Injectable conductive hydrogel and preparation method and application thereof

Abstract

The present application relates to the field of hydrogel tissue engineering, and particularly relates to an injectable conductive hydrogel and a preparation method and application thereof. The preparation method of the injectable conductive hydrogel comprises the following steps: mixing 7-amino beta cyclodextrin and four-arm polyethylene glycol amino to obtain a complex solution containing a slip ring structure; and mixing the complex solution containing the slip ring structure with a four-arm polyethylene glycol maleimide solution containing silver nanowires. The method for preparing the injectable conductive hydrogel with high mechanical properties is simple, and the prepared hydrogel has high mechanical properties, excellent tensile and compressive deformation capacity and fatigue resistance. The present application provides a new method for the application of the injectable hydrogel in the body.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of hydrogel tissue engineering, in particular to an injectable conductive hydrogel and a preparation method and application thereof. BACKGROUND

[0002] Sarcopenia caused by aging, neuromuscular atrophy or other chronic diseases is a pathological change that leads to a decrease in muscle volume, induces physical disability, poor quality of life, and even an increased risk of death. Current treatment strategies for muscle atrophy include physical exercise, nutritional supplements and drug therapy. Many diseases can cause muscle atrophy, and each requires a different treatment regimen.

[0003] Tissue engineering is a new discipline that combines cell biology and material science to construct tissues or organs in vitro or in vivo. Tissue engineering and regenerative medicine are one of the rapidly growing branches of knowledge for the treatment of tissue and organ regeneration. Biomaterials and cells are an integral part of tissue engineering. The delivery of appropriate cells to the defect area and the engineering matrix provide appropriate conditions for tissue repair. Therefore, a wide range of materials have been developed to achieve this goal. Hydrogel is one of the most promising biomaterials widely used in this field. Hydrogel is a three-dimensional (3D) cross-linked network that can absorb water / biological fluids and swell under physiological conditions. Hydrogels are composed of hydrophilic segments that interact with water molecules through hydrogen bonding, polarity and ionic interactions to adsorb water. Hydrogels are widely used in tissue engineering due to their unique properties such as high water content, biocompatibility, porosity and biodegradability, solid elasticity, deformability and softness, which are advanced cross-linked 3D hydrophilic polymer network biomaterials.

[0004] Injectable hydrogels are widely used in tissue engineering because they can achieve minimally invasive implantation in vivo, fill irregular body cavities according to the specific conditions of the living body, and carry drugs, cells or biological agents. The gelation mechanisms of the injectable hydrogels developed so far have obvious advantages and disadvantages. For example, hydrogels produced by covalent cross-linking have good mechanical properties, but the related agents and chemical byproducts can damage the surrounding tissues and cells. In order to ensure injectability and biocompatibility, non-toxic byproducts and catalyst-free physical cross-linking are generally selected during the design of injectable hydrogels, but this will result in poor mechanical and compression properties of the injectable hydrogels, thereby limiting their application in tissue engineering. Due to the problems of injectability and biocompatibility, their mechanical properties are often weak and difficult to withstand repeated physiological pressures in vivo. Although researchers have made considerable progress in the study of the rapid recovery and fatigue stability of hydrogels with high mechanical properties, most of the hydrogels studied are not injectable.

[0005] Polyethylene glycol is a high molecular polymer, the chemical formula is HO(CH2CH2O) n H, non-irritating, slightly bitter taste, has good water solubility, and many organic components have good compatibility. It has excellent lubricity, moisturizing, dispersing, adhesion, can be used as antistatic agent and softener, etc. In cosmetics, pharmaceuticals, chemical fibers, rubber, plastics, papermaking, paint, electroplating, pesticides, metal processing and food processing industries, it has extremely wide application. Because the outer edge of cyclodextrin is hydrophilic and the inner cavity is hydrophobic, it can provide a hydrophobic binding site like an enzyme, as a host (Host) to envelope various appropriate guests (Guest), such as organic molecules, inorganic ions and gas molecules. At present, a method for preparing a conductive injectable hydrogel with high mechanical properties is needed. SUMMARY

[0006] In order to solve the above technical problems, the present application provides a high mechanical property injectable conductive hydrogel and its preparation method and application.

