A dehydrated and rehydrated ultrasonically enhanced chitosan gel without a developing unit and its application

Abstract

This invention discloses a dehydrated and rehydrated ultrasound-enhanced chitosan gel without a radiopaque unit and its applications. By controlling the water content of the gel through dehydration and rehydration strategies, this invention constructs a chitosan gel with excellent ultrasound imaging performance without introducing a radiopaque unit. It has significant industrialization potential and clinical application prospects, providing a novel material for the medical and tissue engineering fields. This material can be easily adapted for minimally invasive implantation. After implantation, it can achieve in-situ expansion and anchoring through tissue fluid permeation and rehydration, exhibiting flexibility and no foreign body sensation, making it suitable for reference marking in human soft tissue areas. This process of dehydrating and rehydrating conventional high-water-content hydrogels can increase the acoustic impedance value of the material without introducing a radiopaque unit, and improve the ultrasound imaging effect by controlling the gel's water content.

Description

Technical Field

[0001] This invention belongs to the field of biomedical polymer materials technology, specifically relating to an ultrasound-enhanced chitosan gel without a developing unit and its applications. Background Technology

[0002] Hydrogels are soft materials composed of a three-dimensional cross-linked hydrophilic polymer network, exhibiting excellent biocompatibility. Conventional hydrogels, after swelling equilibrium, typically have a water content exceeding 80%. Their acoustic impedance is highly matched to human soft tissue, making them undetectable by ultrasound. This prevents real-time monitoring of positioning and placement during surgery or post-implantation using ultrasound imaging. However, for specific applications, ultrasound imaging offers irreplaceable advantages in real-time performance, safety, and functional integration. Accurate visualization is crucial for interventional tissue engineering materials, effectively preventing issues such as misplacement, displacement, or delayed efficacy assessment.

[0003] Focusing on relevant research both domestically and internationally, the main technical approaches for endowing hydrogels with ultrasonic imaging capabilities are currently divided into two types: physical doping and chemical bonding. The former involves directly dispersing water-insoluble imaging particles with high acoustic impedance values ​​in the hydrogel precursor solution, achieving ultrasonic imaging through the acoustic impedance difference between the particles and the tissue. However, this method suffers from drawbacks such as easy particle sedimentation and poor gel stability. The latter method often involves covalently incorporating iodine compounds into polymer chains or bonding them to microbubble stabilizers to form internal microbubbles. This locally increases acoustic impedance, enhancing ultrasonic scattering and effectively avoiding the sedimentation problem associated with physical doping. However, it also has limitations such as low chemical modification rates, complex preparation processes, and the trade-off between stability and safety. For example, iodine compounds readily hydrolyze to release iodine ions, and there are issues with insufficient imaging contrast, fundamentally limiting its practical application in medical implants.

[0004] In summary, unlike the mainstream strategy of introducing a developing unit into a hydrogel to achieve ultrasound imaging, this invention provides a gel material that can achieve excellent ultrasound imaging without relying on a developing unit. Based on a dehydration and rehydration strategy, this material not only has excellent acoustic contrast and virtually no echo artifacts, but can also anchor in human tissue and match the mechanical environment of human soft tissue to reduce the feeling of foreign body. Summary of the Invention

[0005] To address the shortcomings and deficiencies of existing technologies, this invention innovatively proposes a dehydration-rehydration strategy to control the water content of the initial chitosan hydrogel. A mechanically compatible, minimally invasive, and safe ultrasound-enhancing hydrogel was designed and prepared at room temperature. Furthermore, this gel can be stored long-term in a dehydrated state and rapidly absorbs tissue fluid and swells after implantation. This not only completely avoids the risk of contrast agent dissolution in previous strategies but also allows for better anchoring within the tissue, exhibiting superior anti-migration properties.

