Radiation-proof hydrogel capable of being used for interventional radiosurgery as well as preparation method and application of radiation-proof hydrogel

Abstract

The invention discloses anti-radiation hydrogel capable of being used for interventional radiosurgery and a preparation method and application thereof.The anti-radiation hydrogel is in bridge connection with polymer chains of sodium alginate and sodium hyaluronate through the physical interaction between Fe < 3 + > and carboxyl, and the reversible interaction between Fe < 3 + > and carboxyl endows the hydrogel with the shear thinning characteristic; the injectability is ensured; the bismuth oxide nano-particles and the barium sulfate nano-particles are doped to achieve efficient attenuation of X-rays in the range of 20-100 keV, and meanwhile, the complementary K-edge absorption characteristics of the bismuth oxide nano-particles and the barium sulfate nano-particles are utilized, and the radiation absorption effect of a hydrogel network structure is combined, so that broad-spectrum radiation protection is achieved; according to the invention, acrylamide is taken as a raw material, an interpenetrating network elastic hydrogel of three polymers is formed under the action of polymerization under thermal initiation of acrylamide, the conversion from an injectable state to a solid state is realized, and at the moment, the cured hydrogel has tough mechanical properties, can also form a protective layer similar to gloves, and can be used for radiation protection in interventional operations.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical radiation-proof hydrogels, and in particular relates to a radiation-proof hydrogel that can be used for interventional radiological surgery, and a preparation method and application thereof. Background Art

[0002] X-rays are increasingly used worldwide, particularly in interventional procedures guided by digital subtraction angiography (DSA). These safe and minimally invasive techniques significantly reduce the risks of infection and anesthesia, while also making it possible to treat previously inaccessible lesions and shortening surgical procedures, providing both time and financial benefits for patients. However, the widespread use of X-rays also poses potential health risks to surgeons.

[0003] Although technological advances have significantly reduced radiation doses for operators, increasingly complex surgeries and higher surgical volumes have further increased the risk of radiation exposure. The effects of long-term, low-dose ionizing radiation on medical professionals have been well established. Accumulated excessive X-rays can pose risks such as radiation dermatitis, cataracts, hair loss, and infertility, and even increase the risk of malignant tumors. Therefore, appropriate shielding is crucial for interventional surgeons.

[0004] As patients and interventional physicians become more aware of radiation exposure, researchers are actively studying ways to reduce unnecessary radiation exposure through the use of lead aprons, lead glasses, and lead neckbands. However, there are very few radiation protection products specifically for the operator's hands. During interventional procedures, the radiation dose to the hands is high and often overlooked. In a comprehensive assessment of radiation doses during vascular interventional procedures, the average radiation dose to the hands of interventional surgeons during an abdominal aortic aneurysm treatment could reach 2000 μSv.

[0005] Although the International Commission on Radiological Protection (ICRP) recommends that operators wear lead gloves during radiological procedures, traditional lead gloves are relatively thick and heavy, hindering the interventionalist's tactile sensation and delicate manipulation. This also increases the risk of infection and lead poisoning, hindering their further clinical application. A radiation protection cream based on bismuth oxide ceramic powder, currently available in the United States, provides radiation protection, but suffers from several significant drawbacks. Each tube costs $41 (enough for only one procedure), significantly higher than the cost of ordinary latex gloves (US$5 per pair). Furthermore, the product faces potential sterility issues and the inconvenience of requiring repeated application. These limitations have severely hindered its widespread adoption in interventional clinical practice. Meanwhile, a radiation-protective skin cream has been recently developed. This cream uses bismuth oxide and barium sulfate, particles smaller than 4μm in diameter, as shielding materials, mixed with an aqueous organic carrier containing lubricants such as glycerin, surfactants, and emulsifiers. By adjusting the concentration, thickness, and mixing process parameters, the resulting skin cream's radiation protection properties have been significantly improved. However, this hand cream still has the rheological property of shear thinning, and will be squeezed as the hands move, resulting in uneven thickness at the joints, affecting the radiation protection effect. Summary of the Invention