[0007] The present application is based on the property of the hydrophobic site of cyclodextrin and polyethylene glycol structural unit, cyclodextrin is inserted into polyethylene glycol to form a sliding ring structure to enhance the mechanical properties of the hydrogel. The present application is based on the property that polyethylene glycol (PEG) with active maleimide group can react with amino group under certain conditions and form stable covalent bond, the present application designs a conductive hydrogel with good mechanical properties.

[0008] In the first aspect, the preparation method of the injectable conductive hydrogel provided by the present application comprises: mixing 7-amino-β-cyclodextrin and four-arm polyethylene glycol amino to obtain a complex solution containing a sliding ring structure; mixing the complex solution containing the sliding ring structure with a four-arm polyethylene glycol maleimide solution containing silver nanowires. The present application provides a simple preparation method of injectable conductive hydrogel with high mechanical properties, which has great application prospect in tissue engineering. The injectable conductive hydrogel prepared by the present application not only expands the types of injectable hydrogel, but also shows great potential in the application of tissue parts with high mechanical property requirements. The high mechanical property of the hydrogel provided by the present application is derived from the sliding ring structure prepared by four-arm polyethylene glycol and 7-amino-β-cyclodextrin, and the conductivity is derived from silver nanowires.

[0009] According to the application, by threading the amino beta-cyclodextrin on the amino chain of the four-arm polyethylene glycol, and then reacting with the four-arm polyethylene glycol maleimide, a stable covalent crosslinking network with a slip ring structure is formed. The addition of silver nanowires enhances the conductivity of the hydrogel. PMN / C+Ag shows significant mechanical strength, can withstand a pressure of 500KPa in vitro, and shows good fatigue resistance. In addition, the invention provides a strategy for the use of the hydrogel in vivo by injecting the hydrogel into the interstitial space. In order to explore the application prospect of the conductive hydrogel in the treatment of muscle atrophy, the invention injects the conductive hydrogel into the interstitial space of the atrophied muscles of the hind limbs of rats, and then uses an electrotherapy instrument to electrically stimulate the atrophied legs of the rats. The results show that the superposition of the two has a certain effect on relieving muscle atrophy, providing a new strategy.

[0010] As a preferred, the 7 amino beta cyclodextrin is seven (6-amino-6-deoxy)-beta-cyclodextrin.

[0011] In the present application, it has been found through experimental research that when the four-arm polyethylene glycol amino (containing amino beta cyclodextrin in an equimolar amount of four-wall polyethylene glycol amino) containing a slip ring structure complex solution and four-arm polyethylene glycol maleimide are mixed in a volume ratio of 1:1, by increasing the mass volume concentration of four-arm polyethylene glycol amino and four-arm polyethylene glycol maleimide, the mechanical properties of the hydrogel can be improved, the tensile deformation resistance and compression ability of the hydrogel can be improved, and the prepared hydrogel exhibits more excellent fatigue resistance, making it more suitable for muscle tissue subjected to repeated physiological stress.

[0012] As a preferred, the relative molecular mass of the four-arm polyethylene glycol amino and / or the four-arm polyethylene glycol maleimide is 10000-30000.

[0013] As a preferred, the diameter of the silver nanowire is 180-220nm, and the length is 35-55μm.

[0014] As a preferred, it further comprises: dissolving the four-arm polyethylene glycol with active maleimide groups in a silver nanowire solution to obtain a four-arm polyethylene glycol maleimide solution containing silver nanowires.

[0015] As a preferred, the concentration of the silver nanowire solution is 2.5-20mg / mL.

[0016] As a preferred, the molar ratio of the four-arm polyethylene glycol amino and the 7 amino beta cyclodextrin is 1:1-1:10.

[0017] As a preferred, the volume ratio of the complex solution containing a slip ring structure and the four-arm polyethylene glycol maleimide solution mixed is 1:1-1:5.

[0018] Further preferably, the concentration of the complex solution containing the slip ring structure is 0.2-1 g / mL; and the concentration of the solution of the four-arm polyethylene glycol maleimide is 0.2-1 g / mL.

[0019] Further preferably, the complexation of the four-arm polyethylene glycol amino and the 7-amino beta cyclodextrin is ultrasonic mixing.

[0020] Further preferably, the ultrasonic time is 20-28 h, and the power is 20-60 kw.

[0021] In the second aspect, the application provides an injectable conductive hydrogel obtained by the method for preparing the injectable conductive hydrogel.