[0006] One aspect of the present invention is to provide an ultrasonically enhanced chitosan gel material without a developing unit, specifically embodied in the following aspects: 1) An ultrasonically enhanced imaging gel, wherein the gel is composed only of a three-dimensional cross-linked chitosan gel network, and the acoustic impedance value of the material is increased by changing the ratio of polymer matrix and aqueous phase in the hydrogel without introducing imaging units. 2) The gel according to 1) above, wherein the chitosan is selected from medical grade or pharmaceutical grade, and has a weight-average molecular weight of 1×10⁻⁶. 4 -10 6 Da, preferably 1×10 5 -6×10 5 Da has a degree of deacetylation of 70-95%.

[0007] A second aspect of the present invention provides a method for preparing and using the gel material described in the first aspect, comprising the following steps: (1) Preparation of concentrated chitosan solution: Chitosan was added to dilute acetic acid solution, stirred until completely dissolved, and then degassed to obtain precursor solution, which was stored for later use. (2) Formation of the initial chitosan hydrogel: At room temperature, the above precursor solution is transferred into a syringe and squeezed into an alkaline solution by a syringe pump to complete cross-linking and wash repeatedly to remove impurities and residues, thus obtaining the initial physically cross-linked hydrogel. (3) Dehydration treatment: The above-mentioned physically cross-linked hydrogel is dried to constant weight to obtain dry gel.

[0008] The method of using the gel is as follows: the dry gel is placed in human tissue fluid or phosphate buffer solution that simulates human tissue fluid for rehydration to achieve swelling equilibrium, thereby obtaining a dehydrated and rehydrated chitosan gel with ultrasound-enhanced imaging effect.

[0009] Furthermore, the mass fraction of chitosan in the precursor solution in step (1) is 3-10 wt%, preferably 6-10 wt%.

[0010] Furthermore, the degassing process in step (1) is vacuum degassing or static degassing, with a time of 3-24 hours.

[0011] Furthermore, the alkaline solution is any one of sodium hydroxide solution, sodium bicarbonate solution, sodium carbonate solution, disodium hydrogen phosphate solution, or potassium hydroxide solution, with a mass concentration of 3-7%.

[0012] Furthermore, in step (2), the time for complete cross-linking in the alkaline solution is 1-6 hours.

[0013] Furthermore, the drying process in step (3) is a stepped drying process, with a temperature of room temperature to 60°C and a time of 6-24 hours, preferably room temperature to 40°C and 12-18 hours.

[0014] Furthermore, a chitosan molecular weight of 1×10⁻⁶ was selected. 5 -6×10 5 The precursor solution contains 6-10 wt% chitosan and 3-7% alkali. The resulting gel has a water content of approximately 40-60% after dehydration, rehydration, swelling, and equilibrium.

[0015] It is worth noting that the water content of the hydrogel obtained in step (2) is approximately 80-99%, and the water content of the swelling-balanced gel obtained in the gel application method is within a more suitable range. Compared to conventional high-water-content (≥80%) hydrogels, hydrogels with moderate water content exhibit superior imaging resolution, extremely high boundary recognition, and precise positioning under ultrasound imaging. Furthermore, compared to anhydrous composite materials prepared by direct melt blending of thermoplastic polymers and imaging particles or through other methods, hydrogels after dehydration-rehydration treatment show clearer outlines in imaging. This is because the acoustic impedance of water is very close to that of soft tissue; an appropriate amount of water filling the material voids effectively reduces interference from strong internal reflections and artifacts. In conclusion, controlling the water content is a crucial factor in designing and preparing an ultrasound-developable gel material. The dehydrable and rehydrated ultrasonic-enhanced developing chitosan gel prepared by this invention can achieve good ultrasonic enhancement and developing effects without loading a developing unit. The preparation process is simple and can effectively avoid the negative effects of dissolution, particle aggregation, process complexity and possible in vivo toxicity caused by the introduction of a developing unit.

[0016] A third aspect of the present invention is to provide an application of the ultrasound-enhanced imaging chitosan hydrogel prepared by the above-described technical solution, which is used as a raw material for implantable medical devices for imaging of human soft tissue areas.

