same time, they prevent water evaporation, maintain a moist environment on the wound surface, form an excellent treatment environment and promote drug absorption. They work together with the magnetic field to promote wound repair and new tissue growth. The middle layer is the drug library structure of the device, which contains functionalized drug-loaded microspheres. The gel layer has high drug delivery efficiency and can be combined with ultrasonic controlled release technology to control the release of drugs on demand in the acute phase. It can also be used to release drugs and active factors slowly in an environment without human intervention for mid- and late-stage treatment and to reduce scar formation. The bottom layer has excellent biocompatibility and antibacterial properties, as well as self-healing properties, to prevent the gel from being damaged by patient activities. More importantly, it can be seamlessly adhered to the wound skin and non-invasively separated to avoid the risk of adhesion between the dressing and the wound skin.

[0037] (4) Intelligent design: The dressing contamination indicator is used to monitor whether the multi-level gel dressing layer is contaminated. If it is contaminated, it will make a sound; the dressing change reminder is used to remind the dressing change, and the flash light will flash when the dressing change is required; the early wound infection alarm is used to prevent and warn of early skin wound infection, and it will vibrate when it indicates early wound infection; the intelligent design can realize real-time monitoring of the wound microenvironment without exposing the patient's wound surface, significantly reducing unnecessary dressing change operations on the wound surface, alleviating the patient's physical and mental pain and economic burden; at the same time, it can effectively manage the local microenvironment of the wound surface and improve the healing rate of the wound surface;

[0038] (5) This device has interactive and bionic characteristics. It can interact with the human body and guide doctors to adjust treatment methods based on the body's feedback, synergizing to provide better healing effects. In addition, this device will change the process of visual observation, dressing change, and treatment of traditional dressings, bringing good news to the treatment of chronic wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 Schematic diagram of the structure of the intelligent multimodal bionic interactive wound repair device

[0040] Figure 2 A microscopic diagram of the longitudinal section structure of the intelligent multimodal bionic interactive wound repair device

[0041] Figure 3 Schematic diagram of multiple cross structures on a highly adaptable flexible structural surface

[0042] Figure 4 Figure 2 shows the results of an in vitro test for natural sustained release.

[0043] Figure 5 The results of in vitro ultrasound-controlled release test

[0044] Figure reference numerals: X, highly adaptable flexible structure, Y, multi-level gel dressing layer, Z, tearable anti-adhesive layer, 1, high elastic fixed rope net, 2, processor, 3, micro magnet, 4, battery, 5, micro hook, 6, positioning column, 7, dressing body contamination indicator, 8, top layer, 9, dressing change reminder, 10, middle layer, 11, bottom layer, 12, early wound infection warning device, 13, quasi-sinusoidal structure layer, 14, drug-loaded microspheres, 15, magnetic nanoparticles, 16, gullies, DETAILED DESCRIPTION

[0045] The technical scheme of the present invention is further described in detail below in conjunction with embodiments and comparative examples, but the present invention is not limited to these specific embodiments.

[0046] The following are examples and comparative examples.

[0047] Example 1

[0048] (1) Scan the geometric contour of the patient's wound, and based on the scanning results, design the positioning of the processor 2, micro hook 5, positioning column 6, micro magnet 3, battery 4, and quasi-sinusoidal structure layer 13, computer modeling, 3D printing, and three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving on the surface. The femtosecond laser engraving parameters are a focused laser beam diameter of 25 µm and a laser energy density of 1.0 J / cm 2 , pulse width of 300fs, pulse frequency of 150kHz, wavelength of 300nm, to obtain a highly adaptable flexible structure X;

[0049] (2) dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding 2.5% 2-hydroxy-2-methylacetophenone and 2% magnetic nanoparticles 15, stirring and mixing under ultrasound to obtain solution A; injecting solution A into a mold matching the highly adaptable flexible structure X, and performing 254 nm ultraviolet light polymerization at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 36 h to obtain a top layer 8;

[0050] (3) 75% pectin, 8.0% growth factor, 8.0% therapeutic drug and organic solvent were ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount 25 times the volume of solution B was added dropwise under ultrasonic stirring, and then stirring was continued; 15% of the volume of the composite oil phase glutaraldehyde ether solution was added under 75w ultrasonic stirring, and then stirring was continued; the precipitate was collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres 14;

[0051] (4) 3.5% methacrylated hyaluronic acid and 15% methacrylated gelatin were dissolved in phosphate buffered saline, and then 5% drug-loaded microspheres 14 were added. After mixing, 0.3% phenyl-2,4,6-trimethylbenzoyl lithium phosphite was added, and then polymerized under 365 nm ultraviolet light for 40 minutes to obtain the middle layer 10;