[0022] In the application, the method for preparing the injectable conductive hydrogel is that the 7-amino beta cyclodextrin is threaded into the molecular chain of the four-arm polyethylene glycol amino to form a slip ring structure. The slip ring structure formed by the 7-amino beta cyclodextrin and the four-arm polyethylene glycol amino can help the hydrogel dissipate the pressure received, thereby avoiding rupture.

[0023] In the third aspect, the application provides the method for preparing the injectable conductive hydrogel, and the application of the injectable conductive hydrogel prepared by the method for preparing the injectable conductive hydrogel in the preparation of a medicine for treating muscle atrophy.

[0024] Further preferably, the injectable conductive hydrogel is added to the hydrogel.

[0025] According to the application, the injectable conductive hydrogel is injected into the muscle fascial space of the atrophic muscle by using the interstitial injection technology, and is assisted by electric stimulation, and can be applied to a medicine for treating muscle atrophy. In the application, the conductive hydrogel is injected into the muscle fascial space by the interstitial injection method, and the muscle atrophy is treated by the support force of the hydrogel and the electric stimulation. The interstitial injection technology is located at the medial recess of the ankle joint of a (rat), the needle tip faces the direction of the thigh of the (rat), is inclined downward by 0-30°, and the penetration depth is 1-2 cm.

[0026] The injectable conductive hydrogel provided by the application is combined with the interstitial injection method, so that the injectable conductive hydrogel is better applied to the medicine for treating muscle atrophy. In the application, the addition of the silver nanowire enhances the conductivity of the hydrogel, so that the hydrogel can serve as a good conductor in the body. In terms of treating muscle atrophy, the hydrogel is injected into the fascial space, and the results show that the weight and muscle tension of the atrophic gastrocnemius muscle are improved, and the muscle atrophy is relieved. The hydrogel has high tensile and compressive deformation capacity and fatigue resistance, and shows high mechanical properties, thereby providing a new method for the application of the injectable hydrogel in the body.

[0027] The application has at least the following beneficial effects:

[0028] 1) The present application provides a high mechanical property injectable conductive hydrogel prepared by a simple method, which has excellent fatigue resistance;

[0029] 2) The hydrogel prepared by the present application has excellent conductivity and adhesion;

[0030] 3) The hydrogel prepared by the present application has good biocompatibility and is suitable for use in high physiological pressure parts in vivo;

[0031] 4) The material selected by the present application is easy to obtain and stable, and can be stored for a long time after preparation. It can be mixed into glue at appropriate time, and is easy to market;

[0032] 5) The present application provides an injection method for the in vivo injection and long-term retention of injectable conductive hydrogel;

[0033] 6) The interstitial injection method of the present application provides a new strategy for the treatment of muscle atrophy. BRIEF DESCRIPTION OF DRAWINGS

[0034] In order to more clearly illustrate the technical solutions of the embodiments of the present application and the prior art, the drawings needed in the embodiments or the prior art description will be briefly introduced. Obviously, the drawings in the following description are some embodiments of the present application, and those skilled in the art can obtain other drawings without creative labor based on these drawings.

[0035] Figure 1 Flowchart for preparation of high mechanical property conductive hydrogel of the present application and treatment of muscle atrophy;

[0036] Figure 2 Gelation reaction mechanism and electron microscope image of the high mechanical property conductive hydrogel of the present application;

[0037] Figure 3 Anti-fatigue effect diagram of the hydrogel of the embodiment of the present application;

[0038] Figure 4 Tissue adhesion effect diagram of the hydrogel of the embodiment of the present application;

[0039] Figure 5 PMN / C+Ag interstitial injection diagram of the embodiment of the present application;

[0040] Figure 6 Biocompatibility test effect diagram of the hydrogel of the embodiment of the present application;

[0041] Figure 7 Effect diagram of the hydrogel of the embodiment of the present application treating muscle atrophy in rats. DETAILED DESCRIPTION

[0042] To make the objectives, technical solutions, and advantages of the embodiments of the invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0043] Unless otherwise stated, all raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods. Where specific techniques or conditions are not specified in the examples, they are performed using conventional methods or in accordance with techniques or conditions described in the literature in this field, or according to the product instructions. Reagents and instruments whose manufacturers are not specified are all conventional products that can be purchased from legitimate channels.

