A magnetic hydrogel and its preparation method and non-invasive skin mechanical loading device

Abstract

The present invention provides a method for preparing a magnetic hydrogel, including fully mixing a gelatin solution, a sodium alginate solution, deionized water and neodymium iron boron particles to obtain a reaction precursor A liquid; fully mixing calcium carbonate, gluconolactone, glutaminase and deionized water to obtain a reaction precursor B liquid; adding the reaction precursor A liquid to the reaction precursor B liquid, and transferring it to a mold after fully stirring and mixing, and then sealing the mold and placing it under a constant temperature environment to prepare a GA-Al@NdFeB magnetic hydrogel, and the prepared GA-Al@NdFeB magnetic hydrogel is magnetized to make the neodymium iron boron particles embedded in the hydrogel have magnetic polarity. The present invention provides a magnetic hydrogel prepared based on the preparation method, and the present invention also provides a non-invasive skin mechanical loading device prepared by the magnetized magnetic hydrogel. The present invention can realize mechanical loading of skin wounds and promote wound contraction to achieve the purpose of wound repair.

Description

Technical Field

[0001] The invention relates to the technical field of skin mechanical loading, in particular to a magnetic hydrogel and a preparation method thereof and a non-invasive skin mechanical loading device. Background Art

[0002] Wound healing is closely related to skin contraction. Surgical suture and skin stretching techniques are also based on contracting the wound to promote wound repair. However, many chronic wounds cannot be sutured directly, and the skin stretcher passes through the skin around the wound with two Kirschner wires, pulls the skin and installs the stretcher, which will cause secondary damage to the wound and affect the blood flow of the wound, and the price is high. Therefore, constructing a device that can load the skin wound mechanically in a minimally invasive or non-invasive manner and promote wound contraction to achieve the purpose of wound repair will bring great convenience to wound repair. In recent years, the use of physical means such as magnetism, sound, light, and electricity to treat major diseases in a minimally invasive or even non-invasive manner, the development of new control devices and systems based on physical methods, and the exploration of non-invasive, safe, and effective treatment methods have become top priorities, and the establishment of higher-precision physical control methods has been highly valued. Magnetic-related technologies have been widely used in many fields of clinical surgery, and their safety in the human body has also been confirmed. At the same time, studies have shown that static magnetic fields and magnetic nanoparticles can promote cell proliferation and migration and promote angiogenesis. Low doses of magnetic nanoparticles are safe and harmless to the body. They have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of iron deficiency anemia. Magnetic nanomaterials are a new type of magnetic material. Compared with ferromagnets, magnetic nanoparticles have good magnetic response after an external magnetic field is applied, and the remanence and coercive force approach zero after the magnetic field is removed. Based on their unique physical and chemical properties, magnetic nanoparticles have been used in in vitro diagnosis and clinical treatment, including in cell diagnosis, tissue repair, drug delivery, magnetic resonance imaging (MRI), magnetic hyperthermia and magnetic transfection. Neodymium iron boron particles are commonly used magnetic nanomaterials. They can connect a variety of bioactive molecules and have strong biocompatibility. They are widely used in the medical field. NdFeB magnetic nanomaterials generate a magnetic field after magnetization. Therefore, when two NdFeB magnetic nanomaterials are placed on both sides of the wound and driven to move relative to the wound, a reaction force of moving toward each other will be generated between the two NdFeB magnetic nanomaterials, making it difficult to accurately control the wound through an external magnetic field, and thus difficult to mechanically load the wound, promote wound contraction, and achieve the purpose of wound repair. Summary of the invention

[0003] In view of the shortcomings of the prior art, the purpose of the present invention is to provide a magnetic hydrogel and a preparation method thereof and a non-invasive skin mechanical loading device, aiming to solve the problems raised in the technical background. The prepared magnetic hydrogel can respond quickly to the external magnetic field, generate attractive or repulsive force to the magnetic field, and control the directionality by regulating the external magnetic field to generate a force in a specific direction to achieve mechanical loading on the wound surface; at the same time, the good biocompatibility of the magnetic hydrogel is utilized to apply the device made of the magnetic hydrogel to both sides of the wound surface, so that the generated magnetic force acts on the wound surface, pulling the wound surface to contract and promoting wound repair.