[0052] (5) A solution of 18% β-cyclodextrin, 16% maleic anhydride and N,N-dimethylformamide was stirred in an ultrasonic water bath at 80°C for 10 h, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 h to obtain powder C; 37.5% acrylic acid, 1.75% aluminum chloride hexahydrate, 0.75% potassium hydroxide, 7.5% 1-vinyl-3-butylimidazolium bromide, 0.25% ammonium persulfate and 5% powder C, 2.75% antibiotics were dissolved in water, ultrasonically stirred for 20 min, and then copolymerized in a water bath at 50°C for 20 min, and then rinsed with running ionized water to obtain a bottom layer 11;

[0053] (6) Fix the highly adaptable flexible structure X, install the battery 4, the micro magnet 3, the dressing body contamination indicator 7, the dressing change reminder 9 and the wound early infection alarm 12, then assemble the multi-level gel dressing layer Y in the order of the top layer 8, the middle layer 10 and the bottom layer 11, and finally install the tearable anti-sticking layer Z and the high elastic fixed rope net 1 to obtain an intelligent multimodal bionic interactive wound repair device.

[0054] Example 2

[0055] (1) Scan the geometric contour of the patient's wound, and based on the scanning results, design the positioning of the processor 2, micro hook 5, positioning column 6, micro magnet 3, battery 4, and quasi-sinusoidal structure layer 13, computer modeling, 3D printing, and three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving of the surface. The femtosecond laser engraving parameters are a focused laser beam diameter of 25 µm and a laser energy density of 1.5 J / cm 2 , pulse width of 350fs, pulse frequency of 250kHz, wavelength of 500nm, to obtain a highly adaptable flexible structure X;

[0056] (2) dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding 3% 2-hydroxy-2-methylacetophenone and 2% magnetic nanoparticles 15, stirring and mixing under ultrasound to obtain solution A; injecting solution A into a mold matching the highly adaptable flexible structure X, and performing 254 nm ultraviolet light polymerization at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 48 h to obtain a top layer 8;

[0057] (3) 80% pectin, 15.0% growth factor, 15.0% therapeutic drug and organic solvent were ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount 30 times the volume of solution B was added dropwise under ultrasonic stirring, and then stirring was continued; 20% of the volume of the composite oil phase glutaraldehyde ether solution was added under 100W ultrasonic stirring, and then stirring was continued; the precipitate was collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres 14;

[0058] (4) 5% methacrylated hyaluronic acid and 20% methacrylated gelatin were dissolved in phosphate buffered saline, and then 10% drug-loaded microspheres 14 were added. After mixing, 0.5% phenyl-2,4,6-trimethylbenzoyl lithium phosphite was added, and then polymerized under 365 nm ultraviolet light for 40 minutes to obtain the middle layer 10;

[0059] (5) A solution of 19% β-cyclodextrin, 17% maleic anhydride and N,N-dimethylformamide was stirred in an ultrasonic water bath at 82°C for 12 h, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 h to obtain powder C; 38% acrylic acid, 2.0% aluminum chloride hexahydrate, 1.0% potassium hydroxide, 10% 1-vinyl-3-butylimidazolium bromide, 0.3% ammonium persulfate and 7.5% powder C, and 5% antibiotics were dissolved in water, ultrasonically stirred for 30 min, and then copolymerized in a water bath at 50°C for 25 min, and then rinsed with running ionized water to obtain a bottom layer 11;

[0060] (6) Fix the highly adaptable flexible structure X, install the battery 4, the micro magnet 3, the dressing body contamination indicator 7, the dressing change reminder 9 and the wound early infection alarm 12, then assemble the multi-level gel dressing layer Y in the order of the top layer 8, the middle layer 10 and the bottom layer 11, and finally install the tearable anti-sticking layer Z and the high elastic fixed rope net 1 to obtain an intelligent multimodal bionic interactive wound repair device.

[0061] Example 3

[0062] (1) Scan the geometric contour of the patient's wound, and based on the scanning results, design the positioning of the processor 2, micro hook 5, positioning column 6, micro magnet 3, battery 4, and quasi-sinusoidal structure layer 13, computer modeling, 3D printing, and three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving of the surface. The femtosecond laser engraving parameters are the focused laser beam diameter of 25µm and the laser energy density of 0.5J / cm 2 , pulse width of 250fs, pulse frequency of 50kHz, wavelength of 100nm, to obtain a highly adaptable flexible structure X;

[0063] (2) dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding 2% 2-hydroxy-2-methylacetophenone and 2% magnetic nanoparticles 15, stirring and mixing under ultrasound to obtain solution A; injecting solution A into a mold matching the highly adaptable flexible structure X, and performing 254 nm ultraviolet light polymerization at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 24 h to obtain a top layer 8;

[0064] (3) 70% pectin, 1.0% growth factor, 1.0% therapeutic drug and organic solvent were ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount 20 times the volume of solution B was added dropwise under ultrasonic stirring, and then stirring was continued; 10% of the volume of the composite oil phase glutaraldehyde ether solution was added under 50w ultrasonic stirring, and then stirring was continued; the precipitate was collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres 14;