[0006] The purpose of the present invention is to provide a radiation-proof hydrogel that can be used for interventional radiosurgery and its preparation method and application. 3+ Physical interactions with carboxyl groups bridge the polymer chains of sodium alginate and sodium hyaluronate, Fe 3+ The reversible interaction with the carboxyl group gives the hydrogel shear-thinning properties, ensuring its injectability; the incorporation of bismuth oxide nanoparticles and barium sulfate nanoparticles achieves efficient attenuation of X-rays in the 20-100keV range, and at the same time utilizes the complementary K-edge absorption characteristics of bismuth oxide nanoparticles and barium sulfate nanoparticles, combined with the radiation absorption effect of the hydrogel network structure itself, to achieve broad-spectrum radiation protection; and through the action of acrylamide thermal initiation polymerization, an interpenetrating network elastic hydrogel of the three polymers is formed, realizing the transition from injectable state to solid state. At this time, the cured hydrogel has strong mechanical properties and can also form a glove-like protective layer, which can be used for radiation protection in interventional surgery.

[0007] The technical solution of the present invention is: a method for preparing a radiation-proof hydrogel that can be used in interventional radiology surgery, comprising the following steps:

[0008] Step S1: adding sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, and potassium persulfate into deionized water at room temperature and stirring until dissolved to obtain a gel monomer solution;

[0009] Step S2: Dissolve EDTA-2Na in deionized water, then add ferric sulfate and ultrasonically dissolve to obtain Fe 3+ -EDTA complex solution;

[0010] Step S3: Under the action of a mechanical stirrer, the Fe 3+ -EDTA complex solution is added dropwise to the gel monomer solution obtained in step S1, and then bismuth oxide nanoparticles and / or barium sulfate nanoparticles are added and continuously stirred and mixed to obtain an injectable radiation-proof hydrogel;

[0011] Step S4: coating the injectable radiation-proof hydrogel obtained in step S3 on the surface of intraoperative radiation protection equipment, and then drying and curing in an oven to obtain a radiation-proof hydrogel that can be used in interventional radiology surgery.

[0012] As a preferred technical solution, in the gel monomer solution obtained in step S1:

[0013] The concentration of sodium alginate is 1.2-6.4 w / v%;

[0014] The concentration of sodium hyaluronate is 0.2-1.6 w / v%;

[0015] The concentration of acrylamide is 10-50 w / v%;

[0016] The concentration of N,N'-methylenebisacrylamide is 0.025% to 10w / v%;

[0017] The concentration of potassium persulfate is 0.1% to 1 w / v%.

[0018] As a preferred technical solution, in step S2, Fe 3+ The concentration of the -EDTA complex solution is 0.05 to 0.2M.

[0019] As a preferred technical solution, the total mass proportion of bismuth oxide nanoparticles and / or barium sulfate nanoparticles in the injectable radiation-proof hydrogel obtained in step S3 is 1 wt% to 50 wt%.

[0020] As a preferred technical solution, in step S3, the stirring speed of the mechanical stirrer is 500 to 2000 rpm;

[0021] At a speed of 500 to 1000 rpm, the Fe 3+ The EDTA complex solution is added dropwise to the gel monomer solution obtained in step S1; then, bismuth oxide nanoparticles and / or barium sulfate nanoparticles are added at a rotation speed of 1000-2000 rpm and stirred to mix evenly.

[0022] As a preferred technical solution, the drying and curing temperature in step S4 is: gradually increasing from room temperature to 40-80° C. within 60 minutes.

[0023] As a preferred technical solution, the thickness of the radiation-proof hydrogel that can be used for interventional radiology surgery obtained in step S4 is 1 to 5 mm.

[0024] A radiation-proof hydrogel for interventional radiosurgery prepared by the above method, comprising sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, potassium persulfate, Fe 3+ -EDTA complex, deionized water, and bismuth oxide nanoparticles and / or barium sulfate nanoparticles.

[0025] An application of the radiation-proof hydrogel for interventional radiology surgery as described above is to coat the injectable radiation-proof hydrogel on the surface of radiation protection equipment during surgery, and after drying and curing, use it as a radiation-proof protective layer for interventional radiology surgery.