[0004] In order to solve the above technical problems, the implementation scheme provided by the present invention is to provide a method for preparing magnetic hydrogel, which is prepared by the following preparation steps:

[0005] The gelatin solution, the sodium alginate solution, the deionized water and the NdFeB particles are fully mixed to obtain a reaction precursor solution A;

[0006] The calcium carbonate, gluconolactone, transglutaminase and deionized water are fully mixed to obtain a reaction precursor solution B;

[0007] The reaction precursor A liquid is added into the reaction precursor B liquid, and the mixture is fully stirred and sealed and placed in a constant temperature environment to prepare a GA-Al@NdFeB magnetic hydrogel. The prepared GA-Al@NdFeB magnetic hydrogel is magnetized using a pulse magnetizer to make the neodymium iron boron particles embedded in the hydrogel have magnetic polarity. The magnetizing voltage of the pulse magnetizer is 3000V, the magnetizing capacitance is 5000UF, and the magnetic field strength is 7T.

[0008] Preferably, a gelatin solution with a mass percentage of 18% to 22%, a sodium alginate solution with a mass percentage of 0.8% to 1.2%, deionized water and neodymium iron boron particles are fully mixed to obtain a reaction precursor A liquid; before preparing the GA-Al@NdFeB magnetic hydrogel, the mixed reaction precursor A liquid is added to the reaction precursor B liquid, sealed and placed in a constant temperature environment of 37°C to 40°C for 2h to 3h.

[0009] Preferably, the volume mass ratio of gelatin solution, sodium alginate solution, deionized water and NdFeB particles is 10:5:1:10; the volume mass ratio of calcium carbonate, gluconolactone, transglutaminase and deionized water is 0.02:0.04:0.2:4.

[0010] Preferably, the particle size of the NdFeB particles is 5 μm to 10 μm.

[0011] The second implementation scheme provided by the present invention is: providing a method for preparing a magnetic hydrogel to prepare the magnetic hydrogel.

[0012] The third implementation scheme provided by the present invention is to provide a non-invasive skin mechanical loading device.

[0013] Preferably, a magnet device for non-invasive skin mechanical loading comprises:

[0014] At least one pair of magnetized GA-Al@NdFeB magnetic hydrogels, wherein the magnetic poles of the pair of GA-Al@NdFeB magnetic hydrogels are opposite, and the pair of GA-Al@NdFeB magnetic hydrogels are symmetrically applied on both sides of the skin wound and closely attached to the edge of the skin wound;

[0015] The driving magnets correspond one to one with the magnetized GA-Al@NdFeB magnetic hydrogels, and each driving magnet is respectively arranged on both sides of the GA-Al@NdFeB magnetic hydrogel away from the skin wound surface, so as to push the wound skin relatively from both sides of the wound surface, and each driving magnet has the same magnetic pole as each GA-Al@NdFeB magnetic hydrogel, so that the repulsive force generated between the driving magnet and the GA-Al@NdFeB magnetic hydrogel pushes the GA-Al@NdFeB magnetic hydrogel to pull the wound surface to contract.

[0016] Preferably, different repulsive forces are obtained by changing the distance between the GA-Al@NdFeB magnetic hydrogel and the driving magnet.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] 1. The present invention prepares GA-Al@NdFeB magnetic hydrogel by reaction precursor A liquid and reaction precursor B liquid, and magnetizes the GA-Al@NdFeB magnetic hydrogel. The obtained magnetized GA-Al@NdFeB magnetic hydrogel is not only a composite material with both magnetic responsiveness and biocompatibility, but also the GA-Al@NdFeB magnetic hydrogel can respond quickly to the external magnetic field. The magnetized GA-Al@NdFeB magnetic hydrogel is placed on both sides of the wound surface. When the magnetized GA-Al@NdFeB magnetic hydrogel is driven to move relative to the wound surface, the two magnetized GA-Al@NdFeB magnetic hydrogels will not generate a reaction force of moving toward each other, thereby achieving precise control through the external magnetic field, and then accurately controlling the direction and size of the generated magnetic force by regulating the direction and distance of the external magnetic field, and mechanically loading the wound surface. The good biocompatibility of the GA-Al@NdFeB magnetic hydrogel is used to attach to both sides of the wound surface, so that the generated magnetic force acts on the wound surface, pulls the wound surface to contract, and promotes wound repair.

