A method of making, using and apparatus for an electrically conductive hydrogel

Abstract

The application provides a preparation method, a use method and a device of a conductive hydrogel, and belongs to the field of biomedical materials.The method comprises the following steps: mixing a PEDOT:PSS solution and polyethylene glycol dimethacrylate, and then performing volatilization concentration to obtain a gel; adding a photoinitiator and a dopant into the gel, and then performing stirring to obtain a conductive hydrogel.Through reasonable design of raw materials for composing the conductive hydrogel, the developed conductive gel has the properties of high conductivity, high charge storage capacity, injectable rheological property, photocurability, strong adhesion, low modulus and stretchability, meets the use requirement of the injectable gel, and has good mechanical matching and functional adaptability of biological tissues, so that the conductive gel can be used for eliminating and treating atrial fibrillation of the heart.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, and particularly relates to a preparation method, a use method and a device of conductive hydrogel. BACKGROUND

[0002] Atrial fibrillation is the most common persistent arrhythmia. When atrial fibrillation occurs, the heart rate is often too fast and irregular, thereby causing the atrium to lose effective contraction function, causing blood to concentrate in the atrium and thrombosis, and being closely related to coronary heart disease, hypertension and heart failure. The reason for the occurrence of atrial fibrillation is that biological electricity is randomly distributed in the atrium, thereby causing conduction disorder of ventricular current, leading to irregular heart contraction and occurrence of related diseases. Therefore, it is of great clinical significance to develop a new means for treating atrial fibrillation.

[0003] At present, the clinical treatment methods for atrial fibrillation mainly include electric conversion, radiofrequency ablation treatment and surgical maze operation treatment. The electric conversion is to restore sinus rhythm by a defibrillator, the radiofrequency ablation treatment is to make part of myocardium degenerate and necrotize to block the transmission of abnormal electrical signals from the outside of the heart to the atrium, and the surgical maze operation treatment is to completely cure atrial fibrillation by cutting and suturing the atrium in a maze route. However, these treatment methods are either not long-term effective, or cause serious tissue trauma, or need extremely complex surgery. Therefore, it is necessary to develop a non-invasive, low-implantation-damage and long-term stable means for eliminating atrial fibrillation. As a non-invasive implantation means, injectable hydrogel is widely used in tissue medical engineering, and due to the low modulus characteristics of the hydrogel, the damage to the tissue is extremely low compared with hard devices. However, at present, there is no conductive gel which can be used for in-situ injection and light curing of the heart for eliminating and treating atrial fibrillation. SUMMARY

[0004] The present application provides a preparation method, a use method and a device of conductive hydrogel to solve the technical problem that there is no conductive gel which can be used for in-situ injection and light curing of the heart for eliminating and treating atrial fibrillation in the prior art.

[0005] In a first aspect, the present application provides a preparation method of conductive hydrogel, and the method comprises the following steps:

[0006] The PEDOT:PSS solution is mixed with polyethylene glycol dimethacrylate, and then concentrated by volatilization to obtain a gel;

[0007] The photoinitiator and the dopant are added to the gel, and then stirred to obtain the conductive hydrogel.

[0008] Optionally, the volume ratio of the PEDOT:PSS solution to the polyethylene glycol dimethacrylate is (20-30):1.

[0009] Optionally, the photoinitiator is a water solution of blue light photoinitiator, the mass concentration of the blue light photoinitiator in the water solution is 60g / L-150g / L, and the blue light photoinitiator is phenyl-2, 4, 6-trimethylbenzoyl lithium phosphite.

[0010] Optionally, the dopant is a water solution of polyether F127 diacrylate, and the mass fraction of the polyether F127 diacrylate in the water solution is 15%-25%.

[0011] Optionally, the volume ratio of the photoinitiator, the dopant and the gel is 1: (0.8-1.2): (5-15).

[0012] Optionally, the mixing of the PEDOT:PSS solution and the polyethylene glycol dimethacrylate, and then the volatilization and concentration to obtain the gel, comprises:

[0013] Filtering the PEDOT:PSS solution;

[0014] Adding the polyethylene glycol dimethacrylate to the filtered PEDOT:PSS solution, and then stirring to obtain a mixed solution;

[0015] Volatilizing and concentrating the mixed solution at 40-50°C to reduce the volume of the mixed solution by 40%-60% to fully separate PEDOT and PSS, and then obtaining the gel.