[0026] The advantages of the present invention are:

[0027] 1. The radiation-proof hydrogel of the present invention is characterized by Fe 3+ Physical interactions with carboxyl groups bridge the polymer chains of sodium alginate and sodium hyaluronate, Fe 3+ The reversible interaction with the carboxyl group gives the hydrogel shear-thinning properties, ensuring its injectability; the incorporation of bismuth oxide nanoparticles and barium sulfate nanoparticles achieves efficient attenuation of X-rays in the 20-100keV range, and at the same time utilizes the complementary K-edge absorption characteristics of bismuth oxide nanoparticles and barium sulfate nanoparticles, combined with the radiation absorption effect of the hydrogel network structure itself, to achieve broad-spectrum radiation protection; and through the action of acrylamide thermal initiation polymerization, an interpenetrating network elastic hydrogel of the three polymers is formed, realizing the transition from injectable state to solid state. At this time, the cured hydrogel has strong mechanical properties and can also form a glove-like protective layer, which can be used for radiation protection in interventional surgery.

[0028] 2. The radiation-proof hydrogel of the present invention is lighter and more flexible, and can be used as a radiation-proof and antibacterial curable coating that does not affect delicate operations. It is injectable at room temperature and can be applied to the surface of intraoperative radiation protection equipment. It can be cured after heating. It is elastic and stretchable, has good mechanical properties, is not easy to be damaged, and can be used as a protective layer material similar to gloves.

[0029] 3. The radiation-proof hydrogel of the present invention can be used to coat the surface of intraoperative radiation protection gloves. It has excellent X-ray absorption performance, which can protect the doctor's hands during interventional surgery and reduce radiation damage. At the same time, it has good biocompatibility and antibacterial properties, making it suitable for use in surgical environments; it achieves a balance between protective effect and ease of use, providing a new perspective for radiation protection in interventional surgery. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. The drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0031] The present invention will be further described below with reference to the accompanying drawings and embodiments:

[0032] Figure 1 This is a schematic digital image of the coatable radiation-proof hydrogel of Example 1;

[0033] Figure 2 Graph showing the storage modulus (G') and loss modulus (G") of the metal-free hydrogel and the hydrogels of Examples 2 and 3 as a function of stress;

[0034] Figure 3 Graph showing the storage modulus (G') and loss modulus (G") of the metal-free hydrogel and the hydrogels of Examples 2 and 3 as a function of angular frequency;

[0035] Figure 4 This is a schematic diagram of the morphological changes of the hydrogel of Example 9 under different stretching states;

[0036] Figure 5 Schematic diagram of stress-strain curves of hydrogels with different component ratios (Examples 5, 6, 9, and 10) in tensile testing;

[0037] Figure 6 Schematic diagram of stress-strain curves and deformation photographs of the hydrogel of Example 9 under various torsional strains;

[0038] Figure 7 Schematic diagram of the stress-strain curve of the hydrogel in Example 9 during the stretching cycle test;

[0039] Figure 8 Schematic diagram of the stability of the hydrogel in Example 9 during a low-strain cycle test;

[0040] Figure 9 Schematic diagram of the cytotoxicity and antibacterial experiments of the metal-free hydrogel and the hydrogels of Examples 5, 6, 12, and 13;

[0041] Figure 10 This is a comparison chart of CCK-8 data of 3T3 cells using the metal-free hydrogel and the hydrogel extracts of Examples 5, 6, 12, and 13;

[0042] Figure 11 Schematic diagram of cell live-dead staining images after incubation of 3T3 cells with the metal-free hydrogel and the gel extracts of Examples 5, 6, 12, and 13 and treatment with AM / PI live-dead staining reagent;

[0043] Figure 12 This is a diagram of the antibacterial test of the hydrogels in Examples 5 and 6 using the coating plate method;

[0044] Figure 13 1 is a comparison chart of the antibacterial rate data of the metal-free hydrogel and the hydrogels of Examples 5 and 6;

[0045] Figure 14 The radiation device and demonstration diagram used for the test;

[0046] Figure 15 This is a comparison of images of the metal-free control group hydrogel and the hydrogel of Example 9 under X-ray irradiation;

[0047] Figure 16 The graph shows the relationship between the X-ray shielding efficiency of hydrogels with different metal components (Examples 4 to 11) and the tube voltage;

[0048] Figure 17 Graph showing the relationship between the mass absorption coefficient of the hydrogels of Examples 4 to 11 and the tube voltage. DETAILED DESCRIPTION

[0049] The above scheme is further described below in conjunction with specific examples. It should be understood that these examples are used to illustrate the present invention and are not intended to limit the scope of the present invention. The implementation conditions adopted in the examples can be further adjusted according to the conditions of the specific manufacturer. The implementation conditions not specified are generally those in routine experiments.