[0065] (4) 2% methacrylated hyaluronic acid and 10% methacrylated gelatin were dissolved in phosphate buffered saline, and then 0.5% drug-loaded microspheres 14 were added. After mixing, 0.1% phenyl-2,4,6-trimethylbenzoyl lithium phosphite was added, and then polymerized under 365 nm ultraviolet light for 40 min to obtain the middle layer 10;

[0066] (5) A solution of 17% β-cyclodextrin, 15% maleic anhydride and N,N-dimethylformamide was stirred in an ultrasonic water bath at 78°C for 8 h, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 h to obtain powder C; 37% acrylic acid, 1.5% aluminum chloride hexahydrate, 0.5% potassium hydroxide, 5% 1-vinyl-3-butylimidazolium bromide, 0.2% ammonium persulfate and 2.5% powder C, and 0.5% antibiotics were dissolved in water, ultrasonically stirred for 10 min, and then copolymerized in a water bath at 50°C for 15 min, and then rinsed with running ionized water to obtain a bottom layer 11;

[0067] (6) Fix the highly adaptable flexible structure X, install the battery 4, the micro magnet 3, the dressing body contamination indicator 7, the dressing change reminder 9 and the wound early infection alarm 12, then assemble the multi-level gel dressing layer Y in the order of the top layer 8, the middle layer 10 and the bottom layer 11, and finally install the tearable anti-sticking layer Z and the high elastic fixed rope net 1 to obtain an intelligent multimodal bionic interactive wound repair device.

[0068] Example 4

[0069] (1) Scan the geometric contour of the patient's wound, and based on the scanning results, design the positioning of the processor 2, micro hook 5, positioning column 6, micro magnet 3, battery 4, and quasi-sinusoidal structure layer 13, computer modeling, 3D printing, and three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving on the surface. The femtosecond laser engraving parameters are a focused laser beam diameter of 25 µm and a laser energy density of 1.0 J / cm 2 , pulse width of 250fs, pulse frequency of 250kHz, wavelength of 500nm, to obtain a highly adaptable flexible structure X;

[0070] (2) dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding 1.5% 2-hydroxy-2-methylacetophenone and 2% magnetic nanoparticles 15, stirring and mixing under ultrasound to obtain solution A; injecting solution A into a mold matching the highly adaptable flexible structure X, and polymerizing under 254 nm ultraviolet light at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 36 h to obtain a top layer 8;

[0071] (3) 80% pectin, 15.0% growth factor, 1.0% therapeutic drug and organic solvent were ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount 25 times the volume of solution B was added dropwise under ultrasonic stirring, and then stirring was continued; 10% of the volume of the composite oil phase glutaraldehyde ether solution was added under 75w ultrasonic stirring, and then stirring was continued; the precipitate was collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres 14;

[0072] (4) 3.5% methacrylated hyaluronic acid and 20% methacrylated gelatin were dissolved in phosphate buffered saline, and then 10% drug-loaded microspheres 14 were added. After mixing, 0.5% phenyl-2,4,6-trimethylbenzoyl lithium phosphite was added, and then polymerized under 365 nm ultraviolet light for 40 minutes to obtain the middle layer 10;

[0073] (5) A solution of 19% β-cyclodextrin, 16% maleic anhydride and N,N-dimethylformamide was stirred in an ultrasonic water bath at 82°C for 12 h, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 h to obtain powder C; 37% acrylic acid, 1.5% aluminum chloride hexahydrate, 0.5% potassium hydroxide, 5% 1-vinyl-3-butylimidazolium bromide, 0.2% ammonium persulfate and 2.5% powder C, and 0.5% antibiotics were dissolved in water, ultrasonically stirred for 20 min, and then copolymerized in a water bath at 50°C for 20 min, and then rinsed with running ionized water to obtain a bottom layer 11;

[0074] (6) Fix the highly adaptable flexible structure X, install the battery 4, the micro magnet 3, the dressing body contamination indicator 7, the dressing change reminder 9 and the wound early infection alarm 12, then assemble the multi-level gel dressing layer Y in the order of the top layer 8, the middle layer 10 and the bottom layer 11, and finally install the tearable anti-sticking layer Z and the high elastic fixed rope net 1 to obtain an intelligent multimodal bionic interactive wound repair device.

