Multifunctional hydrogel coupling patch, preparation method and application thereof

Abstract

The application belongs to the technical field of hydrogel, and particularly relates to a multifunctional hydrogel coupling patch, a preparation method thereof and application thereof. The multifunctional hydrogel coupling patch is prepared from betaine, glycerol, gelatin, tannic acid and water in a mass ratio of 1-3.57:2.5-8.43:0.5-2:0.05-0.2:1.5-6. The betaine and the glycerol are mixed to form a eutectic solvent. The eutectic solvent and water are mixed, and then the gelatin and the tannic acid are added. After standing, the multifunctional hydrogel coupling patch is obtained. The multifunctional hydrogel coupling patch has excellent adhesion, antibacterial property, environmental stability, biocompatibility and recyclability. The preparation method of the multifunctional hydrogel coupling patch is simple, low in cost, recyclable and reusable, and can be applied to the field of ultrasonic imaging to reduce detection cost.

Description

Technical Field

[0001] This invention belongs to the field of hydrogel technology, specifically relating to a multifunctional hydrogel coupling patch, its preparation method, and its application. Background Technology

[0002] Ultrasound technology is widely used in medical imaging. Compared with X-rays and computed tomography (CT), ultrasound imaging has advantages such as portability, low cost, and high safety, and does not pose a risk of ionizing radiation. It can visualize physiological signals emitted by deep tissues and their internal structures, providing an important means of obtaining information on health status and disease, and has been widely used in soft tissue, organ, and prenatal examinations. In ultrasound examinations, the coupling agent plays a crucial role. To ensure high-quality imaging, it is essential in clinical applications to ensure that the coupling agent adheres well to the skin surface and the ultrasound probe. It eliminates air bubbles between the ultrasound probe and the skin, reduces sound energy attenuation, and thus ensures image clarity. However, currently commonly used liquid coupling agents have problems such as high fluidity and poor user experience. Furthermore, due to the geometric limitations of areas with high curvature, such as skin tumors, fingers, and elbows, the probe often cannot make full contact with the skin surface, easily trapping air between the probe and the skin, thus affecting image quality.

[0003] Hydrogels are three-dimensional cross-linked polymer networks with high water content, similar in structure to the extracellular matrix, and exhibit excellent biocompatibility. Due to their similar acoustic impedance to water, hydrogels have become an ideal medium for sound wave propagation. In ultrasound examinations, hydrogel coupling agents, compared to traditional liquid coupling agents, can reversibly adsorb and separate from the ultrasound probe without leaving residue. This characteristic not only improves the ease of operation for doctors but also enhances patient comfort, addressing the issues of high fluidity and poor user experience associated with liquid coupling agents. Furthermore, the adjustable elastic modulus of hydrogels provides unique adaptability, allowing them to conform to highly curved surfaces, preventing air bubble formation and effectively mitigating stress concentration. This makes hydrogels a promising candidate for applications in medical imaging, especially on complex surfaces and in localized areas requiring precise imaging. However, current hydrogel coupling agents have relatively limited functionality and are not reusable. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a multifunctional hydrogel coupling patch, its preparation method, and its application.

[0005] To facilitate understanding of this invention, the materials used in this invention and their abbreviations are listed below: Eutectic solvent, abbreviated as DES. Multifunctional coupling patch, abbreviated as GTD. Polyacrylamide, abbreviated as PAAm. Acrylamide monomer, abbreviated as AAM. N,N′-Methylenebisacrylamide, abbreviated as MBAA.

[0006] The first objective of this invention is to provide a multifunctional hydrogel coupling patch made of betaine, glycerin, gelatin, tannic acid and water in a mass ratio of 1~3.57:2.5~8.43:0.5~2:0.05~0.2:1.5~6.

[0007] In this process, betaine and glycerol are mixed to form a eutectic solvent.

[0008] The eutectic solvent and water are mixed, gelatin and tannin are added, and after standing, a multifunctional hydrogel coupling patch is obtained.

[0009] Preferably, the molar ratio of betaine to glycerol is 1:3.

[0010] Preferably, the mass ratio of gelatin, tannic acid and water is 2:0.2:6.

[0011] Preferably, the mass ratio of betaine, glycerol and water is 3.57:8.43:6.

[0012] The second objective of this invention is to provide a method for preparing a multifunctional hydrogel coupling patch, comprising the following steps: Betaine and glycerol were mixed in the specified mass ratio and subjected to a first water bath reaction until a homogeneous transparent solution was formed, yielding a eutectic solvent. The eutectic solvent was mixed with water, and then gelatin and tannic acid were added, followed by a second water bath reaction to form a homogeneous transparent solution. The transparent solution was poured into a mold, allowed to stand, and then demolded to obtain a multifunctional hydrogel coupling patch.

[0013] Preferably, the conditions of the first water bath are: temperature 55℃~75℃, rotation speed 100rpm~500rpm.

[0014] Preferably, the conditions for the second water bath are: temperature 70℃~90℃, rotation speed 100rpm~500rpm, and time 0.5h~3h.

[0015] Preferably, the mass ratio of the eutectic solution to water is 2:1.

[0016] Preferably, the mold is made of polytetrafluoroethylene (PTFE). PTFE does not easily adhere to the gel, facilitating demolding. The shape of the PTFE mold can be customized according to the size of the ultrasonic probe, producing a gel that meets the required shape and size.

