Hydrogel as well as preparation method and application thereof

Abstract

The invention discloses hydrogel as well as a preparation method and application thereof, and the preparation method of the hydrogel comprises the following steps: dissolving polyvinyl alcohol and gelatin in water to form a gel precursor solution; mixing a developing filler with the gel precursor solution to form a composite precursor solution; wherein the mass content of the developing filler in the composite precursor solution is 0.2%-0.5%; and carrying out crosslinking treatment on the composite precursor solution by adopting a freeze thawing method to obtain the hydrogel. According to the preparation method of the hydrogel, the addition amount of the developing filler is controlled within the range of 0.2%-0.5%, so that the developing effect of the hydrogel can be highly matched with the actual surgical developing effect of human tissues, and more real and accurate visual feedback can be provided, so that the authenticity of surgical simulation can be effectively improved; and a more reliable training model can be provided for medical education and operation training.

Description

Technical Field

[0001] The present invention belongs to the technical field of surgical training, and particularly relates to a hydrogel, a preparation method thereof, and an application thereof. Background Art

[0002] Interventional ultrasound is an important branch of modern ultrasonic medicine. It completes various puncture operations under real-time ultrasonic monitoring or guidance, such as interventional diagnosis such as biopsy and contrast imaging, and interventional treatment such as aspiration, catheter placement, drug injection, and ablation. Compared with traditional surgical operations, interventional ultrasound has the advantages of high safety, good accuracy, simple and rapid operation, small trauma, quick recovery, strong repeatability, and no radiation. Usually, only local anesthesia is required, which greatly reduces the anesthesia risk. Bedside operations can also be carried out when necessary, and the effect equivalent to that of surgical operations can be achieved. With the rapid development of interventional ultrasound technology, human organ models that are similar to the human body and can achieve good imaging effects are crucial for the training and learning of medical workers and medical students.

[0003] However, currently existing training models are mostly made of materials such as silica gel and resin. Their surface friction is relatively large, not smooth enough, and they are quite different from the characteristics of actual human organs such as the heart. More critically, under ultrasonic equipment, the imaging effects of these traditional models are poor, it is difficult to clearly present tissue structures, and they cannot provide real and accurate visual feedback for surgical simulation under ultrasonic guidance by medical staff. Therefore, they cannot meet the requirements for imaging effects in surgical simulation, seriously affecting the authenticity of surgical simulation and restricting the quality and effect of medical education and surgical training. Summary of the Invention

[0004] The first object of the present invention is to provide a new technical solution for a hydrogel preparation method, which can at least solve the technical problem of the unrealistic imaging effect of existing human organ models.

[0005] The second object of the present invention is to provide a new technical solution for a hydrogel.

[0006] The third object of the present invention is to provide an application of a hydrogel in a cardiac imaging model.

[0007] According to the first aspect of the present invention, there is provided a hydrogel preparation method, comprising:

[0008] Dissolving polyvinyl alcohol and gelatin in water to form a gel precursor solution;

[0009] Mixing a developing filler with the gel precursor solution to form a composite precursor solution;

[0010] Wherein, the mass content of the developing filler in the composite precursor solution is 0.2% - 0.5%;

[0011] The composite precursor solution is crosslinked by the freeze-thaw method to obtain a hydrogel.

[0012] Optionally, the developing filler is talcum powder, and the mass content of the developing filler is configured to be 0.3%.

[0013] Optionally, the method of dissolving polyvinyl alcohol and gelatin in water to form a gel precursor solution includes:

[0014] Dissolve polyvinyl alcohol in water to form a polyvinyl alcohol solution;

[0015] Dissolve gelatin in the polyvinyl alcohol solution to form a gel precursor solution.

[0016] Optionally, the method of dissolving polyvinyl alcohol in water to form a polyvinyl alcohol solution includes:

[0017] Disperse polyvinyl alcohol into water to swell the polyvinyl alcohol;

[0018] Heat the swollen polyvinyl alcohol and water to 60°C - 90°C and continuously stir to form a polyvinyl alcohol solution.

[0019] Optionally, after controlling the temperature of the polyvinyl alcohol solution to 40°C - 60°C, add gelatin to the polyvinyl alcohol solution and stir until dissolved to form a gel precursor solution.

[0020] Optionally, the weight ratio of polyvinyl alcohol to gelatin is (10 - 3):1.

[0021] Optionally, the weight content of polyvinyl alcohol is 10%, the weight content of gelatin is 3%, the weight content of the developing filler is 0.3%, and the balance is water.

[0022] Optionally, the method of crosslinking the composite precursor solution by the freeze-thaw method is: freeze and thaw the composite precursor solution multiple times.