[0016] In a second aspect, the application provides a use method of the conductive hydrogel prepared by the method of any one of the first aspect, the method comprising:

[0017] Injecting a set mass of the conductive hydrogel into a target position, and then performing in-situ photocuring.

[0018] Optionally, the set mass is 15-25μL, the in-situ photocuring uses 405nm blue light, and the in-situ photocuring time is 15-25s.

[0019] In a third aspect, the application provides a device for in-situ injection and photocuring of a conductive hydrogel, the device comprising:

[0020] An injection assembly for injecting a set mass of the conductive hydrogel into a target position;

[0021] A blue light lamp for in-situ photocuring of the conductive hydrogel injected into the target position.

[0022] Optionally, the injection assembly comprises:

[0023] The application discloses an injection device, which comprises an injection needle, a hose and an injection tube.

[0024] The endoscope comprises a camera, an illuminating lamp and a mobile device interface.

[0025] Compared with the prior art, the above technical scheme provided by the embodiment of the application has the following advantages.

[0026] The application provides a preparation method of conductive hydrogel, by reasonably designing the raw materials of the conductive hydrogel, the developed conductive hydrogel has high conductivity, high charge storage capacity, injectable rheology, photocurability, strong adhesion, low modulus and stretchable performance, which meets the use requirements of the injectable hydrogel, and the mechanical matching and functional adaptability of the biological tissue, so as to be used for eliminating and treating atrial fibrillation of the heart; by long-time volatilization and concentration and adding a dopant, the PEDOT and the PSS are fully stripped, the PEDOT is a conductive phase, and after being stripped from the PSS, self-polymerization is formed, so as to improve the conductivity of the hydrogel. BRIEF DESCRIPTION OF DRAWINGS

[0027] The drawings incorporated into the specification and constituting a part of the specification show embodiments consistent with the application and, together with the specification, serve to explain the principles of the application.

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced as follows, and obviously, other drawings can also be obtained by those skilled in the art without creative labor under the premise of not paying the creative labor.

[0029] Figure 1 A flowchart of the preparation method of the conductive hydrogel provided by the embodiment of the application is shown in the figure.

[0030] Figure 2 A device structure diagram of in-situ injection and photocuring of the conductive hydrogel provided by the embodiment of the application is shown in the figure.

[0031] Figure 3 A schematic diagram of the use method of the conductive hydrogel provided by the embodiment 2 of the application is shown in the figure.

[0032] Figure 4 An electrocardiogram for showing the effect of the conductive hydrogel provided by the embodiment 2 of the application on eliminating atrial fibrillation is shown in the figure.

[0033] Reference signs:

[0034] 1. injection assembly; 10. syringe 10; 101. injection needle; 102. hose; 103. injection tube 103; 11. endoscope; 111. camera; 112. illuminating lamp; 113. mobile device interface;

[0035] 2. blue light lamp. DETAILED DESCRIPTION

[0036] In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the scope of the present application.

[0037] Various embodiments of the present application can exist in the form of a range; it should be understood that the description in the form of a range is merely for the convenience and brevity, and should not be understood as a hard limit on the scope of the present application; therefore, it should be considered that the described range has specifically disclosed all possible sub-ranges and single values in the range. For example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers in the described range, such as 1, 2, 3, 4, 5 and 6, which applies to any range. In addition, whenever a numerical range is indicated in this document, it refers to any cited number (fraction or integer) in the indicated range.

[0038] In addition, in the description of the present application, the terms "comprise", "contain" and the like mean "comprise but not limited to". In this paper, such as "first" and "second" and other relational terms are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between the entities or operations. In this paper, "and / or" describes the relationship between the associated objects, which means that there can be three kinds of relationships, for example, A and / or B can represent: A exists alone, A and B exist together, and B exists alone. Where A, B can be singular or plural. In this paper, "at least one" means one or more, and "multiple" means two or more. "At least one", "at least one of the following" or the like means any combination of the items, including single item or any combination of multiple items. For example, "at least one of a, b, or c", or "at least one of a, b, and c", can represent a, b, c, a-b (i.e. a and b), a-c, b-c, or a-b-c, where a, b, and c can be single or multiple.