[0017] A third objective of this invention is to provide an application of a multifunctional hydrogel coupling patch in ultrasound imaging.

[0018] Compared with the prior art, the present invention has the following beneficial effects: 1. A multifunctional hydrogel coupling patch, comprising betaine, glycerin, gelatin, tannic acid, and water in a mass ratio of 1~3.57:2.5~8.43:0.5~2:0.05~0.2:1.5~6. The gelatin, glycerin, betaine, and tannic acid in the multifunctional hydrogel coupling patch of this invention are derived from natural substances, and these components have good biocompatibility. Tannic acid, as a natural polyphenol compound, can exert an antibacterial effect by disrupting the integrity of bacterial cell membranes and inhibiting bacterial metabolic activity. Gelatin, as a natural protein, is rich in active groups such as amino, carboxyl, and hydroxyl groups. Tannic acid, as a polyphenol compound, contains multiple phenolic hydroxyl and carboxyl groups. These abundant functional groups can generate various non-covalent interactions with different material surfaces, including hydrogen bonding, π-π stacking, and electrostatic interactions. The synergistic effect of gelatin and tannic acid gives the patch excellent adhesion, enabling it to adhere to various substrate surfaces. Therefore, the multifunctional hydrogel coupling patch of the present invention has excellent biocompatibility, antibacterial properties and adhesion.

[0019] In this process, betaine and glycerol are mixed to form a eutectic solvent. Both betaine and glycerol are non-volatile hydrophilic substances that can interact with water molecules through hydrogen bonds, effectively anchoring water molecules within the polymer network and maintaining gel stability. The eutectic solvent is then mixed with water, followed by the addition of gelatin and tannin, and allowed to stand to obtain a multifunctional hydrogel coupling patch. This multifunctional hydrogel coupling patch forms a network structure through physical cross-linking, exhibiting dynamically reversible cross-linking properties. At high temperatures, the gel network dissociates, and the material becomes fluid. At low temperatures, the hydrogen bond interactions between polymer chains in the gel strengthen, the network is rebuilt, and the material returns to an elastomer state. This dynamically reversible property endows the multifunctional hydrogel coupling patch with excellent recyclability and reusability.

[0020] 2. Preparation method of the multifunctional hydrogel coupling patch of the present invention: Betaine and glycerol are mixed in the specified mass ratio and subjected to a first water bath until a uniform transparent solution is formed, obtaining a eutectic solvent. The eutectic solvent is mixed with water, and then gelatin and tannic acid are added. A second water bath is then conducted to form a uniform transparent solution. The transparent solution is poured into a mold, allowed to stand, and then demolded to obtain the multifunctional hydrogel coupling patch. The present invention uses betaine, glycerol, gelatin, tannic acid, and water as raw materials. These raw materials are common, readily available, inexpensive, and low in cost. Furthermore, the preparation method of the multifunctional hydrogel coupling patch of the present invention obtains the multifunctional hydrogel coupling patch material through two water baths, and then obtains a multifunctional hydrogel coupling patch of a specific shape and size through a mold. Therefore, the preparation method of the multifunctional hydrogel coupling patch of the present invention is simple in steps, time-saving, and has significant advantages for commercial mass production. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of the preparation process of the GTD of the present invention.

[0022] Figure 2 The images shown are FTIR images and XRD patterns of G, GD, and GTD according to the present invention. (a) is the FTIR image of G, GD, and GTD. (b) is the XRD pattern of G, GD, and GTD.

[0023] Figure 3 The tensile stress-strain curves, strength and toughness, storage modulus and loss modulus, and stress-strain graphs of G, GD, and GTD of the present invention are shown. (a) is the tensile stress-strain curve of G, GD, and GTD. (b) is the strength and toughness of G, GD, and GTD. (c) is the value of the storage modulus and loss modulus of G, GD, and GTD at different frequencies. (d) is the stress-strain curve of GTD after 10 loading-unloading cycles at a strain of 1.0.

[0024] Figure 4 This is a transmission diagram of the GTD of the present invention in the visible light wavelength range of 500nm~800nm.

[0025] Figure 5 This is a frequency dependence diagram of the energy storage modulus and loss modulus of the GTD of the present invention at different temperatures.

[0026] Figure 6 The diagram shows the different states and plasticity of the GTD of the present invention. Among them, (a) shows the different states exhibited by the GTD at 80°C and room temperature. (b) shows the shape plasticity of the GTD: (i) goldfish shape, (ii) flower and leaf shape.

[0027] Figure 7 The diagram shows the stress-strain curves of the GTD (Gross Tolerancing Device) of this invention. (a) shows the compressive stress-strain curves of the original GTD and the remolded GTD. (b) shows the tensile stress-strain curves of the original GTD and the remolded GTD. (c) shows the loading-unloading curves of the original GTD and the remolded GTD at a strain of 1.0.

[0028] Figure 8 The figures show a comparison of the morphology and weight changes of GTD and G after 15 days of storage at room temperature. (a) shows the morphology of GTD and G after 15 days at room temperature. (b) shows the weight changes of GTD and G after 15 days of storage at room temperature with a humidity of 50%–60%.

[0029] Figure 9This is a diagram illustrating the adhesion performance of the GTD of the present invention. (a) shows the adhesion performance of the GTD: it can adhere to various material surfaces, including aluminum, acrylic blocks, polytetrafluoroethylene, pigskin, wood, and glass. (b) shows the adhesion strength of the GTD to different substrates.