[0044] The flowchart for the preparation of high-mechanical-performance conductive hydrogels and the treatment of muscle atrophy provided in this embodiment of the invention (e.g.) Figure 1 (As shown). In some specific embodiments of the present invention, the hydrogel is prepared by mixing 0.3 g / mL of four-arm polyethylene glycol amino and 0.3 g / mL of four-arm polyethylene glycol maleimide at a molar ratio of 1:1 to 2. In some preferred embodiments of the present invention, 0.3 g of amino-tetra-arm polyethylene glycol (4Arm-PEG-NH2, MW = 20000) and 0.01695 g of 7-aminoβ-cyclodextrin (7NH2-βCD, MW = 1130) are dissolved in 1 mL of deionized water, and the mixture is intermittently sonicated for 3 hours. After the mixture is left to stand overnight, a homogeneous composite solution (4Arm-PEG-NH2 / CD) is obtained. Subsequently, 0.3 g of four-arm polyethylene glycol (4Arm-PEG-Mal, MW = 10000) with active maleimide groups is dissolved in a 5 mg / mL solution of silver nanowires (AgNWs). Next, 4Arm-PEG-NH2 / CD (0.3 g / mL) and 4Arm-PEG-Mal (0.3 g / mL, containing 5 mg / mL AgNWs) were uniformly mixed at a 1:1 volume ratio, and high mechanical properties were obtained after 5–10 minutes at 37 °C. Conductive hydrogels (0.3 g / mL PMN / C+Ag) and AgNW-free hydrogels (PMN / C) were prepared as described above, using distilled water instead of 5 mg / mL AgNWs.

[0045] In the embodiments of the present application, 7-amino-β-cyclodextrin, i.e., heptakis(6-amino-6-deoxy)-β-cyclodextrin, is purchased from Shandong Binzhou Zhiyuan Biotechnology Co., Ltd. Silver nanowires (AgNWs) are purchased from Aladdin Industrial Corporation (Shanghai, China). Four-arm polyethylene glycol amino (4Arm-PEG-NH2, MW = 20000) and active maleimide group (4Arm-PEG-Mal, MW = 10000) are purchased from Guangzhou Carbohydrate Biotechnology Co., Ltd.

[0046] The present application will be further described below in conjunction with examples.

[0047] Example 1

[0048] In this example, 0.3 grams of four-arm polyethylene glycol amino (4Arm-PEG-NH2, MW = 20000) and 0.01695 grams of 7-amino-β-cyclodextrin (7NH2-βCD, MW = 1130) are dissolved in 1 milliliter of deionized water, and the mixture is intermittently ultrasonically treated for 3 hours. After the mixture is left overnight, a uniform complex solution (4Arm-PEG-NH2 / CD) is obtained. Subsequently, 0.3 grams of four-arm polyethylene glycol with an active maleimide group (4Arm-PEG-Mal, MW = 10000) is dissolved in a 5 milligrams / milliliter silver nanowire (AgNWs) solution. Next, 4Arm-PEG-NH2 / CD (0.3 grams / milliliter) and 4Arm-PEG-Mal (0.3 grams / milliliter, containing 5 milligrams / milliliter of AgNWs) are uniformly mixed at a volume ratio of 1:1, and a high mechanical property is obtained at 37°C after 5-10 minutes. The conductive hydrogel (0.3g / mL PMN / C+Ag) and the hydrogel without AgNWs (PMN / C) are prepared as described above, with distilled water instead of 5mg / mL AgNWs. The injection technique is as follows: 100μL of the conductive hydrogel is drawn with a 1mm syringe, the injection site is in the medial depression of the rat ankle joint, the needle tip is directed towards the rat thigh, and the needle is inclined downward by 30°, with a penetration depth of 1cm. There is a clear sense of cavity, indicating that the insertion site is near the fascial space of the rat calf. The syringe is pushed downward to inject the hydrogel, and no obvious blockage is found during the process. After injection, the injection area should be massaged to allow the hydrogel solution to diffuse into some fascial spaces around the muscle.