[0039] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present application can be purchased or prepared by existing methods.

[0040] Figure 1 A flowchart of a preparation method of a conductive hydrogel provided in an embodiment of the present application.

[0041] See Figure 1 The present application provides a preparation method of a conductive hydrogel, which comprises:

[0042] S1, mixing PEDOT:PSS solution and polyethylene glycol dimethacrylate, and then performing volatilization and concentration to obtain a gel;

[0043] PEDOT:PSS solution (1.3wt% aqueous solution) is a poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) solution, which is an aqueous solution of a high molecular polymer with very high conductivity. According to different formulations, aqueous solutions with different conductivities can be obtained. From the name of the compound, we can see that the product is composed of two substances, PEDOT and PSS. PEDOT is a polymer of EDOT (3,4-ethylenedioxythiophene monomer), and PSS is polystyrene sulfonate. The combination of the two substances greatly improves the solubility of PEDOT.

[0044] Polyethylene glycol dimethacrylate (PEGDMA) is an organic substance with the chemical formula C 50 H 94 O24 , white to white-like solid.

[0045] In some embodiments, the volume ratio of the PEDOT:PSS solution to the polyethylene glycol dimethacrylate is (20-30):1.

[0046] The volume ratio of the PEDOT:PSS solution to the polyethylene glycol dimethacrylate is controlled to be PEDOT:PSS solution:polyethylene glycol dimethacrylate=(20-30):1, which has the positive effects that if the proportion of the polyethylene glycol dimethacrylate is too low, the gel cannot achieve the effect of photocuring; if the proportion of the polyethylene glycol dimethacrylate is too high, the proportion of the insulating substance is too high, resulting in too low conductivity of the gel. For example, the volume ratio of the PEDOT:PSS solution to the polyethylene glycol dimethacrylate can be 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, etc.

[0047] In some embodiments, the mixing of the PEDOT:PSS solution and the polyethylene glycol dimethacrylate, followed by volatilization and concentration, to obtain the gel, comprises:

[0048] Filtering the PEDOT:PSS solution;

[0049] Adding the polyethylene glycol dimethacrylate to the filtered PEDOT:PSS solution, followed by stirring, to obtain a mixed solution;

[0050] Volatilizing and concentrating the mixed solution at 40-50°C to reduce the volume of the mixed solution by 40-60%, so that the PEDOT and PSS are fully stripped, to obtain the gel.

[0051] In this application, the PEDOT:PSS solution is filtered to remove the aggregated PEDOT particles in the PEDOT:PSS solution; the PEDOT and PSS are fully stripped by sufficient mixing and long-time volatilization and concentration, to slowly form a viscous gel, and the PEDOT, which is the conductive phase, will form self-polymerization after being stripped from the PSS, thereby improving the conductivity of the hydrogel. For example, the volatilization and concentration temperature of the mixed solution is 40°C, 41°C, 42°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C, 50°C, etc.; the volatilization and concentration can reduce the volume of the mixed solution by 40%, 42%, 44%, 46%, 50%, 52%, 55%, 58%, 59%, 60%, etc.

[0052] In some embodiments, the time for the mixed solution to be volatilized and concentrated to a volume reduction of 40-60% can be 24-48 hours. If the volatilization time is too long, the gel will be physically cross-linked and no longer have rheological properties, resulting in the inability to inject. For example, the time can be 24 hours, 26 hours, 30 hours, 32 hours, 35 hours, 38 hours, 40 hours, 42 hours, 45 hours, 48 hours, etc.

[0053] In some embodiments, trimethylchlorosilane can be used to volatilize to the surface of the sample bottle used for volatilization and concentration at room temperature, to achieve surface hydrophobicity, and then washed with deionized water for 3 times.

[0054] By volatilizing trimethylchlorosilane to the surface of the glass sample bottle at room temperature, the surface hydrophobicity is achieved, and then washed with deionized water for 3 times.

