Conductive structural color hydrogel for monitoring and treating MI as well as preparation method and application of conductive structural color hydrogel

Abstract

The invention discloses conductive structural color hydrogel for MI monitoring and treatment as well as a preparation method and application of the conductive structural color hydrogel. Comprising a conductive nano-material, and the conductive nano-material has a catechol group; an HPC cholesteric liquid crystal; a matrix material; a cross-linking agent; the conductive structural color hydrogel is formed through physical and / or chemical interaction among the conductive nano material, the HPC cholesteric liquid crystal, the matrix material and the cross-linking agent. The conductive structural color hydrogel has enhanced electromechanical response and force-induced discoloration response characteristics, has a photoelectric double-signal sensing function, can accurately and visually monitor mechanical stimulation in real time, can be used as a flexible sensing material, is used for preparing products capable of realizing visual feedback and digital feedback of mechanical stimulation, and has wide application prospects. And the hydrogel can be used for preparing a product for compensating and / or repairing electrical conduction of biological tissues, especially can be used for preparing a conductive structural color hydrogel patch for monitoring and / or treating myocardial infarction (MI), and has a wide application prospect.

Description

Technical Field

[0001] The present invention relates to the field of biomaterials, in particular to a conductive structural color hydrogel and its preparation method and application, and more particularly to a conductive structural color hydrogel that can be used for myocardial infarction (MI) monitoring and treatment, and its preparation method and application. Background Art

[0002] Myocardial infarction (MI) is one of the main causes of death from cardiovascular diseases, mainly leading to ischemic necrosis of myocardial tissue and forming non-conductive fibrotic scars, which seriously affect the electrophysiological function of the heart. Although current clinical treatment methods (such as drug treatment and myocardial reperfusion) can relieve symptoms, it is difficult to accurately repair the electrophysiological function or inhibit ventricular remodeling.

[0003] In recent years, conductive hydrogel patches have attracted much attention due to their electrocoupling repair ability, but there are still two major problems in their application. On the one hand, it is difficult to accurately locate and lacks a visualization function. The therapeutic effect of conductive hydrogel patches depends on the accuracy of the implantation position. It is necessary to accurately implant the pathological position of the heart to fully exert the electrocoupling treatment effect. However, identifying the pathological position of the heart is complex and cumbersome, and requires a variety of detection means such as electrocardiogram, echocardiogram test, histological evaluation, and clinical cardiovascular angiography. Currently, most research focuses on improving the biocompatibility, conductivity, mechanical properties, etc. of the materials in order to improve the treatment effect, and less attention is paid to how to achieve accurate positioning and visualization monitoring of the cardiac pathological state, resulting in insufficient integration of diagnosis and treatment capabilities and poor treatment accuracy. On the other hand, there is a lack of real-time monitoring. The process of myocardial infarction is complex and unpredictable, and the infarct microenvironment may change unfavorably at any time, leading to serious problems such as infarct expansion and coronary artery spasm. Traditional conductive hydrogel patches cannot real-time monitor cardiac mechanical physiological signals, and it is difficult to timely feedback the dynamic changes of the infarct area, affecting the clinical treatment effect.

[0004] Therefore, there is an urgent need to develop a new conductive hydrogel material that can accurately, real-time, and visually monitor mechanical stimuli, in order to develop a conductive hydrogel patch that can integrate diagnostic and therapeutic functions, and open up a new path for the efficient treatment of myocardial infarction. Summary of the Invention

[0005] The present invention aims to at least partly solve at least one of the technical problems existing in the prior art. For this purpose, the present invention provides a conductive structural color hydrogel and its preparation method and application. The conductive structural color hydrogel of the present invention has enhanced electromechanical response and force-induced color change response characteristics, has a photoelectric dual-signal sensing function, can accurately, real-time, and visually monitor mechanical stimuli, can be used as a flexible sensing material, and is used to prepare products that can achieve visual feedback and digital feedback of mechanical stimuli, as well as products that can compensate and / or repair the electrical conduction of biological tissues, especially conductive structural color hydrogel patches for myocardial infarction (MI) monitoring and / or treatment, with broad application prospects.

[0006] The present invention is made based on the inventor's discovery and understanding of the following problems:

[0007] In the field of materials, effectively integrating materials with force-induced color change response characteristics and conductive hydrogel materials is the key technology to achieve visual monitoring of external spatio-temporal mechanical stimuli by conductive hydrogels. Although existing studies have attempted to combine these two types of materials in various ways, they often face challenges such as the inability to synchronize color change and conductivity, and insensitive response. The inventor found in experiments that dopamine (DA)-modified MXene nanosheets can be synergistically integrated with HPC cholesteric liquid crystals to construct a hydrogel with excellent electromechanical response and force-induced color change response properties. The results show that the hydrogel can achieve optoelectronic dual-signal sensing, with strong response signals and high sensitivity. Further analysis reveals that the modified conductive nanomaterials (such as dopamine-modified MXene nanosheets, dopamine-modified black phosphorus nanosheets, etc.) have catechol groups, which can serve as anchoring sites to fix the pitch of HPC cholesteric liquid crystals. Thereby, the conductive structural color hydrogel of the present invention has enhanced electromechanical response and force-induced color change response characteristics, and the sensitivity of the response signal is significantly improved, thus realizing the optoelectronic dual-signal sensing function. Using its optical signal sensing function, the location of infarcted myocardium can be located, and using its electrical signal sensing function, the mechanical physiological state of the heart can be monitored. Further experimental results show that the hydrogel of the present invention can be used as a flexible sensing material for preparing products that can realize visual feedback and digital feedback of mechanical stimuli, such as conductive structural color hydrogel patches for visual and digital monitoring of myocardial infarction (MI), and for preparing products that can compensate for and / or repair the electrical conduction of biological tissues, such as conductive structural color hydrogel patches for treating myocardial infarction (MI) ( Figure 1 ), and has broad application prospects.

[0008] Therefore, in the first aspect of the present invention, the present invention proposes a conductive structural color hydrogel. According to an embodiment of the present invention, it includes: a conductive nanomaterial having a catechol group; an HPC cholesteric liquid crystal; a matrix material; a crosslinking agent; and the conductive structural color hydrogel is formed by physical and / or chemical interactions between the conductive nanomaterial, the HPC cholesteric liquid crystal, the matrix material, and the crosslinking agent. The conductive structural color hydrogel according to the embodiment of the present invention has enhanced electromechanical response and force-induced color change response characteristics, can achieve an optoelectronic dual-signal sensing function, can accurately, real-time, and visually monitor mechanical stimuli, can be used as a flexible sensing material for preparing products that can realize visual feedback and digital feedback of mechanical stimuli, and products for compensating for and / or repairing the electrical conduction of biological tissues, especially for preparing conductive structural color hydrogel patches for monitoring and / or treating myocardial infarction (MI), and has broad application prospects.

[0009] According to an embodiment of the present invention, the conductive structural color hydrogel may further include at least one of the following additional technical features:

[0010] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the mass fraction of HPC in the HPC cholesteric liquid crystal is 50% to 56%.

[0011] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the mass fraction of HPC in the HPC cholesteric liquid crystal is 50% to 52%.

[0012] According to an embodiment of the present invention, the HPC cholesteric liquid crystal is self-assembled from HPC in water.

[0013] In some specific embodiments of the present invention, the mass ratio of HPC to water is 50:(35 - 40). In a specific embodiment of the present invention, the mass ratio of HPC to water is 50:37.

[0014] According to an embodiment of the present invention, the conductive nanomaterial is modified by dopamine or a pharmaceutically acceptable salt thereof or tannic acid or a pharmaceutically acceptable salt thereof.

[0015] According to an embodiment of the present invention, the pharmaceutically acceptable salt of dopamine is dopamine hydrochloride.

[0016] In some embodiments of the present invention, the pharmaceutically acceptable salt of tannic acid is an alkali metal salt of tannic acid.

[0017] In some embodiments of the present invention, the conductive nanomaterial is selected from graphene, carbon nanotubes, black phosphorus, MXene, MoS modified by dopamine or a pharmaceutically acceptable salt thereof and / or tannic acid or a pharmaceutically acceptable salt thereof 2 and at least one of them.

[0018] According to an embodiment of the present invention, the conductive nanomaterial is MXene@PDA, and the MXene@PDA is MXene nanosheets modified by dopamine or a pharmaceutically acceptable salt thereof.

[0019] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the mass fraction of MXene@PDA is not less than 1%.

[0020] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the mass fraction of HPC in the HPC cholesteric liquid crystal is 50% to 52%, and the mass fraction of MXene@PDA is 1% to 1.5%.

[0021] In some embodiments of the present invention, the matrix material is selected from at least one of sodium alginate, dopamine-grafted sodium alginate, hyaluronic acid, dopamine-grafted hyaluronic acid, gelatin, carboxymethyl chitosan, and sodium caseinate.

[0022] According to an embodiment of the present invention, the matrix material is sodium alginate and / or dopamine-grafted sodium alginate.

[0023] In some embodiments of the present invention, the mass ratio of HPC in the HPC cholesteric liquid crystal to the matrix material is 50∶(4 - 12).

[0024] According to an embodiment of the present invention, the matrix material is sodium alginate, and the mass ratio of HPC in the HPC cholesteric liquid crystal to the sodium alginate is 50∶(6 - 10).

[0025] In a specific embodiment of the present invention, the matrix material is sodium alginate, and the mass ratio of HPC in the HPC cholesteric liquid crystal to the sodium alginate is 50∶8.

[0026] According to an embodiment of the present invention, the cross-linking agent is a metal ion.

[0027] According to an embodiment of the present invention, the metal ion is a polyvalent cation.

[0028] In some specific embodiments of the present invention, the metal ion is selected from Ca 2+ , Zn 2+ , Mg 2+ , Fe 3+ , Cu 2+ and at least one of them.

[0029] According to an embodiment of the present invention, the metal ion comes from its halide salt.

[0030] According to an embodiment of the present invention, the halide salt is a chloride salt.

[0031] According to an embodiment of the present invention, the metal ion is Ca 2+ .

[0032] According to an embodiment of the present invention, the Ca 2+ comes from calcium chloride.

[0033] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the mass fraction of calcium chloride is 0.5% - 0.56%.