[0017] Furthermore, the ultrasound-enhanced chitosan hydrogel can be used as a reference marker for certain parts of the human body to indicate lesions, particularly for the diagnosis or treatment of superficial breast lesions.

[0018] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention achieves excellent and stable ultrasonic imaging effect without the introduction of a imaging unit by controlling the water content of chitosan hydrogel. The preparation process is simple and has great industrialization potential and clinical application prospects. 2. The dehydrated dry gel has a great advantage in small size, which makes it easy to store for a long time. When used, it can be implanted in a minimally invasive manner through a puncture needle under ultrasound guidance. After implantation, it will quickly absorb tissue fluid and swell. Through volume expansion, it can better anchor in the tissue and exhibit better anti-migration and mechanical compatibility. 3. This material has a certain recycling value. In the dry gel storage state, it can undergo repeated hydration-dehydration cycles without changing the basic properties of the material. Attached Figure Description

[0019] Figure 1 The results show the water content test results of the chitosan hydrogels obtained in Examples 1-3, both initially and after dehydration and rehydration to swelling equilibrium. Figure 2 The bending stress-strain curves of the chitosan dry gels prepared in Examples 1-3 after swelling equilibrium and the chitosan gels obtained in Comparative Examples 3-4 are shown. Figure 3 This is a schematic diagram of ultrasound imaging after the chitosan dry gel prepared in Example 2 has swelled to equilibrium. Figure 4 A schematic diagram of real-time ultrasound imaging of the chitosan gels prepared in Comparative Examples 1-4. Figure 5 This is a schematic diagram showing the appearance of the dry gels prepared in Example 1 and Comparative Example 5 and their rehydration to equilibrium state. Figure 6 This is a schematic diagram of the ultrasonic imaging of the chitosan / calcium carbonate composite gels prepared in Comparative Examples 5-6. Detailed Implementation

[0020] The technical solutions of the present invention are described in detail below through specific embodiments. These embodiments are intended to illustrate the implementation of the present invention and are not intended to constitute any limitation. It should be understood that the described embodiments are only a part of the typical implementation of the present invention and not all possible forms.

[0021] Example 1

[0022] This embodiment provides a method for preparing a pure chitosan gel with ultrasound-enhanced imaging effect without a developing unit, comprising the following steps: (1) Preparation of chitosan concentrated solution: 2g of chitosan was added to 31.33ml of 5% dilute acetic acid solution and stirred at 800rpm for 4h until the solution was clear and transparent. Then, the solution was degassed under vacuum to obtain a chitosan concentrated solution with a mass concentration of 6wt%, which was stored for later use. (2) Initial chitosan hydrogel formation: At room temperature, the above concentrated solution was transferred into a syringe and squeezed into a 5wt% sodium hydroxide solution at an appropriate speed using an injection pump for cross-linking for 3 hours to complete solidification. After washing with deionized water multiple times, the initial physically cross-linked chitosan hydrogel was obtained. (3) Dehydration treatment: First, place the initial hydrogel in a ventilated place to dry at room temperature. After a large amount of water has been lost and the shape is stable, place it in a 60℃ oven to dry to constant weight to obtain dry gel. In use, the dry gel is placed in a phosphate buffer solution at 37°C and pH 7.4, simulating human tissue fluid, to swell for 12 hours until it reaches swelling equilibrium, yielding a dehydrated and rehydrated chitosan gel material (its appearance as dry gel and rehydrated to equilibrium state are shown in the image). Figure 5 ).