[0023] According to the second aspect of the present invention, a hydrogel is provided, which is made by the hydrogel preparation method described in any one of the above.

[0024] According to the third aspect of the present invention, an application of the above hydrogel in a cardiac imaging model is provided.

[0025] According to the method for preparing a hydrogel of the present invention, by controlling the addition amount of the imaging filler within the range of 0.2% to 0.5%, the imaging effect of the hydrogel can be highly matched with the actual surgical imaging effect of human tissues, providing more real and accurate visual feedback, thereby effectively improving the authenticity of surgical simulation and providing a more reliable training model for medical education and surgical training. Moreover, by cross-linking the composite precursor solution, the polyvinyl alcohol and gelatin can undergo a cross-linking reaction, effectively improving the mechanical properties of the hydrogel and further ensuring the durability of the training model during simulated surgery.

[0026] Other features and advantages of the present invention will become apparent from the following detailed description of exemplary embodiments of the present invention with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The drawings incorporated in and constituting a part of this specification illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.

[0028] Figure 1 is a flowchart of a method for preparing a hydrogel according to an embodiment provided by the present invention.

[0029] Figure 2 is an ultrasonic imaging diagram of a hydrogel heart model according to Embodiment 2 provided by the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0030] Various exemplary embodiments of the present invention will now be described in detail with reference to the accompanying drawings. It should be noted that: unless otherwise specifically stated, the relative arrangements of components and steps, numerical expressions, and numerical values set forth in these embodiments do not limit the scope of the present invention.

[0031] The following description of at least one exemplary embodiment is merely illustrative in nature and in no way limits the present invention, its application, or its use.

[0032] Techniques, methods, and devices known to those of ordinary skill in the relevant art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered as part of the specification.

[0033] In all examples shown and discussed herein, any specific values should be construed as merely exemplary and not as limitations. Thus, other examples of exemplary embodiments may have different values.

[0034] It should be noted that: like reference numerals and letters denote like items in the following drawings; thus, once an item is defined in one drawing, it need not be further discussed in subsequent drawings.

[0035] The preparation method of the hydrogel according to the embodiment of the present invention will be specifically described below in conjunction with the accompanying drawings.

[0036] As Figure 1 shown, the hydrogel preparation method according to the embodiment of the present invention includes: S100 to S300.

[0037] S100. Dissolve polyvinyl alcohol and gelatin in water to form a gel precursor solution.

[0038] S200. Mix the developing filler with the gel precursor solution to form a composite precursor solution; wherein, the mass content of the developing filler in the composite precursor solution is 0.2% to 0.5%.

[0039] S300. Crosslink the composite precursor solution by the freeze-thaw method to obtain a hydrogel.

[0040] In other words, the hydrogel according to the embodiment of the present invention can be prepared by using polyvinyl alcohol, gelatin, water and a developing filler. Specifically, polyvinyl alcohol (PVA) can be used as a matrix material to provide the basic framework structure of the hydrogel; while gelatin can crosslink with polyvinyl alcohol, thereby enhancing the network structure and mechanical properties of the gel; the developing filler, as a functional additive, can improve the ultrasonic imaging effect of the hydrogel.

[0041] During the preparation process, first, polyvinyl alcohol and gelatin can be dissolved in water. After polyvinyl alcohol and gelatin are fully dissolved, a gel precursor solution for preparing the hydrogel can be formed. Then, the developing filler is added to the gel precursor solution, and the developing filler and the gel precursor solution are fully mixed. After full mixing, a composite precursor solution can be formed; since the gel precursor solution has a certain viscosity, it is beneficial for the developing filler to be uniformly dispersed in the gel precursor solution, thereby ensuring the uniformity of the composite precursor solution. After the composite precursor solution is formed, the composite precursor solution can be crosslinked by the freeze-thaw method to crosslink polyvinyl alcohol and gelatin. After the crosslinking treatment is completed, the required hydrogel can be obtained.

[0042] It should be noted that if the content of the developing filler is too low, the imaging effect of the hydrogel will be relatively weak, and the tissue structure cannot be clearly displayed, making it difficult to meet the requirements for the imaging effect in surgical simulation, thereby affecting the authenticity of surgical simulation; on the contrary, if the content of the developing filler is too high, the imaging effect of the hydrogel will be too strong, which does not conform to the actual imaging effect of human tissues, and the real surgical experience cannot be simulated either. In this embodiment, the mass content of the developing filler is 0.2% to 0.5%, for example, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45% and 0.5%, etc. Within this range, the imaging effect of the hydrogel can be guaranteed to match the actual imaging effect of human tissues, thereby effectively simulating the surgical scenario and improving the authenticity of the simulation.