[0034] In a second aspect of the present invention, the present invention provides a method for preparing the aforementioned conductive structural color hydrogel. According to an embodiment of the present invention, the method includes: mixing the conductive nanomaterial, the HPC cholesteric liquid crystal, and the matrix material to form a mixture; and subjecting the mixture to a cross-linking reaction with the cross-linking agent to form the conductive structural color hydrogel. According to the method of the embodiment of the present invention, by first integrating the conductive nanomaterial and the HPC cholesteric liquid crystal into the three-dimensional system of the matrix material and then performing a cross-linking reaction with the cross-linking agent, it is beneficial for the hydrogel to form bright colors visible to the naked eye and enhance its optoelectronic dual-signal sensing function.

[0035] According to an embodiment of the present invention, the method may further include at least one of the following additional technical features:

[0036] According to an embodiment of the present invention, the temperature of the mixing process is room temperature.

[0037] According to an embodiment of the present invention, the temperature of the cross-linking reaction is 3°C to 7°C. In a specific embodiment of the present invention, the temperature of the cross-linking reaction is 5°C.

[0038] According to an embodiment of the present invention, the method further includes: subjecting the conductive structural color hydrogel to degassing treatment and / or standing treatment.

[0039] According to an embodiment of the present invention, the temperature of the degassing treatment is 3°C to 7°C. In a specific embodiment of the present invention, the temperature of the degassing treatment is 5°C.

[0040] In a third aspect of the present invention, the present invention provides a conductive structural color hydrogel. According to an embodiment of the present invention, the conductive structural color hydrogel is prepared according to the aforementioned method.

[0041] Those skilled in the art can understand that the features and advantages described above for the conductive structural color hydrogel and its preparation method also apply to this conductive structural color hydrogel, and will not be elaborated herein.

[0042] In the fourth aspect of the present invention, the present invention proposes the use of the aforementioned conductive structural color hydrogel in the preparation of products. According to an embodiment of the present invention, the product has at least one of the following uses: visualizing and / or digitally feedbacking the response of non-biological tissues to mechanical stimuli; visualizing and / or digitally monitoring the movement of biological tissues; compensating and / or repairing the electrical conduction of biological tissues. The aforementioned conductive structural color hydrogel, through its mechanochromic response performance, enables the product to have the use of visually detecting mechanical stimuli; through its electrical signal sensing performance, enables the product to have the use of digitally monitoring mechanical stimuli; through its electrical conduction function, enables the product to have the use of compensating and / or repairing the electrical conduction of biological tissues. Thus, the conductive structural color hydrogel can be used to prepare products with visualization and digital monitoring functions, so as to display the dynamic changes of non-biological tissues under mechanical stimuli and the movement state of biological tissues in real time. According to an embodiment of the present invention, the visual feedback and / or the numerical feedback are synchronized with the mechanical stimuli.

[0043] According to an embodiment of the present invention, the product includes, but is not limited to: medical devices, wearable sensors, and biosensors.

[0044] According to an embodiment of the present invention, the medical devices include, but are not limited to: cardiac sensing patches, myocardial infarction monitoring and / or treatment patches, and bionic skins.

[0045] According to an embodiment of the present invention, the biosensors include, but are not limited to: pressure sensors and strain sensors.

[0046] According to an embodiment of the present invention, the wearable sensors include, but are not limited to: inertial sensors, optical sensors, electrodes and electrochemical sensors, flexible sensors, and interactive sensors.

[0047] In some embodiments of the present invention, the movement of biological tissues includes, but is not limited to: respiratory movement, expansion and contraction of the chest, inflation and retraction of the lungs, contraction / diastole of the heart, contraction and relaxation of blood vessels, gastrointestinal peristalsis, peristalsis of the esophagus, contraction and relaxation of skeletal muscles, peristalsis of renal tubules, peristalsis of the ureter, contraction and relaxation of the bladder, peristalsis of the fallopian tubes, contraction and relaxation of the uterus, contraction and relaxation of the vagina, blinking of the eyes, rotation of the eyeballs, and swallowing action of the larynx.

[0048] According to an embodiment of the present invention, the biological tissues include, but are not limited to: skeletal muscle tissue, smooth muscle tissue, cardiac muscle tissue, connective tissue, and nerve tissue.

[0049] According to an embodiment of the present invention, the product is used to monitor biological tissue necrosis and / or prevent and / or treat diseases caused by the necrosis of the biological tissue.

[0050] In some embodiments of the present invention, the diseases include but are not limited to: myocardial infarction, myocardial sclerosis, cerebral infarction, cerebral malacia, gastric and duodenal ulcer, typhoid fever, acute pancreatitis, pulmonary tuberculosis, pulmonary infarction, renal tubular necrosis, renal infarction, ovarian cyst torsion, ruptured tubal pregnancy, necrotizing fasciitis, frostbite.

[0051] According to an embodiment of the present invention, the product is used for monitoring and / or treating myocardial infarction.

[0052] Compared with the prior art, the conductive structural color hydrogel of the present invention has at least one of the following beneficial effects:

[0053] 1. It has optoelectronic dual-signal response. When monitoring cardiac mechanical physiological signals, the relative resistance change rate of the preferred conductive structural color hydrogel of the present invention is 5%, and the sensitivity is better than 2.5% of the nanoclay sensor; the blue shift range of the reflection wavelength is 640 nm → 482 nm (sensitivity -2.85 nm% ﹣1 ), and the infarction area can be visually identified.

[0054] 2. It has good biocompatibility. The results of the cytotoxicity test show that the cell survival rate of the conductive structural color hydrogel of the present invention is >95% (better than 80% of the traditional polypyrrole hydrogel), and there is no risk of fiber encapsulation.

[0055] 3. It has excellent tissue repair effect on myocardial infarction (MI). The animal test results of the preferred conductive structural color hydrogel of the present invention show that it can effectively improve cardiac function, and the ejection fraction (EF) is increased from 47.38% to 81.55%; it has anti-inflammatory and angiogenesis functions, the polarization rate of M2 macrophages is increased to 20.63%, and the blood vessel density is increased by 3 times.

[0056] The additional aspects and advantages of the present invention will be partially given in the following description, partially will become obvious from the following description, or be understood through the practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] The above and / or additional aspects and advantages of the present invention will become obvious and easy to understand from the description of the embodiments in conjunction with the following drawings, wherein:

[0058] Figure 1 is a schematic diagram of the patch prepared from the conductive structural color hydrogel of the present invention for monitoring and treating myocardial infarction;

[0059] Figure 2 is the material characterization result diagram of MXene and MXene@PDA in Example 1 of the present invention, wherein, (A) is the TEM morphology and surface spectrum element scanning result diagram; (B) is the element content investigation result diagram; (C) is the infrared spectrum diagram;

[0060] Figure 3These are the material characterization results of the conductive structural color hydrogel of the present invention. Among them, (A) is the appearance diagram of the conductive structural color hydrogel with different HPC contents; (B) is the investigation result diagram of the reflection wavelength of the conductive structural color hydrogel with different HPC contents; (C) is the SEM morphology of the conductive structural color hydrogel; (D) is the polarized light microscope photos of the conductive structural color hydrogel with different HPC contents.

[0061] Figure 4 These are the investigation results of the composition and mechanical properties of the conductive structural color hydrogel of the present invention. Among them, (A) is the full XPS spectrum; (B) is the C 1s sub-spectrum; (C) is the Ti 2p sub-spectrum; (D) is the variation of the storage modulus G' and the loss modulus G'' with frequency.

[0062] Figure 5 These are the investigation results of the tensile-color sensing performance of the conductive structural color hydrogel of the present invention. Among them, (A) is the photo of the change in the color of the conductive structural color with the compression rate. From red to blue, the external tensile rates of the material are 0%, 8%, 20%, 40%, and 60% respectively; (B) is the curve of the reflection wavelength changing with the compression rate, Δλ / Δη = -2.85 nm %. ﹣1 ;

[0063] Figure 6 These are the investigation results of the compression-color sensing performance of the conductive structural color hydrogel of the present invention. Among them, (A) is the photo of the change in the color of the conductive structural color with the compression rate. From red to blue, the external compression rates of the material are 0%, 10%, 20%, 30%, 40%, and 50% respectively; (B) is the curve of the reflection wavelength changing with the compression rate, Δλ / Δε = -3.50 nm %. ﹣1 ;

[0064] Figure 7 These are the investigation results of the swelling-color sensing performance of the conductive structural color hydrogel of the present invention. Among them, (A) is the photo of the change in the color of the conductive structural color with the swelling rate. From red to blue, the swelling rates of the material are 0%, 10%, 20%, 30%, and 40% respectively; (B) is the curve of the reflection wavelength changing with the swelling rate, Δλ / Δs = -4.47 nm %. ﹣1 ;

[0065] Figure 8 These are the investigation results of the conductive structural color hydrogel in the in vitro simulation of myocardial infarction monitoring. Among them, (A) is the visual difference diagram after the balloon simulates local infarction; (B) is the visual difference diagram after the duck heart simulates myocardial infarction.

[0066] Figure 9These are the result graphs for investigating the electrical signal sensing function of the conductive structural color hydrogel of the present invention. Among them, (A) is the resistance curve graph; (B) is the result graph for investigating the change of the conductivity of the conductive structural color hydrogel with the concentration of MXene@PDA; (C) is the conductivity comparison result graph; (D) is the CV curve;

[0067] Figure 10 These are the result graphs for investigating the tensile electrical signal sensing performance of the conductive structural color hydrogel of the present invention. Among them, (A) shows the change in relative resistance during the stretching process of the hydrogel; (B) shows the change in relative resistance during the mechanical deformation process with amplitude changes, and the amplitude changes are 15%, 3.0%, 50%, 100%; (C) shows the change in relative resistance during the mechanical deformation process with frequency changes, and the frequency changes are 0.025 HZ, 0.05 HZ, 0.1 HZ, 0.25 HZ, 0.5 HZ, 1.0 HZ; (D) is the result graph for investigating the response time and recovery time; (E) is the result graph for investigating the fatigue and durability of the sensor;

[0068] Figure 11 These are the result graphs for investigating the swelling electrical signal sensing performance of the conductive structural color hydrogel of the present invention. Among them, (A) shows the change in relative resistance during the swelling process of the hydrogel; (B) shows the change in relative resistance during the volume swelling process at different degrees, and the volume swelling degrees are 10%, 20%, 30%, 40%, 50%;

[0069] Figure 12 These are the application result graphs of the conductive structural color hydrogel of the present invention in in vitro mechanical motion monitoring. Among them, (A) is finger bending motion; (B) is balloon inflation motion; (C) is in vitro heartbeat motion of a duck heart; (D) is rat breathing motion;