[0049] In this example, equimolar 7NH2-βCD and 4Arm-PEG-NH2 are ultrasonically mixed, and a gel chromatograph is used to characterize the state of the solution, Figure 2Gel chromatogram of complexation of (a) PEG and cyclodextrin; (b) infrared spectrum of gelation reaction; (c) scanning electron microscope images of the preparation process of conductive hydrogel (PMN / C+Ag), from top to bottom are: PEG cyclodextrin sliding ring hydrogel, silver nanowire, PMN / C+Ag conductive hydrogel, and on the right is the elemental analysis of the hydrogel after incorporating silver nanowires, such as Figure 2 (a) shows that the retention peak of 7NH2-βCD (6 mg / mL) in gel chromatography is 6.49 min, and the retention peak of 4Arm-PEG-NH2 (10 mg / mL) in gel chromatography is 6.025 min; after ultrasonic mixing of the two solutions, the retention peak becomes 5.9 min, because part of the 7NH2-βCD is tangled on the 4Arm-PEG-NH2, which increases the molecular chain mass of the 4Arm-PEG-NH2, ultimately leading to a decrease in the retention time of the 4Arm-PEG-NH2 in the chromatographic column. This embodiment uses a micro-infrared spectrometer to simply characterize the gelation mechanism of PMN / C. Figure 2 (b) are the Fourier infrared spectra of 4Arm-PEG-NH2 and 4Arm-PEG-Mal respectively and their reaction product. As can be seen from the figure, the carbon-carbon double bond (-C=C-, peak value: 1548 cm -1 ) disappears after mixing reaction with 4Arm-PEG-NH2. Subsequently, this embodiment incorporates 5 mg / mL of silver nanowires (AgWNs) in the preparation process of the hydrogel to obtain a conductive hydrogel (0.3PMN / C+Ag), and the morphology of the hydrogel before and after the addition of AgWNs is characterized, such as Figure 2 (c). It can be seen that the PMN / C hydrogel is relatively dense, and when AgWNs are added to PMN / C, the morphology of the hydrogel also changes to a certain extent, and it can be seen that the surface of PMN / C+Ag becomes more dense. This embodiment scans the surface elements of the selected area, and from the figure it can be seen that the silver element is uniformly distributed in the area, which indicates that the introduction of AgWNs is successful.

[0050] The fatigue resistance of PMN / C+Ag is described by compression cycle data, as shown in Figure 3 . The test cycle speed is 500 mm / min, and the cycle number is 7000 times. It can be seen that PMN / C+Ag reaches the load limit at 5000-7000 cycles. Compared with the maximum compression stress in the first compression cycle, the maximum compression stress in the 7000th cycle decreases by 30%, but in the 5000th cycle, it only decreases by 3.2%. This embodiment tests the adhesion of the hydrogel using pigskin, as shown in Figure 4As shown, when the hydrogel (0.3PMN / C+Ag) adheres between two pieces of pigskin, the maximum adhesive force for separation of the pigskin, as shown by the tensiometer, is approximately 7N. According to the formula (σ=F / LW, L: 2cm, W: 3cm), the adhesive force applied per unit area is approximately 11.7KPa. Figure 5 This is an anatomical diagram of PMN / C+Ag interstitial injection, showing that PMN / C+Ag is injected and dispersed among muscle groups. Figure 6 The results of the biocompatibility and cell compatibility tests of the hydrogel are as follows: (a) Tissue inflammatory characterization 14 days after PMN / C+Ag interstitial injection; (b) Cell viability detection (CCK8) after co-culturing PMN / C+Ag with cells. As can be seen from the figure, the inflammatory response of the tissue after hydrogel injection is no different from that of the normal group, which indicates that the hydrogel has good biocompatibility. The cell compatibility test shows that the hydrogel has very low toxicity to cells.