[0075] Example 5

[0076] (1) Scan the geometric contour of the patient's wound, and based on the scanning results, design the positioning of the processor 2, micro hook 5, positioning column 6, micro magnet 3, battery 4, and quasi-sinusoidal structure layer 13, computer modeling, 3D printing, and three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving of the surface. The femtosecond laser engraving parameters are the focused laser beam diameter of 25µm and the laser energy density of 0.5J / cm 2 , pulse width of 250fs, pulse frequency of 150kHz, wavelength of 300nm, to obtain a highly adaptable flexible structure X;

[0077] (2) dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding 1.5% 2-hydroxy-2-methylacetophenone and 2% magnetic nanoparticles 15, stirring and mixing under ultrasound to obtain solution A; injecting solution A into a mold matching the highly adaptable flexible structure X, and performing 254 nm ultraviolet light polymerization at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 48 h to obtain a top layer 8;

[0078] (3) 80% pectin, 8.0% growth factor, 8.0% therapeutic drug and organic solvent were ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount 30 times the volume of solution B was added dropwise under ultrasonic stirring, and then stirring was continued; 10% of the volume of the composite oil phase glutaraldehyde ether solution was added under 75w ultrasonic stirring, and then stirring was continued; the precipitate was collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres 14;

[0079] (4) 3.5% methacrylated hyaluronic acid and 10% methacrylated gelatin were dissolved in phosphate buffered saline, and then 0.5% drug-loaded microspheres 14 were added. After mixing, 0.5% phenyl-2,4,6-trimethylbenzoyl lithium phosphite was added, and then polymerized under 365 nm ultraviolet light for 40 minutes to obtain the middle layer 10;

[0080] (5) A solution of 19% β-cyclodextrin, 15% maleic anhydride and N,N-dimethylformamide was stirred in an ultrasonic water bath at 78°C for 12 h, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 h to obtain powder C; 37.5% acrylic acid, 1.5% aluminum chloride hexahydrate, 0.75% potassium hydroxide, 10% 1-vinyl-3-butylimidazolium bromide, 0.3% ammonium persulfate and 7.5% powder C, and 2.75% antibiotics were dissolved in water, ultrasonically stirred for 20 min, and then copolymerized in a water bath at 50°C for 25 min, and then rinsed with running ionized water to obtain a bottom layer 11;

[0081] (6) Fix the highly adaptable flexible structure X, install the battery 4, the micro magnet 3, the dressing body contamination indicator 7, the dressing change reminder 9 and the wound early infection alarm 12, then assemble the multi-level gel dressing layer Y in the order of the top layer 8, the middle layer 10 and the bottom layer 11, and finally install the tearable anti-sticking layer Z and the high elastic fixed rope net 1 to obtain an intelligent multimodal bionic interactive wound repair device.

[0082] Example 6

[0083] (1) Scan the geometric contour of the patient's wound, and based on the scanning results, design the positioning of the processor 2, micro hook 5, positioning column 6, micro magnet 3, battery 4, and quasi-sinusoidal structure layer 13, computer modeling, 3D printing, and three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving of the surface. The femtosecond laser engraving parameters are the focused laser beam diameter of 25µm and the laser energy density of 0.5J / cm 2 , pulse width of 250fs, pulse frequency of 150kHz, wavelength of 300nm, to obtain a highly adaptable flexible structure X;

[0084] (2) dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding 1.5% 2-hydroxy-2-methylacetophenone and 2% magnetic nanoparticles 15, stirring and mixing under ultrasound to obtain solution A; injecting solution A into a mold matching the highly adaptable flexible structure X, and polymerizing under 254 nm ultraviolet light at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 36 h to obtain a top layer 8;

[0085] (3) 70% pectin, 1.0% growth factor, 1.0% therapeutic drug and organic solvent were ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount 20 times the volume of solution B was added dropwise under ultrasonic stirring, and then stirring was continued; 10% of the volume of the composite oil phase glutaraldehyde ether solution was added under 50w ultrasonic stirring, and then stirring was continued; the precipitate was collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres 14;

[0086] (4) 3.5% methacrylated hyaluronic acid and 15% methacrylated gelatin were dissolved in phosphate buffered saline, and then 5% drug-loaded microspheres 14 were added. After mixing, 0.3% phenyl-2,4,6-trimethylbenzoyl lithium phosphite was added, and then polymerized under 365 nm ultraviolet light for 40 minutes to obtain the middle layer 10;

[0087] (5) A solution of 19% β-cyclodextrin, 17% maleic anhydride and N,N-dimethylformamide was stirred in an ultrasonic water bath at 82°C for 12 h, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 h to obtain powder C; 38% acrylic acid, 2.0% aluminum chloride hexahydrate, 1.0% potassium hydroxide, 10% 1-vinyl-3-butylimidazolium bromide, 0.3% ammonium persulfate and 7.5% powder C, and 5% antibiotics were dissolved in water, ultrasonically stirred for 30 min, and then copolymerized in a water bath at 50°C for 25 min, and then rinsed with running ionized water to obtain a bottom layer 11;

[0088] (6) Fix the highly adaptable flexible structure X, install the battery 4, the micro magnet 3, the dressing body contamination indicator 7, the dressing change reminder 9 and the wound early infection alarm 12, then assemble the multi-level gel dressing layer Y in the order of the top layer 8, the middle layer 10 and the bottom layer 11, and finally install the tearable anti-sticking layer Z and the high elastic fixed rope net 1 to obtain an intelligent multimodal bionic interactive wound repair device.