[0070] Figure 13 These are the result graphs of the cytotoxicity test of the conductive structural color hydrogel of the present invention. Among them, (A) is the live / dead staining graph of H9C2 cells; (B) is the live / dead staining graph of HUCVECs; (C) is the result graph of the activity analysis of H9C2 cells; (D) is the result graph of the activity analysis of HUCVECs cells;

[0071] Figure 14 These are the result graphs for investigating the tissue surface adhesion performance of the conductive structural color hydrogel of the present invention. Among them, (A) shows the situations of the conductive structural color sensing patch of the present invention adhered to pigskin after bending, twisting, stretching, and loading; (B) is the optical photograph of the conductive structural color sensing patch - pigskin interface of the present invention; (C) is the SEM image of the conductive structural color sensing patch - heart tissue interface of the present invention; (D) is the result graph for investigating the adhesion strength of the conductive structural color sensing patch of the present invention on different interfaces;

[0072] Figure 15 This is the application result diagram of the conductive structural color hydrogel of the present invention in the real-time monitoring of cardiac mechanical physiological activities and the visual identification of infarcted myocardium. Among them, (A) is the schematic diagram of real-time monitoring and visual identification of cardiac mechanical physiological activities; (B) is the real-time monitoring result diagram of the mechanical physiological signals of a normal heart; (C) is the real-time monitoring result diagram of the mechanical physiological signals of a heart with myocardial infarction; (D) is the visual identification result diagram of infarcted myocardium by the conductive structural color hydrogel of the present invention;

[0073] Figure 16 This is the investigation result diagram of the influence of the conductive structural color hydrogel of the present invention on cardiac function. Among them, (A) is the echocardiogram; (B) is the investigation result diagram of the cardiac function evaluation indexes ejection fraction (EF), fractional shortening (FS), end-diastolic volume (EDV), and end-systolic volume (ESV);

[0074] Figure 17 This is the investigation result diagram of the repair effect of the conductive structural color hydrogel of the present invention on cardiac morphology. Among them, (A) is the H&E and Masson staining diagrams; (B) is the analysis result diagram of infarct wall thickness; (C) is the analysis result diagram of infarct area;

[0075] Figure 18 This is the investigation result diagram of the anti-inflammatory performance of the conductive structural color hydrogel of the present invention. Among them, (A) is the CD86 / CD206 fluorescence staining result diagram; (B) is the analysis result diagram of the proportion of CD86-positive cells; (C) is the analysis result diagram of the proportion of CD206-positive cells;

[0076] Figure 19 This is the investigation result diagram of the influence of the conductive structural color hydrogel of the present invention on neovascularization. Among them, (A) is the vWF / CD31 fluorescence staining result diagram; (B) is the analysis result diagram of neovascular density;

[0077] The data in the present invention are presented in the form of mean ± standard deviation (mean ± SD); an independent samples t-test is used between two groups. When P < 0.05, it indicates a significant statistical significance. * indicates P < 0.05, ** indicates P < 0.01, *** indicates P < 0.001, and ns indicates no significant difference. Detailed implementation manners

[0078] The embodiments of the present invention are described in detail below. The following described embodiments are exemplary and are only used to explain the present invention, and should not be construed as a limitation to the present invention.

[0079] It should be noted that the terms "first" and "second" are only used for descriptive purposes and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include one or more of such features. Further, in the description of the present invention, unless otherwise specified, the meaning of "a plurality" is two or more.

[0080] The endpoints and any values disclosed in this text for a range are not limited to that precise range or value. These ranges or values should be understood to include values close to those ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values, they can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed in this text.

[0081] Terms and Definitions

[0082] Unless otherwise indicated, the technical and scientific terms used in the present invention have the same meaning as those commonly understood by those skilled in the technical field to which the present invention pertains, unless otherwise indicated.

[0083] In this text, the term "comprising" or "including" is an open expression, that is, it includes the content specified in the present invention, but does not exclude other aspects of the content.

[0084] The present invention provides a conductive structural color hydrogel, its preparation method and application, which will be described in detail below respectively.

[0085] Hydrogel

[0086] The present invention provides a conductive structural color hydrogel. According to an embodiment of the present invention, it includes: a conductive nanomaterial having a catechol group; HPC cholesteric liquid crystal; a matrix material; a crosslinking agent; and the conductive structural color hydrogel is formed through physical and / or chemical interactions between the conductive nanomaterial, the HPC cholesteric liquid crystal, the matrix material, and the crosslinking agent. The conductive structural color hydrogel according to the embodiment of the present invention has enhanced electromechanical response and force-induced color change response characteristics, has a photoelectric dual-signal sensing function, can accurately, real-time, and visually monitor mechanical stimuli, can be used as a flexible sensing material for preparing products that can achieve visual feedback and digital feedback of mechanical stimuli, and products for compensating and / or repairing the electrical conduction of biological tissues, especially for preparing a conductive structural color hydrogel patch for monitoring and / or treating myocardial infarction (MI), and has broad application prospects.

[0087] In this text, the term "HPC" is equivalent to "hydroxypropyl cellulose", which is a class of visual substances with a unique supramolecular structure and good biocompatibility. In an aqueous environment, it can self-assemble into a cholesteric liquid crystal with a periodic helical structure by means of intermolecular forces, such as the repulsive force induced by molecular chirality and the hydrogen bond force between hydroxyl groups. This liquid crystal structure scatters and reflects visible light, making the material exhibit bright structural colors.

[0088] In this text, the term "matrix material" is one of the main components of the hydrogel, which is a continuous three-dimensional cross-linked network that provides structural stability.

[0089] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the HPC mass fraction of the HPC cholesteric liquid crystal is 50% to 56%. Exemplarily, the mass fraction of HPC in the HPC cholesteric liquid crystal can be 50%, 50.5%, 51%, 51.5%, 52%, 52.5%, 53%, 53.5%, 54%, 54.5%, 55%, 55.5%, 56%. The inventors determined this optimal HPC mass fraction through a large number of experiments. Within this numerical range, before and after the conductive structural color hydrogel of the present invention is subjected to spatiotemporal mechanical stimuli, the color difference is obvious, and the color change can be observed with the naked eye, intuitively showing the position and range of the mechanical stimulus source.

[0090] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the HPC mass fraction of the HPC cholesteric liquid crystal is 50% to 52%. Exemplarily, the mass fraction of HPC in the HPC cholesteric liquid crystal can be 50%, 50.1%, 50.2%, 50.3%, 50.4%, 50.5%, 50.6%, 50.7%, 50.8%, 50.9%, 51%, 51.1%, 51.2%, 51.3%, 51.4%, 51.5%, 51.6%, 51.7%, 51.8%, 51.9%, 52%. Thereby, the intuitiveness of the visual feedback of the conductive structural color hydrogel of the present invention to mechanical stimuli is further improved.

[0091] According to an embodiment of the present invention, the HPC cholesteric liquid crystal is formed by the self-assembly of HPC in water. For the conductive structural color hydrogel according to the embodiment of the present invention, the component of the structural color unit material is simple, and the safety is further improved. Exemplarily, the "water" can be drinking water, purified water, water for injection, sterile water for injection, water for the production of in vitro diagnostic reagents.

[0092] According to an embodiment of the present invention, the mass ratio of the HPC to the water is 50∶(35 - 40). Exemplarily, the mass ratio of HPC to water can be 50∶35, 50∶36, 50∶37, 50∶38, 50∶39, 50∶40. The inventors determined the optimal HPC cholesteric liquid crystal assembly conditions through a large number of experiments. This numerical range is beneficial for the formation of a vivid color visible to the naked eye in the conductive structural color hydrogel of the present invention.

[0093] In a specific embodiment of the present invention, the mass ratio of the HPC to the water is 50∶37. Thus, the formed HPC cholesteric liquid crystal has a vivid color.

[0094] In some embodiments of the present invention, the conductive nanomaterial is modified by dopamine or a pharmaceutically acceptable salt thereof or tannic acid. According to an embodiment of the present invention, the surface of the modified conductive nanomaterial has a thin layer of biomimetic coating with anchor points (catechol groups).

[0095] In this text, the term "dopamine" is equivalent to "DA", "Dopamine", and has the following structural formula:

[0096] .

[0097] According to an embodiment of the present invention, the pharmaceutically acceptable salt of dopamine is dopamine hydrochloride. Dopamine hydrochloride is highly soluble in water, which is beneficial for the modification reaction of the conductive nanomaterial.

[0098] In some embodiments of the present invention, the pharmaceutically acceptable salt of tannic acid is an alkali metal salt of tannic acid. Exemplarily, the alkali metal salt of tannic acid can be sodium tannate or potassium salt, and its average degree of salification can be 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8. Thus, the alkali metal salt of tannic acid has beneficial effects such as good stability and low biological toxicity and side effects.

[0099] In some embodiments of the present invention, the conductive nanomaterial is selected from graphene, carbon nanotubes, black phosphorus, MXene, MoS 2 at least one of which is modified by dopamine or a pharmaceutically acceptable salt thereof and / or tannic acid or a pharmaceutically acceptable salt thereof.

[0100] According to an embodiment of the present invention, the conductive nanomaterial is MXene@PDA, and the MXene@PDA is MXene nanosheets modified by dopamine or a pharmaceutically acceptable salt thereof. According to an embodiment of the present invention, the surface of the MXene nanosheets modified by dopamine has a thin layer of biomimetic coating with anchor points (catechol groups).

[0101] In this text, the term "nanosheet" refers to a sheet-like material with a thickness in the nanoscale (usually 1 to 100 nanometers) and a lateral dimension much larger than the thickness.

[0102] According to an embodiment of the present invention, dopamine forms a polydopamine (PDA) coating through oxidative polymerization, which wraps around the surface of the nanosheet to form the aforementioned conductive nanomaterial with catechol groups.

[0103] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the mass fraction of MXene@PDA is not less than 1%. The inventors determined this optimal mass fraction of MXene@PDA through a large number of experiments. At this mass fraction, the conductivity of the conductive structural color hydrogel of the present invention is relatively large.