[0019] 2. The present invention achieves the purpose of promoting wound repair safely and non-invasively by preparing a magnet device for non-invasive skin mechanical loading, thereby improving the clinical treatment effect of chronic wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 SEM observation of the network structure of the magnetic hydrogel material and the distribution of NdFeB particles in the hydrogel network, where A is a SEM image at a magnification of 1000 times; B is a SEM image at a magnification of 2000 times; and C is a SEM image at a magnification of 8000 times.

[0021] Figure 2 These are the tensile test diagrams of GA-Al@NdFeB magnetic hydrogel, where A is the actual tensile test diagram and B is the stress-strain curve.

[0022] Figure 3 This is the detection diagram of the magnetic field distribution of GA-Al@NdFeB magnetic hydrogel.

[0023] Figure 4 This is the biocompatibility test diagram of GA-Al@NdFeB magnetic hydrogel.

[0024] Figure 5 This is a diagram of the actual application experiment of the non-invasive skin mechanical loading device on animals.

[0025] Figure 6 Detection diagram of non-invasive skin mechanical loading device promoting wound healing. DETAILED DESCRIPTION

[0026] In order to make the above-mentioned purposes, features and advantages of the embodiments of the present invention more obvious and understandable, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments in 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.

[0027] The inventors found that the prepared GA-Al@NdFeB magnetic hydrogel is a composite material with both magnetic responsiveness and biocompatibility. The composite material can respond quickly to the external magnetic field, generate attractive or repulsive forces to the magnetic field, and can control the direction and magnitude of the magnetic force by regulating the direction and distance of the external magnetic field; by utilizing the good biocompatibility of the hydrogel material, it is attached to both sides of the wound surface, so that the generated magnetic force acts on the wound surface, pulling the wound surface to contract and promoting wound repair.

[0028] In view of this, the present invention provides a magnetic hydrogel and a preparation method thereof and a non-invasive skin mechanical loading device. The magnetic hydrogel is prepared and the prepared magnetic hydrogel is magnetized to obtain the magnetized magnetic hydrogel which is applied to the non-invasive skin mechanical loading device to complete the mechanical loading of the skin wound and promote the contraction of the wound to achieve the purpose of wound repair.

[0029] like Figure 1 to Figure 6 As shown, the present invention provides a method for preparing a magnetic hydrogel, which is prepared by the following preparation steps:

[0030] The gelatin solution, the sodium alginate solution, the deionized water and the NdFeB particles are fully mixed to obtain a reaction precursor A solution.

[0031] Calcium carbonate, gluconolactone, transglutaminase and deionized water are fully mixed to obtain a reaction precursor solution B.

[0032] The reaction precursor A liquid is added into the reaction precursor B liquid, and after being fully stirred and mixed, it is transferred into a mold, and then the mold is sealed and placed in a constant temperature environment to prepare GA-Al@NdFeB magnetic hydrogel. The prepared GA-Al@NdFeB magnetic hydrogel is magnetized using a pulse magnetizer to make the neodymium iron boron particles embedded in the hydrogel have magnetic polarity. The magnetizing voltage of the pulse magnetizer is 3000V, the magnetizing capacitance is 5000UF, and the magnetic field strength is 7T.

[0033] Specifically, a gelatin solution with a mass percentage of 18% to 22%, a sodium alginate solution with a mass percentage of 0.8% to 1.2%, deionized water and neodymium iron boron particles are fully mixed to obtain a reaction precursor A liquid; before preparing the GA-Al@NdFeB magnetic hydrogel, the mold needs to be sealed and placed in a constant temperature environment of 37°C to 40°C for 2h to 3h.

[0034] Specifically, the volume mass ratio of 20% gelatin solution, 1% sodium alginate solution, deionized water and neodymium iron boron particles is 10:5:1:10; the volume mass ratio of calcium carbonate, gluconolactone, glutaminase and deionized water is 0.02:0.04:0.2:4.

[0035] Specifically, the particle size of NdFeB is 5 μm to 10 μm.

[0036] The present invention provides a preparation method based on the above magnetic hydrogel to prepare GA-Al@NdFeB magnetic hydrogel.

[0037] The invention provides a non-invasive skin mechanical loading device based on the magnetic hydrogel.

[0038] Specifically, a magnet device for non-invasive skin mechanical loading comprises:

[0039] Two magnetized GA-Al@NdFeB magnetic hydrogels are set, and the magnetic poles of the two GA-Al@NdFeB magnetic hydrogels are opposite. The two GA-Al@NdFeB magnetic hydrogels are symmetrically applied on both sides of the skin wound and close to the edge of the skin wound.