[0043] Thus, according to the hydrogel preparation method of the embodiments of the present invention, by controlling the addition amount of the developing filler within the range of 0.2% to 0.5%, the developing effect of the hydrogel can be highly matched with the actual surgical developing effect of human tissues, providing more real and accurate visual feedback, thereby effectively improving the authenticity of surgical simulation and providing a more reliable training model for medical education and surgical training. Moreover, by crosslinking the composite precursor solution, the polyvinyl alcohol and gelatin can undergo a crosslinking reaction, effectively improving the mechanical properties of the hydrogel and further ensuring the durability of the training model during simulated surgery.

[0044] According to an embodiment of the present invention, the developing filler is talc powder, and the mass content of the developing filler is configured to be 0.3%.

[0045] That is to say, talc powder is selected as the developing filler in the present invention. Talc powder can not only significantly improve the developing effect of the hydrogel, making it more clearly presented in imaging devices such as ultrasound, but also has good lubricity itself, enabling the surface of the training model prepared from the hydrogel to be smoother.

[0046] In this embodiment, the mass content of the developing filler (i.e., talc powder) is controlled within the range of 0.2% to 0.5%. Within this range, not only can the developing effect of the gel be ensured to match the actual developing effect of human tissues, but also the friction characteristics of the surface of the training model prepared from the hydrogel can be made to match those of human tissues. Thus, the training model prepared from the hydrogel of this embodiment can provide a more real and practical operation-like experience for medical staff in surgical simulation under ultrasound guidance.

[0047] In some specific embodiments of the present invention, the method of dissolving polyvinyl alcohol and gelatin in water to form a gel precursor solution includes: S110 and S120.

[0048] S110: Dissolve polyvinyl alcohol in water to form a polyvinyl alcohol solution;

[0049] S120: Dissolve gelatin in the polyvinyl alcohol solution to form a gel precursor solution.

[0050] Specifically, when polyvinyl alcohol is dissolved in water, it is easy to form lumps. If polyvinyl alcohol and gelatin are directly added to water together, the polyvinyl alcohol particles will be wrapped by gelatin, making it difficult to dissolve completely. Adding polyvinyl alcohol to water first and stirring it to disperse it fully can effectively avoid the uneven phenomenon caused by the aggregation of polyvinyl alcohol particles.

[0051] According to an embodiment of the present invention, the method of dissolving polyvinyl alcohol in water to form a polyvinyl alcohol solution includes: S111 and S112.

[0052] S111. Add polyvinyl alcohol dispersedly into water to swell the polyvinyl alcohol.

[0053] S112. Heat the swollen polyvinyl alcohol and water to 60°C - 90°C and continuously stir to form a polyvinyl alcohol solution.

[0054] That is to say, when preparing the polyvinyl alcohol solution, first add the polyvinyl alcohol powder into a container filled with water, then stir evenly with a stirrer to ensure that the polyvinyl alcohol powder is fully dispersed in water, and then let it stand for 10 min - 30 min, for example, 10 min, 15 min, 20 min, 25 min, 30 min, etc., so that the polyvinyl alcohol fully absorbs water and swells. Then heat the polyvinyl alcohol and water in the container to 60°C - 90°C, for example, 60°C, 70°C, 80°C, 90°C, etc., and continuously stir at this temperature to make the polyvinyl alcohol fully dissolve in water, thereby obtaining a uniform polyvinyl alcohol solution.

[0055] During the preparation of the polyvinyl alcohol solution, through the steps of first stirring and then standing, the polyvinyl alcohol powder can fully absorb water and swell, thereby reducing the possible particle agglomeration phenomenon during the dissolution process; subsequently heating it to the temperature range of 60°C to 90°C and stirring can effectively improve the dissolution rate of the polyvinyl alcohol, and then significantly improve the production efficiency of the hydrogel.

[0056] In some specific embodiments of the present invention, after controlling the temperature of the polyvinyl alcohol solution to 40°C - 60°C, add gelatin to the polyvinyl alcohol solution and stir until dissolved to form a gel precursor solution.

[0057] Specifically, after the polyvinyl alcohol solution is prepared, the temperature of the polyvinyl alcohol solution is usually relatively high. If gelatin is directly added, it will cause the gelatin to denature, thereby affecting the subsequent cross-linking with the polyvinyl alcohol; if the temperature of the polyvinyl alcohol solution is too low, the dissolution rate of the gelatin will become slow. To avoid the above problems, before adding gelatin, the polyvinyl alcohol solution can be cooled to 40°C - 60°C, for example, 40°C, 45°C, 50°C, 55°C, 60°C, etc. In this temperature range, the dissolution rate of the gelatin can be guaranteed, and the gelatin can be effectively prevented from denaturing, thereby ensuring the product performance of the hydrogel.

