Injectable hydrogel combination reagent, self-curing conductive hydrogel and application thereof

Abstract

The application belongs to the technical field of biological medicine, and discloses an injectable hydrogel combination reagent, a self-curing conductive hydrogel and application thereof. The injectable hydrogel combination reagent comprises solution A and solution B. The solution A is a first precursor solution formed by dissolving modified poloxamer PFUDAm and ammonium persulfate in deionized water. The solution B is a second precursor solution formed by dissolving N-isopropyl acrylamide NIPAM, ferrous gluconate and PEDOT: PSS in deionized water. After the injectable hydrogel combination reagent is injected and mixed, PFUDAm, poly-N-isopropyl acrylamide and PEDOT: PSS are polymerized and constructed into the self-curing conductive hydrogel through the redox reaction of ammonium sulfate and ferrous gluconate. The self-curing conductive hydrogel has controllable curing time, excellent anti-swelling performance, conductive performance, good elasticity and toughness, and is expected to be applied to the treatment of arrhythmia in combination with a cardiac pacemaker.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to an injectable hydrogel combination reagent, a self-curing conductive hydrogel, and their applications. Background Technology

[0002] Scar tissue can form in the heart due to various reasons, including myocardial infarction, surgery, and inflammation. This scar tissue can disrupt the normal conduction of electrical signals in the heart, causing delays or blockages in signal propagation. When electrical signals re-enter near scar tissue—that is, when the signals repeatedly veer back and stimulate myocardial cells—it can trigger arrhythmias. Re-entry is an important mechanism of arrhythmias, especially in certain types of tachycardia. When re-entry occurs, the propagation path of the electrical signal in the heart forms a loop, causing repeated stimulation of myocardial cells, resulting in a sustained rapid heart rhythm. This re-entry loop can form in any part of the heart, including the ventricles, atria, or atrioventricular node. For arrhythmias caused by scar tissue and re-entry, injectable conductive hydrogel can be injected into the veins of the scar tissue. Combined with a traditional pacemaker, this can achieve pacing similar to the heart's natural conduction, effectively mimicking the heart's natural electrical rhythm and providing painless defibrillation to eliminate arrhythmias.

[0003] Elizabeth Cosgriff-Hernandez et al. at the University of Texas at Austin (Nat Commun., 2024, 15, 64) developed a self-curing, injectable conductive hydrogel that can be intravenously delivered to fill epicardial coronary veins and bronchioles, transforming them into flexible electrodes that can extend into the mid-myocardium. However, its high swelling rate at body temperature (around 200%) poses a significant risk of insufficient mechanical strength due to excessive water absorption and excessive mechanical stress on the fragile cardiovascular system under long-term use, potentially leading to inflammation and tissue damage. Furthermore, high swelling can easily cause a decrease in the concentration of conductive salt ions, which then slowly leak into the tissue, affecting the hydrogel's long-term conductive stability. It may also lead to rapid degradation or dissolution in the body, resulting in functional loss. Therefore, developing a conductive hydrogel with low (or no) swelling rate, stable conductivity, and good mechanical properties is a current research hotspot. Summary of the Invention

[0004] The present invention aims to provide an injectable hydrogel combination reagent with controllable curing time. The self-curing conductive hydrogel formed after injection has excellent anti-swelling properties, conductivity, and good elasticity and toughness, and is expected to be used in combination with cardiac pacemakers for the treatment of arrhythmias.

[0005] In a first aspect, the present invention provides an injectable hydrogel combination reagent, the injectable hydrogel combination reagent comprising solution A and solution B; solution A is a first precursor solution formed by dissolving modified poloxamer PFUDAm and ammonium persulfate in deionized water; solution B is a second precursor solution formed by dissolving N-isopropylacrylamide NIPAM, ferrous gluconate, and PEDOT:PSS in deionized water; wherein, the chemical structural formula of the modified poloxamer PFUDAm is shown below:

[0006]

[0007] In solution A, the mass of PFUDAm is 20-25 wt% of the total mass of solution A, and the concentration of ammonium persulfate is 2.5-7.5 mM; in solution B, the mass of NIPAM is 5-10 wt% of the total mass of solution B, the concentration of ferrous gluconate is 2.5-7.5 mM, and the mass of PEDOT:PSS is 1-1.3 wt% of the total mass of solution B.