[0040] There are two driving magnets, and the two driving magnets are symmetrically arranged on both sides of the GA-Al@NdFeB magnetic hydrogel away from the skin wound, and the magnetic poles of each driving magnet and each GA-Al@NdFeB magnetic hydrogel are the same. By attaching the driving magnets to both sides of the GA-Al@NdFeB magnetic hydrogel, the repulsive force generated between the driving magnets and the GA-Al@NdFeB magnetic hydrogel pushes the GA-Al@NdFeB magnetic hydrogel to achieve traction and contraction of the wound.

[0041] Specifically, by changing the distance between GA-Al@NdFeB magnetic hydrogel and the driving magnet, different repulsive forces are obtained.

[0042] Example 1

[0043] A method for preparing a magnetic hydrogel is prepared by the following preparation steps:

[0044] 10 ml of a 20% gelatin solution, 5 ml of a 1% sodium alginate solution, 1 ml of deionized water, and 10 g of NdFeB particles with a particle size of 5 μm were fully mixed to obtain a reaction precursor A solution.

[0045] 0.02 g of calcium carbonate, 0.04 g of gluconolactone GDL, 0.2 g of transglutaminase TG and 4 ml of deionized water were fully mixed to obtain a reaction precursor B solution.

[0046] The reaction precursor A liquid was added into the reaction precursor B liquid, and the mixture was fully stirred and transferred into a mold. The mold was then sealed and placed in a constant temperature environment of 37° C. for 2 h to prepare GA-Al@NdFeB magnetic hydrogel.

[0047] The obtained GA-Al@NdFeB magnetic hydrogel was then cut into uniform sizes of 10 mm × 10 mm × 2 mm for later use.

[0048] The GA-Al@NdFeB magnetic hydrogel cut into size is then magnetized through a pulse magnetizer. The specific parameters are magnetizing voltage 3000V, magnetizing capacitance 5000UF, and magnetic field intensity 7T. The GA-Al@NdFeB hydrogel can be magnetized instantly when the machine is turned on.

[0049] After magnetization, two GA-Al@NdFeB magnetic hydrogels are set, and the magnetic poles of the two magnetic hydrogels are opposite. The two magnetic hydrogels are symmetrically applied to both sides of the skin wound and close to the edge of the skin wound.

[0050] There are two driving magnets, and the two driving magnets are symmetrically arranged on both sides of the magnetic hydrogel away from the skin wound, and the magnetic poles of each driving magnet and each magnetic hydrogel are the same. By attaching the driving magnets to both sides of the magnetic hydrogel, the repulsive force generated between the driving magnets and the magnetic hydrogel pushes the magnetic hydrogel to achieve traction and contraction of the wound.

[0051] Example 2

[0052] A method for preparing a magnetic hydrogel is prepared by the following preparation steps:

[0053] 10 ml of a gelatin solution with a mass percentage of 18%, 5 ml of a sodium alginate solution with a mass percentage of 0.8%, 1 ml of deionized water, and 10 g of NdFeB particles with a particle size of 8 μm were fully mixed to obtain a reaction precursor A solution.

[0054] 0.02 g of calcium carbonate, 0.04 g of gluconolactone GDL, 0.2 g of transglutaminase TG and 4 ml of deionized water were fully mixed to obtain a reaction precursor B solution.

[0055] The reaction precursor A liquid was added into the reaction precursor B liquid, and the mixture was fully stirred and transferred into a mold. The mold was then sealed and placed in a constant temperature environment of 38° C. for 2.5 h to prepare GA-Al@NdFeB magnetic hydrogel.

[0056] The obtained GA-Al@NdFeB magnetic hydrogel was then cut into uniform sizes of 10 mm × 10 mm × 2 mm for later use.

[0057] The GA-Al@NdFeB magnetic hydrogel cut into size is then magnetized through a pulse magnetizer. The specific parameters are magnetizing voltage 3000V, magnetizing capacitance 5000UF, and magnetic field intensity 7T. The GA-Al@NdFeB hydrogel can be magnetized instantly when the machine is turned on.

[0058] After magnetization, two GA-Al@NdFeB magnetic hydrogels are set, and the magnetic poles of the two magnetic hydrogels are opposite. The two magnetic hydrogels are symmetrically applied to both sides of the skin wound and close to the edge of the skin wound.