[0104] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the mass fraction of HPC in the HPC cholesteric liquid crystal is 50% - 52%, and the mass fraction of MXene@PDA is 1% - 1.5%. Exemplarily, the mass fraction of MXene@PDA can be 1.1%, 1.2%, 1.3%, 1.4%, 1.5%. Thus, the conductive structural color hydrogel of the present invention provides a more intuitive visual feedback to mechanical stimuli, while having good electrical conductivity, biosecurity, and improved biocompatibility. A heart patch with a conductivity slightly higher than that of natural human heart tissue can be prepared using the conductive structural color hydrogel of the present invention. This heart patch can compensate for electrophysiological conduction in tissues, reconstruct the conductive pathway of infarcted myocardium through an electrocoupling process, and repair damaged fibrotic tissue. According to an embodiment of the present invention, this heart patch can effectively inhibit ventricular remodeling and inflammatory responses, promote angiogenesis, reduce the formation of fibrotic scars, repair the morphology and function of the myocardium, and achieve the repair of the morphology and electrophysiological function of the infarcted heart.

[0105] In some embodiments of the present invention, the matrix material is selected from at least one of sodium alginate, dopamine-grafted modified sodium alginate, hyaluronic acid, dopamine-grafted modified hyaluronic acid, gelatin, carboxymethyl chitosan, and sodium caseinate.

[0106] According to an embodiment of the present invention, the matrix material is sodium alginate and / or dopamine-grafted modified sodium alginate.

[0107] According to an embodiment of the present invention, the mass ratio of HPC in the HPC cholesteric liquid crystal to the matrix material is 50∶(4 - 12). The inventors determined this optimal mass ratio of HPC to the matrix material through a large number of experiments, which is beneficial for the integrated material to form a bright color visible to the naked eye.

[0108] According to an embodiment of the present invention, the matrix material is sodium alginate, and the mass ratio of HPC in the HPC cholesteric liquid crystal to the sodium alginate is 50:(6-10). Exemplarily, the mass ratio of the HPC to the sodium alginate may be: 50:6, 50:7, 50:8, 50:9, 50:10. Through a large number of experiments, the inventors determined that this preferred mass ratio of HPC to sodium alginate is beneficial for the integrated material to form a bright color visible to the naked eye.

[0109] In a specific embodiment of the present invention, the matrix material is sodium alginate, and the mass ratio of HPC in the HPC cholesteric liquid crystal to the sodium alginate is 50:8.

[0110] According to an embodiment of the present invention, the cross-linking agent is a metal ion. The metal ion cross-linking agent can effectively carry out metal ion coordination and ion chelation with the carboxyl group of sodium alginate and the catechol group of the conductive nanomaterial, further improving the mechanical properties of the conductive structural color hydrogel of the present invention. Thus, based on the conductive structural color hydrogel of the present invention, a medical hydrogel material with good injection performance can be obtained, realizing targeted and personalized injection, which is beneficial for minimally invasive treatment.

[0111] According to an embodiment of the present invention, the metal ion is a polyvalent cation. Exemplarily, the "polyvalent cation" can be: Ca 2 ⁺, Zn 2 ⁺, Ba 2 ⁺, Mg 2+ , Cu 2 ⁺, Fe 3+ , Al 3+ , Ga 3+ , Zr 4+ .

[0112] According to an embodiment of the present invention, the metal ion is selected from at least one of Ca 2+ , Zn 2+ , Mg 2+ , Fe 3+ , Cu 2+ .

[0113] According to an embodiment of the present invention, the metal ion comes from its halide salt, preferably chloride salt. Thus, it is beneficial for the metal ion cross-linking agent to play its role.

[0114] According to an embodiment of the present invention, the metal ion is Ca 2+ . Thus, it is beneficial to improve the mechanical properties and biosecurity of the conductive structural color hydrogel of the present invention.

[0115] According to an embodiment of the present invention, the Ca 2+from calcium chloride. Thus, it is beneficial to improve the mechanical properties and biosecurity of the conductive structural color hydrogel of the present invention.

[0116] According to an embodiment of the present invention, based on the total mass of the conductive structural color hydrogel, the mass fraction of the calcium chloride is 0.5% - 0.56%. Exemplarily, the mass fraction of the calcium chloride may be: 0.50%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%.

[0117] Method and product

[0118] The present invention provides a method for preparing the aforementioned conductive structural color hydrogel. According to an embodiment of the present invention, it includes: mixing the conductive nanomaterial, the HPC cholesteric liquid crystal, and the matrix material to form a mixture; performing a crosslinking reaction on the mixture with the crosslinking agent to form the conductive structural color hydrogel. According to the method of the embodiment of the present invention, first integrating the conductive nanomaterial and the HPC cholesteric liquid crystal into the three-dimensional system of the matrix material and then performing a crosslinking reaction with the crosslinking agent is beneficial for the hydrogel to form a bright color visible to the naked eye and enhance the optoelectronic dual-signal sensing function.

[0119] According to an embodiment of the present invention, the method may further include at least one of the following additional technical features:

[0120] According to an embodiment of the present invention, the temperature of the mixing treatment is room temperature. The preparation temperature of the HPC cholesteric liquid crystal is usually room temperature. Thus, using room temperature to mix the main raw materials of the conductive structural color hydrogel can further promote the synergistic integration of the conductive nanomaterial and the HPC cholesteric liquid crystal, which is beneficial for the conductive nanomaterial and the HPC cholesteric liquid crystal to be incorporated into the matrix material to form a stable elastic gel network structure.

[0121] In this article, the term "room temperature" is 20°C - 25°C.

[0122] According to an embodiment of the present invention, the temperature of the crosslinking reaction is 3°C - 7°C. By controlling the temperature of the crosslinking reaction, the crosslinking reaction process can be controlled, and thus an elastic gel network structure with stable performance can be constructed.

[0123] In a specific embodiment of the present invention, the temperature of the crosslinking reaction is 5°C. Thus, the structure and performance of the hydrogel are further improved, and the quality and function are enhanced.

[0124] According to an embodiment of the present invention, the method further includes: performing an exhaust treatment and / or a standing treatment on the conductive structural color hydrogel. Thus, the quality and function of the hydrogel product are further improved, an injectable conductive structural color hydrogel is constructed, and its application in the field of minimally invasive treatment is realized.

[0125] According to an embodiment of the present invention, the temperature of the exhaust treatment is 3°C to 7°C. Thereby, the structure and performance of the hydrogel are further optimized, and the quality and function are improved.

[0126] In a specific embodiment of the present invention, the temperature of the exhaust treatment is 5°C.

[0127] The present invention also provides a conductive structural color hydrogel. According to an embodiment of the present invention, the conductive structural color hydrogel is prepared according to the foregoing method.

[0128] Those skilled in the art can understand that the features and advantages described above for the conductive structural color hydrogel and its preparation method also apply to this conductive structural color hydrogel, and will not be elaborated here.

[0129] Use

[0130] The present invention provides the use of the foregoing conductive structural color hydrogel in the preparation of products. According to an embodiment of the present invention, the product has at least one of the following uses: visualizing and / or digitally feedbacking the response of non-biological tissues to mechanical stimuli; visualizing and / or digitally monitoring the movement of biological tissues; compensating and / or repairing the electrical conduction of biological tissues. The foregoing conductive structural color hydrogel, through its mechanochromic response performance, enables the product to have the use of visually detecting mechanical stimuli; through its electrical signal sensing performance, enables the product to have the use of digitally monitoring mechanical stimuli; through its electrical conduction function, enables the product to have the use of compensating and / or repairing the electrical conduction of biological tissues. Thereby, the conductive structural color hydrogel can be used to prepare products with visualization and digital monitoring functions, so as to display the dynamic changes of non-biological tissues under mechanical stimuli and the movement state of biological tissues in real time.

[0131] Exemplarily, the foregoing conductive structural color hydrogel is adhered to the surface of the heart, and the contraction / diastolic signals are monitored in real time through the change in resistance (in some embodiments of the present invention, the sensitivity can reach GF = 3.6), and the infarction location is identified according to the local color difference (such as the color of the infarction area remains unchanged, and the normal area has a blue shift) (in some embodiments of the present invention, the blue shift sensitivity of the reflection wavelength reaches -2.85 nm% ﹣1 );Utilize the electrical conduction function of the conductive structural color hydrogel (in some embodiments of the present invention, the conductivity is 1.05 S / m), reduce the scar resistance, promote angiogenesis (in some embodiments of the present invention, the vascular density is increased to 30.95%, which is 3 times higher than that of the myocardial infarction model group), inhibit the inflammatory response (in some embodiments of the present invention, the polarization rate of M2 macrophages can be increased to 20.63%), and improve the cardiac function (in some embodiments of the present invention, the ejection fraction EF of the SD rat myocardial infarction (MI) model is increased from 47.38% to 81.55%).

[0132] Exemplarily, the possible application scenarios of the product are as follows: monitoring the necrosis of tissues such as skeletal muscle tissue, smooth muscle tissue, cardiac muscle tissue, connective tissue, and nerve tissue, so as to evaluate their functions, study their physiological mechanisms, assist in disease diagnosis, screen and evaluate drugs, optimize treatment plans, support rehabilitation treatment and training, etc. For example, developing rehabilitation treatment devices based on mechanical stimulation and the aforementioned conductive structural color hydrogels, such as cardiac rehabilitation trainers and muscle rehabilitation trainers, to formulate personalized rehabilitation treatment plans by real-time monitoring and feedback of the patient's movement state and improve the rehabilitation treatment effect. Exemplarily, the possible application scenarios of the product are as follows: real-time monitoring of the operating status of artificial hearts and heart assist devices; monitoring the force and deformation of cardiac stents in blood vessels, studying the opening and closing performance and durability of heart valves under mechanical stimulation simulating heart beating, and developing biosensors that can real-time monitor the response of non-biological tissues to mechanical stimulation, such as pressure sensors and strain sensors, to improve the monitoring accuracy and reliability and provide technical support for the research and development and clinical application of medical devices.

[0133] According to an embodiment of the present invention, the visual feedback and / or the numerical feedback are synchronized with the mechanical stimulation. Thus, the above product has the functions of visualizing, digitizing, and real-time monitoring of mechanical stimulation.

[0134] According to an embodiment of the present invention, the product includes, but is not limited to: medical devices, wearable sensors, and biosensors.

[0135] According to an embodiment of the present invention, the medical devices include, but are not limited to: cardiac sensing patches, myocardial infarction monitoring and / or treatment patches, and bionic skins.

[0136] According to an embodiment of the present invention, the biosensors include, but are not limited to: pressure sensors and strain sensors.