[0050] Example 1: Preparation of the coatable radiation-proof hydrogel 1:

[0051] Step S1: suspending 640 mg of sodium alginate and 160 mg of sodium hyaluronate in 20 mL of deionized (DI) water at room temperature and stirring with a mechanical stirrer until completely dissolved to prepare a gel monomer solution;

[0052] Step S2: Dissolve EDTA-2Na in deionized water, add ferric sulfate, and dissolve under ultrasonication to obtain 0.2MFe 3+ -EDTA complex solution;

[0053] Step S3: 3 mL of Fe 3+ The EDTA complex solution was added dropwise to 20 mL of the gel monomer solution, which was stirred at 1000 rpm on a mechanical stirrer. Stir for 1 minute to thoroughly mix. The stirring speed was then increased to 2000 rpm, and 10 g of bismuth oxide nanoparticles and 3.3 g of barium sulfate nanoparticles (the metal addition) were slowly added and stirred for 10 minutes. This resulted in a coatable radiation-protective hydrogel.

[0054] Example 2: Preparation of Coatable Radiation-Proofing Hydrogel 2:

[0055] The same as Example 1, except that in step S3 the amount of metal added is changed to: 100 mg of bismuth oxide nanoparticles and 100 mg of barium sulfate nanoparticles.

[0056] Example 3: Preparation of Coatable Radiation-Proofing Hydrogel 3:

[0057] The same as Example 1, except that in step S3 the amount of metal added is changed to: 525 mg of bismuth oxide nanoparticles and 525 mg of barium sulfate nanoparticles.

[0058] Example 4: Preparation of heat-cured radiation-proof hydrogel 1:

[0059] Step S1: suspending 640 mg of sodium alginate, 160 mg of sodium hyaluronate, 6 g of acrylamide, 60 mg of N,N'-methylenebisacrylamide, and 60 mg of potassium persulfate in 20 mL of deionized (DI) water at room temperature and stirring with a mechanical stirrer until completely dissolved to prepare a gel monomer solution;

[0060] Step S2: Dissolve EDTA-2Na in deionized water, add ferric sulfate, and dissolve under ultrasonication to obtain 0.2MFe 3+ -EDTA complex solution;

[0061] Step S3: 3 mL of Fe 3+ The -EDTA complex solution was added dropwise to 20 mL of the gel monomer solution stirred at 1000 rpm by a mechanical stirrer and stirred for 1 minute to mix thoroughly. The stirring speed was then increased to 2000 rpm, and 6.5 g of bismuth oxide nanoparticles (i.e., the metal addition amount) was slowly added and stirred for 10 minutes. At this time, a coatable radiation-proof hydrogel was obtained.

[0062] Step S4: After coating and filling a 5 mm deep mold, place it in an oven and gradually heat it from room temperature to 50°C. After 30 minutes, a solid radiation-proof hydrogel can be obtained.

[0063] Example 5: Preparation of heat-cured radiation-proof hydrogel 2:

[0064] The same as Example 4, except that in step S3 the amount of metal added was changed to: 4.875 g of bismuth oxide nanoparticles and 1.625 g of barium sulfate nanoparticles.

[0065] Example 6: Preparation of heat-cured radiation-proof hydrogel 3:

[0066] The same as Example 4, except that in step S3 the amount of metal added was changed to: 1.625 g of bismuth oxide nanoparticles and 4.875 g of barium sulfate nanoparticles.

[0067] Example 7: Preparation of heat-cured radiation-proof hydrogel 4:

[0068] The same as Example 4, except that the amount of metal added in step S3 is changed to 6.5 g of barium sulfate nanoparticles.