[0008] It should be noted that in the actual preparation process, NIPAM and ferrous gluconate are dissolved in the directly purchased raw material PEDOT:PSS aqueous solution to form solution B, wherein the mass ratio of PEDOT:PSS in the raw material PEDOT:PSS aqueous solution is 1 to 1.3 wt%.

[0009] In a preferred embodiment of the injectable hydrogel combination reagent of the present invention, in solution A, the mass of PFUDAm is 20 wt% of the total mass of solution A, and the concentration of ammonium persulfate is 5 mM; in solution B, the mass of NIPAM is 10 wt% of the total mass of solution B, the concentration of ferrous gluconate is 5 mM, and the mass of PEDOT:PSS is 1 wt% of the total mass of solution B.

[0010] A preferred preparation method for the modified poloxamer PFUDAm includes the following steps: First, N,N'-carbonyldiimidazole and poloxamer are dissolved separately in anhydrous dichloromethane. Under nitrogen protection, the poloxamer solution is added dropwise to the N,N'-carbonyldiimidazole solution. After stirring at room temperature, the product is precipitated with excess diethyl ether, filtered, and vacuum dried to obtain the activated poloxamer intermediate. The obtained poloxamer intermediate is dissolved in anhydrous dichloromethane and condensed with ethylenediamine under nitrogen protection. After the reaction is completed, the product is washed with water, dried, and precipitated with ice-cold diethyl ether. After filtration and vacuum drying, an amino-functionalized poloxamer derivative is obtained. The amino-functionalized poloxamer derivative is dissolved in anhydrous dichloromethane, triethylamine is added, and an acylation reaction is carried out by adding acryloyl chloride solution dropwise under ice bath conditions. After the reaction is completed, the product is precipitated with ice-cold diethyl ether, filtered, and vacuum dried to obtain the final product PFUDAm.

[0011] Preferably, the molar ratio of N,N'-carbonyldiimidazole to poloxamer is (10-20):1; the molar amount of ethylenediamine is (10-20) times the molar amount of the poloxamer intermediate; and the molar amount of acryloyl chloride is (3-5) times the molar amount of the amino-functionalized poloxamer derivative.

[0012] Secondly, the present invention also provides a self-curing conductive hydrogel, which is prepared by mixing solution A and solution B in a 1:1 volume ratio and then gelling them in situ. For example, solution A and solution B are placed in a double-barreled syringe, and the syringe is pushed simultaneously to expel the precursor solution. After the two precursor solutions come into contact, a redox reaction occurs, initiating polymerization to construct a self-crosslinking and curing conductive hydrogel.

[0013] Thirdly, the present invention provides the application of the self-curing conductive hydrogel in the preparation of conductive hydrogel fibers for the treatment of arrhythmia.

[0014] Beneficial effects:

[0015] The first aspect of this invention provides an injectable hydrogel combination reagent, such as... Figure 7 As shown, the main component of solution A is modified poloxamer PFUDAm. Poloxamer itself is a thermosensitive nanomicelle that forms thermally responsive fragments by creating hydrophobic collapses to counteract the tendency of hydrogel expansion. It exhibits excellent anti-swelling properties under normal human body temperature of 37°C. The modified poloxamer PFUDAm provided by this invention modifies the original poloxamer structure with hydrolysis-resistant urethane and amide groups, and combines it with N-isopropylacrylamide in solution B. The resulting hydrogel material, which self-cures after mixing, has an extremely low swelling rate and excellent mechanical properties, and is more stable in the body fluid environment.

[0016] The first aspect of this invention provides an injectable hydrogel combination reagent using PEDOT:PSS as a conductive polymer. PEDOT:PSS can stably exist in the self-curing hydrogel, without the loss of conductive materials caused by swelling in conventional hydrogels. Furthermore, the degradation cycle of PEDOT:PSS in vivo can be adjusted over months or years. PEDOT:PSS exhibits good stability in biological environments such as under electrical stimulation and can resist oxidative degradation. Partially modified PEDOT:PSS, such as by adding tannic acid or hydrophobic materials, can further extend its in vivo lifespan, potentially reaching months or even longer. This ensures that the self-curing conductive hydrogel maintains relatively stable conductivity over a long period. Combined with the good elasticity and toughness of the self-curing conductive hydrogel, it can withstand the external force of heartbeats and maintain structural integrity during application, exhibiting good anti-fatigue properties. Therefore, it is a highly promising conductive hydrogel fiber material for the treatment of arrhythmias.