[0030] Figure 10 The diagram shows the skin contact test results of the GTD of the present invention. (a) shows that the GTD adheres to human skin. (b) shows that the GTD leaves no residue after being peeled off the skin.

[0031] Figure 11 The images show the culture of Staphylococcus aureus with G, GD, and GTD of the present invention. (a) represents G. (b) represents GD. (c) represents GTD.

[0032] Figure 12 This is a biocompatibility test diagram of the GTD of the present invention. Among them, (a) is a quantitative analysis of the survival rate of HUVEC cells in the control group and GTD. (b) is a fluorescence image of HUVEC cells in the control group and GTD.

[0033] Figure 13 The diagram shows the experimental setup and acoustic parameters of the GTD (Glass Detergent) according to the present invention. (a) is a schematic diagram of the ultrasonic performance measurement experimental setup. (b) shows the acoustic signal of pure water and the GTD. (c) shows the sound velocity of the GTD at different frequencies. (d) shows the attenuation coefficient of the GTD at different frequencies.

[0034] Figure 14 These are related diagrams for ultrasound imaging using the GTD of the present invention. (a) shows that the GTD can be designed in different shapes for different types of ultrasound probes. (b) is a schematic diagram of an ultrasound imaging experiment. (c) shows cardiac ultrasound images taken using the initial GTD and the GTD placed for 30 days as coupling patches, respectively. (d) shows cardiac ultrasound images taken using a liquid coupling agent. (e) shows cardiac ultrasound images taken using the original PAAm hydrogel and the PAAm hydrogel placed for 2 days as coupling patches, respectively. Detailed Implementation

[0035] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the following detailed description, in conjunction with preferred embodiments and accompanying drawings, provides a clear and complete account of the technical solutions of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0036] It should be noted that all technical terms used in this invention are for the purpose of describing specific embodiments only and are not intended to limit the scope of protection of this invention. Unless otherwise specified, all raw materials, reagents, instruments and equipment used in the following embodiments of this invention can be purchased from the market or prepared by existing methods.

[0037] Example 1 A method for preparing a multifunctional hydrogel coupling patch includes the following steps: Mix 3.57g betaine and 8.43g glycerol, then stir continuously in a constant temperature water bath at 65℃ and 500rpm until a homogeneous transparent solution is formed, yielding DES. Mix DES with 6g water, then add 2g gelatin and 0.2g tannic acid, and stir at 80℃ and 500rpm for 0.5h to form a homogeneous transparent solution. Pour the transparent solution into a polytetrafluoroethylene mold. Let it stand at room temperature for 3h, then demold to obtain GTD.

[0038] Example 2 A method for preparing a multifunctional hydrogel coupling patch includes the following steps: Mix 1g betaine and 2.5g glycerol, then stir continuously in a constant temperature water bath at 55℃ and 100rpm until a homogeneous transparent solution is formed, yielding DES. Mix DES with 1.5g water, then add 0.5g gelatin and 0.05g tannic acid, and stir at 70℃ and 100rpm for 3 hours to form a homogeneous transparent solution. Pour the transparent solution into a polytetrafluoroethylene mold. Let it stand at room temperature for 0.5 hours, then demold to obtain GTD.

[0039] Example 3 A method for preparing a multifunctional hydrogel coupling patch includes the following steps: Mix 1.785g betaine and 4.215g glycerol, then stir continuously in a constant temperature water bath at 75℃ and 300rpm until a homogeneous transparent solution is formed, yielding DES. Mix DES with 3g water, then add 1g gelatin and 0.1g tannic acid, and stir at 90℃ and 400rpm for 2 hours until a homogeneous transparent solution is formed. Pour the transparent solution into a polytetrafluoroethylene mold. Let it stand at room temperature for 2 hours, then demold to obtain GTD.

[0040] Comparative Example 1 A method for preparing a multifunctional hydrogel coupling patch includes the following steps: Mix 2g of gelatin and 0.2g of tannin in 18g of water and stir at 80℃ for 1 hour until a homogeneous, transparent solution is formed. Pour the solution into a polytetrafluoroethylene mold. Let it stand at room temperature for 3 hours, then demold to obtain a hydrogel coupling patch, denoted as G.

[0041] Comparative Example 2 A method for preparing a multifunctional hydrogel coupling patch includes the following steps: Mix 12g of DES and 6g of water, then add 2g of gelatin. Stir at 80℃ for 1 hour until a uniform, transparent solution is formed. Pour the solution into a polytetrafluoroethylene mold. Let it stand at room temperature for 3 hours, then demold to obtain a hydrogel coupling patch, denoted as GD.

[0042] Comparative Example 3 A method for preparing a multifunctional hydrogel coupling patch includes the following steps: 8 g of AAM, 32 mg of 2′-hydroxy-4′-(2-hydroxyethoxy)-2-methacryloylphenyl ketone, 400 μL of N,N′-methylenebisacrylamide (MBAA solution concentration 10 mg / mL) were added to 32 g of water. The solution was then stirred at room temperature for 1 h to obtain a precursor solution. The resulting precursor solution was then degassed and poured into a polytetrafluoroethylene mold. Next, the precursor gel was photopolymerized by irradiation with 8W, 365 nm ultraviolet light for 1 h to obtain a hydrogel coupling patch, denoted as PAAm.