[0055] S2, adding a photoinitiator and a dopant to the gel, and then stirring to obtain a conductive hydrogel.

[0056] In some embodiments, the photoinitiator is an aqueous solution of a blue light initiator, the mass concentration of the blue light initiator in the aqueous solution is 60-150 g / L, and the blue light initiator is

[0057] Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) is a photoinitiator with good water solubility and biocompatibility, which is widely used for the photocuring of hydrogels and biological inks. Compared with the traditional initiator Irgacure 2959, it has higher water solubility and photoinitiation efficiency, and the photoexcitation wavelength band covers 365-405 nm, which is more suitable for biological applications.

[0058] In the present application, a blue light initiator is added to achieve its photopolymerization ability. For example, the mass concentration of the blue light initiator in the aqueous solution can be 60 g / L, 70 g / L, 80 g / L, 90 g / L, 100 g / L, 120 g / L, 140 g / L, 150 g / L, etc.

[0059] In some embodiments, the dopant is an aqueous solution of polyether F127 diacrylate, and the mass fraction of polyether F127 diacrylate in the aqueous solution is 15-25%.

[0060] Polyether F127 Diacrylate (PF127DA) is an acrylated polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer. PF127 has excellent thermal gelation (warm gelation) properties and good biological safety, and is a highly stretchable, puncture-resistant and self-healing hydrogel. PF127-based material systems can be applied in the biomedical field, such as used as a drug carrier, a wound dressing, a cell carrier shear protection agent, a biological 3D printing, etc. The hydrogel has good adhesion to fabrics, and can improve the adhesion between the fabric and the yarn.

[0061] In the present application, a dopant is added to better separate PEDOT and PSS. PEDOT is a conductive phase, and after being stripped from PSS, self-polymerization occurs, thereby improving the conductivity of the hydrogel. For example, the mass fraction of polyether F127 diacrylate in the aqueous solution can be 15%, 16%, 18%, 20%, 21%, 23%, 24%, 25%, etc.

[0062] In some embodiments, the method further comprises synthesis of polyether F127 diacrylate, comprising:

[0063] 12.5 g of F127 and 40 mL of toluene were added to a three-necked flask, stirred at 600 rpm, vacuumed, and then continuously supplied with nitrogen. The mixture was heated in a 60°C water bath for 4 h to fully dissolve. After cooling to room temperature, the mixture was cooled to 0°C in an ice bath, and 0.6 mL of triethylamine was slowly added dropwise. Then, 10 mL of dichloromethane was added, and 0.25 mL of acryloyl chloride was diluted in 10 mL of dichloromethane and slowly added. Continuous stirring was performed, and the nitrogen supply was continued. The mixture was stirred at room temperature for 12 h, and the precipitate was filtered by suction filtration with filter paper. The solvent was evaporated from the solution by a rotary evaporator to obtain a viscous oil solution. Hexane was added to precipitate the product, which was filtered by suction filtration. The precipitate was transferred to a plastic dish, and dried in a vacuum drying oven at 30°C for 24 h to obtain a powder.

[0064] F127DA was dissolved in water and stirred at 300 rpm for 12 h to fully dissolve. After standing for 6 h to remove bubbles, a 20 wt% aqueous solution was prepared and stored at 4°C.

[0065] In the present application, polyether F127 diacrylate is synthesized to eliminate the batch-to-batch differences of commercial polyether F127 diacrylate and improve the accuracy of experimental results.

[0066] In some embodiments, the volume ratio of the photoinitiator, the dopant and the gel is 1:(0.8-1.2):(5-15).

[0067] The volume ratio of the photo initiator, the dopant and the gel is photo initiator: dopant: gel = 1: (0.8-1.2): (5-15), and the positive effects are as follows: if the content of the photo initiator is too low, the gel cannot be photo-cured; if the content of the initiator is too high, the harm to the heart tissue will be increased. For example, the volume ratio of the photo initiator, the dopant and the gel can be 1:0.8:5, 1:0.8:10, 1:0.8:15, 1:0.9:5, 1:0.9:10, 1:0.9:15, 1:1:5, 1:1:10, 1:1:15, 1:1.2:5, 1:1.2:10, 1:1.2:15, etc.