[0017] The conductive hydrogel provided by this invention has a controllable curing time, which can be adjusted by regulating the concentrations of ferrous gluconate and ammonium persulfate. Since both only serve to initiate the reaction and their mass concentrations in the hydrogel are low, their impact on other properties is negligible. The conductive strength of the conductive hydrogel provided by this invention is also controllable, which can be adjusted by regulating the concentration of PEDOT:PSS. Due to its low viscosity and low mass concentration in the hydrogel, its impact on other properties is negligible. Furthermore, the viscosity of the conductive hydrogel precursor solution provided by this invention is controllable. Within the precursor solution concentration range defined by this invention, the mechanical and degradation properties of the hydrogel can be slightly adjusted by changing the concentrations of PFDAm and NIPAM to adapt to different technical requirements, demonstrating functional scalability and significant application potential in the biomedical field. Attached Figure Description

[0018] Figure 1 The PFUDAm proton NMR spectrum in Example 1;

[0019] Figure 2A This is a swelling curve of sample 2 in PBS buffer over 60 hours in Example 2;

[0020] Figure 2B This is a swelling curve of sample 1 in PBS buffer over 60 hours in Example 2;

[0021] Figure 3 Mechanical properties of hydrogels with different PFUDAm and NIPAM contents in Example 3;

[0022] Figure 4 The rheological properties of hydrogels using different concentrations of ammonium persulfate and ferrous gluconate in Example 4;

[0023] Figure 5 The electrical conductivity of hydrogels with different PEDOT:PSS contents in Example 5;

[0024] Figure 6 This is a schematic diagram of in vitro vascular in-situ solidification characterization in Example 6;

[0025] Figure 7 This is a schematic diagram illustrating the principle of hydrogel formation after injection of the injectable hydrogel combination reagent described in this invention. Detailed Implementation

[0026] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. The described embodiments are merely 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 inventive effort are within the scope of protection of the present invention.

[0027] The main sources of raw materials involved in the following examples are as follows:

[0028] PEDOT: PSS aqueous solution purchased from Clevios TM PH1000 Heraeus;

[0029] Polosham was purchased from Maclean's (item number 768502);

[0030] NIPAM was purchased from McLean (item number N811777).

[0031] Example 1: Preparation and structural characterization of PFUDAm

[0032] PFUDAm was synthesized using poloxamer as a raw material and subjected to Bruck AVANCE III HD 600MHz. 1 The polymer structure was characterized by 1H NMR (CDCl3). The specific preparation process is as follows:

[0033] 24.3225 g of N,N'-carbonyldiimidazole was dissolved in 100 ml of anhydrous dichloromethane, and 126 g of poloxamer was dissolved in 840 ml of anhydrous dichloromethane. Under a nitrogen atmosphere, the poloxamer solution was slowly added dropwise to the N,N'-carbonyldiimidazole solution, and the reaction was stirred continuously at room temperature for 12 hours. After the reaction was completed, excess diethyl ether was added to the mixture to allow the product to precipitate completely. The precipitate was separated and dried under vacuum at 40 °C for 6 hours to obtain the activated poloxamer intermediate. 129.243 g of the intermediate was dissolved in 100 ml of anhydrous dichloromethane. In a separate solution, 9.015 g of ethylenediamine was dissolved in 60 ml of anhydrous dichloromethane. Under nitrogen protection, the intermediate solution was slowly added dropwise to the ethylenediamine solution, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction solution was washed three times with 3 L of deionized water. Then, 500 g of anhydrous sodium sulfate was added to dry the organic phase, and the desiccant was removed by filtration. The filtrate was concentrated and slowly added dropwise to 10 times its volume of ice-cold diethyl ether. The precipitate was collected and dried under vacuum at 40 °C for 6 hours to obtain an amino-functionalized poloxamer derivative. The above product was dissolved in 1000 ml of anhydrous dichloromethane, and 2.204 g of anhydrous triethylamine was added. Under ice-water bath conditions, 3.62 g of acryloyl chloride diluted in 30 ml of dichloromethane was slowly added dropwise, and the reaction was continued at room temperature for 12 hours. After the reaction was complete, the mixture was slowly poured into 10 times its volume of ice-cold ether, and a white flocculent precipitate was formed. The product PFUDAm was collected by filtration and vacuum drying and stored at room temperature away from light.