[0058] According to an embodiment of the present invention, the weight ratio of the polyvinyl alcohol to the gelatin is (10 - 3):1.

[0059] That is to say, when the weight ratio of polyvinyl alcohol to gelatin is greater than 10:1, it means that the content of gelatin is too small. If the content of gelatin is too small, the strength of the hydrogel will be insufficient, which will cause the hydrogel training model to be easily broken during use. When the weight ratio of polyvinyl alcohol to gelatin is less than 3:1, it means that the content of gelatin is too large. Excessive gelatin will cause the hydrogel to be too hard, and the too hard texture will seriously affect the realism of the surgical operation. In this embodiment, the weight ratio of polyvinyl alcohol to gelatin is configured to be (10 - 3):1. For example, 10:1, 8:1, 6:1, 4:1, 3:1, etc. The hydrogel can be controlled to have an appropriate hardness within this ratio range.

[0060] In some specific embodiments of the present invention, the weight content of polyvinyl alcohol is 10%, the weight content of gelatin is 3%, the weight content of the imaging filler is 0.3%, and the balance is water. In this embodiment, using the above contents of polyvinyl alcohol, gelatin, imaging filler and water can ensure that the hydrogel has sufficient elastic modulus and elasticity, and at the same time can provide a more realistic imaging effect, and can simulate the touch and operation feeling of real tissues, thereby effectively improving the realism of surgical simulation.

[0061] According to an embodiment of the present invention, the method for crosslinking the composite precursor solution by the freeze-thaw method is: freezing and thawing the composite precursor solution multiple times.

[0062] That is to say, when crosslinking the composite precursor solution, the composite precursor solution can be frozen at about -20°C for about 12 hours, then taken out and thawed at room temperature for about 4 hours. Repeat the freeze-thaw cycle multiple times, for example, 2 times, 3 times or 4 times, etc. After the cycle of freezing and thawing, the required hydrogel can be obtained. When a training model needs to be prepared, such as a heart model, the composite precursor solution can be poured into a heart mold, and then the cycle of freezing and thawing is carried out, and then demolded to obtain the required hydrogel heart model.

[0063] The preparation method of the hydrogel of the embodiment of the present invention will be specifically described below with reference to specific embodiments.

[0064] Example 1

[0065] Disperse polyvinyl alcohol in water to swell it, then heat the swollen polyvinyl alcohol and water to 90 °C and vigorously stir for 2 h at 90 °C. After completely dissolving the polyvinyl alcohol in water, lower the temperature of the polyvinyl alcohol solution to 60 °C, then add gelatin to the polyvinyl alcohol solution and stir the resulting mixture at 60 °C for 1 h to obtain a gel precursor solution. Then add talcum powder to the gel precursor solution and stir evenly to form a composite precursor solution, and let the composite precursor solution stand for 10 minutes to remove bubbles; subsequently, pour the composite precursor solution into a heart mold, freeze it at -20 °C for 12 h, then take it out and thaw it at room temperature for 4 h. Repeat the freezing-thawing cycle 3 times to obtain a hydrogel heart model.

[0066] Among them, the content of polyvinyl alcohol is 10%, the content of gelatin is 1%, and the content of talcum powder is 0.3%.

[0067] Example 2

[0068] The difference from the example is that the content of gelatin is 3%.

[0069] Example 3

[0070] The difference from the example is that the content of gelatin is 5%.

[0071] Comparative Example 1

[0072] Disperse polyvinyl alcohol in water to swell it, then heat the swollen polyvinyl alcohol and water to 90 °C and vigorously stir for 2 h at 90 °C. After completely dissolving the polyvinyl alcohol in water, obtain a polyvinyl alcohol solution; then add talcum powder to the polyvinyl alcohol and stir evenly to form a composite precursor solution, then let the composite precursor solution stand for 10 minutes to remove bubbles; subsequently, pour the composite precursor solution into a heart mold, freeze it at -20 °C for 12 h, then take it out and thaw it at room temperature for 4 h. Repeat the freezing-thawing cycle 3 times to obtain a hydrogel heart model.

[0073] Among them, the content of polyvinyl alcohol is 10%, and the content of talcum powder is 0.3%.

[0074] The test results of the above examples and comparative examples are shown in the following table.