[0059] There are two driving magnets, and the two driving magnets are symmetrically arranged on both sides of the magnetic hydrogel away from the skin wound, and the magnetic poles of each driving magnet and each magnetic hydrogel are the same. By attaching the driving magnets to both sides of the magnetic hydrogel, the repulsive force generated between the driving magnets and the magnetic hydrogel pushes the magnetic hydrogel to achieve traction and contraction of the wound.

[0060] Example 3

[0061] A method for preparing a magnetic hydrogel is prepared by the following preparation steps:

[0062] 10 ml of a 22% by mass gelatin solution, 5 ml of a 1.2% by mass sodium alginate solution, 1 ml of deionized water, and 10 g of NdFeB particles with a particle size of 10 μm were fully mixed to obtain a reaction precursor A solution.

[0063] 0.02 g of calcium carbonate, 0.04 g of gluconolactone GDL, 0.2 g of transglutaminase TG and 4 ml of deionized water were fully mixed to obtain a reaction precursor B solution.

[0064] The reaction precursor A liquid was added into the reaction precursor B liquid, and the mixture was fully stirred and transferred into a mold. The mold was then sealed and placed in a constant temperature environment of 40°C for 3 hours to prepare GA-Al@NdFeB magnetic hydrogel.

[0065] The obtained GA-Al@NdFeB magnetic hydrogel was then cut into uniform sizes of 10 mm × 10 mm × 2 mm for later use.

[0066] The GA-Al@NdFeB magnetic hydrogel cut into size is then magnetized through a pulse magnetizer. The specific parameters are magnetizing voltage 3000V, magnetizing capacitance 5000UF, and magnetic field intensity 7T. The GA-Al@NdFeB hydrogel can be magnetized instantly when the machine is turned on.

[0067] After magnetization, two GA-Al@NdFeB magnetic hydrogels are set, and the magnetic poles of the two magnetic hydrogels are opposite. The two magnetic hydrogels are symmetrically applied to both sides of the skin wound and close to the edge of the skin wound.

[0068] There are two driving magnets, and the two driving magnets are symmetrically arranged on both sides of the magnetic hydrogel away from the skin wound, and the magnetic poles of each driving magnet and each magnetic hydrogel are the same. By attaching the driving magnets to both sides of the magnetic hydrogel, the repulsive force generated between the driving magnets and the magnetic hydrogel pushes the magnetic hydrogel to achieve traction and contraction of the wound.

[0069] The above-mentioned Examples 1 to 3 can all prepare magnetic hydrogels, and the prepared magnetic hydrogels are magnetized and used in a non-invasive skin mechanical loading device for wound repair. Now, one of the examples, i.e., Example 1, is selected to perform SEM detection, tensile test, magnetic field distribution detection, measurement of the repulsive force generated on the magnetic hydrogel at different distances, biocompatibility detection, preparation of mechanical loading devices of different sizes, and in vivo animal experiments.

[0070] Experimental Section

[0071] (1) SEM detection of GA-Al@NdFeB magnetic hydrogel.

[0072] The network structure of the magnetic hydrogel material and the distribution of NdFeB particles in the hydrogel network were observed by SEM. Figure 1 As shown, the hydrogel material has a uniform pore structure and a relatively dense structure. Figure 1 A, B and C in the figure are SEM images at different magnifications. Figure 1 In A, B and C, it can be seen that NdFeB particles are distributed on the pores, ensuring that the material has isotropic mechanical properties and magnetization ability.

[0073] (2) Tensile test of GA-Al@NdFeB magnetic hydrogel.

[0074] Fix the two ends of the dumbbell-shaped (tensile specimen) magnetic hydrogel on the clamp of the electronic universal testing machine, and adjust the initial position of the clamp so that the prepared sample is fully stretched and tension-free (such as Figure 2 After zeroing and calibrating the universal testing machine, move the clamp at a constant speed of 5 mm / min to stretch the sample until the sample breaks. Record the maximum stress when the sample breaks and draw a stress-stretch curve based on the tensile stress and the corresponding sample stretch length data (as shown in Figure 2 The Young's modulus is 395Kpa, indicating that the material has high mechanical properties and can meet the subsequent mechanical loading.

[0075] (3) Detection of magnetic field distribution of GA-Al@NdFeB magnetic hydrogel.