[0034] like Figure 1 As shown in the 1H NMR spectrum, new characteristic proton peaks corresponding to the acryloyl chloride double bond appeared around 5.6 ppm, 6.1 ppm and 6.3 ppm, respectively, indicating that the double bond was successfully grafted onto poloxamer, and PFUDAm was synthesized.

[0035] Example 2: Swelling Behavior Test of Hydrogels

[0036] Preparation steps for Sample 1: Dissolve 2.0g PFUDAm and 0.01g ammonium persulfate in 10mL of deionized water and stir until homogeneous; dissolve 1.0g NIPAM and 0.024g ferrous gluconate in 10mL of deionized water and stir until homogeneous. Inject the two precursor solutions obtained above into a twin-barrel syringe and simultaneously extrude to form a self-curing hydrogel.

[0037] Preparation steps for Sample 2: Dissolve 2.0 g PFUDAm and 0.01 g ammonium persulfate in 10 mL of deionized water and stir until homogeneous; dissolve 0.024 g ferrous gluconate in 10 mL of deionized water and stir until homogeneous. Inject the two precursor solutions obtained above into a twin-barrel syringe and simultaneously extrude to form a self-curing hydrogel.

[0038] Weigh the hydrogel sample and record the weight as W0. Then, place the sample in a centrifuge tube containing 10 mL of PBS buffer and immerse it at an ambient temperature of 4°C or 37°C. Set up three replicates for each group, and periodically weigh the sample and record the weight as W0. t Swelling rate curves were plotted based on weight changes at different time points. The swelling rate (SR) at time t was calculated using the following formula: SR(%) = (W / t) * ... t -W0) / W0×100%.

[0039] like Figure 2A The swelling properties of sample 2 in PBS are shown; as shown Figure 2B The swelling properties of Sample 1 in PBS are shown. It can be seen that the swelling rates of the hydrogels in both Sample 1 and Sample 2 gradually increase with soaking time at different temperatures. Sample 2 containing only PFUDAm showed a swelling rate of approximately 6% after soaking at 37℃ for 60 hours, and approximately 160% after soaking at 4℃ for 60 hours. Sample 1 containing both PFUDAm and NIPAM showed a swelling rate of approximately 24% after soaking in PBS at 37℃ for 60 hours, and approximately 200% after soaking at 4℃ for 60 hours. The results indicate that the low swelling performance of the hydrogel mainly depends on the PFUDAm component, but the addition of NIPAM has little effect on the swelling properties. Therefore, all the above hydrogel materials exhibit significant anti-swelling properties, and their anti-swelling properties are even better at 37℃. The hydrogel provided by this invention has excellent anti-swelling properties. Unlike at 4℃, the swelling rate of the hydrogel is lower at the human body temperature of 37℃, which is beneficial for hydrogel implantation applications.

[0040] It should be noted that the hydrogel prepared in this application is a network framework of hydrogel prepared by copolymerization of PFUDAM and NIPAM. In the precursor solution, NIPAM and ferrous gluconate are dissolved in PEDOT:PSS aqueous solution. In this embodiment, the mass percentage of PEDOT:PSS itself in the raw material PEDOT:PSS aqueous solution is only 1%, and PEDOT:PSS is a copolymerized polymer. Under the conditions of mixing the two precursor solutions of this invention, it does not have the ability to react with PFUDAM and NIPAM. Therefore, the influence of PEDOT:PSS on the gel properties and curing properties of the self-curing conductive hydrogel prepared after mixing the two precursor solutions, except for conductivity, is negligible. Therefore, the swelling characteristics of the self-curing hydrogel prepared in this embodiment can represent the swelling characteristics of the self-curing hydrogel of this invention.