[0137] According to an embodiment of the present invention, the wearable sensors include, but are not limited to: inertial sensors, optical sensors, electrodes and electrochemical sensors, flexible sensors, and interactive sensors. An example of an inertial sensor is an acceleration sensor, which monitors the motion state of the human body, such as the number of steps, running speed, jump height, etc., by measuring the change in acceleration. It is commonly used in devices such as smart bracelets and smart watches to help users record their daily activity levels and exercise data. An example of an optical sensor is an ECG sensor, which monitors the potential difference generated by the electrical activity of the heart through a monitoring electrode. It is commonly used in devices such as smart watches and electrocardiogram monitoring patches. An example of an electrode and an electrochemical sensor is an electronic skin electrode, which has good flexibility and conformability and can be used to monitor various physiological signals, such as heart rate and muscle activity. It is often integrated into devices such as smart patches and smart clothing to provide users with a comfortable and convenient monitoring method. An example of a flexible sensor is a flexible pressure sensor, which can be used to manufacture wearable blood pressure monitoring devices. By wrapping it around the arm or wrist and measuring the deformation of the sensor caused by the change in blood vessel pressure, the blood pressure value can be calculated. An example of an interactive sensor is a touch screen: a capacitive or resistive touch screen is used to achieve the interaction between the user and the smart wearable device. For example, on devices such as smart watches and smart bracelets, users can operate by touching the screen, such as checking the time, answering calls, adjusting settings, etc.

[0138] Exemplarily, the biological tissue movement may be the breathing movement of a human or an animal, the expansion and contraction of the chest, the inflation and deflation of the lungs, the contraction / diastole of the heart, the contraction and relaxation of blood vessels, gastrointestinal peristalsis, esophageal peristalsis, the contraction and relaxation of skeletal muscles, the peristalsis of renal tubules, the peristalsis of ureters, the contraction and relaxation of the bladder, the peristalsis of fallopian tubes, the contraction and relaxation of the uterus, the contraction and relaxation of the vagina, the blinking of eyes, the rotation of eyeballs, and the swallowing action of the larynx.

[0139] Exemplarily, the biological tissue may be skeletal muscle tissue, smooth muscle tissue, cardiac muscle tissue, connective tissue, and nerve tissue.

[0140] According to an embodiment of the present invention, the product is used for monitoring biological tissue necrosis and / or preventing and / or treating diseases caused by the biological tissue necrosis. According to an embodiment of the present invention, by monitoring the biological tissue movement, necrotic biological tissue can be accurately identified, thereby achieving disease prevention; by compensating and / or repairing the electrical conduction of biological tissue, the biological function of the tissue can be effectively improved, thereby achieving disease prevention and treatment.

[0141] In some embodiments of the present invention, the diseases include, but are not limited to: myocardial infarction, myocardial sclerosis, cerebral infarction, cerebral softening, gastric and duodenal ulcer, typhoid fever, acute pancreatitis, pulmonary tuberculosis, pulmonary infarction, renal tubular necrosis, renal infarction, ovarian cyst torsion, ruptured tubal pregnancy, necrotizing fasciitis, frostbite. Myocardial infarction: Necrosis occurs in myocardial tissue due to obstruction of coronary artery blood flow, which can lead to arrhythmia, heart failure, and even sudden death. Myocardial sclerosis: Extensive small focal necrosis of the myocardium eventually leads to myocardial sclerosis, affecting the heart's pumping function. Cerebral infarction: Necrosis occurs in brain tissue due to cerebrovascular obstruction or rupture and bleeding, which can cause paralysis, coma, speech disorders, etc. Cerebral softening: Liquefactive necrosis occurs in brain tissue, commonly seen in diseases such as suppurative encephalitis. Gastric and duodenal ulcer: Necrosis occurs in the mucosa and muscular layer of the stomach or duodenum, which can lead to upper abdominal pain, bleeding, perforation, etc. Typhoid fever: Necrosis of the intestinal wall caused by Salmonella typhi infection can lead to complications such as intestinal bleeding and perforation. Acute pancreatitis: Necrosis occurs in pancreatic tissue, which can cause severe abdominal pain, nausea, vomiting, and in severe cases, multiple organ failure. Pulmonary tuberculosis: Caseous necrosis caused by Mycobacterium tuberculosis infection can lead to cough, expectoration, hemoptysis, low fever, etc. Pulmonary infarction: Necrosis occurs in lung tissue due to pulmonary artery embolism, which can present symptoms such as chest pain, hemoptysis, and dyspnea. Renal tubular necrosis: Commonly seen in acute renal failure, which can lead to oliguria or anuria, azotemia, etc. Renal infarction: Necrosis occurs in renal tissue due to obstruction of the renal artery, which can cause low back pain and hematuria. Ovarian cyst torsion: Necrosis occurs in ovarian tissue due to obstruction of blood supply, which can lead to sudden severe lower abdominal pain. Ruptured tubal pregnancy: Necrosis of the fallopian tube tissue can cause abdominal pain, vaginal bleeding, shock, etc. Necrotizing fasciitis: Necrosis occurs in subcutaneous tissue and fascia, which can lead to local severe pain, fever, systemic toxic symptoms, and can be life-threatening in severe cases. Frostbite: Necrosis occurs in local tissue due to low temperature, which can present symptoms such as pale skin, numbness, pain, and in severe cases, tissue necrosis and exfoliation.

[0142] According to an embodiment of the present invention, the product is used for monitoring and / or treating myocardial infarction.

[0143] In a specific embodiment of the present invention, the conductive structural color hydrogel of the present invention is prepared by the following method:

[0144] Add 5.0 g of HPC to 3.7 g of water. After stirring well for 12 h, slowly add 0.8 g of sodium alginate and 9.6 - 10 mg of MXene@PDA conductive nanosheets to the solution respectively. Stir continuously at room temperature for 6 h and then let it stand overnight. Slowly add 0.05 g of CaCl 2 to the above system, and continue to stir at 5°C for 3 h. Centrifuge the uniformly mixed hydrogel at high speed (10000 r / min, 5°C, 10 min) to remove the air bubbles therein, and then let it stand for 6 h to obtain an injectable conductive structural color hydrogel.

[0145] Further test results show that the above conductive structural color hydrogel exhibits excellent tensile color-changing performance (sensitivity: -2.85 nm % ﹣1 ), pressing color-changing response (sensitivity of -3.50 nm %), ﹣1 and swelling color-changing response (sensitivity of -4.47 nm %), ﹣1 with excellent tensile strain sensitivity, fast response performance, and a relatively wide strain sensing window, showing periodic frequency-dependent characteristics at a frequency of 0.025 - 1.0 Hz. Measuring its conductivity value, it is about 1.05 ± 0.053 S / m, slightly higher than the conductivity range of natural human heart tissue (about 0.3 - 0.7 S / m), making it an ideal heart patch material.

[0146] Further test results show that as a conductive structural color sensing patch, this conductive structural color hydrogel has good cell safety (cell viability > 95%, better than 80% of traditional polypyrrole hydrogels), biocompatibility (no risk of fiber encapsulation), and conformal adhesion (can firmly adhere to the human skin without external tape assistance), and can safely and closely adhere to the heart surface, achieving visual precise diagnosis while effectively restoring heart function. Among them, the restoration of heart function is reflected in: it can effectively inhibit ventricular remodeling, significantly relieve the process of ventricular thinning, effectively prevent the expansion of the infarct area and fibrotic deposition. The test results also show that as a conductive structural color sensing patch, this conductive structural color hydrogel can inhibit inflammatory responses and promote angiogenesis.

[0147] Therefore, as a heart patch, the conductive structural color hydrogel of the present invention can effectively inhibit ventricular remodeling and inflammatory responses, promote angiogenesis, reduce fibrotic scar formation, and repair the myocardial morphology and function, thereby achieving the repair of the infarcted heart morphology and electrophysiological function.

[0148] The solution of the present invention will be explained below in conjunction with embodiments. Those skilled in the art will understand that the following embodiments are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. For those not specified in the embodiments regarding specific techniques or conditions, they shall be carried out according to the techniques or conditions described in the literature in this field or according to the product specifications. For reagents or instruments not specified for the manufacturer, they are all conventional products that can be obtained through commercial purchase. In the following embodiments, unless otherwise specified, the "MI group" is the "myocardial infarction (MI) model group".

[0149] Example 1: Preparation and material characterization of modified MXene nanosheets (MXene@PDA)

[0150] In this example, ultrathin Ti 3 C 2Tx MXene nanosheets (MXene), modified MXene nanosheets (MXene@PDA) were obtained by the oxidative polymerization of dopamine. The specific method is as follows:

[0151] MXene preparation: 1.6 g of LiF and 20 mL of aqueous HCl solution (9 mol / L) were placed in a polytetrafluoroethylene reactor and uniformly mixed with a magnetic stirrer to obtain a mixed solution. Then, 1.0 g of Ti 3 AlC 2 powder was added to the above mixed solution in batches, and the reaction was continued to stir at 35 °C for 24 h to obtain an aqueous dispersion of MXene powder. Finally, under nitrogen protection, this aqueous dispersion of MXene powder was ultrasonically treated in an ice-water bath for 1 h to obtain an MXene aqueous dispersion for subsequent use. MXene@PDA preparation: 100 mg of MXene aqueous dispersion (8 wt%) was washed three times with Tris-HCl buffer solution (10 mM, pH 8.5), and then dispersed in 200 mL of Tris-HCl buffer solution. Then, 400 mg of dopamine hydrochloride was added to the buffer solution, and the mixture was magnetically stirred at room temperature for 6 h, and then the resulting mixture was centrifuged three times with deionized water. After freeze-drying treatment, finally, PDA-modified MXene (MXene@PDA) nanosheets were obtained.

[0152] Furthermore, a transmission electron microscope (TEM, Talos F200S) was used to observe the morphology and microstructure of MXene and MXene@PDA, and the functional group structure and surface characteristics were detected by attenuated total reflection infrared spectroscopy (ATR-FTIR, PerkinElmer Spectrometer 3) and X-ray photoelectron spectroscopy (XPS, Thermo Scientific KAlpha), thereby characterizing the modification of MXene. The results are as Figure 2 shown.

[0153] The results show that: compared with unmodified MXene, (1) a large number of nanoaggregates can be observed on the surface of the modified MXene nanosheets, and the thickness of the nanosheets has increased significantly ( Figure 2 A); (2) a large amount of N element appears on the surface of the modified MXene (accounting for 8.04%), while the content of C element increases from 13.91% to 20.04%, and the content of O element increases from 64.49% to 65.46%. Dopamine rich in C, N, and O elements has been in-situ polymerized onto the surface of MXene ( Figure 2 B); (3) The MXene@PDA material is in the range of 3650-2693 cm ﹣1The range shows stretching vibration peaks of hydroxyl and amino groups derived from dopamine; there are several absorption peaks of carbon-carbon double bonds on the benzene ring in the range of 1500 - 600 cm ﹣1 interval; there is also an out-of-plane bending vibration absorption peak of hydrogen on the aromatic ring near 815 cm ﹣1 ( Figure 2 C). The above results prove that PDA is successfully loaded on the surface of the MXene material, forming a thin-layer biomimetic coat with anchor points.