[0069] Example 8: Preparation of heat-cured radiation-proof hydrogel 5:

[0070] The same as Example 4, except that the amount of metal added in step S3 is changed to 17.3 g of bismuth oxide nanoparticles.

[0071] Example 9: Preparation of heat-cured radiation-proof hydrogel 6:

[0072] The same as Example 4, except that in step S3 the amount of metal added was changed to: 13 g of bismuth oxide nanoparticles and 4.3 g of barium sulfate nanoparticles.

[0073] Example 10: Preparation of heat-cured radiation-proof hydrogel 7:

[0074] The same as Example 4, except that in step S3 the amount of metal added was changed to: 4.3 g of bismuth oxide nanoparticles and 13 g of barium sulfate nanoparticles.

[0075] Example 11: Preparation of heat-cured radiation-proof hydrogel 8:

[0076] The same as Example 4, except that the amount of metal added in step S3 is changed to 17.3 g of barium sulfate nanoparticles.

[0077] Example 12: Preparation of heat-cured radiation-proof hydrogel 9:

[0078] The same as Example 4, except that in step S3 the amount of metal added was changed to: 1.03 g of bismuth oxide nanoparticles and 342 mg of barium sulfate nanoparticles.

[0079] Example 13: Preparation of heat-cured radiation-proof hydrogel 10:

[0080] The same as Example 4, except that in step S3 the amount of metal added was changed to: 342 mg of bismuth oxide nanoparticles and 1.03 g of barium sulfate nanoparticles.

[0081] Performance testing experiment 1:

[0082] The rheological properties of the hydrogels were analyzed using a rheometer under steady-state shear conditions. Five milliliters of each hydrogel were placed in a flat-plate rheometer at 25°C and subjected to oscillatory rheological testing within the linear viscoelastic region. Dynamic strain sweeps were performed at a frequency of 1 rad / s over the strain range from 0.01% to 100%, and at a strain of 0.1%, over a dynamic frequency range of 0.1 to 100 rad / s. The storage modulus, G', and loss modulus, G", were recorded during the test.

[0083] in Figure 1 This is a digital image schematic diagram of the radiation-proof hydrogel that can be applied in Example 1, showing that it has a viscous and uniform cream-like appearance.

[0084] Figure 2 and Figure 3 Schematic diagram of strain and angular frequency scanning measurement of the metal-free hydrogel and the coatable radiation-proof hydrogels of Examples 2 and 3 at 25°C; Figure 2 Figure 3 is a graph of the storage modulus (G') and loss modulus (G") versus strain, used to evaluate the linear viscoelastic region (LVR) and strain-dependent mechanical properties of hydrogel materials. For the metal-free hydrogels and hydrogels from Examples 2 and 3 (hydrogels containing 1% and 5% metal components (bismuth oxide nanoparticles and / or barium sulfate nanoparticles)), each component exhibits a steadily decreasing storage modulus with increasing strain. As can be seen from the curves, Example 3 (hydrogel containing 5% metal components (blue curve)) has the highest storage modulus, indicating that the metal component imparts a higher elastic response and mechanical strength to the material. It can also be seen that the shear strength of the material gradually decreases with increasing strain, exhibiting shear-thinning properties. Figure 3 The graph shows the storage modulus (G') and loss modulus (G") as a function of angular frequency, indicating the frequency response behavior of the hydrogel. In the metal-free hydrogel and samples with different metal addition contents, G' is always higher than G", indicating that the radiation-proof hydrogel of the present invention mainly exhibits solid-state elastic behavior within the frequency range studied. With the increase of metal content, both the storage modulus and the loss modulus increase significantly, among which the hydrogel with 5% metal content shows the best frequency-dependent behavior, and the storage modulus (G') exceeds 10,000Pa in the high frequency band, indicating that the high metal content improves the mechanical rigidity and energy storage capacity of the hydrogel, while also improving its anti-viscoelastic loss performance.