[0041] Example 3: Mechanical property testing of hydrogels

[0042] The sample preparation steps for this Example 3 are the same as those for Sample 1 in Example 2. The only difference is that, in order to facilitate tensile testing, when using a double-barrel syringe to extrude simultaneously, the sample is directly extruded into a standard type 3 dumbbell-shaped polytetrafluoroethylene mold to form a self-curing hydrogel. Then, a universal testing machine is used to measure the tensile strength and elongation at break of the hydrogel.

[0043] like Figure 3 As shown, the hydrogel provided by the present invention has a fracture stress of 1.66 MPa and an elongation at fracture of 274.5% when the PFUDAm content is 20 wt% and the poly-N-isopropylacrylamide content is 10 wt%, indicating good elasticity and toughness.

[0044] Example 4: Rheological property testing of hydrogels

[0045] The sample preparation for Example 4 was the same as that for Sample 1 in Example 2, except for the concentrations of ammonium persulfate and ferrous gluconate in the precursor solution. Three concentrations of samples were prepared. After testing the viscosity of the precursor solution and the self-crosslinking curing time using an Anton Paar MCR 301 rheometer, the two precursor solutions were loaded into a double-barrel syringe and injected through a mixing head onto a parallel plate at 37°C. During testing, mineral oil was used to seal the edges of the hydrogel to prevent moisture evaporation. Under a constant frequency, constant strain oscillation test mode, with a strain of 0.5% and a constant frequency of 10 rad / s, the composite modulus was measured every 3 seconds with a 1 mm gap. A change in composite viscosity of less than 1% was considered a complete crosslinking network formation.

[0046] like Figure 4 As shown, the viscosity of the hydrogel precursor solution of the three samples in Example 4 is about 200 Pa·s, and the self-curing time is relatively short. For example, the sample with a concentration of 5 mM ammonium persulfate and ferrous gluconate completely forms a gel network in about 4 minutes, which can meet the needs of clinical application.

[0047] Clevios TM The viscosity of the 1 wt% PEDOT:PSS solution provided by PH1000 Heraeus is 50 cP, or 50 mPa·s, which is much lower than the 200 Pa·s of the hydrogel precursor solution. Therefore, its effect on the solution viscosity can be ignored. The sample prepared in Example 4 can represent the rheological properties of the injectable hydrogel combination reagent of the present invention.

[0048] Example 5: Conductivity test of hydrogel

[0049] The self-curing conductive hydrogel sample prepared in Example 5 differs from sample 1 prepared in Example 2 only in that different proportions of PEDOT:PSS solution were added, namely 0.6wt%, 0.8wt%, and 1wt%, respectively, thus preparing three kinds of self-curing conductive hydrogel samples. The conductivity of the three hydrogel samples prepared in Example 5 was measured using a four-probe tester. The conductivity σ was calculated as follows: the reciprocal of the resistance multiplied by the gel thickness L, and then divided by the area A, i.e., σ = L / (R*A).

[0050] To activate the myocardium beyond single-point contact in vivo, the conductivity of the hydrogel must be higher than that of the myocardium (0.1–6.0 mS / cm). For example... Figure 5 As shown, when the PEDOT:PSS solution is added at a ratio of 1 wt%, the hydrogel conductivity is 12.0 ± 0.8 mS / cm, which meets the application requirements.

[0051] Example 6: In vitro in situ vascular solidification characterization test

[0052] The self-curing conductive hydrogel sample prepared in Example 5 differs from sample 1 prepared in Example 2 only in that 1 wt% PEDOT:PSS solution is added, and in vitro in situ vascular curing characterization is performed based on porcine heart. A 16G vascular catheter is inserted into the central venous vein (MCV), the proximal end is sutured, a double-barreled syringe is connected to the vascular catheter, and the hydrogel precursor solution is injected into the central venous vein. After curing, the heart epidermis is peeled off, and the self-curing hydrogel is observed to form in the central venous vein. After removal, it is photographed and recorded.

[0053] like Figure 6 As shown, from left to right, Figure 1 on the left represents the insertion of the injection cannula into the cardiovascular system; Figure 2 on the left represents the in-situ injection of the injectable hydrogel combination reagent to form a prepolymer solution; Figure 3 on the left represents the in-situ formation of hydrogel from the prepolymer solution; Figure 4 on the left represents the removal of the hydrogel; Example 6 completed the self-curing characterization of conductive hydrogel in the myocardial vein of a pig heart.