[0154] Example 2: Preparation and Component Optimization of Conductive Structural Color Hydrogel

[0155] In this example, a conductive structural color hydrogel is prepared by using static self-assembly and ion cross-linking strategies. The specific method is as follows:

[0156] Preparation of conductive structural color hydrogel: First, 5.0 g of HPC (hydroxypropyl cellulose, hydroxypropyl substitution degree is 74.1%, viscosity is 4.8 mPa·s, MW = 100,000) is gradually added to a container containing 3.7 g of water, and it is fully stirred with a mechanical stirrer for 12 h. Subsequently, 0.8 g of sodium alginate (SA) and 0 - 100 mg of MXene@PDA conductive nanosheets are slowly added to the solution respectively, and it is continuously stirred at room temperature for 6 h and then left to stand overnight. Then, 0.05 g of CaCl 2 is slowly added to the above system, and it is continuously stirred at 5°C for 3 h. Finally, the well-mixed hydrogel is quickly transferred to a centrifuge tube, and the air bubbles in the system are discharged by high-speed centrifugation (10,000 r / min, 5°C, 10 min), and then left to stand for 6 h to obtain an injectable conductive structural color hydrogel.

[0157] In this example, the effects of the HPC content, the introduction of sodium alginate and calcium ions on the structural color of the hydrogel are also investigated. The specific method is as follows: Change the HPC concentration of the HPC cholesteric liquid crystal (based on the total mass of the conductive structural color hydrogel, the mass fraction of HPC is 50%, 52%, 54%, 56%), add sodium alginate, introduce calcium ions, and investigate the effects of each parameter condition on the structural color of the conductive structural color hydrogel. The results are as Figure 3 A, Figure 3 B shown.

[0158] The results show that: (1) As the HPC concentration gradually increases from 50% to 56%, the initial color of the conductive structural color hydrogel gradually changes from red to blue, and the reflection wavelength peak of the structural color also gradually shifts from 656 nm (red), 586 nm (yellow), 521 nm (green) to 461 nm (blue) ( Figure 3 A, Figure 3B). (2) When sodium alginate is added to HPC cholesteric liquid crystal, the color of the HPC / SA system gradually changes from dark red (781 nm) to yellow-green (568 nm). (3) The introduction of calcium ions causes ionic cross-linking of the sodium alginate polymer network structure, which compresses the pitch of the liquid crystal phase to a certain extent, resulting in a blue shift of the reflection wavelength. (4) After the addition of MXene@PDA with catechol groups on the surface, the cross-linking degree of the hydrogel system is greatly improved, and at the same time, the black conductive substance enhances the contrast of the structural color, making the reflection wavelength significantly shift from 557 nm (green) to 511 nm (blue-green). The above results prove that by changing the HPC concentration, the initial color of the structural color can be quickly regulated, and the matrix materials (such as sodium alginate and metal ion cross-linked network) and conductive materials (such as MXene@PDA) affect the final color of the structural color.

[0159] The existence of periodic cholesteric liquid crystal is the key factor for the formation of structural color. In this example, the existence of the cholesteric liquid crystal structure in the above hydrogel was further verified by scanning electron microscopy (TEM, Talos F200S) and polarized light microscopy. The results are as Figure 3 C, Figure 3 as shown in D.

[0160] The results show that: (1) Through the SEM image, it can be clearly observed that the inside of the hydrogel presents an obvious spiral lamellar morphology structure, and the colored liquid crystal phase in the hydrogel can be clearly seen by using a polarized light microscope ( Figure 3 C, Figure 3 D). (2) The opaque black flakes under the polarized light microscope are MXene@PDA nanosheets dispersed in the hydrogel ( Figure 3 D). The above results fully confirm the existence of the cholesteric liquid crystal structure in the hydrogel of the present invention, and the conductive material MXene@PDA is relatively uniformly dispersed therein, and a continuous conductive network structure can be formed.

[0161] Example 3: Investigation on the composition and mechanical properties of the conductive structural color hydrogel of the present invention

[0162] Referring to Example 1 and 2, HPC / SA, structural color hydrogel (without MXene@PDA) and conductive structural color hydrogel (containing 1.0% MXene@PDA) were prepared, and the mechanical properties of each sample were further investigated. Among them, compared with the conductive structural color hydrogel, (1) the difference in the preparation method of HPC / SA is that MXene@PDA conductive nanosheets are not added, and CaCl 2 is not added; (2) the difference in the preparation method of the structural color hydrogel is that MXene@PDA conductive nanosheets are not added. The results are as Figure 4 shown.

[0163] The results show that: (1) The conductive structural color hydrogel of the present invention successfully introduces CaCl 2 , Mxene@PDA conductive nanosheets ( Figure 4 A); effective metal ion coordination and ion chelation occur between calcium ions and the carboxyl groups of sodium alginate and the catechol groups of MXene@PDA ( Figure 4 B); Mxene@PDA has a two-dimensional structure and good stability ( Figure 4 C). (2) In the rheological frequency sweep measurement, when the angular frequency range is from 1 to 100 rad·s ﹣1 , the storage modulus G' of the hydrogel is always higher than the loss modulus G'', indicating that the material always maintains a very stable gel state. At the same time, with the addition of calcium ions and Mxene@PDA conductive materials, both the storage modulus G' and the loss modulus G'' of the material are significantly improved, meaning that its mechanical properties are also correspondingly enhanced. In the rheological strain sweep test, when the strain is less than 200%, the storage modulus G' of the hydrogel is always higher than the loss modulus G''; when the strain is higher than 200%, the storage modulus G' of the hydrogel drops below the loss modulus G'', which is due to the obvious fracture of the gel network structure, indicating that the hydrogel can maintain a stable elastic gel network structure below 200% strain.

[0164] Further investigation results show that the conductive structural color hydrogel of the present invention has good injectability and can be used for targeted and personalized injection with a medical syringe. The injection force during the injection process is about 12 N, which is beneficial for realizing minimally invasive treatment of medical hydrogel materials.

[0165] Example 4: Investigation of the visual sensing function of the conductive structural color hydrogel of the present invention

[0166] For flexible wearable sensors and cardiac monitoring patches, intuitive visual signal output is extremely crucial, which can achieve fast and visually recognizable signal detection. In this example, the visual response sensitivity of the conductive structural color hydrogel of the present invention to external mechanical stimuli was further investigated. The results are as shown in Figure 5 , Figure 6 , Figure 7 .

[0167] The results show that: (1) As the material of the conductive structural color hydrogel of the present invention is gradually stretched, the color of the hydrogel gradually changes from red to blue, showing a visually recognizable optical signal change. By detecting the change in the reflection wavelength during the stretching process, it can be seen that as the material is stretched from 0% to 60%, the reflection wavelength of the hydrogel gradually blue-shifts from 640 nm to 482 nm, demonstrating excellent stretch-induced color change performance (sensitivity: -2.85 nm % ﹣1 ) ( Figure 5). (2) When the hydrogel material is stimulated by external pressure, as the pressure increases, the color of the hydrogel gradually undergoes a blue shift, exhibiting excellent pressure-induced color change response (sensitivity is -3.50 nm / %). ﹣1 ). ( Figure 6 ). (3) When the hydrogel material is adhered to the surface of a balloon, when the balloon is deformed by extrusion, the color of the hydrogel will also change significantly accordingly. As the degree of balloon expansion and deformation increases, the color of the hydrogel gradually changes from red, yellow, green to blue, showing excellent inflation-induced color change response (sensitivity is -4.47 nm / %). ﹣1 ). During the inflation and deformation sensing process, the color and reflection wavelength change of the hydrogel have good stability and recoverability, and there is almost no hysteresis in its reflection wavelength.

[0168] Furthermore, the results of 100 stretching cycle tests show that after the conductive structural color hydrogel of the present invention is stretched 100 times, its reflection wavelength can still be stably switched from about 620 nm (red) to about 458 nm (blue), and there is no obvious attenuation phenomenon, having a stable visual signal transmission ability.

[0169] The above results indicate that the conductive structural color hydrogel of the present invention has excellent stimulus visualization ability and shows broad application prospects in the fields of human-computer interaction and dynamic visual display.

[0170] Example 5: Application of the conductive structural color hydrogel of the present invention in visual monitoring of myocardial infarction pathological location

[0171] According to the investigation results of Example 4, the inventor pasted an inelastic tape on the surface of the balloon to limit the local inflation and deformation of the balloon, and then evenly adhered the hydrogel on it. By inflating / deflating the balloon to simulate the heartbeat movement, the application of the conductive structural color hydrogel of the present invention in visual monitoring of myocardial infarction pathological location was investigated. The results are as Figure 8 shown in A.

[0172] The results show that as the balloon inflates and deforms, the hydrogel on the surface of the normal balloon undergoes an obvious color change, changing from yellow to cyan, while the hydrogel on the surface of the tape has no obvious color change and always maintains the original yellow. The above results indicate that the conductive structural color hydrogel of the present invention can visually sense external spatio-temporal mechanical stimuli by changing the pitch of the cholesteric liquid crystal and has important application value in the direction of biological mechanical signal monitoring.

[0173] Furthermore, the inventor ligated the left ventricular myocardium of a duck's heart to simulate the situation of local myocardial infarction in the heart. Subsequently, the hydrogel sensing patch was adhered to the surface of the duck's heart, and the external heartbeat movement was simulated by inflating / deflating operations. The results are as Figure 8 shown in B.

[0174] The results showed that: with the overall contraction / diastolic movement of the heart, the overall color of the hydrogel continuously switched between green and cyan, while the color of the hydrogel at the infarcted position of the left ventricle showed no obvious change and still maintained the initial red-yellow color (the surface of the ligated duck heart was not smooth). The above results indicate that the conductive structural color hydrogel of the present invention can achieve visual recognition of the pathological position of myocardial infarction.