[0089] Comparative Example 1

[0090] Comparative Example 1 is basically the same as Example 1, except that Example 1 uses a 3D printed highly adaptable flexible structure X, while Comparative Example 1 uses an ordinary nylon backing layer without using 3D printing technology.

[0091] Comparative Example 2

[0092] Comparative Example 2 is basically the same as Example 1, except that Example 1 uses a multi-level gel dressing layer Y containing a top layer 8, a middle layer 10 and a bottom layer 11, while Comparative Example 2 only uses a single middle layer 10 without a top layer 8 and a bottom layer 11.

[0093] Comparative Example 3

[0094] Comparative Example 3 is substantially the same as Example 1, except that the middle layer 10 in Example 1 contains drug-loaded microspheres 14 , while the middle layer 10 in Comparative Example 3 does not contain drug-loaded microspheres 14 .

[0095] Comparative Example 4

[0096] Comparative Example 4 is basically the same as Example 1, except that Example 1 contains a processor 2, a battery 4, a dressing body contamination indicator 7, a dressing change reminder 9 and an early wound infection alarm 12, while Comparative Example 4 does not have a processor 2, a battery 4, a dressing body contamination indicator 7, a dressing change reminder 9 and an early wound infection alarm 12.

[0097] Comparative Example 5

[0098] Comparative Example 5 is basically the same as Example 1, except that Example 1 uses a multi-stage gel dressing layer Y containing a top layer 8, a middle layer 10 and a bottom layer 11, while Comparative Example 2 uses a middle layer 10 and a top layer 8 without a bottom layer 11.

[0099] Comparative Example 6

[0100] (1) Scan the geometric contour of the patient's wound, and based on the scanning results, design the positioning of the processor 2, micro hook 5, positioning column 6, micro magnet 3, battery 4, and quasi-sinusoidal structure layer 13, computer modeling, 3D printing, and three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving of the surface. The femtosecond laser engraving parameters are the focused laser beam diameter of 25µm and the laser energy density of 0.1J / cm 2 , pulse width of 50fs, pulse frequency of 10kHz, wavelength of 10nm, to obtain a highly adaptable flexible structure X;

[0101] (2) dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding 0.2% 2-hydroxy-2-methylacetophenone and 0.2% magnetic nanoparticles 15, stirring and mixing under ultrasound to obtain solution A; injecting solution A into a mold matching the highly adaptable flexible structure X, and performing 254 nm ultraviolet light polymerization at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 24 h to obtain a top layer 8;

[0102] (3) 60% pectin, 0.1% growth factor, 0.1% therapeutic drug and organic solvent were ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount 20 times the volume of solution B was added dropwise under ultrasonic stirring, and then stirring was continued; 10% of the volume of the composite oil phase glutaraldehyde ether solution was added under 10w ultrasonic stirring, and then stirring was continued; the precipitate was collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres 14;

[0103] (4) 2% methacrylated hyaluronic acid and 10% methacrylated gelatin were dissolved in phosphate buffered saline, and then 0.5% drug-loaded microspheres 14 were added. After mixing, 0.1% phenyl-2,4,6-trimethylbenzoyl lithium phosphite was added, and then polymerized under 365 nm ultraviolet light for 40 min to obtain the middle layer 10;

[0104] (5) A solution of 35% β-cyclodextrin, 30% maleic anhydride and N,N-dimethylformamide was stirred in an ultrasonic water bath at 78°C for 8 h, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 h to obtain powder C; 50% acrylic acid, 0.1% aluminum chloride hexahydrate, 0.1% potassium hydroxide, 1% 1-vinyl-3-butylimidazolium bromide, 2% ammonium persulfate and 10% powder C, and 0.1% antibiotics were dissolved in water, ultrasonically stirred for 10 min, and then copolymerized in a 50°C water bath for 15 min, and then rinsed with running ionized water to obtain a bottom layer 11;

[0105] (6) Fix the highly adaptable flexible structure X, the battery 4, the micro magnet 3, the dressing body contamination indicator 7, the dressing change reminder 9 and the wound early infection alarm 12, then assemble the multi-level gel dressing layer Y in the order of the top layer 8, the middle layer 10 and the bottom layer 11, and finally install the tearable anti-sticking layer Z and the high elastic fixed rope net 1 to obtain an intelligent multimodal bionic interactive wound repair device.

[0106] The present invention adopts the following method to detect the intelligent multi-modal bionic interactive wound repair device:

[0107] 1. In vitro effect evaluation test of ultrasound controlled release and natural sustained release

[0108] Growth promoting factors were used as test objects and determined by high performance liquid chromatography;

[0109] 2. In vitro testing of antibacterial properties and tensile strength of top layer 8

[0110] (1) The antibacterial properties of the top layer 8 were evaluated using the nutrient solution dilution method.