[0076] After the prepared GA-Al@NdFeB magnetic hydrogel material is magnetized, the spatial magnetic field distribution and size of the magnetic hydrogel are detected by a spatial magnetic field distribution instrument system. Figure 3 As shown, the prepared magnetic hydrogel material has magnetism after being magnetized by a pulse magnetizer, and the maximum magnetic field intensity at the magnetic pole is 18mT, which is within the safe range.

[0077] (4) A universal testing machine was used to measure the repulsive force exerted by the driving magnet on the magnetic hydrogel at different distances from the magnetized GA-Al@NdFeB magnetic hydrogel.

[0078] Table 1 Relationship between the distance between the driving magnet and GA-Al@NdFeB magnetic hydrogel and the loading force applied to the wound surface

[0079]

[0080] As shown in Table 1, by using the principle of like magnetic poles repelling each other, different loading forces on the wound surface can be generated by adjusting the distance between the driving magnet and the magnetized GA-Al@NdFeB magnetic hydrogel. For example, when the distance between the driving magnet and the GA-Al@NdFeB magnetic hydrogel is 2 mm, the loading force applied to the wound surface is 0.081 N; when the distance between the driving magnet and the GA-Al@NdFeB magnetic hydrogel is 4 mm, the loading force applied to the wound surface is 0.044 N. Therefore, mechanical loading of different sizes on the wound surface can be achieved by changing the distance between the driving magnet and the magnetized GA-Al@NdFeB magnetic hydrogel.

[0081] (5) Magnetic hydrogel biocompatibility testing.

[0082] Since GA-Al@NdFeB magnetic hydrogels need to be applied to both sides of the wound surface later, it is necessary to evaluate the excellent biocompatibility of the GA-Al@NdFeB magnetic hydrogels to ensure that they do not cause any discomfort when in contact with human and animal skin. To evaluate this property, we soaked the GA-Al@NdFeB magnetic hydrogels in DMEM complete medium overnight, cultured fibroblasts with this medium, and performed CCK-8 assay on the cells at 48 hours to evaluate the cell activity, such as Figure 4 The CCK-8 test results showed that the cell activity of the GA-Al@NdFeB magnetic hydrogel group was comparable to that of the control group, with no statistical difference, indicating that the GA-Al@NdFeB magnetic hydrogel had no cytotoxicity, verifying the biosafety of the GA-Al@NdFeB magnetic hydrogel, which can be used for subsequent in vivo animal experiments and further clinical applications.

[0083] (6) Preparation of mechanical loading devices of different sizes and in vivo animal experiments.

[0084] The following 4mm group, 2mm group and blank control group all used rats weighing about 330g to construct the wound model. When constructing the wound model, the rats were anesthetized and skin was prepared and hair was removed. A full-thickness skin defect with a diameter of 10mm was created in the middle of the rat's back with surgical scissors. The wounds were treated according to the following groups, and the treatment was the same as Figure 5 As shown:

[0085] (a) 4 mm group wound treatment: A pair of magnetized GA-Al@NdFeB magnetic hydrogels were attached to the wound edges along the long axis of the rat body in opposite directions of the magnetic poles using clinical surgical glue, and driving magnets were attached to the GA-Al@NdFeB magnetic hydrogels at a distance of 4 mm from the two sides of the GA-Al@NdFeB magnetic hydrogels using 3M medical breathable tape in the same arrangement of the magnetic poles, so that the driving magnets could push the magnetic hydrogels and thus pull the wound to contract. The wound was covered with oil sand and protected with 3M waterproof tape, and finally an adhesive bandage was used to fix the magnetic hydrogel, the driving magnet and the wound as a whole.

[0086] (b) 2 mm group: The difference from group (1) is that the distance between the driving magnet and the GA-Al@NdFeB magnetic hydrogel is 2 mm, and the other operations are the same.

[0087] (c) Blank control group: After the wound was made, it was covered with oil sand and protected with 3M waterproof patch. Finally, the wound was fixed with adhesive bandage.

[0088] All wounds were covered with vaseline gauze, and photographs were taken every three days to record the wound size and change the material.