[0175] In summary, the conductive structural color hydrogel of the present invention does not require any external instruments, and can accurately detect external stretching, pressure, expansion deformation and spatial mechanical stimuli only through its own bright color change. Moreover, through the difference in local color, the stimulation position can be accurately located, and the stimulation intensity and range can be identified. This provides a simple and effective method for the development of intelligent bionic skin and cardiac sensing patches.

[0176] Example 6: Investigation of the electrical signal sensing function of the conductive structural color hydrogel of the present invention

[0177] Having a conductivity matching that of tissues and a stable charge injection ability is the basis for constructing bioelectronic devices for electrical diagnosis and treatment. For flexible sensing materials, electrical signal sensing and monitoring can quickly output various digital information that can be read by a computer, and show broad application prospects in many fields such as human motion monitoring, physiological signal recognition, and human-machine interaction. In this example, the conductive properties, stretching electrical signal sensing performance, and swelling electrical signal sensing performance of the conductive structural color hydrogel of the present invention were further investigated. The results are as Figure 9 、 Figure 10 、 Figure 11 shown.

[0178] The results of the investigation of the conductive properties showed that: (1) Electrochemical impedance spectroscopy (EIS) can reflect the charge transfer resistance of the conductive hydrogel. Among them, the charge transfer resistance (R ct ) is manifested as the semicircle diameter of the Nyquist curve, and the intersection of the curve on the X-axis represents the comprehensive resistance of the material. The semicircle diameter and intersection value of the conductive structural color hydrogel of the present invention (containing 1.0% MXene@PDA) are smaller than those of HPC / SA and smaller than those of the structural color hydrogel (without MXene@PDA). It shows that the charge transfer resistance and comprehensive resistance of the conductive structural color hydrogel of the present invention are lower ( Figure 9 A). (2) With the addition of calcium ions and MXene@PDA conductive nanosheet materials, the comprehensive resistance of the hydrogel material gradually decreases. With the increase of the MXene@PDA concentration, the conductivity of the hydrogel rises rapidly. When the concentration reaches 1.0%, the increase amplitude of the conductivity begins to slow down ( Figure 9 B, Figure 9C). (3) The conductive structural color hydrogel of the present invention (containing 1.0% MXene@PDA) has a larger CV loop, which means that the material has a larger charge capacity ( Figure 9 D). The above results show that the conductive structural color hydrogel of the present invention has good electrical conductivity. Combining the results of the cytotoxicity investigation of this material, the conductive structural color hydrogel containing 1.0% MXene@PDA is an ideal cardiac patch material, with a conductivity value of 1.05 ± 0.053 S / m, slightly higher than the conductivity range of natural human heart tissue (about 0.3 - 0.7 S / m), and thus can compensate for the electrophysiological conduction in the tissue. Therefore, the conductive structural color hydrogel of the present invention is expected to reconstruct the conductive pathway of infarcted myocardium through the electrocoupling process, thereby repairing the damaged fibrotic tissue.

[0179] The results of the investigation on the tensile electrical signal sensing performance show that: due to the continuous increase in the electrical conduction path, the relative resistance of the conductive structural color hydrogel of the present invention gradually increases with the increase in strain. This indicates that the material can make an electrical signal response to tensile deformation. The response factor (GF) is a key index to measure the sensitivity of the sensing response, which can be obtained by calculating the slope of the tensile - electrical signal curve. Further, for the conductive structural color hydrogel of the present invention, (1) its GF is 1.6 in the strain range of 0 - 72%; when the strain further increases, in the strain range of 72 - 100%, GF sharply rises to 3.6 ( Figure 10 A). This shows that the material has excellent tensile strain sensitivity in a large range of deformations. (2) It can accurately identify mechanical deformations with different amplitudes (0 - 100%) ( Figure 10 B). This shows that the material has a relatively wide strain sensing window and can repeatedly monitor various mechanical strain stimuli with different intensities. (3) At a frequency of 0.025 - 1.0 HZ, it exhibits a periodic frequency - dependent characteristic ( Figure 10 C). This characteristic can meet the requirements of the sensing material for collecting information in a complex and changing environment. (4) It shows a fast response time (550 ms) and recovery time (450 ms) ( Figure 10 D). This high sensitivity to tensile stimuli and the ability of fast response contribute to the real - time feedback of signals in the actual sensing process.

[0180] The results of further large - strain tensile sensing tests show that the conductive structural color hydrogel of the present invention can withstand more than 800 large - strain tensile sensing tests, and there is almost no signal attenuation phenomenon ( Figure 10 E).

[0181] The results of the investigation of the expansion electrical signal sensing performance show that the conductive structural color hydrogel of the present invention can respond to external expansion and deformation stimuli by quickly adjusting the conductive pathway. (1) When the balloon simulating the heart is inflated, the internal pressure of the balloon increases, causing the balloon to expand and deform. The conductive hydrogel of the present invention has excellent adhesion and can be attached to the surface of the balloon, expanding and changing with the balloon. As the amount of balloon expansion deformation increases, the relative resistance value of the conductive structural color hydrogel of the present invention also increases linearly, showing excellent volume-resistance response characteristics, and its response sensitivity (GF) is 1.05. When the balloon changes from a relaxed state to a contracted state, due to the close fit between the hydrogel and the balloon, the relative resistivity can also be quickly and reversibly restored to the initial value ( Figure 11 A). (2) The conductive structural color hydrogel of the present invention can convert expansion deformation into precise electrical signal changes and accurately identify different degrees of volume expansion (0-50%) ( Figure 11 B). This indicates that the material can meet the needs of real-time monitoring of cardiac contraction / relaxation processes.

[0182] The above results indicate that the conductive structural color hydrogel of the present invention has excellent electrical signal sensing function and can be used as a flexible sensor to monitor various mechanical movements.

[0183] Example 7: Application of the conductive structural color hydrogel of the present invention as a flexible material in in vitro mechanical motion monitoring

[0184] Based on the results of Example 6, the inventors further investigated the application of the conductive structural color hydrogel of the present invention in monitoring mechanical movements such as finger bending, balloon inflation, heartbeat, and breathing. Figure 12 shown.

[0185] The results show that: (1) the conductive structural color hydrogel of the present invention can firmly adhere to human skin without the aid of external tape, achieving a comfortable fit, and thus accurately monitoring human movement in real time ( Figure 12 A), and good repeatability ( Figure 12 B). (2) The conductive structural color hydrogel of the present invention adheres to the surface of the duck heart. When the heart is inflated / deflated, the electrical signal curve shows a single peak with weak jagged fluctuations ( Figure 12 C); The conductive structural color hydrogel of the present invention was installed on the surface of the chest muscles of anesthetized mice, and it was also able to accurately identify the slight chest movement of the mice when they were breathing ( Figure 12 D). This indicates that the material can accurately identify the tiny fluctuations of the myocardium during the heartbeat and accurately capture the subtle mechanical stimulation of the interface. The above results show that the conductive structural color hydrogel of the present invention can realize real-time monitoring of mechanical movement in vitro.

[0186] In summary, the conductive structural color hydrogel of the present invention has excellent stimulus visualization ability and excellent electrical signal sensing function, and has the function of digitally and visually monitoring weak external interfacial mechanical stimuli and spatio-temporal mechanical stimuli in real time. It can be used for real-time monitoring of human movement and physiological health status, opening up a new way for the development of intelligent sensing materials.

[0187] Example 8: Application of the conductive structural color hydrogel of the present invention in visual monitoring of the pathological location of myocardial infarction

[0188] According to the above test results, the inventors further investigated the application of the conductive structural color hydrogel of the present invention as a cardiac sensing patch in the monitoring of cardiac mechanical physiological signals and the visual identification of infarcted myocardium.

[0189] Before implanting the conductive structural color sensing patch of the present invention, its cytotoxicity and adhesion performance on the tissue surface were first investigated. The results are as Figure 13 、 Figure 14 。

[0190] The investigation results of cytotoxicity and adhesion performance on the tissue surface show that: (1) The traditional polypyrrole hydrogel (OGGP3) contains: polypyrrole grafted gelatin (GP), oxidized xanthan gum (OXG) Schiff base crosslinking. Compared with the cell survival rate of 80% of this traditional polypyrrole hydrogel, the cell survival rate of the conductive structural color hydrogel of the present invention exceeds 95%, and the cytotoxicity is significantly reduced. Therefore, the conductive structural color hydrogel of the present invention has good cell compatibility and biosafety and can be used as an implantable biomedical material ( Figure 13 ). (2) The conductive structural color hydrogel of the present invention has stable adhesion performance. Compared with traditional adhesive hydrogels, the conductive structural color hydrogel of the present invention has a closer fitting performance at the micro-nano scale, can adjust the interfacial adhesion behavior at any time with the dynamic changes of the substrate, and exhibits good shape retention and compliance ( Figure 14 A、 Figure 14 B、 Figure 14 C). (3) The conductive structural color hydrogel of the present invention has excellent adhesion performance, and the adhesion strength on pig skin can reach about 5.7 kPa. It has excellent universal adhesion and has a certain adhesion ability on the surfaces of various objects such as glass, plastic, pig skin, and duck heart ( Figure 14 D).

[0191] Based on the above test results of cytotoxicity and adhesion performance, the inventors adhered the conductive structural color hydrogel (1) of the present invention to the surface of the left ventricle of the heart to monitor the mechanical physiological signals of the heart in real time; (2) adhered it to the surface of the infarcted heart to observe the color signal output by the hydrogel in real time. The specific method is as follows: An animal myocardial infarction model was constructed by ligating the left anterior descending branch of the rat heart. Ischemic myocardial injury can induce cardiomyocyte apoptosis and myocardial tissue fibrosis, which is directly manifested as a decrease in the amplitude of heartbeat movement. Placing the hydrogel patch on the heart surface can monitor the cardiac function after infarction. The results are as Figure 15 shown.

[0192] The results showed that: (1) As the heart beats, the relative resistance of the conductive structural color hydrogel of the present invention continuously varies between 0 and 5.1%, presenting a multi-serrated continuous single-peak curve. The relative resistance change rate represents the deformation amplitude of the hydrogel during heartbeat movement, which can indirectly reflect the pulsation and pumping function of the heart and be further used for the diagnosis of myocardial infarction ( Figure 15 B, Figure 15 C). (2) As the heart relaxes, the overall color of the conductive structural color hydrogel of the present invention significantly changes from green to blue-violet; when the heart contracts, the color returns to its original state. At the same time, there are obvious abnormalities in the color of the hydrogel at the ligation position (infarction position) near the left ventricle. As the heart beats, the color of the hydrogel here almost maintains the initial yellowish-green ( Figure 15 D).