[0043] To illustrate the beneficial effects of this invention, the following experiments were conducted using GTD prepared in Example 1, G prepared in Comparative Example 1, GD prepared in Comparative Example 2, and PAAm prepared in Comparative Example 3. The GTD preparation of this invention employs an efficient and simple one-pot synthesis strategy, and the preparation process is as follows: Figure 1 As shown.

[0044] I. Experimental Materials The main materials used in this invention are gelatin, betaine, glycerin, tannic acid, and a CCK-8 detection kit.

[0045] The gelatin, with a purity of AR, was purchased from Sigma-Aldrich (Shanghai) Trading Co., Ltd. The betaine, with a purity of AR, was purchased from Shanghai Yuanye Biotechnology Co., Ltd. The glycerol, with a purity of AR, was purchased from Aladdin Reagents (Shanghai) Co., Ltd. The tannic acid, with a purity of AR, was purchased from Sigma-Aldrich (Shanghai) Trading Co., Ltd. The CCK-8 test kit was purchased from Shanghai Weihuan Biotechnology Co., Ltd.

[0046] II. Experimental Methods 1. Analytical and testing methods for hydrogels 1.1 Fourier Transform Infrared Spectroscopy Analysis The GTD prepared in Example 1, the GD prepared in Comparative Example 1, and the GD prepared in Comparative Example 2 were tested using the infrared attenuated total internal reflection accessory of a Fourier transform infrared spectrometer. The wavelength range of the tests was 4000 cm⁻¹. -1 ~500cm-1 The number of scans is set to 32.

[0047] 1.2 X-ray diffraction analysis X-ray diffraction (XRD) utilizes the diffraction effect of X-rays interacting with matter to perform in-depth analysis of the crystal structure of materials. XRD analyses were performed on GTD prepared in Example 1, G prepared in Comparative Example 1, and GD prepared in Comparative Example 2. The XRD instrument used a copper target as the X-ray source, emitting Kα lines, and was equipped with a nickel monochromatic light filter. The X-ray wavelength was 0.15406 nm, and the current and voltage were set to 40 mA and 40 kV, respectively. During the test, the scanning time interval was 1 second, and the scanning angle range was 5°–50°.

[0048] 1.3 Environmental stability test The GTD prepared in Example 1, the G prepared in Comparative Example 1, and the GD prepared in Comparative Example 2 were placed at room temperature, and their weights were measured periodically to record the changes in sample mass. All tests were performed with three parallel samples to ensure the reliability and repeatability of the data.

[0049] 1.4 Mechanical Performance Testing The mechanical properties of GTD prepared in Example 1, G prepared in Comparative Example 1, and GD prepared in Comparative Example 2 were tested. Tensile and compressive tests were performed on an Instron 5948 micro tensile tester at a speed of 50 mm / min. To improve measurement accuracy, the average of three test results for each sample was taken. Rheological tests were performed using an MCR302 rheometer equipped with a 25 mm rotor. Frequency scanning was conducted at 25°C with a constant strain of 0.1%, ranging from 0.1 rad / s to 100 rad / s.

[0050] 1.5 Adhesion performance test The adhesion properties of GTD prepared in Example 1, G prepared in Comparative Example 1, and GD prepared in Comparative Example 2 were characterized using an Instron 5948 micro tensile tester. The gels were adhered to different substrates with an adhesion area of ​​10 mm × 10 mm, and were pressed with a weight of 200 g for 1 h at room temperature. Shear adhesion properties were measured. The tensile speed was 5 mm / min, and the substrate size was 20 mm × 20 mm. Adhesion strength, abbreviated as AS, was calculated according to formula (1).

[0051] Formula (1): AS=F max / S; Among them, F max The maximum shear force experienced during the stretching process is given by , and S is the adhesive area between the gel and the substrate. All tests were performed with three parallel samples to ensure data reliability and repeatability.

[0052] 1.6 Cell compatibility test MC3T3-E1 cells and HUVEC cells were selected as model cells for testing the biocompatibility of the test materials. Cells were seeded in MEM-α medium containing 10% fetal bovine serum and cultured at 37°C with 5% CO2 for 24 h. The cytotoxicity of the gel to MC3T3-E1 or HUVEC cells was assessed using the CCK-8 assay. 50 mg of the GTD prepared in Example 1 was immersed in 1 mL of FBS-free medium and incubated at 37°C for 24 h to obtain the hydrogel extract. 10% (v / v) FBS was added to the hydrogel extract before cell culture. The medium containing 10% (v / v) FBS was used as a control group. MC3T3-E1 or HUVEC cells were seeded in 96-well plates and cultured for 24 h, then co-cultured with different extracts. After further incubation for 24 h and 72 h, the cytotoxicity of the cells was measured using the CCK-8 assay according to the kit instructions. The absorbance of the solution was recorded at 450 nm using a microplate reader. To further assess cell proliferation, live cell staining was used for observation. Cells were stained with Calcein-AM at predetermined time points. After staining, the cells were incubated at 37°C for 20 hours, followed by washing twice with PBS, and images were captured and analyzed using a fluorescence microscope IX71.