[0068] The application provides a use method of the conductive hydrogel, and the method comprises the following steps:

[0069] A set quality of the conductive hydrogel is injected into a target position, and then in-situ photo-curing is performed.

[0070] In some embodiments, the set quality is 15-25 μL; the in-situ photo-curing uses blue light with a wavelength of 405 nm, and the in-situ photo-curing time is 15-25 s.

[0071] The gel in-situ injection and photo-curing biological material implantation method developed by the application has the advantages of non-invasiveness, low implantation damage and long-term implantation stability, and solves the problems of tissue damage and complex operation caused by hard implantation devices. For example, the set quality can be 15 μL, 16 μL, 17 μL, 19 μL, 20 μL, 21 μL, 22 μL, 23 μL, 24 μL, 25 μL, etc.; and the in-situ photo-curing time can be 15 s, 16 s, 18 s, 19 s, 20 s, 22 s, 23 s, 24 s, 25 s, etc.

[0072] Figure 2 A device structure diagram for in-situ injection and photo-curing of the conductive hydrogel is provided in the embodiments of the application.

[0073] Please refer to Figure 2 The application provides an in-situ injection and photo-curing device for a conductive hydrogel, which comprises:

[0074] The injection assembly 1 is used for injecting a set quality of the conductive hydrogel into a target position.

[0075] The blue light lamp 2 is used for in-situ photo-curing of the conductive hydrogel injected into the target position.

[0076] In some embodiments, the injection assembly 1 comprises:

[0077] Syringe 10, comprising injection needle 101, hose 102 and injection tube 103, the lower end of the injection tube 103 penetrates and fixedly connects the hose 102, the lower end of the hose 102 penetrates and fixedly connects the injection needle 101;

[0078] Endoscope 11, comprising camera 111, illuminating lamp 112 and mobile device interface 113, the bottom of the camera 111 is fixedly connected with the injection needle 101, and the illuminating lamp 112 is fixedly installed around the camera 111.

[0079] Specifically, the function integrated device for gel injection and photocuring is composed of the following: the device is composed of four parts of a miniature endoscope camera, a green light illuminating LED lamp, a blue light curing LED lamp and a syringe, wherein the endoscope camera is composed of a front-end miniature camera, three green light auxiliary illuminating LED lamps (wavelength 560 nm), three blue light curing LED lamps (wavelength 405 nm), an LED lamp switch switching button, a hard wire and a mobile device interface, and the syringe is composed of a front-end injection needle and a rear-end micro-injection tube, the injection needle is bound together with the camera, the lens diameter is 4 mm, the focal length is adjustable in the range of 2 cm to 10 cm, the switches of the green light auxiliary illuminating LED lamp and the blue light curing LED lamp are switchable, and the endoscope can be connected to a mobile terminal for observation and shooting. The device structure diagram for in-situ injection and photocuring of conductive hydrogel is shown in Figure 2 .

[0080] The present application will be further described in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present application and not used to limit the scope of the present application. The experimental methods not specified in the following examples are generally determined according to the industry standards. If there is no corresponding industry standard, the general international standards, conventional conditions or the conditions suggested by the manufacturers are used.

[0081] Example 1

[0082] The present embodiment provides a preparation method of conductive hydrogel, which is composed of the following steps:

[0083] S11: 200ul of trimethylchlorosilane is taken by a pipette and added into a dry 5mL glass sample bottle, a cover is put on, and the bottle is placed for 10min, the cover is opened in a fume hood, trimethylchlorosilane is volatilized, the bottle is placed for 10min, a hydrophobic layer is attached to the surface of the glass, and the glass is rinsed with deionized water three times to remove excess trimethylchlorosilane.