[0023] Example 2

[0024] This embodiment provides a method for preparing a pure chitosan gel with ultrasound-enhanced imaging effect without a developing unit, comprising the following steps: (1) Preparation of chitosan concentrated solution: 2g of chitosan was added to 23ml of 5% dilute acetic acid solution and stirred at 800rpm for 4h until the solution was clear and transparent. Then, the solution was degassed under vacuum to obtain a chitosan concentrated solution with a mass concentration of 8wt%, which was stored for later use. (2) Initial chitosan hydrogel formation: At room temperature, the above concentrated solution was transferred into a syringe and squeezed into a 5wt% sodium hydroxide solution at an appropriate speed using an injection pump for cross-linking for 3 hours to complete solidification. After washing with deionized water multiple times, the initial physically cross-linked chitosan hydrogel was obtained. (3) Dehydration treatment: First, place the initial hydrogel in a ventilated place to dry at room temperature. After a large amount of water has been lost and the shape is stable, place it in a 60℃ oven to dry to constant weight to obtain dry gel. When using the material, the dry gel is placed in a phosphate buffer solution at 37°C and pH 7.4, which simulates human tissue fluid, and swells for 12 hours to reach swelling equilibrium, thus obtaining a dehydrated and rehydrated chitosan gel material.

[0025] Example 3

[0026] This embodiment provides a method for preparing a pure chitosan gel with ultrasound-enhanced imaging effect without a developing unit, comprising the following steps: (1) Preparation of chitosan concentrated solution: 2g of chitosan was added to 18ml of 5% dilute acetic acid solution and stirred at 800rpm for 4h until the solution was clear and transparent. Then, the solution was degassed under vacuum to obtain a chitosan concentrated solution with a mass concentration of 10wt%, which was stored for later use. (2) Initial chitosan hydrogel formation: At room temperature, the above concentrated solution was transferred into a syringe and squeezed into a 5wt% sodium hydroxide solution at an appropriate speed using an injection pump for cross-linking for 3 hours to complete solidification. After washing with deionized water multiple times, the initial physically cross-linked chitosan hydrogel was obtained. (3) Dehydration treatment: First, place the initial hydrogel in a ventilated place to dry at room temperature. After a large amount of water has been lost and the shape is stable, place it in a 60℃ oven to dry to constant weight to obtain dry gel. When using the material, the dry gel is placed in a phosphate buffer solution at 37°C and pH 7.4, which simulates human tissue fluid, and swells for 12 hours to reach swelling equilibrium, thus obtaining a dehydrated and rehydrated chitosan gel material.

[0027] Comparative Example 1 This comparative example provides a chitosan hydrogel with high water content (>80%). Its raw materials and steps (1) and (2) are the same as those in Example 2. The difference is that it does not undergo the treatment in step (3) and is only the initial high water content chitosan hydrogel obtained in step (2).

[0028] Comparative Example 2 This comparative example provides a chitosan gel with a medium to high water content (approximately 70 ± 5%). The raw materials and steps are the same as in Example 2, except that in step (3), the initial high water content hydrogel is subjected to controlled dehydration, i.e., dried at 40°C for 3 hours. At this time, the gel is not completely dried, and then it is immediately placed in a phosphate buffer solution at 37°C and pH 7.4, which simulates human tissue fluid, to swell to equilibrium.

[0029] Comparative Example 3 This comparative example provides a chitosan gel with a medium to low water content (approximately 30% ± 5%). The raw materials and steps are the same as in Example 2, except that the chitosan dry gel obtained in step (3) is placed in a phosphate buffer solution at 37°C and pH 7.4, which simulates human tissue fluid, and only swells for about 60 minutes. At this time, the gel has not yet reached the swelling equilibrium state, and is then immediately removed for use.

[0030] Comparative Example 4 This comparative example provides a chitosan gel with low water content (approximately 10% ± 5%). The raw materials and steps are the same as in Example 2, except that the chitosan dry gel obtained in step (3) is placed in a phosphate buffer solution at 37°C and pH 7.4, which simulates human tissue fluid, and only swells for about 10 minutes. At this time, the gel has not yet reached the swelling equilibrium state, and is then immediately removed for use.