[0053] 1.7 Antibacterial test Cylindrical samples of GTD (Prepared in Example 1), G (Prepared in Comparative Example 1), and GD (Prepared in Comparative Example 2), each with a diameter of 10 mm and a thickness of 2 mm, were irradiated under ultraviolet light for 12 hours to ensure that the sample surface was free of microbial contamination. After sterilization, they were placed in sterile petri dishes for later use. The preserved Staphylococcus aureus was inoculated into liquid culture medium and cultured with shaking at 37°C and 180 rpm. The bacteria were diluted to an appropriate concentration using PBS buffer (pH=7.4). Then, 100 μL of the diluted bacterial suspension was evenly spread on the surface of the solid culture medium using a sterile glass rod. Next, the UV-sterilized hydrogel was carefully placed in the center of the petri dish using sterile forceps, avoiding slippage or tilting. The petri dish was incubated in a 27°C incubator for 24 hours, and the bacterial growth was then observed and photographed.

[0054] 1.8 Morphology testing of hydrogels The microstructure and surface morphology of the GTD prepared in Example 1, the G prepared in Comparative Example 1, and the GD prepared in Comparative Example 2 were investigated using scanning electron microscopy (ΣIGMA-HD). First, the samples were rapidly frozen in liquid nitrogen, followed by freeze-drying to remove moisture, effectively preserving the original microstructural characteristics of the gel. To improve the conductivity of the samples and ensure the quality of microscopic observation, a uniformly thick gold film was deposited on the sample surface using magnetron sputtering. Finally, the microstructure of the treated gel samples was characterized using SEM at an accelerating voltage of 8 kV, obtaining the final surface morphology characteristics. Finally, the pore size of the samples was recorded and analyzed using ImageJ software.

[0055] 1.9 Acoustic parameters of hydrogels A cylindrical GTD sample with a radius of 40 mm prepared in Example 1 was placed between two ultrasonic transducers, ensuring that the sample surface was perpendicular to the acoustic excitation direction of the ultrasonic transducers. The system generates pulse signals of different frequencies using an underwater-mounted ultrasonic transducer (HPCTN) and employs an AFG 31000 SERIES signal generator. A Tektronix excites the transducer. After the ultrasonic waves propagate through the water medium to the sample, the received signal is converted from analog to digital using a 100 MHz digital oscilloscope (MDO32) and a Tektronix, and then post-processed using a MATLAB script. Based on the reflection / transmission law and sound pressure attenuation law of ultrasonic waves at the two-phase interface, the sound velocity and sound attenuation coefficient of the hydrogel are derived, as shown in formulas (2) and (3). Formula (2): ; Formula (3): ; Among them, c L denoted as λ, where λ is the velocity of sound in the hydrogel. d represents the thickness of the cylindrical hydrogel sample. Δt is the time difference between the received pulse waveforms with and without the hydrogel sample. w The speed of ultrasound in water is 1483 m / s. α is the sound attenuation coefficient. w α is the amplitude of the acoustic signal measured by the transducer when the hydrogel sample is placed in the transducer. A is the amplitude of the acoustic signal measured by the transducer when the hydrogel sample is not placed in the transducer. w Z represents the acoustic attenuation coefficient of water at a specific temperature and frequency. Z is the acoustic impedance of the hydrogel. w The acoustic impedance of water.

[0056] To ensure the reliability of the experimental results, each sample was prepared in triplicate for parallel testing, and the average value was taken as the result.

[0057] III. Experimental Results 1. Structural characterization of GTD To investigate the internal structure of GTD, Fourier transform infrared spectroscopy was used to characterize it. To further explore the roles of DES and tannic acid in the system, gelatin and a gelatin-eutectic solvent were prepared as control samples for comparative studies. The FTIR images and XRD patterns of G, GD, and GTD of this invention are shown below. Figure 2 As shown. The results show that all gels were at 1536 cm⁻¹. -1 and 1627cm -1 Absorption peaks were observed at all locations, corresponding to the bending vibrations of NH bonds and the stretching vibrations of C=O bonds in gelatin, respectively. Furthermore, all gels showed absorption peaks at 3000 cm⁻¹. -1 ~3600cm -1 Both exhibit broad absorption peaks within the range, attributed to the stretching vibrations of the -NH and -OH groups. Notably, compared to G, the broad absorption peaks of GD and GTD are narrower, indicating that the introduction of DES enhances the hydrogen bonding interactions between polymer chains. GD and GTD show peaks at 1390 cm⁻¹. -1 An absorption peak appears at 1037 cm⁻¹, corresponding to the NH vibration of the quaternary ammonium group in betaine. Meanwhile, GD and GTD show absorption peaks at 1037 cm⁻¹. -1 2940cm -1 and 2880cm -1 Absorption peaks were observed at [location missing], corresponding to the stretching vibrations of CO and CH bonds in glycerol, respectively. These results indicate that the addition of DES not only altered the hydrogen bond network structure of the gel but also introduced new functional groups, thus providing a molecular-level explanation for the multifunctional properties of GTD. X-ray diffraction tests were performed to further elucidate the structural differences between G, GD, and GTD. Figure 2 As shown in (b), G exhibits a major broad diffraction peak at 2θ = 28°, which is related to the randomly coiled structure in gelatin. With the introduction of DES, this diffraction peak shifts to a lower angle of 2θ = 21°, indicating an increase in its short-range order. This phenomenon may be attributed to the stronger hydrogen bonding interactions formed between the components in DES, such as betaine and glycerol, and the gelatin molecular chains, thereby altering the local arrangement of the gel. These structural changes provide an important theoretical basis for optimizing the mechanical and functional properties of GTD.