[0085] Performance testing experiment 2:

[0086] The hydrogels of Examples 5, 6, 9, and 10 were subjected to tensile tests and cyclic unloading tests using a universal testing machine. The hydrogels were cut into dumbbell shapes (12 mm × 2 mm) using a mold and the following experiments were performed:

[0087] 1. Perform uniaxial tensile test at a speed of 50 mm / min;

[0088] 2. After stretching the sample to a specific strain (10%, 20%, 30%, 50%, 100%), unload it to its initial state.

[0089] 3. The hydrogel was stretched to 20% strain and then unloaded to the initial level. The whole process was repeated 300 times.

[0090] 4. The hydrogel was stretched to 200% strain and then unloaded to its initial state, with the entire process repeated 50 times. All experiments were performed at room temperature, with each sample repeated at least three times.

[0091] in Figure 4 Figure 9 shows the morphological changes of the hydrogel from Example 9 under different stretching conditions. The left side shows an unstretched hydrogel sample, while the middle and right sides show its deformation at 100% and 2000% strain, respectively. This demonstrates that the hydrogel has excellent tensile properties and can withstand stretching up to 2000% without breaking.

[0092] Figure 5 The stress-strain curves of hydrogels (Examples 5, 6, 9, and 10) with different component ratios during tensile testing are shown (percentages are metal mass fractions, with the preceding ratio representing the ratio of the two metal additions). Overall, increasing the (bismuth oxide and / or barium sulfate) nanoparticle content significantly enhanced the tensile modulus and tensile strength of the hydrogels. In particular, the hydrogel with a 3 bismuth oxide nanoparticle:1 barium sulfate nanoparticle ratio of 40% (Example 9) exhibited the best mechanical properties, with maximum fracture strain and fracture stress reaching 2030% and 1.30 MPa, respectively.

[0093] Figure 6 The stress-strain curves and deformation photographs of the hydrogel from Example 9 are shown at various torsional strains (ε = 10%, 20%, 30%, 50%, and 100%). The results demonstrate that the hydrogel maintains good deformation recovery even at high torsional strains, demonstrating excellent tolerance to torsional deformation.

[0094] Figure 7 The stress-strain curves of the hydrogel from Example 9 during the stretching cycle test (cycles 1 to 50) are shown. The curves stabilize with increasing stretching cycles, indicating that the material maintains good mechanical properties during repeated stretching and exhibits high cyclic durability.

[0095] Figure 8The stability of the hydrogel of Example 9 was further demonstrated in low-strain cyclic tests (1 to 300 cycles). The results indicate that although the stress slightly decays with increasing cycle number, the material as a whole exhibits high cyclic recovery and has good service life and stability.

[0096] comprehensive Figures 4 to 8 As shown, the radiation-proof hydrogel of the present invention exhibits excellent tensile properties, torsional properties and good cyclic stability, indicating that it has durability and application potential under harsh usage conditions.

[0097] Performance testing experiment 3:

[0098] The cytotoxicity of the metal-free hydrogel (SHA) and the hydrogels of Examples 5, 6, 12, and 13 was evaluated using 3T3 cells. 3T3 cells were cultured in DMEM complete medium containing 10% fetal bovine serum and 1% penicillin-streptomycin at 37°C in a 5% CO2 incubator. 1 g of the hydrogel was immersed in 10 mL of DMEM complete medium for 72 h to obtain an extract (0.1 g / mL). 3T3 cells were seeded in 96-well plates at an initial cell density of 5 × 10 3 / well, incubate for 24 hours until the cells adhere. Afterwards, the experimental group (n=5) added the extract, and the control group added complete culture medium, and incubated with 3T3 cells at 37°C for 24 hours and 48 hours, and the cell viability was analyzed using a CCK-8 kit. The formula for calculating cell viability is: cell viability (%) = (OD value of the experimental group - OD value of the control group) / OD value of the control group × 100%. Finally, 3T3 cells were stained with an AM / PI live-dead staining kit, and the activity of 3T3 cells was observed using an inverted fluorescence microscope.