[0111] Sterile LB broth medium was used to culture bacteria (Staphylococcus aureus), and pure bacterial solution was used as the control group. The absorbance (Optical Density, OD) of the control group and the sample group at a wavelength of 600 nm was measured respectively. The relative inhibition rate was calculated as follows:

[0112]

[0113] (2) The tensile strength is tested using a universal testing machine. The tensile strength is the maximum stress when the sample breaks.

[0114] 3. In vitro testing of biocompatibility (cytotoxicity, sensitization, skin irritation) and antibacterial properties of the bottom layer 11

[0115] (1) Biocompatibility is determined in accordance with GB / T 16886;

[0116] (2) The antibacterial property test method is the same as the antibacterial property test method of top 8;

[0117] 4. Animal experiment 1: Multimodal interaction module response test

[0118] The test was conducted on the hairless invasive skin on the back of rabbits, and the early infection of wounds, the replacement of drugs and the contamination of dressing devices were simulated.

[0119] 5. Animal experiment 2: seamless adhesion and non-invasive separation test

[0120] The measurement was performed on the hairless invasive skin on the back of rabbits.

[0121] The intelligent multimodal bionic interactive wound repair device was tested according to the above test methods. The results are shown in Table 1. Figure 4 and Figure 5 shown.

[0122] Table 1 is the performance test results of the embodiments and comparative examples

[0123]

[0124] By comparing Table 1, Figure 4 and Figure 5 Analysis shows that the multimodal bionic interactive intelligent wound repair device designed by the present invention has high drug controlled release and sustained release, and is intelligent. With the protection of the highly adaptable flexible structure X, the device is more stable, including structure, drug release and drug content; it has good biocompatibility and can controllably release drugs in combination with ultrasonic technology; seamless adhesion and non-invasive separation further reduce the pain of patients.

[0125] From the comparison between Example 1 and Comparative Example 1, it can be seen that without the highly adaptable flexible structure X, the device structure is unstable, and the device structure cannot be connected, fixed and protected, so that the device cannot stably exert its therapeutic effect; it is very easy to deform and shift, and detach from the wound surface, and is easily polluted by the environment, harbors dirt and wastes resources; the drug release is unstable, and sudden release occurs, and precise wound treatment cannot be performed; magnets cannot be embedded, and synergistic enhancement cannot be achieved to promote stable and sustained drug release and promote wound healing;

[0126] From the comparison between Example 1 and Comparative Example 2, it can be seen that the single-layer structure has a simple function, many drugs are mixed together, and it is impossible to achieve staged treatment of the wound surface; multiple drugs are easy to react with each other and become ineffective; the single-layer structure cannot effectively seal the wound surface, is easily infected by microorganisms, cannot maintain a moist environment on the wound surface, and cannot cooperate with the magnetic field for treatment and growth promotion;

[0127] From the comparison between Example 1 and Comparative Example 3, it can be seen that without microspheres, controlled release cannot be achieved by combining with ultrasound, and it cannot be used for controlled release of drugs on demand in the acute phase, and the functionality is poor;

[0128] From the comparison between Example 1 and Comparative Example 4, it can be seen that without intelligent design and interactive module, the device body cannot be prompted after being contaminated, and the drug usage cannot be prompted, resulting in unnecessary waste;

[0129] From the comparison between Example 1 and Comparative Example 5, it can be seen that without the bottom layer 11, the dressing cannot be seamlessly adhered to the wound skin and non-invasively separated, resulting in the dressing adhering to the wound skin, causing secondary injury and increasing the risk of secondary infection;

[0130] From the comparison between Example 1 and Comparative Example 6, it can be seen that when the preparation process parameters are not appropriate, various test indicators are not ideal.

[0131] The results show that the intelligent multimodal bionic interactive wound repair device designed in the present invention has good properties and clinical application value.

[0132] Although the content of the present invention has been described in detail through the above preferred embodiments, it should be appreciated that the above description should not be considered as a limitation of the present invention. After reading the above content, it will be apparent to those skilled in the art that various modifications and substitutions of the present invention can be made, and any changes that can be thought of by those skilled in the art should be within the scope of protection of the present invention.