[0031] Comparative Example 5 0.5g of calcium carbonate particles for development were ultrasonically dispersed in 23ml of 5% dilute acetic acid solution. 2g of chitosan was then added and stirred at 800rpm for 4 hours to dissolve. The solution was then degassed under vacuum to obtain a concentrated chitosan / calcium carbonate solution. At room temperature, the concentrated solution was transferred to a syringe and extruded at an appropriate rate into a 5% sodium hydroxide solution using a syringe pump. Crosslinking was carried out for 3 hours to ensure complete solidification. After washing repeatedly with deionized water, the initial physically crosslinked chitosan / calcium carbonate hydrogel was obtained.

[0032] The initial hydrogel was dried at room temperature in a ventilated area until it lost a large amount of water and its shape stabilized. Then, it was dried in a 60°C oven until constant weight to obtain a dry gel. This composite dry gel was then placed in a phosphate buffer solution (pH 7.4, 37°C, simulating human tissue fluid) to swell for 12 hours until swelling equilibrium was reached, yielding a dehydrated and rehydrated chitosan / calcium carbonate composite gel (its appearance as dry gel and rehydrated to equilibrium state are shown in the image). Figure 5 ).

[0033] Comparative Example 6 This comparative example provides a high water content composite hydrogel, the raw materials and steps (1) and (2) are the same as those of comparative example 5, the difference is that the final dehydration and rehydration treatment is not performed, and the initial high water content chitosan / calcium carbonate hydrogel is obtained.

[0034] Performance testing 1. Moisture content test: The test employs a gravimetric method. First, the wet weight of the hydrogel sample to be tested is accurately measured (denoted as W1). Then, the sample is placed in a vacuum drying oven at 60-80℃ and dried to constant weight (the weight difference is ≤0.1% after 2 hours), and the dry weight is recorded (denoted as W2). Finally, the result is calculated using the formula "water content (%) = (W1-W2) / W1×100%". The water content of the samples in all embodiments and comparative examples of this invention was measured using this method.

[0035] The water content of the initial high-water-content hydrogels obtained in Examples 1-3 before dehydration and the chitosan hydrogels after dehydration and rehydration treatment were tested. The results are as follows: Figure 1 As shown.

[0036] from Figure 1 It can be seen that the initial high-water-content hydrogels in Examples 1-3 had a water content of approximately 80-95% before dehydration, while the chitosan hydrogels after the final dehydration and rehydration treatment had a water content of approximately 40-60%. In Examples 1-3, the dehydration and rehydration treatment induced crystallization and enhanced hydrogen bonding, transforming the high-water-content state into a state with moderate water content.

[0037] 2. Three-point bending performance test: Three-point bending tests were performed on the chitosan gels obtained after dehydration and rehydration treatment in Examples 1-3 and the chitosan gels obtained in Comparative Examples 3-4. The results are as follows: Figure 2 As shown, the flexural strength of Examples 1-3 is approximately 1.5 MPa, and the elastic modulus is approximately 18 MPa. At this point, the material's water content is maintained at 40-60%, and its modulus falls within the range of common soft tissue mechanical properties in the human body (from a few kPa to tens of MPa), achieving a balance between clinical positioning accuracy and biomechanical adaptability. Firstly, it exhibits excellent mechanical compliance. A modulus of approximately 18 MPa is far lower than that of metals or other rigid markers (GPa level), significantly reducing stress shielding effects and avoiding tissue damage and foreign body sensation caused by excessive material rigidity. If the gel's water content is below 40% (as in Comparative Examples 3-4), the material modulus remains at a low GPa level, exhibiting excessive rigidity and losing the flexibility characteristic of hydrogels. Secondly, it ensures functional stability. Although hydrogels with a water content higher than 60% have a modulus closer to that of specific soft tissues, they have obvious defects: First, insufficient acoustic impedance difference leads to a decrease in the clarity of ultrasound imaging; second, they have poor structural stability. When subjected to physiological stress or compressive deformation, materials with extremely low modulus are prone to undergo synchronous high deformation with the tissue, resulting in the displacement of the geometric center of the marker and loss of reference value.