[0193] The above results indicate that the conductive structural color hydrogel of the present invention can achieve accurate diagnosis of myocardial infarction and rapid positioning of the infarction location ( Figure 15 A), and can be used for the monitoring of mechanical physiological signals and the visual and precise identification of pathological states during myocardial infarction.

[0194] Example 9: Investigation on the electrocoupling repair function of the conductive structural color hydrogel of the present invention on infarcted heart

[0195] The conductive hydrogel has an electrical conductivity matching that of cardiac tissue. It can reduce the resistance of the scar tissue after infarction, reconstruct the conductive pathway, thereby compensating for the integrity of electrical conduction, enhancing the synchronous contraction and relaxation function of the infarcted heart, and promoting the repair of myocardial infarction. Therefore, the inventors further investigated the repair potential of the conductive structural color hydrogel of the present invention as a cardiac patch for infarcted myocardium. The specific method and investigation results are as follows:

[0196] An SD rat myocardial infarction (MI) model was constructed by left anterior descending (LAD) coronary artery ligation surgery. Then, using the optoelectronic dual-signal sensing function of the conductive structural color hydrogel, the location of the infarcted myocardium was accurately positioned, and precise implantation treatment was carried out for the pathological location. After 14 days and 28 days of treatment, echocardiography was performed to evaluate the changes in cardiac function, and the evaluation indicators included ejection fraction (EF), fractional shortening (FS), end-diastolic volume (EDV), and end-systolic volume (ESV) and other indicators. The results are as Figure 16 shown.

[0197] The preliminary results showed that compared with the myocardial infarction group and the structural color hydrogel group, the EF (increased from 47.38 ± 3.4% to 81.55 ± 5.8%) and FS (increased from 21.40 ± 2.1% to 50.53 ± 1.4%) of the conductive structural color hydrogel group of the present invention were significantly improved, and the EDV (decreased from 0.96 ± 0.08 mL to 0.41 ± 0.03 mL) and ESV (decreased from 0.51 ± 0.03 mL to 0.06 ± 0.02 mL) were significantly decreased ( Figure 16 B).

[0198] Referring to the above method, the electrocoupling repair function of the existing conductive hydrogel patch (PPG hydrogel) on the infarcted heart was also investigated. The composition of the PPG hydrogel includes: polydopamine hybrid PEDOT nanoparticles (PPEDOT NPs), polygallic acid-gelatin methacrylamide (PGA-GelMA). The results showed that the EF of the PPG hydrogel test group increased from 47.38% to 70%. The conductive structural color hydrogel group of the present invention has obvious advantages compared with it.

[0199] The above results indicate that the conductive hydrogel of the present invention can improve the electrocoupling contractility by compensating for the electrical conduction in the fibrous tissue, thereby preventing left ventricular dilation and improving cardiac function.

[0200] Furthermore, the inventors performed morphological analysis of the heart using hematoxylin-eosin (H&E) and Masson's trichrome staining methods on the 14th day and 28th day. The results are as Figure 17 shown.

[0201] The test results showed that: (1) Myocardial infarction often causes severe ventricular remodeling, manifested as thinning of the wall thickness, collagen deposition, etc. ( Figure 17 A). It was significantly found by H&E staining analysis that compared with the myocardial infarction group, the left ventricular infarct wall thickness of all hydrogel groups was significantly increased. It can be seen from Masson staining analysis that compared with the myocardial infarction group and the structural color hydrogel group without MXene@PDA conductive material, the survival rate of myocardial fibers (red) in the conductive structural color hydrogel group of the present invention is higher and the collagen fibers (blue) are less (Figure 17 B). (2) Compared with the structural color hydrogel without MXene@PDA conductive material, the conductive structural color hydrogel patch of the present invention can effectively inhibit ventricular remodeling and significantly relieve the process of ventricular thinning (infarct wall thickness in the myocardial infarction group: 924.3 ± 157.4 μm; infarct wall thickness in the conductive structural color hydrogel group of the present invention: 2727.4 ± 265.4 μm) ( Figure 17 B), can effectively prevent the expansion of infarct area and fibrotic deposition, and reduce the infarct area from 55.66 ± 4.0% to 6.31 ± 2.0% ( Figure 17 C).

[0202] The above results indicate that the conductive structural color hydrogel patch of the present invention can effectively restore cardiac function while achieving visual and accurate diagnosis.

[0203] Furthermore, the inventors used CD86 / CD206 double staining analysis and found that the conductive structural color hydrogel of the present invention can promote the polarization of M1 macrophages in the inflammatory region to the M2 phenotype with repair function, and the polarization rate of M2 macrophages in the conductive structural color hydrogel group increased to 20.63% ( Figure 18 ). This result indicates that the conductive structural color hydrogel of the present invention can inhibit the inflammatory response of myocardial infarction.

[0204] The inventors used immunofluorescence staining to analyze the expression of vWF (for microvascularization) and CD31 (vascular endothelial marker), and found that compared with the myocardial infarction group, the vascular density in the conductive structural color hydrogel group increased by 3 times ( Figure 19 ). This result indicates that the conductive structural color hydrogel of the present invention has the function of blood vessel regeneration and is beneficial to restoring blood supply to the ischemic area.

[0205] In summary, as a cardiac patch, the conductive structural color hydrogel of the present invention can effectively inhibit ventricular remodeling and inflammatory response, promote blood vessel regeneration, reduce the formation of fibrotic scars, repair the morphology and function of the myocardium, thereby achieving the repair of the morphology and electrophysiological function of the infarcted heart.

[0206] In the description of this specification, the description referring to terms such as "one embodiment", "some embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0207] Although the embodiments of the present invention have been shown and described above, it can be understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those of ordinary skill in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of the present invention.

Claims

1. A conductive structural color hydrogel, characterized in that: include: A conductive nanomaterial having a catechol group; HPC cholesteric liquid crystal; Base material; Cross-linking agent; The conductive structural color hydrogel is formed by physical and / or chemical interactions among the conductive nanomaterial, the HPC cholesteric liquid crystal, the matrix material and the cross-linking agent; Based on the total mass of the conductive structural color hydrogel, the HPC mass fraction of the HPC cholesteric liquid crystal is 50% to 56%.

2. The conductive structural color hydrogel according to claim 1, characterized in that: Based on the total mass of the conductive structural color hydrogel, the HPC mass fraction of the HPC cholesteric liquid crystal is 50% to 52%.

3. The conductive structural color hydrogel according to claim 1, characterized in that: The HPC cholesteric liquid crystal is formed by self-assembly of HPC in water, and the mass ratio of the HPC to the water is 50:(35-40).

4. The conductive structural color hydrogel according to claim 1, characterized in that: The conductive nanomaterial is modified by dopamine or a pharmaceutically acceptable salt thereof or tannic acid or a pharmaceutically acceptable salt thereof.

5. The conductive structural color hydrogel according to claim 1, characterized in that: The conductive nanomaterial is MXene@PDA, and the MXene@PDA is a MXene nanosheet modified by dopamine or a pharmaceutically acceptable salt thereof.

6. The conductive structural color hydrogel according to claim 5, characterized in that: Based on the total mass of the conductive structural color hydrogel, the mass fraction of the HPC cholesteric liquid crystal is 50% to 52%, and the mass fraction of the MXene@PDA is 1% to 1.5%.

7. The conductive structural color hydrogel according to claim 1, characterized in that: The matrix material is sodium alginate and / or dopamine-grafted modified sodium alginate, and the mass ratio of the HPC of the HPC cholesteric liquid crystal to the matrix material is 50:(4-12).

8. The conductive structural color hydrogel according to claim 1, characterized in that: The cross-linking agent is a metal ion, and the metal ion is selected from Ca 2+ 、Zn 2+ Mg 2+ , Fe 3+ , Cu 2+ At least one of .

9. A method for preparing the conductive structural color hydrogel according to any one of claims 1 to 8, characterized in that: include: Mixing the conductive nanomaterial, the HPC cholesteric liquid crystal and the matrix material to form a mixture; The mixture is subjected to a cross-linking reaction with the cross-linking agent to form the conductive structural color hydrogel.

10. The method according to claim 9, characterized in that The temperature of the mixing treatment is room temperature; the temperature of the cross-linking reaction is 3°C to 7°C.

11. A conductive structural color hydrogel, characterized in that: The conductive structural color hydrogel is prepared according to the method according to any one of claims 9 or 10.

12. Use of the conductive structural color hydrogel according to any one of claims 1 to 8 or the conductive structural color hydrogel according to claim 11 in preparing products, characterized in that: The product has at least one of the following uses: Visualize and / or digitize feedback on the response of non-biological tissues to mechanical stimulation; Visualize and / or digitally monitor biological tissue movement; Compensate and / or repair electrical conduction in biological tissues.

13. The use according to claim 12, characterized in that The products include but are not limited to: medical devices, wearable sensors, biosensors; among which, The medical devices include but are not limited to: cardiac sensor patches, myocardial infarction monitoring and / or treatment patches, bionic skin; The wearable sensors include but are not limited to: inertial sensors, optical sensors, electrodes and electrochemical sensors, flexible sensors, and interactive sensors; The biosensor includes but is not limited to: a pressure sensor and a strain sensor.

14. The use according to claim 12, characterized in that The biological tissue movement includes but is not limited to: breathing movement, expansion and contraction of the thorax, expansion and retraction of the lungs, contraction / relaxation of the heart, contraction and relaxation of blood vessels, gastrointestinal peristalsis, esophageal peristalsis, contraction and relaxation of skeletal muscles, peristalsis of renal tubules, peristalsis of ureters, contraction and relaxation of bladders, peristalsis of fallopian tubes, contraction and relaxation of uterus, contraction and relaxation of vagina, blinking of eyes, rotation of eyeballs, swallowing movement of throat; And / or, the biological tissue includes but is not limited to: skeletal muscle tissue, smooth muscle tissue, myocardial tissue, connective tissue, and neural tissue.

15. The use according to claim 12, characterized in that The product is used for monitoring biological tissue necrosis and / or preventing and / or treating diseases caused by the biological tissue necrosis; The diseases include but are not limited to: myocardial infarction, myocardial sclerosis, cerebral infarction, encephalomalacia, gastroduodenal ulcer, typhoid fever, acute pancreatitis, tuberculosis, pulmonary infarction, tubular necrosis, renal infarction, ovarian cyst pedicle torsion, tubal pregnancy rupture, necrotizing fasciitis, and frostbite.

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