[0099] The antibacterial properties of the metal-free hydrogel (SHA) and the hydrogels of Examples 5, 6, 12, and 13 were evaluated using the spread plate method and colony counting method. Staphylococcus epidermidis was inoculated in LB broth and grown overnight at 37°C with shaking at 75 rpm. The bacterial suspension was then collected, centrifuged at 1000 rpm for 10 minutes, washed with PBS, and concentrated to 1×10 7 CFU / mL concentration was resuspended in LB broth. Afterwards, 5 mL of pre-sterilized hydrogel was added to 10 mL of bacterial broth and incubated at 37 ° C, 150 rpm for 12 hours. The collected bacterial suspension was diluted 10 times and spread on a nutrient agar plate, cultured under appropriate conditions for 12-24 hours and photographed. Finally, the colony count was performed using imageJ software and the antibacterial properties of the SHA composite hydrogel were calculated. Calculation formula: Inhibition rate (%) = (number of colonies in the control group - number of colonies in the experimental group) / number of colonies in the control group × 100%.

[0100] in Figure 9 Schematic diagram of the cytotoxicity and antibacterial experiments of the metal-free hydrogel (SHA) and the hydrogels of Examples 5, 6, 12, and 13; Figure 10 This is a comparison of the CCK-8 data of the metal-free hydrogel (SHA) and the hydrogel extracts of Examples 5, 6, 12, and 13 on 3T3 cells. It can be seen that the hydrogels of different components all have good biocompatibility. Cell viability analysis of the hydrogel extracts of different components was performed after incubation with 3T3 cells for 24 or 48 hours using the CCK-8 assay. The results show that all materials have good biocompatibility with cells at certain concentrations. The intensity of the green fluorescence signal indicates that all materials have good cell compatibility.

[0101] Figure 11 Schematic diagram of cell live-dead staining of 3T3 cells treated with AM / PI live-dead staining reagent after incubation of metal-free hydrogel (SHA) and gel extracts of Examples 5, 6, 12, and 13, which also demonstrates good biocompatibility.

[0102] Figure 12 and Figure 13 The antibacterial test of the hydrogels in Examples 5 and 6 using the coating plate method and the antibacterial rate data of the hydrogels indicate that the hydrogels have significant antibacterial properties against Staphylococcus epidermidis.

[0103] Performance testing experiment 4:

[0104] The integrated test setup was constructed using a medical rotating anode X-ray tube (MWHX7360A, Ming Wei, China) and a radiation dose monitor (i2x, RaySafe, Sweden). The radiation shielding effectiveness of hydrogels of varying mass, ratio, and thickness was evaluated by adjusting the tube voltage (20, 40, 60, 80, 100, and 120 kV) to generate monoenergetic X-ray photons in the 20-120 keV range while maintaining the tube current at 80 mA.

[0105] Shielding effectiveness (SE) is calculated using the following formula:

[0106]

[0107] Where I0 and I are the emission dose and transmission dose of the X-ray tube, respectively.

[0108] The mass absorption coefficient (MAC) is calculated according to the following formula:

[0109]

[0110] where ln is the natural logarithm, ρ is the density thickness of the material, and MAC is the X-ray mass absorption coefficient.

[0111] Figure 14 The radiation device and demonstration diagram used for testing.

[0112] Figure 15 Comparison of X-ray images of a metal-free control hydrogel and the hydrogel sample from Example 9. The X-ray image of the control hand, uncoated with the radiation-shielding gel, is clear, with visible bone structure. However, in the experimental group covered with the radiation-shielding hydrogel, the X-rays are clearly shielded, with the bone area obscured, further validating the shielding properties of the hydrogel material.

[0113] Figure 16 The relationship between the X-ray shielding efficiency of hydrogels with different metal components (Examples 4-11) and tube voltage is shown. This demonstrates the excellent X-ray shielding effectiveness of the hydrogels of the present invention. At a low tube voltage of 20 kV, hydrogels containing 40% bismuth oxide nanoparticles or mixed bismuth oxide nanoparticles / barium sulfate nanoparticles (Examples 8-10) both achieved near-100% shielding efficiency.

[0114] Figure 17 The relationship between the mass absorption coefficient (Mass Absorption Coefficient) and the tube voltage in Examples 4 to 11 is shown in FIG. Figure 16 and Figure 17 In the figure, the percentage is the total mass fraction of bismuth oxide nanoparticles and barium sulfate nanoparticles, and the proportion behind is the ratio of bismuth oxide nanoparticles to barium sulfate nanoparticles).