[0058] 2. Mechanical properties of GTD The tensile stress-strain curves, strength and toughness, storage modulus and loss modulus, and stress-strain curves of G, GD and GTD of the present invention are as follows: Figure 3 As shown in the figure. The results show that GTD exhibits significantly stronger tensile properties, with a tensile strength of 52.3 kPa and a toughness of 49.5 kJ / m. 3 The tensile strength (33.6 kPa) and toughness (21.1 kJ / m) are significantly higher than those of GD. 3The tensile strength of G is 1.6 kPa, and the toughness is 0.3 kJ / m. 3 .

[0059] Meanwhile, the rheological characterization results are as follows Figure 3 As shown in (c), GTD has a higher storage modulus than GD and G, which indirectly proves that GTD has superior mechanical properties. Gelatin itself is brittle and easily broken by external forces, while the introduction of DES and TA significantly improves the mechanical properties of the gel. Furthermore, tensile cycle tests were performed on GTD to evaluate its mechanical property changes under multiple deformations. The results are as follows... Figure 3 As shown in (d) of the figure. In ten cycles of tensile testing, GTD exhibited excellent durability. Notably, after the second load-unload cycle, the hysteresis loops almost completely overlapped, and the mechanical strength at strain 1 remained almost unchanged, indicating good fatigue resistance. The superior mechanical properties of GTD can be attributed to the synergistic effect of multiple interactions, including: (i) hydrogen bonding between glycerol and gelatin, (ii) electrostatic interaction between betaine and gelatin, and (iii) hydrogen bonding between tannic acid and gelatin. These interactions collectively construct a higher-strength network structure for GTD, laying a solid foundation for its biomedical applications.

[0060] 3. The versatility of GTD 3.1 High Transparency of GTD The transmission results of the GTD of the present invention in the visible light wavelength range of 500nm~800nm ​​are as follows: Figure 4 As shown in the figure. The results show that the GTD of the present invention exhibits excellent transparency, as shown in the figure. Figure 4 As shown, its average optical transmittance reaches over 80% in the wavelength range of 500nm to 800nm. This makes GTD difficult to detect in photographs, further demonstrating its high transparency. Based on this characteristic, GTD shows broad application prospects in fields such as optical devices and biomedicine, where material transparency is crucial.

[0061] 3.2. The shape flexibility and recyclability of GTD The frequency dependence results of the storage modulus and loss modulus of the GTD of the present invention at different temperatures are as follows: Figure 5 As shown in the figure. The results show that GTD is formed through physical cross-linking, and its network structure has dynamically reversible cross-linking characteristics, thus endowing the material with excellent shape plasticity and recyclability. Rheological characterization results show that at a high temperature of 80°C, the loss modulus of GTD is significantly higher than its storage modulus, indicating that the material behaves in a liquid-like state at this temperature. Conversely, at room temperature, the storage modulus of GTD is higher than its loss modulus, indicating that the material exhibits a typical solid-like state at this temperature. The different states and plasticity of the GTD of this invention are as follows. Figure 6 As shown in the figure. The results show that GTD is in a sol state at 80℃, but reversibly returns to a gel state after cooling, demonstrating its excellent thermal response characteristics. Furthermore, the used GTD samples exhibit excellent recyclability; its fragments can be reprocessed using a heat-dissolve-cool-set method and shaped into various complex forms, such as goldfish, flowers, and grass, etc. Figure 6 As shown in (b) of the diagram.

[0062] To further investigate the effect of heat reshaping on the mechanical properties of the GTD, systematic compression and tensile tests were conducted. The stress-strain curve of the GTD of this invention is shown below. Figure 7 As shown in the figure, the stress-strain curves of the reshaped GTD in compression and tensile tests almost completely overlap with those of the original GTD. This phenomenon indicates that the non-covalent interactions within the GTD matrix are completely reconstructed during the heating-cooling process, thus restoring the material's original mechanical properties. Furthermore, the energy dissipation behavior of the GTD was analyzed in depth through load-unload experiments. A significant hysteresis loop was observed in the first load-unload cycle, indicating that the GTD can effectively dissipate energy. In the subsequent second cycle, the hysteresis decreased, indicating that the network structure of the GTD changed, leading to a decline in its mechanical properties. Interestingly, after the heating-cooling process, the network structure of the GTD was restored, and the hysteresis loop area returned to its initial state. This finding suggests that the recovery performance of the GTD is mainly attributed to its temperature-responsive sol-gel transition characteristics. This unique dynamic reversibility not only significantly broadens the application range of the GTD but also meets the personalized needs of different application scenarios, providing broad prospects for its innovative applications in smart materials, flexible electronics, biomedicine, and other fields.

[0063] 3.3. GTD's water retention GTD material not only exhibits excellent mechanical properties and dynamic reversibility, but its water retention performance is also remarkable. The morphology and weight changes of GTD and G after 15 days at room temperature are shown in the figure. Figure 8As shown in the figure, the results indicate that betaine and glycerol in DES, as non-volatile hydrophilic substances, can form hydrogen bonds with water molecules, effectively anchoring water molecules within the polymer network and endowing GTD with excellent environmental stability. Ordinary hydrogel G exhibits significant dehydration shrinkage within 3 days, while GTD retains its original shape for 15 days. Further mass change analysis shows that ordinary hydrogel G experiences a sharp 90% mass decrease after 3 days of exposure at room temperature, while GTD retains at least 95% of its original mass after 15 days. These results demonstrate that GTD possesses significant anti-drying ability, fully showcasing its excellent environmental stability. This superior water retention not only extends the material's service life but also provides a reliable guarantee for its long-term application in flexible electronics, biomedicine, and other fields.