[0075] Table 1: Elastic Modulus Test Table

[0076] Item Elastic modulus (kPa) Example 1 57 Example 2 75 Example 3 103 Comparative Example 1 34

[0077] As can be seen from the above table, in the examples of the present invention, the added gelatin can crosslink with polyvinyl alcohol, thereby increasing the elastic modulus of the hydrogel and further improving the mechanical properties of the hydrogel.

[0078] In summary, according to the hydrogel preparation method of the embodiments of the present invention, by controlling the addition amount of the imaging filler within the range of 0.2% to 0.5%, the imaging effect of the hydrogel can be highly matched with the actual surgical imaging effect of human tissues, providing more real and accurate visual feedback, thereby effectively improving the authenticity of surgical simulation and providing a more reliable training model for medical education and surgical training. Moreover, by crosslinking the composite precursor solution, the crosslinking reaction between polyvinyl alcohol and gelatin can occur, effectively improving the mechanical properties of the hydrogel, and further ensuring the durability of the training model during simulated surgery.

[0079] The embodiments of the present invention also provide a hydrogel, which is made by the hydrogel preparation method described in any of the above embodiments. Since the hydrogel preparation method according to the embodiments of the present invention has the above technical effects, the hydrogel according to the embodiments of the present invention also has corresponding technical effects, which will not be elaborated in this embodiment.

[0080] The embodiments of the present invention also provide the application of the hydrogel described in the above embodiments in a cardiac imaging model. In this embodiment, the hydrogel is configured as a cardiac model, such as a cardiac model of a case of hypertrophic obstructive cardiomyopathy. Using this cardiac model for surgical training can effectively improve the authenticity of surgical simulation.

[0081] In addition, the hydrogel can also be configured as structures such as heart valves, and its settings can be adjusted according to actual needs, which will not be elaborated in this embodiment.

[0082] Since the hydrogel preparation method according to the embodiments of the present invention has the above technical effects, the application of the hydrogel solution according to the embodiments of the present invention in a cardiac imaging model also has corresponding technical effects, which will not be elaborated in this embodiment.

[0083] Although some specific embodiments of the present invention have been described in detail by way of examples, those skilled in the art should understand that the above examples are only for illustration and not for limiting the scope of the present invention. Those skilled in the art should understand that the above embodiments can be modified without departing from the scope and spirit of the present invention. The scope of the present invention is defined by the appended claims.

Claims

1. A method for preparing a hydrogel, characterized in that: include: Dissolve polyvinyl alcohol and gelatin in water to form a gel precursor solution; Mixing the developing filler with the gel precursor solution to form a composite precursor solution; Wherein, the mass content of the developing filler in the composite precursor solution is 0.2% to 0.5%; The composite precursor solution is cross-linked by freeze-thaw method to obtain a hydrogel.

2. The method for preparing a hydrogel according to claim 1, characterized in that: The developer filler is talc, and the mass content of the developer filler is configured to be 0.3%.

3. The method for preparing a hydrogel according to claim 1, characterized in that: The method of dissolving polyvinyl alcohol and gelatin in water to form a gel precursor solution comprises: dissolving polyvinyl alcohol in water to form a polyvinyl alcohol solution; Gelatin is dissolved in the polyvinyl alcohol solution to form a gel precursor solution.

4. The method for preparing a hydrogel according to claim 3, characterized in that: The method of dissolving polyvinyl alcohol in water to form a polyvinyl alcohol solution comprises: Dispersing polyvinyl alcohol into water to make the polyvinyl alcohol swell; The swollen polyvinyl alcohol and water are heated to 60° C. to 90° C. and stirred continuously to form a polyvinyl alcohol solution.

5. The method for preparing a hydrogel according to claim 3, characterized in that: After the temperature of the polyvinyl alcohol solution is controlled to be 40° C. to 60° C., gelatin is added to the polyvinyl alcohol solution and stirred until dissolved to form a gel precursor solution.

6. The method for preparing a hydrogel according to claim 1, characterized in that: The weight ratio of the polyvinyl alcohol to gelatin is (10-3):

1.

7. The method for preparing a hydrogel according to claim 1, characterized in that: The weight content of the polyvinyl alcohol is 10%, the weight content of the gelatin is 3%, the weight content of the developing filler is 0.3%, and the water is the balance.

8. The method for preparing a hydrogel according to claim 1, characterized in that: The method of cross-linking the composite precursor solution by freeze-thaw method is: freezing and thawing the composite precursor solution multiple times.

9. A hydrogel, characterized in that: The hydrogel is prepared by the hydrogel preparation method according to any one of claims 1 to 8.

10. Use of the hydrogel according to claim 9 in a cardiac imaging model.

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