Claims

1. An intelligent multi-modal bionic interactive wound repair device, characterized in that: The main body of the wound repair device is a multi-level sandwich structure, which is divided into a highly adaptable flexible structure, a multi-level gel dressing layer and a tearable anti-sticking layer from the distal end to the proximal end of the skin; the highly adaptable flexible structure is made of flexible material through 3D technology, with a double-sided cross-groove structure, and a self-cleaning micro-nano structure formed by laser engraving on the surface, with a processor, battery, micro-magnet, and positioning column embedded inside, and micro-hooks are provided at the edge, with a highly elastic fixed rope net attached; the multi-level gel dressing layer is composed of a bionic three-layer hydrogel embedded with an interactive module; the self-cleaning micro-nano structure is composed of a series of micro-nano columnar or conical structures, the height of which is 50 nm-100µm, the diameter is 50 nm-100 µm, and the structural spacing is 10 nm-10 µm; the bionic three-layer hydrogel is divided into a top layer, a middle layer and a bottom layer from the far skin end to the near skin end, and the layers are embedded together by quasi-sinusoidal structure layers; the interactive module is composed of a dressing body contamination indicator, a dressing change reminder and a wound early infection alarm, which are fixed by a positioning column; the dressing body contamination indicator is located at the edge of the multi-level gel dressing layer and runs through the entire multi-level gel dressing layer; the dressing change reminder is located at 2 / 3 of the height of the middle layer; the wound early infection alarm is an integrated sensor that can receive and transmit a variety of information, located in the center of the bottom layer close to the skin, and the size is 5-30% of the total area of ​​the bottom layer near the skin; The preparation method comprises the following steps: (1) Preparation of highly adaptable flexible structures: Scan the geometric contours of the patient's wound, combine the scanning results with the design requirements of the processor, micro hooks, positioning columns, micro magnets, batteries, and quasi-sinusoidal structural layers to perform computer modeling and 3D printing, and then perform three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving on the surface to obtain a highly adaptable flexible structure; (2) Preparation of the top layer: dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding a photoinitiator 2-hydroxy-2-methylacetophenone and magnetic nanoparticles, and stirring and mixing under ultrasound to obtain a solution A; injecting solution A into a mold matching the highly adaptable flexible structure, and polymerizing the solution under 254 nm ultraviolet light at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 24-48 h to obtain a top layer; (3) Preparation of drug-loaded microspheres: Pectin, growth-promoting factors, therapeutic drugs and organic solvents are ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount of 20-30 times the volume of solution B is added dropwise under ultrasonic stirring, and then stirring is continued; 10-20% of the volume of the composite oil phase glutaraldehyde ether solution is added under ultrasonic stirring, and then stirring is continued; the precipitate is collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres; (4) Preparation of the middle layer: 2-5% methacrylated hyaluronic acid and 10-20% methacrylated gelatin are dissolved in phosphate buffered saline, and then 0.5-10% drug-loaded microspheres are added. After mixing, 0.1-0.5% photoinitiator is added, and then polymerized under 365 nm ultraviolet light to obtain the middle layer; (5) Preparation of the bottom layer: β-cyclodextrin, maleic anhydride and N,N-dimethylformamide solution were stirred in an ultrasonic water bath at 78-82°C for 8-12 hours, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 hours to obtain powder C; acrylic acid, aluminum chloride hexahydrate, potassium hydroxide, 1-vinyl-3-butylimidazolium bromide, ammonium persulfate and 2.5-7.5% powder C and antibacterial drugs were dissolved in water, ultrasonically stirred for 10-30 minutes, and then copolymerized in a water bath at 50°C for 15-25 minutes, and then rinsed with running ionized water to obtain the bottom layer; (6) Preparation of intelligent multimodal bionic interactive wound repair device: fix the highly adaptable flexible structure, install batteries, micro magnets, dressing body contamination indicator, dressing change reminder and wound early infection alarm, then assemble them in the order of top layer, middle layer and bottom layer, and finally install a tearable anti-sticking layer to obtain a multimodal bionic interactive intelligent wound repair device.

2. The intelligent multi-modal bionic interactive wound repair device according to claim 1, characterized in that: The flexible material is PVC; the cross-groove structure is a structure composed of multiple grooves that cross each other horizontally and vertically.

3. The intelligent multi-modal bionic interactive wound repair device according to claim 1, characterized in that: The quasi-sinusoidal structure layer is a mesh tray structure for fixing a multi-stage gel dressing layer; the early wound infection warning device is an integrated sensor composed of any two or more of a pH sensor, a uric acid sensor, a temperature sensor, a humidity sensor, a nitric oxide sensor, a pressure sensor, and a bacterial metabolite sensor.

4. The intelligent multi-modal bionic interactive wound repair device according to claim 1, characterized in that: The processor, the interaction module and the battery are electrically connected by wires.