[0064] 3.4. Adhesion of GTD The GTD material exhibits excellent adhesion properties, primarily due to the synergistic effect of gelatin and tannic acid in its components. Gelatin, a natural protein, is rich in active groups such as amino, carboxyl, and hydroxyl groups. Tannic acid, a polyphenol compound, contains multiple phenolic hydroxyl groups. These abundant functional groups can generate various non-covalent interactions with different material surfaces, including hydrogen bonding, π-π stacking, and electrostatic interactions, thereby enabling GTD to adhere to a variety of substrate surfaces. The adhesion results of the GTD of this invention on different substrate materials are shown below. Figure 9 As shown in the figure. The results show that the adhesion strength of GTD to aluminum, acrylic block, polytetrafluoroethylene, pigskin, wood and glass reached 4.5 kPa, 4.7 kPa, 9.9 kPa, 10.9 kPa, 16.3 kPa and 17.2 kPa, respectively.

[0065] The results of the GTD skin contact test of the present invention are as follows: Figure 10 As shown in the figure. The results show that the GTD material exhibits excellent skin adhesion properties, able to closely adhere to the surface of human skin, forming a stable conformal interface, such as... Figure 10 As shown in (a) above. This property allows it to effectively reduce air gaps when used as a coupling agent in medical ultrasound imaging, thereby reducing acoustic impedance mismatch, reducing energy loss of sound waves at the probe-skin interface, and significantly improving image quality. Furthermore, its adhesiveness allows GTD to adapt to body curves, such as joints and the neck, ensuring good acoustic contact and imaging in these difficult-to-access areas. Adhesion also allows the patch to be firmly fixed to the detection site without additional fixing devices or manual pressing, simplifying the operation process and improving ease of use. In addition, GTD leaves no residue after peeling off the skin surface, and no skin irritation or allergic reactions were observed after multiple uses. Figure 10As shown in (b) above. This residue-free and non-irritating characteristic not only ensures patient comfort but also reduces the risk of cross-infection, providing a reliable guarantee for the safe application of GTD in clinical ultrasound diagnosis.

[0066] 3.5. Antibacterial properties of GTD Staphylococcus aureus is a common pathogenic bacterium, therefore it was chosen as a model strain to evaluate the antibacterial properties of GTD. The results of culturing G, GD, and GTD with Staphylococcus aureus in this invention are as follows: Figure 11 As shown in the figure, the results indicated that GTD formed a clearly visible inhibition zone around Staphylococcus aureus in agar plates, demonstrating significant antibacterial activity against the bacteria. In contrast, no obvious inhibition zones were observed around G and GD materials, suggesting that their antibacterial properties were almost nonexistent. The antibacterial mechanism of GTD is mainly attributed to tannins in its components. Tannins are natural polyphenolic compounds that exert their antibacterial effect by disrupting the integrity of bacterial cell membranes and inhibiting bacterial metabolic activity. This antibacterial property allows GTD to effectively reduce the risk of infection when used as an ultrasound coupling agent.

[0067] 3.6 Biocompatibility of GTD Since GTD is composed entirely of natural substances, including gelatin, glycerin, betaine, and tannic acid, all of which have been widely proven to have good biocompatibility, it is reasonable to infer that GTD materials also possess excellent biocompatibility. The biocompatibility test results of the GTD of this invention are shown in the figure below. Figure 12 As shown in the figure. The results showed that in a culture environment containing GTD extract, HUVEC cells maintained vigorous proliferative activity after 3 days of culture, with cell viability consistently remaining above 90%. Figure 12 As shown in (a), the excellent biocompatibility of GTD is fully demonstrated. This experimental result is highly consistent with the quantitative analysis results of in vivo staining assays, further confirming that the effect of GTD material on normal cell proliferation and metabolism is negligible. Figure 12 As shown in (b) of the paper. These experimental data provide important biological safety evidence for the application of GTD as a biomedical imaging coupling agent, indicating its broad clinical application prospects.

[0068] 4. Acoustic performance of GTD To systematically evaluate the acoustic performance of the GTD (Glass Deposition Device), a detailed characterization was performed using an underwater acoustic wave transmission experiment. A schematic diagram of the experimental setup and acoustic parameter diagrams for the GTD of this invention are shown below. Figure 13 As shown. Figure 13Figure (b) shows typical waveform signals for water and GTD. It is noteworthy that the GTD signal arrives earlier than the water reference signal because the average propagation speed of ultrasound in the GTD gel is 1875 m / s, higher than the speed of sound in water (1480 m / s). Figure 13 (c) indicates that there is no time delay when ultrasound propagates in GTD, ensuring real-time imaging. More importantly, GTD exhibits extremely low acoustic attenuation characteristics over a wide frequency range of 1MHz to 12MHz, with an attenuation coefficient consistently below 0.8dB / cm. Figure 13 As shown in (d) in the figure. This low attenuation characteristic ensures minimal energy loss of the ultrasound signal during propagation, thereby enabling clearer imaging results.