[0054] Based on the above test results, the self-curing conductive hydrogel provided by this invention has excellent anti-swelling properties and is stable in body fluid environments; it has good elasticity and toughness, and can withstand the external force of heartbeats to maintain structural integrity; the curing time, conductivity, and precursor solution viscosity are controllable and can be adjusted to meet different technical requirements, and it is expected to be combined with cardiac pacemakers for application in the biomedical field.

[0055] The preferred embodiments of the present invention have been described above, but the scope of protection of the present invention is not limited thereto. Various modifications and substitutions to the present invention made by those skilled in the art within the scope of the technology disclosed herein should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be defined by the appended claims.

Claims

1. An injectable hydrogel combination reagent, characterized in that, The injectable hydrogel combination reagent includes solution A and solution B; solution A is a first precursor solution formed by dissolving modified poloxamer PFUDAm and ammonium persulfate in deionized water; solution B is a second precursor solution formed by dissolving N-isopropylacrylamide NIPAM, ferrous gluconate, and PEDOT:PSS in deionized water. The chemical structural formula of the modified poloxamer PFUDAm is shown below: ； In solution A, the mass of PFUDAm is 20-25 wt% of the total mass of solution A, and the concentration of ammonium persulfate is 2.5-7.5 mM; in solution B, the mass of NIPAM is 5-10 wt% of the total mass of solution B, the concentration of ferrous gluconate is 2.5-7.5 mM, and the mass of PEDOT:PSS is 1-1.3 wt% of the total mass of solution B. The PEDOT:PSS does not participate in the polymerization reaction of PFUDAm and NIPAM, and is dispersed in the three-dimensional network skeleton formed by the polymerization of PFUDAm and NIPAM.

2. The injectable hydrogel combination reagent according to claim 1, characterized in that, In solution A, the mass of PFUDAm is 20 wt% of the total mass of solution A, and the concentration of ammonium persulfate is 5 mM; in solution B, the mass of NIPAM is 10 wt% of the total mass of solution B, the concentration of ferrous gluconate is 5 mM, and the mass of PEDOT:PSS is 1 wt% of the total mass of solution B.

3. The injectable hydrogel combination reagent according to claim 1, characterized in that, The preparation method of the modified poloxamer PFUDAm includes the following steps: First, N,N'-carbonyldiimidazole and poloxamer are dissolved separately in anhydrous dichloromethane. Under nitrogen protection, the poloxamer solution is added dropwise to the N,N'-carbonyldiimidazole solution. After stirring at room temperature, the product is precipitated with excess diethyl ether, filtered, and vacuum dried to obtain the activated poloxamer intermediate. The obtained poloxamer intermediate is dissolved in anhydrous dichloromethane and condensed with ethylenediamine under nitrogen protection. After the reaction is completed, the product is washed with water, dried, and precipitated with ice-cold diethyl ether. After filtration and vacuum drying, an amino-functionalized poloxamer derivative is obtained. The amino-functionalized poloxamer derivative is dissolved in anhydrous dichloromethane, triethylamine is added, and an acylation reaction is carried out by adding acryloyl chloride solution dropwise under ice bath conditions. After the reaction is completed, the product is precipitated with ice-cold diethyl ether, filtered, and vacuum dried to obtain the final product PFUDAm.

4. The injectable hydrogel combination reagent according to claim 3, characterized in that, The molar ratio of N,N'-carbonyldiimidazole to poloxamer is (10~20):

1.

5. The injectable hydrogel combination reagent according to claim 3, characterized in that, The molar amount of the ethylenediamine is (10~20) times the molar amount of the poloxamer intermediate.

6. The injectable hydrogel combination reagent according to claim 3, characterized in that, The molar amount of acryloyl chloride is (3 to 5) times the molar amount of the amino-functionalized poloxamer derivative.

7. A self-curing conductive hydrogel, characterized in that, The self-curing conductive hydrogel is a self-curing conductive hydrogel prepared by mixing solution A and solution B in a 1:1 volume ratio as described in claim 1 and then gelling them in situ.

8. The use of the self-curing conductive hydrogel of claim 7 in the preparation of conductive hydrogel fibers for the treatment of arrhythmia.

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