[0038] Therefore, chitosan hydrogels with a water content of 40-60% achieve a synergistic balance between imaging visibility, structural stiffness, and mechanical compliance. They can achieve clear imaging through moderate acoustic impedance differences while providing the necessary resistance to deformation, ensuring the pose of the marker remains constant under complex mechanical environments, thus achieving a precise reference marking function.

[0039] 3. Ultrasonic imaging performance and image analysis of hydrogels: The chitosan gels prepared in Examples 1-3 were cut into regular cylindrical shapes and placed in simulated tissue. Ultrasonic images of the chitosan gels at swelling equilibrium in the simulated tissue were monitored using a vivo 3100 ultrasound imaging system (Fujifilm Visualsoncs, USA). Figure 3 The image shown is an ultrasound image of the chitosan dry gel prepared in Example 2 after swelling equilibrium, where the arrows indicate the location of the gel in the ultrasound image.

[0040] from Figure 3It can be seen that chitosan hydrogels with a water content in the range of 40-60% can form bright areas at both the upper and lower interfaces of the tissue-material contact under ultrasound, clearly displaying the upper and lower contours of the entire material. This is because the acoustic impedance difference between the chitosan hydrogel with a water content of 40-60% and the tissue interface is moderate. The echo signal generated by the microscopic interface formed by the chitosan backbone and water molecules is significantly different in intensity from that of soft tissue, without producing artifacts due to excessive reflection. Simultaneously, this range coincides with the swelling equilibrium state of the initial chitosan hydrogel after dehydration and rehydration. When implanted into the human body, it can maintain a stable imaging state for a long time, making it more suitable as a reference marker for precise positioning within the body.

[0041] The chitosan gels prepared in Comparative Examples 1-4 were cut into regular cylindrical shapes and placed in simulated tissues. Real-time ultrasound images of the chitosan gels in the simulated tissues were monitored using a vivo 3100 ultrasound imaging system (Fujifilm Visualsoncs, USA). Figure 4 As shown in the figure, arrows indicate the location of the gel in each ultrasound image.

[0042] from Figure 4 As can be seen from the ultrasound images of Comparative Example 2, the chitosan hydrogel with a water content >80% in Comparative Example 1 almost completely merges with the surrounding tissue under ultrasound and is basically invisible; the chitosan hydrogel with a water content of about 70±5% in Comparative Example 2 still has insufficient contrast under ultrasound, and the boundary merges with the background tissue, making it difficult to identify; the chitosan hydrogel with a water content of about 30%±5% in Comparative Example 3 has better contrast under ultrasound, but its lower contour is not clear due to the strong echo; the chitosan hydrogel with a water content of about 10%±5% in Comparative Example 4 forms strong surface reflection at the upper surface of the material due to the high acoustic impedance difference between the tissue and the material interface, making it impossible to display the lower contour.

[0043] The chitosan / calcium carbonate gels prepared in Comparative Examples 5-6 were cut into regular cylindrical shapes and placed in simulated tissue. Ultrasound images of the chitosan / calcium carbonate gels in the simulated tissue were monitored using a vivo 3100 ultrasound imaging system (Fujifilm Visualsoncs, USA). Figure 6 As shown, arrows indicate the location of the gel in each ultrasound image.

[0044] from Figure 3 and Figure 6As can be seen from the comparison of the ultrasonic images of Example 2 and Comparative Example 5, it can be found that, under the premise of both undergoing dehydration and rehydration treatment, the chitosan gel and the composite gel with a higher mass fraction of calcium carbonate particles for enhancing ultrasonic development have comparable ultrasonic development effects. However, the chitosan gel without the introduction of a development unit is not only simpler to prepare, but also effectively avoids safety risks such as the dissolution of development particles. At the same time, comparing the ultrasonic images of Example 2 and Comparative Example 6, it was found that for the composite hydrogel that has not undergone dehydration and rehydration treatment, even with the introduction of a higher mass fraction of calcium carbonate particles for enhancing ultrasonic development, its ultrasonic development effect is far inferior to that of the chitosan gel with a water content of 40-60%.