[0115] In summary, the radiation-proof hydrogel prepared by the present invention exhibits excellent X-ray shielding performance through the addition of (such as bismuth oxide nanoparticles, barium sulfate nanoparticles and their composite systems), and the material thickness and metal content (bismuth oxide nanoparticles and / or barium sulfate nanoparticles) have a significant impact on the shielding efficiency and absorption capacity, indicating that the optimized formula of this material is suitable for a variety of radiation environments.

[0116] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the present invention. Anyone skilled in the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by one of ordinary skill in the art without departing from the spirit and technical principles disclosed herein are intended to be covered by the claims of the present invention.

Claims

1. A method for preparing a radiation-proof hydrogel that can be used for interventional radiosurgery, characterized in that: The following steps are involved: Step S1: adding sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, and potassium persulfate into deionized water at room temperature and stirring until dissolved to obtain a gel monomer solution; Step S2: Dissolve EDTA-2Na in deionized water, then add ferric sulfate and ultrasonically dissolve to obtain Fe 3+ -EDTA complex solution; Step S3: Under the action of a mechanical stirrer, the Fe 3+ -EDTA complex solution is added dropwise to the gel monomer solution obtained in step S1, and then bismuth oxide nanoparticles and / or barium sulfate nanoparticles are added and continuously stirred and mixed to obtain an injectable radiation-proof hydrogel; Step S4: coating the injectable radiation-proof hydrogel obtained in step S3 on the surface of intraoperative radiation protection equipment, and then drying and curing in an oven to obtain a radiation-proof hydrogel that can be used in interventional radiology surgery.

2. The method for preparing the radiation-proof hydrogel that can be used for interventional radiosurgery according to claim 1, characterized in that: In the gel monomer solution obtained in step S1: The concentration of sodium alginate is 1.2-6.4 w / v%; The concentration of sodium hyaluronate is 0.2-1.6 w / v%; The concentration of acrylamide is 10-50 w / v%; The concentration of N,N'-methylenebisacrylamide is 0.025% to 10w / v%; The concentration of potassium persulfate is 0.1% to 1 w / v%.

3. The method for preparing the radiation-proof hydrogel that can be used for interventional radiosurgery according to claim 1, characterized in that: In step S2, Fe 3+ The concentration of the -EDTA complex solution is 0.05 to 0.2M.

4. The method for preparing the radiation-proof hydrogel for interventional radiosurgery according to claim 1, wherein: The total mass proportion of bismuth oxide nanoparticles and / or barium sulfate nanoparticles in the injectable radiation-proof hydrogel obtained in step S3 is 1 wt% to 50 wt%.

5. The method for preparing the radiation-proof hydrogel that can be used for interventional radiosurgery according to claim 1, characterized in that: In step S3, the stirring speed of the mechanical stirrer is 500 to 2000 rpm; At a speed of 500 to 1000 rpm, the Fe 3+ The EDTA complex solution is added dropwise to the gel monomer solution obtained in step S1; then, bismuth oxide nanoparticles and / or barium sulfate nanoparticles are added at a rotation speed of 1000-2000 rpm and stirred to mix evenly.

6. The method for preparing the radiation-proof hydrogel that can be used for interventional radiosurgery according to claim 1, characterized in that: The drying and curing temperature in step S4 is gradually increased from room temperature to 40-80° C. within 60 minutes.

7. The method for preparing the radiation-proof hydrogel for interventional radiosurgery according to claim 1, wherein: In step S4, the thickness of the radiation-proof hydrogel that can be used for interventional radiology surgery is 1 to 5 mm.

8. A radiation-proof hydrogel for use in interventional radiology surgery prepared by the method according to any one of claims 1 to 7, characterized in that: Including sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, potassium persulfate, Fe 3+ -EDTA complex, deionized water, and bismuth oxide nanoparticles and / or barium sulfate nanoparticles.

9. A use of the radiation-proof hydrogel for interventional radiology surgery as claimed in claim 8, characterized in that: The injectable radiation-proof hydrogel is coated on the surface of intraoperative radiation protection equipment, dried and solidified, and used as a radiation-proof protective layer for interventional radiology surgery.

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