[0089] like Figure 6 As shown in the figure, a full-thickness skin defect with a diameter of 10 mm was created on the back of the rat. A magnetic hydrogel material and a steady-state magnet were applied to the corresponding positions on both sides of the wound. The distance between the steady-state magnet and the magnetic hydrogel material was set to 2 mm and 4 mm (d=2mm, d=4mm) respectively, to achieve different forces on both sides of the wound. The wound healing was observed every 3 days and a new device was replaced. In vivo animal experiments showed that at each time point, the wound healing area was significantly higher when the distance between the steady-state magnet and the magnetic hydrogel material was 2 mm and 4 mm than that of the control group, indicating that mechanical loading on both sides of the wound can effectively promote wound healing; among them, the wound healing was best when the distance was adjusted to 2 mm, and it was basically completely healed on the 9th day, indicating that when the force on both sides of the wound is increased, the wound healing can be further promoted.

[0090] NdFeB particles are magnetic nanomaterials with strong biocompatibility and can be connected to a variety of bioactive molecules. Based on their unique physical and chemical properties, they can be used in in vitro diagnosis and clinical treatment, including in the fields of cell diagnosis, tissue repair, drug delivery, MRI, magnetic thermotherapy and magnetic transfection. NdFeB particles are superparamagnetic, which means that they can exhibit strong magnetism under the action of an external magnetic field, but will not maintain magnetism in the absence of an external magnetic field. In other words, NdFeB particles themselves cannot generate a magnetic field and can only have magnetism by responding to an external magnetic field. Therefore, the hydrogel material of NdFeB particles is a magnetic hydrogel constructed using the magnetic responsiveness of NdFeB particles and the biocompatibility of hydrogel materials. The magnetic hydrogel is used to mechanically load the wound surface to promote wound contraction and achieve the purpose of wound repair.

[0091] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A non-invasive skin mechanical loading device, characterized in that: include: At least one pair of magnetized GA-Al@NdFeB magnetic hydrogels, wherein the magnetic poles of the pair of GA-Al@NdFeB magnetic hydrogels are opposite, and the pair of GA-Al@NdFeB magnetic hydrogels are symmetrically applied on both sides of the skin wound and closely attached to the edge of the skin wound; The driving magnets correspond to the magnetized GA-Al@NdFeB magnetic hydrogels one by one, and each driving magnet is respectively arranged on both sides of the GA-Al@NdFeB magnetic hydrogel away from the skin wound surface, and is used to push the wound skin from both sides of the wound surface relative to each other, and each driving magnet has the same magnetic pole as each GA-Al@NdFeB magnetic hydrogel, so that the repulsive force generated between the driving magnet and the GA-Al@NdFeB magnetic hydrogel pushes the GA-Al@NdFeB magnetic hydrogel to pull the wound surface to contract; The preparation method of the GA-Al@NdFeB magnetic hydrogel included in the non-invasive skin mechanical loading device is prepared by the following preparation steps: The gelatin solution, the sodium alginate solution, the deionized water and the NdFeB particles are fully mixed to obtain a reaction precursor solution A; The calcium carbonate, gluconolactone, transglutaminase and deionized water are fully mixed to obtain a reaction precursor solution B; The reaction precursor A liquid is added into the reaction precursor B liquid, and the mixture is fully stirred and sealed and placed in a constant temperature environment to prepare a GA-Al@NdFeB magnetic hydrogel. The prepared GA-Al@NdFeB magnetic hydrogel is magnetized so that the NdFeB particles embedded in the hydrogel have magnetic polarity.

2. A non-invasive skin mechanical loading device according to claim 1, characterized in that: A gelatin solution with a mass percentage of 18% to 22%, a sodium alginate solution with a mass percentage of 0.8% to 1.2%, deionized water and neodymium iron boron particles are fully mixed to obtain a reaction precursor liquid A; before preparing GA-Al@NdFeB magnetic hydrogel, the mixed reaction precursor liquid A is added to the reaction precursor liquid B, sealed and placed in a constant temperature environment of 37°C to 40°C for 2h to 3h.

3. The non-invasive skin mechanical loading device according to claim 1, characterized in that: The volume mass ratio of gelatin solution, sodium alginate solution, deionized water and NdFeB particles is 10:5:1:10; the volume mass ratio of calcium carbonate, gluconolactone, glutaminase and deionized water is 0.02:0.04:0.2:

4.

4. The non-invasive skin mechanical loading device according to claim 1, characterized in that: The particle size of the NdFeB particles is 5 μm to 10 μm.

5. The non-invasive skin mechanical loading device according to claim 1, characterized in that: By changing the distance between GA-Al@NdFeB magnetic hydrogel and the driving magnet, different repulsive forces can be obtained.

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