[0045] Although calcium carbonate particles can enhance ultrasound imaging by increasing the acoustic impedance of the composite hydrogel, conventional hydrogels are over 80% water. Introducing a high-quality imaging unit directly without controlling the water content of the hydrogel results in far less effective ultrasound enhancement than hydrogels that have undergone dehydration and rehydration treatment. It can be seen that this invention, by employing a chitosan hydrogel system combined with a dehydration and rehydration strategy, achieves excellent ultrasound enhancement without an imaging unit, demonstrating broad application prospects.

[0046] The embodiments described above are merely some preferred embodiments of the present invention, and are not intended to limit the invention. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, all technical solutions obtained by equivalent substitution or equivalent transformation fall within the protection scope of the present invention.

Claims

1. A dehydrated and rehydrated ultrasonically enhanced chitosan gel without a developing unit, characterized in that, Its preparation method includes the following steps: (1) Preparation of concentrated chitosan solution: Chitosan was added to dilute acetic acid solution, stirred until completely dissolved, and then degassed to obtain precursor solution; (2) Formation of the initial chitosan hydrogel: At room temperature, the above precursor solution was transferred into a syringe and squeezed into an alkaline solution by a syringe pump to complete cross-linking. After multiple washings, the initial physically cross-linked hydrogel was obtained. (3) Dehydration treatment: The above-mentioned physically cross-linked hydrogel is dried to constant weight to obtain dry gel; The method of using the gel is as follows: the dry gel is placed in human tissue fluid or phosphate buffer solution that simulates human tissue fluid for rehydration to achieve swelling equilibrium, thereby obtaining a dehydrated and rehydrated chitosan gel with ultrasound-enhanced imaging effect.

2. The dehydrated and rehydrated ultrasonically enhanced chitosan gel without a developing unit according to claim 1, characterized in that, The chitosan is medical-grade or pharmaceutical-grade chitosan with a weight-average molecular weight of 1×10⁻⁶. 4 -10 6 Da has a degree of deacetylation of 70-95%.

3. The dehydrated and rehydrated ultrasonically enhanced chitosan gel without a developing unit according to claim 1, characterized in that, The alkaline solution is any one of sodium hydroxide solution, sodium bicarbonate solution, sodium carbonate solution, disodium hydrogen phosphate solution, or potassium hydroxide solution, with a mass concentration of 3-7%.

4. The dehydrated and rehydrated ultrasonically enhanced chitosan gel without a developing unit according to claim 1, characterized in that, The mass fraction of chitosan in the precursor solution in step (1) is 3-10 wt%, preferably 6-10 wt%.

5. The dehydrated and rehydrated ultrasonically enhanced chitosan gel without a developing unit according to claim 1, characterized in that, The degassing process in step (1) is either vacuum degassing or static degassing, and the time is 3-24 hours.

6. The dehydrated and rehydrated ultrasonically enhanced developing chitosan gel without a developing unit according to claim 1, characterized in that, In step (2), the time for complete cross-linking in the alkaline solution is 1-6 hours.

7. The dehydrated and rehydrated ultrasonically enhanced chitosan gel without a developing unit according to claim 1, characterized in that, The drying process in step (3) is a stepped drying process, with a temperature of room temperature to 60°C and a time of 6-24 hours, preferably room temperature to 40°C and 12-18 hours.

8. The dehydrated and rehydrated ultrasonically enhanced chitosan gel without a developing unit according to claim 1, characterized in that, The swelling equilibrium time specified in the instructions is 6-24 hours, and the water content of the gel remains stable after equilibrium.

9. The application of the chitosan gel as described in claim 8 in the preparation of implantable ultrasound-enhanced imaging materials for human soft tissue sites.

10. The application of the chitosan gel as described in claim 8 in the preparation of implantable ultrasound labeling materials for human soft tissue sites.

Images