[0084] S21: The PEDOT:PSS solution (1.3wt% aqueous solution) is filtered with a 0.22μm filter membrane to remove spontaneously aggregated PEDOT particles, 2mL of the filtered PEDOT:PSS solution is added to a sample bottle, and then 80uL of PEGDMA is gradually added in several portions, and the mixture is fully vortexed for 10min to make the PEDOT and PSS uniformly mixed to strip the PEDOT from the PSS;

[0085] S31: The sample bottle is opened and placed on a 45℃ hot plate to slowly evaporate the water in the solution, and the evaporation time is controlled between 24-48h, during which the cooled water on the bottle wall is removed with a dust-free paper, and the final volume of the gel remaining in the sample bottle is between 0.8-1.2mL, and the gel is in a viscous state, to obtain a hydrogel.

[0086] S41: 10mg of the photoinitiator LAP is taken and added to 100uL of deionized water to fully dissolve, and mixed into the gel obtained in S31, and then fully stirred for 1min to make the mixture uniform.

[0087] S51: 2g of the F127DA synthesized in Example 1 is added to a sample bottle containing 8mL of deionized water, and stirred at 300rpm at room temperature for 12h to fully dissolve, and then placed at 4℃ for 6h to naturally defoam, to finally prepare a 20wt% aqueous solution;

[0088] S61: The aqueous solution prepared in S5 is placed on ice to keep it flowing, and 100ul of the F127DA aqueous solution is added to the gel obtained in S4, and then fully stirred for 1min to make the mixture uniform, and finally the conductive gel is slowly sucked into the injection device, and placed at 4℃ for use, and can be stored in the refrigerator for one week. The volume ratio of the photoinitiator, the dopant, and the gel is 1:1:10, and when the volume ratio of the PEDOT:PSS solution and the polyethylene glycol dimethacrylate is 20:1, 25:1, and 30:1, the conductivity of the gel after solidification is 7.2, 10.3, and 8.1mS / cm respectively, which is higher than the conductivity of normal tissue 0.1mS / cm; and the area capacitance measured by the electrochemical workstation is 0.23, 0.42, and 0.38mC / cm 2 , which is higher than the 0.06mC / cm 2 of the pure platinum electrode.

[0089] Example 2

[0090] Figure 3 A schematic diagram of the use method of the conductive hydrogel provided in Example 2 of the present application.

[0091] In order to study the effect of the hydrogel on the elimination of atrial fibrillation in vivo, a rat atrial fibrillation disease model is established. Please refer to Figure 3 , the use method of the conductive hydrogel prepared in Example 1 is provided, which consists of the following steps:

[0092] S11: Rats were anesthetized by intraperitoneal injection of sodium pentobarbital (50 mg / kg), fixed in a supine position on the experimental table, and their chest hair was removed with a razor and then disinfected with 75% alcohol.

[0093] S21: Make a small incision in the rat's chest with a scalpel, insert the endoscope into the mouse's body, and push the gel in the injection tube to the needle tip;

[0094] S31: Turn on the green light auxiliary illumination LED, connect the endoscope to the mobile phone, inject 20μl of gel on the surface of the right atrium with the assistance of the endoscope, and then switch to the blue light curing LED to irradiate for 20 seconds to achieve in-situ photocuring of the gel on the surface of the atrium.

[0095] Example 2 demonstrates the effect of conductive gel in eliminating atrial fibrillation. The operation includes the following steps:

[0096] S11: After rats were anesthetized with sodium pentobarbital, they were fixed in a supine position on the experimental table, and electrocardiograms of lead II were recorded subcutaneously in the limbs.

[0097] S21: Cut open the skin of the rat's neck, separate the muscles in front of the trachea, expose the trachea, insert the trachea through the mouth and fix it, and connect the ventilator;

[0098] S31: The pacing electrode is inserted through the esophagus to the location where the atrial electrocardiogram is captured. The tail end is connected to the physiological stimulator, which emits pulse waves to pace the atrium. The voltage is 20V, the current is 4mA, the interval is 20ms, and the pulse width is 6ms. Each stimulation lasts for 30s.

[0099] S41: Continuously record the electrocardiogram of rats to observe the effect of the gel on the elimination of atrial fibrillation, as well as the health status and various indicators of the rats.

[0100] Figure 4 An electrocardiogram demonstrates the effect of the conductive gel provided in Embodiment 2 of this application in eliminating atrial fibrillation.