5. A method for preparing an intelligent multi-modal bionic interactive wound repair device according to any one of claims 1 to 4, characterized in that: The preparation method comprises the following steps: (1) Preparation of highly adaptable flexible structures: Scan the geometric contours of the patient's wound, combine the scanning results with the design requirements of the processor, micro hooks, positioning columns, micro magnets, batteries, and quasi-sinusoidal structural layers to perform computer modeling and 3D printing, and then perform three-dimensional ultrasonic nitrogen jet-assisted femtosecond laser engraving on the surface to obtain a highly adaptable flexible structure; (2) Preparation of the top layer: dissolving acryloyl glycinamide and 1-vinyl-1,2,4-triazole in deionized water, adding a photoinitiator 2-hydroxy-2-methylacetophenone and magnetic nanoparticles, and stirring and mixing under ultrasound to obtain a solution A; injecting solution A into a mold matching the highly adaptable flexible structure, and polymerizing the solution under 254 nm ultraviolet light at room temperature for 45 min to obtain a polymer; washing the polymer in a flowing phosphate buffer solution, and then drying at 45° C. for 24-48 h to obtain a top layer; (3) Preparation of drug-loaded microspheres: Pectin, growth-promoting factors, therapeutic drugs and organic solvents are ultrasonically homogenized to obtain solution B; a composite oil phase consisting of 40% glycerol, 40% sesame oil and 20% organic solvent containing 2% emulsifier in an amount of 20-30 times the volume of solution B is added dropwise under ultrasonic stirring, and then stirring is continued; 10-20% of the volume of the composite oil phase glutaraldehyde ether solution is added under ultrasonic stirring, and then stirring is continued; the precipitate is collected and washed with deionized water, and finally suspended and dried at low temperature to obtain drug-loaded microspheres; (4) Preparation of the middle layer: 2-5% methacrylated hyaluronic acid and 10-20% methacrylated gelatin are dissolved in phosphate buffered saline, and then 0.5-10% drug-loaded microspheres are added. After mixing, 0.1-0.5% photoinitiator is added, and then polymerized under 365 nm ultraviolet light to obtain the middle layer; (5) Preparation of the bottom layer: β-cyclodextrin, maleic anhydride and N,N-dimethylformamide solution were stirred in an ultrasonic water bath at 78-82°C for 8-12 hours, then washed with excess ethyl acetate for multiple times and resuspended, and vacuum freeze-dried for 48 hours to obtain powder C; acrylic acid, aluminum chloride hexahydrate, potassium hydroxide, 1-vinyl-3-butylimidazolium bromide, ammonium persulfate and 2.5-7.5% powder C and antibacterial drugs were dissolved in water, ultrasonically stirred for 10-30 minutes, and then copolymerized in a water bath at 50°C for 15-25 minutes, and then rinsed with running ionized water to obtain the bottom layer; (6) Preparation of intelligent multimodal bionic interactive wound repair device: fix the highly adaptable flexible structure, install batteries, micro magnets, dressing body contamination indicator, dressing change reminder and wound early infection alarm, then assemble them in the order of top layer, middle layer and bottom layer, and finally install a tearable anti-sticking layer to obtain an intelligent multimodal bionic interactive wound repair device.

6. The method for preparing the intelligent multi-modal bionic interactive wound repair device according to claim 5, characterized in that: The three-dimensional ultrasonic nitrogen jet in step (1) combines an ultrasonic system, a nitrogen emission system and a three-dimensional motion system to reduce the fall and adhesion of laser ablation products generated by femtosecond laser in the laser working area on the surface of the highly adaptable flexible structure, so as to improve the laser processing efficiency and microstructure quality; the femtosecond laser engraving parameters are a focused laser beam diameter of 25µm and a laser energy density of 0.5-1.5J / cm 2 , pulse width is 250-350fs, pulse frequency is 50-250kHz, and wavelength is 100-500nm.

7. The method for preparing the intelligent multi-modal bionic interactive wound repair device according to claim 5, characterized in that: The amount of the photoinitiator added in step (2) is 2-3% of the total mass of acryloyl glycinamide and 1-vinyl-1,2,4-triazole; and the pH of the phosphate buffer solution is 7.3-7.

5.

8. The method for preparing the intelligent multi-modal bionic interactive wound repair device according to claim 5, characterized in that: In step (3), the concentrations of pectin, growth promoting factor and therapeutic drug are 70-80%, 1.0-15.0% and 1.0-15.0% respectively; the power of ultrasound is 50-100w.

9. The method for preparing the intelligent multi-modal bionic interactive wound repair device according to claim 5, characterized in that: The pH of the phosphate buffer solution in step (4) is 7.3-7.5; and the photoinitiator is phenyl-2,4,6-trimethylbenzoyl lithium phosphite.

10. The method for preparing the intelligent multi-modal bionic interactive wound repair device according to claim 5, characterized in that: In step (5), the concentrations of β-cyclodextrin and maleic anhydride in the N,N-dimethylformamide solution are 17-19% and 15-17%, respectively; the concentrations of acrylic acid, aluminum chloride hexahydrate, potassium hydroxide, 1-vinyl-3-butylimidazolium bromide, ammonium persulfate, powder C, and antibacterial drug are 37-38%, 1.5-2.0%, 0.5-1.0%, 5-10%, 0.2-0.3%, 2.5-7.5%, and 0.5-5%, respectively.

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