[0069] 5. Applications of GTD in Biomedical Imaging Combining its excellent water retention, adhesion, and acoustic transparency, GTD demonstrates great potential as a medical ultrasound coupling agent. Therefore, we further explored the practical effects of GTD in biomedical imaging. Compared to traditional liquid coupling agents, GTD can reversibly adhere to and easily peel off ultrasound probes without leaving any residue. This innovation provides doctors with significant operational convenience and improves patient comfort. In terms of manufacturing processes, GTD can be flexibly customized into coupling patches with ideal sizes and shapes to meet the needs of different ultrasound probes, demonstrating excellent customizability and clinical applicability.

[0070] Compared to ordinary hydrogel coupling patches, GTD, with its unique molecular structure design, exhibits superior water retention, ensuring long-term stability. Clinical comparative trials have demonstrated that, in the initial application phase, GTD, commercial liquid coupling agents, and PAAm hydrogel coupling patches all effectively acquired clear ultrasound images of the left ventricle in volunteers' hearts. The ultrasound imaging correlation diagram of the GTD of this invention is shown below. Figure 14 As shown in the figure. The results show that even after 30 days of placement, the GTD still maintains excellent imaging performance, successfully acquiring clear left ventricular ultrasound images, such as... Figure 14 As shown in (c) above. In contrast, while liquid coupling agents offer good imaging results, they suffer from inconvenience in use, difficulty in collection, and reusability. The PAAm hydrogel coupling patch, however, exhibited significant dehydration and shrinkage after two days, resulting in a substantial increase in material rigidity. This structural change disrupted the acoustic impedance matching at the material-skin interface, causing a significant increase in ultrasound signal attenuation and ultimately leading to a complete loss of ultrasound imaging capability, as shown in [example missing]. Figure 14As shown in (e) above. The superior properties of GTD not only solve many pain points of traditional coupling agents in clinical use, but also provide a more reliable and durable solution for ultrasound diagnosis. Its long-term stable imaging performance and excellent ease of operation make it a promising candidate for applications in emergency medicine, telemedicine, and long-term monitoring.

[0071] In summary, all components of the GTD of this invention are derived from natural substances, including biodegradable gelatin, plant-derived tannins, and DES composed of glycerol and betaine. Its preparation process employs a highly efficient and simple one-pot synthesis strategy, such as... Figure 1 As shown. The specific preparation process is as follows: First, gelatin and tannic acid are added to a mixed solution of deionized water and eutectic solvent, and stirred continuously in a constant temperature water bath at 80°C until a uniform precursor sol is formed. Then, the precursor sol is poured into a polytetrafluoroethylene mold and allowed to stand and solidify at room temperature for 3 hours to obtain GTD with multifunctional properties. This preparation method has the following significant advantages: (1) The operation process is simple and easy to carry out, and no complicated equipment is required. (2) The entire process adopts green and environmentally friendly technology, avoiding the use of toxic and harmful chemical reagents. (3) The raw materials are widely available and renewable, fully reflecting the concept of sustainable design. (4) The reaction conditions are mild and the energy consumption is low, making it suitable for large-scale production. This preparation strategy based on natural substances provides a new idea for the development of environmentally friendly functional materials.

[0072] It should be noted that when numerical ranges are involved in this invention, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. Since the steps and methods used are the same as in the embodiments, preferred embodiments are described in this invention to avoid redundancy. Although preferred embodiments of this invention have been described, those skilled in the art, once they understand the inventive concept of this invention, can make other changes and modifications to these embodiments, and all such changes and modifications fall within the scope of this invention.

[0073] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. If such modifications and variations fall within the scope of equivalents of this invention, then this invention is also intended to include such modifications and variations.

Claims

1. A multifunctional hydrogel coupling patch, characterized in that, It is made from the following raw materials in parts by weight: betaine, glycerin, gelatin, tannic acid and water in a mass ratio of 1~3.57: 2.5~8.43: 0.5~2: 0.05~0.2: 1.5~6; In this mixture, betaine and glycerol form a eutectic solvent; The eutectic solvent and water are mixed, gelatin and tannic acid are added, and after standing, a multifunctional hydrogel coupling patch is obtained.

2. The multifunctional hydrogel coupling patch according to claim 1, characterized in that, The molar ratio of betaine to glycerol is 1:

3.

3. The method for preparing a multifunctional hydrogel coupling patch according to claim 1, characterized in that, Includes the following steps: The betaine and glycerol in the specified mass ratio are mixed and subjected to a first water bath reaction until a uniform transparent solution is formed, thus obtaining a eutectic solvent. The eutectic solvent is mixed with water, and then gelatin and tannic acid are added, and a second water bath reaction is carried out to form a uniform transparent solution. The transparent solution is poured into a mold, allowed to stand, and then demolded to obtain a multifunctional hydrogel coupling patch.

4. The method for preparing a multifunctional hydrogel coupling patch according to claim 3, characterized in that, The conditions for the first water bath are: temperature 55℃~75℃, rotation speed 100rpm~500rpm.

5. The method for preparing a multifunctional hydrogel coupling patch according to claim 3, characterized in that, The conditions for the second water bath are: temperature 70℃~90℃, rotation speed 100rpm~500rpm, and time 0.5h~3h.

6. The method for preparing a multifunctional hydrogel coupling patch according to claim 3, characterized in that, The mass ratio of the eutectic solution to water is 2:

1.

7. The method for preparing a multifunctional hydrogel coupling patch according to claim 3, characterized in that, The mold is made of polytetrafluoroethylene.

8. The application of the multifunctional hydrogel coupling patch according to claim 1 in ultrasound imaging.

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