[0101] Depend on Figure 4 As can be seen from the electrocardiogram results, atrial fibrillation occurred under programmed electrical stimulation, with significant fluctuations in heart rate, manifesting as obvious arrhythmia. When the conductive gel prepared in this invention was injected onto the surface of the atrium, programmed electrical stimulation did not induce atrial fibrillation, and the heart rate remained stable, indicating that the conductive gel can effectively prevent the occurrence of atrial fibrillation.

[0102] Furthermore, one or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages:

[0103] (1) In the embodiment of the present application, the prepared conductive gel has high conductivity, high charge storage capacity, injectable rheology, photocurability, strong adhesion, low modulus, and stretchable performance, meeting the use requirements of the injectable gel, and good mechanical matching and functional adaptability of the biological tissue.

[0104] (2) In the embodiment of the present application, the gel in-situ injection and photocured biological material implantation method has the advantages of non-invasiveness, low implantation damage, and long-term implantation stability, and solves the problems of tissue damage and complex operation caused by hard implantation devices.

[0105] (3) In the embodiment of the present application, the injectable conductive gel is applied to the field of heart disease treatment, can effectively eliminate the atrial fibrillation caused by biological electric conduction disorder, provides a new treatment method for the treatment of related diseases, and has certain reference role for the application of conductive materials in heart-related diseases.

[0106] The above is only the specific embodiment of the present application, which enables those skilled in the art to understand or implement the present application. Various modifications of these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features applied herein.

Claims

1. A method for preparing a conductive hydrogel, characterized in that, The method includes: PEDOT:PSS solution was mixed with polyethylene glycol dimethacrylate, and then concentrated by evaporation to obtain a gel. A photoinitiator and a dopant are added to the gel, and then the mixture is stirred to obtain a conductive hydrogel. The volume ratio of the PEDOT:PSS solution to the polyethylene glycol dimethacrylate is (20~30):1; The photoinitiator is an aqueous solution of a blue photoinitiator, wherein the mass concentration of the blue photoinitiator in the aqueous solution is 60 g / L to 150 g / L, and the blue photoinitiator is lithium phenyl-2,4,6-trimethylbenzoyl phosphite. The dopant is an aqueous solution of polyether F127 diacrylate, wherein the mass fraction of polyether F127 diacrylate in the aqueous solution is 15%~25%; The volume ratio of the photoinitiator, the dopant, and the gel is 1:(0.8~1.2):(5~15).

2. The method according to claim 1, characterized in that, The process of mixing PEDOT:PSS solution with polyethylene glycol dimethacrylate, followed by evaporation and concentration to obtain a gel, comprises: Filter the PEDOT:PSS solution; Polyethylene glycol dimethacrylate was added to the filtered PEDOT:PSS solution and then stirred to obtain a mixture. The mixture is evaporated and concentrated at 40°C to 50°C until the volume of the mixture is reduced by 40% to 60%, so that PEDOT and PSS can be fully separated to obtain a gel.

3. A conductive hydrogel prepared by the method according to any one of claims 1-2, characterized in that, The method of using the conductive hydrogel includes: The conductive hydrogel of a set mass is injected into the target location and then cured in situ using photocuring.

4. The conductive hydrogel according to claim 3, characterized in that, The set mass is 15μL~25μL; the in-situ photocuring uses 405nm blue light, and the in-situ photocuring time is 15s~25s.

5. An apparatus for in-situ injection and photocuring of the conductive hydrogel as described in claim 3, characterized in that, The device includes: An injection assembly (1) is used to inject a predetermined mass of the conductive hydrogel into a target location. Blue light lamp (2) is used to perform in-situ photocuring of the conductive hydrogel injected at the target location; The injection assembly (1) includes: The syringe (10) includes an injection needle (101), a tubing (102) and an injection tube (103), wherein the lower end of the injection tube (103) passes through and is fixedly connected to the tubing (102), and the lower end of the tubing (102) passes through and is fixedly connected to the injection needle (101). The endoscope (11) includes a camera (111), a light (112), and a mobile device interface (113). The bottom of the camera (111) is fixedly connected to the injection needle (101), and the light (112) is fixedly installed around the camera (111).

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