[0051] Figure 7 This is an illustration of the effect of hydrogel treatment on rat muscle atrophy in Example 1 of the present invention; the muscle atrophy treatment is divided into four groups: blank group, electric shock treatment group (ES), hydrogel injection treatment group (PMN / C+Ag), and hydrogel injection + electric shock treatment group (PMN / C+Ag ES). (a) Schematic diagram of each group of muscle atrophy treatment. Figure 7 (b) shows HE and Masson slice scans of the gastrocnemius muscle in each group. The comparison reveals that, compared to healthy muscle, the atrophied gastrocnemius muscle fibers and muscle bundles are much smaller and less uniform. The muscle fibers and fiber bundles in the PMN / C+Ag ES and PMN / C+Ag groups are thicker and more uniform than those in the Blank and ES groups, but there is no significant difference between PMN / C+Ag ES and PMN / C+Ag groups. Furthermore, this embodiment statistically analyzed the ratio of the area of ​​a single muscle fiber to the area of ​​muscle fibers in the healthy leg in each group, obtaining... Figure 7 (c) Muscle fiber area comparison of each group: As shown in the figure, the cross-sectional area of ​​a single muscle fiber in the PMN / C+Ag ES group is significantly larger than that in the Blank and ES groups. However, there is no significant statistical difference between the PMN / C+Ag and ES groups, or between the PMN / C+Ag ES groups. This indicates that PMN / C+Ag ES can slow down the thinning of muscle fibers during muscle atrophy, and this effect is the result of combined stimulation by PMN / C+Ag and ES. Masson staining showed obvious collagen deposition between fibers and fiber bundles in each group, but there was no significant difference between the groups. Figure 7(d) is the ratio of the atrophied gastrocnemius muscle mass to the healthy gastrocnemius muscle mass of the opposite side of each experimental group. It can be seen from the figure that the muscle mass ratio of the PMN / C+Ag ES and PMN / C+Ag groups is significantly higher than that of the Blank and ES groups, the PMN / C+Ag ES group is higher than the PMN / C+Ag group, and the ES group is slightly higher than the Blank group. This shows that the mechanical support of the gel and the certain electrical stimulation can slow down the loss of muscle mass. Figure 7 (e) is the statistical result of the muscle tension ratio of the atrophied gastrocnemius muscle to the healthy gastrocnemius muscle of the opposite side of each experimental group. It can be seen from the figure that the muscle tension ratio of the PMN / C+Ag ES and PMN / C+Ag groups is significantly higher than that of the Blank and ES groups, the ES group is higher than the Blank group, and the PMN / C+Ag ES group is slightly higher than the PMN / C+Ag group. This result shows that the mechanical support of the hydrogel and the certain electrical stimulation have obvious effect on strengthening the muscle tension of the atrophied muscle. Through the gastrocnemius muscle mass statistics and muscle tension test and pathological section, it has been seen in this embodiment that the PMN / C+Ag ES has good therapeutic effect on relieving muscle atrophy.

[0052] Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present application, and not to limit them; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that: it can still modify the technical solutions recorded in the foregoing embodiments, or make equivalent replacement for part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for preparing an injectable conductive hydrogel, characterized in that, include: 7-aminoβ-cyclodextrin and four-armed polyethylene glycol amino were mixed to obtain a complex solution containing a slip ring structure; The composite solution containing the slip ring structure is mixed with a four-armed polyethylene glycol maleimide solution containing silver nanowires; The molar ratio of the four-arm polyethylene glycol amino group to the 7-aminoβ-cyclodextrin is 1:1, the volume ratio of the complex solution containing the slip ring structure to the four-arm polyethylene glycol maleimide solution is 1:1, and the 7-aminoβ-cyclodextrin is hepta(6-amino-6-deoxy)-β-cyclodextrin; the complexation method of the four-arm polyethylene glycol amino group and the 7-aminoβ-cyclodextrin is ultrasonic mixing.

2. The method for preparing the injectable conductive hydrogel according to claim 1, characterized in that, The relative molecular mass of the four-armed polyethylene glycol amino group is 10,000 to 30,000; the relative molecular mass of the four-armed polyethylene glycol maleimide group is 10,000 to 30,000.

3. The method for preparing the injectable conductive hydrogel according to claim 1, characterized in that, The silver nanowires have a diameter of 180~220 nm and a length of 35~55 μm.

4. The method for preparing the injectable conductive hydrogel according to claim 1, characterized in that, The concentration of the composite solution containing the slip ring structure is 0.2~1 g / mL; the concentration of the four-arm polyethylene glycol maleimide solution is 0.2~1 g / mL.

5. The method for preparing the injectable conductive hydrogel according to any one of claims 1-4, characterized in that, The ultrasound duration is 20-28 hours, and the power is 20-60 kW.

6. An injectable conductive hydrogel, characterized in that, It is obtained by the preparation method of the injectable conductive hydrogel according to any one of claims 1-5.

7. The application of the injectable conductive hydrogel prepared by the method of any one of claims 1-5, characterized in that, Its application in the preparation of drugs for treating muscle atrophy.

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