Preparation of core-shell structure hydrogel and application thereof in preparation of magnetically controlled flexible micro robot

Abstract

The application discloses preparation of a core-shell structure hydrogel and application of the core-shell structure hydrogel in preparation of a magnetic control flexible micro robot, and belongs to the technical field of biomedical soft micro robot. The application adopts a core-shell structure to construct a hydrogel micro robot, wherein, a vanadium disulfide nanosheet rich in sulfur defects is used as a functional inner core, and has magnetic response and photoacoustic imaging capacity; a polyacrylamide polymer chain is used as a flexible outer shell, free radical initiation is carried out on the surface of the vanadium disulfide through vanadium-sulfur dynamic coordination bonds, and simple amide bond hydrogen bond crosslinking endows the hydrogel with three-dimensional printable performance. The prepared flexible micro robot can realize precise controllable movement under the action of an external magnetic field, and can realize robot posture monitoring and navigation positioning functions with the aid of photoacoustic imaging capacity, and has good application prospect in the fields of drug delivery, minimally invasive surgery and tissue treatment.

Description

Technical Field

[0001] This invention belongs to the field of biomedical soft microrobot technology, specifically relating to the preparation of a core-shell structured hydrogel and its application in the preparation of magnetically controlled flexible microrobots. Background Technology

[0002] Flexible microrobots are robotic devices constructed from flexible materials, capable of controlled deformation and precise movement in response to external stimuli. Compared to traditional rigid microrobots, flexible microrobots possess biomechanical compatibility, deformability, and environmental adaptability, making them more suitable for operation in confined, complex, and soft biological environments. Based on their response to external stimuli, flexible intelligent robots are categorized into magnetically responsive, electrically responsive, thermally responsive, optically responsive, and chemically responsive types. Among these various types of microrobots, magnetically responsive robots have become an important research direction in the field of flexible microrobots due to their advantages such as remote non-contact control, fast response speed, and strong tissue penetration capabilities.

[0003] In recent years, flexible microrobots have developed rapidly, showing broad application prospects in drug delivery, minimally invasive surgery, and tissue therapy. However, most current magnetically driven systems rely mainly on rolling, tumbling, and dragging motions, resulting in relatively simple movement patterns and a lack of structural design and magnetic orientation alignment capabilities. Furthermore, existing magnetically driven flexible robots largely focus on achieving motion functions, generally lacking effective imaging feedback and navigation and positioning capabilities, making it difficult to achieve real-time monitoring of motion posture and position, thus limiting their further application in the biomedical field. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a method for preparing a core-shell hydrogel and its application in the fabrication of magnetically controlled flexible microrobots. This invention utilizes vanadium-sulfur dynamic coordination bonds to initiate the formation of a core-shell structure via surface free radicals. Sulfur-rich defective vanadium disulfide nanosheets serve as a functional core possessing both magnetic response and photoacoustic imaging capabilities, while polyacrylamide polymer chains form a flexible outer shell. The polymer chains are cross-linked via simple amide and hydrogen bonds, endowing the system with 3D printing properties. During the printing process, an external magnetic field is applied to regulate the orientation of the core-shell structure, thereby achieving magnetic alignment and endowing the flexible microrobot with magnetic alignment and photoacoustic imaging capabilities.

[0005] The method for preparing the core-shell structured hydrogel of the present invention includes the following steps:

[0006] Step 1: Synthesis of vanadium disulfide nanosheets rich in sulfur defects

[0007] The vanadium source and sulfur source are added to deionized water and mixed evenly. The mixture is then transferred to a stainless steel reactor lined with polytetrafluoroethylene, sealed, and placed in an oven for hydrothermal reaction. After the reaction is completed and cooled to room temperature, the product is removed, washed with ethanol and deionized water, and dried in a vacuum drying oven to obtain vanadium disulfide nanosheets rich in sulfur defects.

[0008] Step 2: Synthesis of core-shell hydrogels

[0009] The vanadium disulfide nanosheets rich in sulfur defects were placed in deionized water with a thiol-type photoinitiator, and the adsorption of the initiator on the nanosheet surface was promoted by near-infrared light irradiation to obtain a precursor solution. Acrylamide monomer was then added to the precursor solution and dissolved completely by ultrasonic treatment. Finally, the mixture was placed in a photocuring chamber and irradiated with visible light from a xenon lamp filtered through a 420 nm cutoff filter for 25 minutes to obtain a core-shell structured hydrogel.

[0010] In step 1, the vanadium source is ammonium metavanadate, and the sulfur source is thiourea, with a molar ratio of vanadium source to sulfur source of 1:15. For example, 0.1 mmol of ammonium metavanadate and 1.5 mmol of thiourea are added to 30 ml of deionized water.

[0011] In step 1, the hydrothermal reaction temperature is 160 ℃ and the reaction time is 12 h.

[0012] In step 1, the temperature of the vacuum drying oven is 40℃ and the drying time is 8 hours.

[0013] In step 2, the structural formula of the thiol-type photoinitiator is as follows:

[0014] .

[0015] In step 2, the mass ratio of sulfur-defect-rich vanadium disulfide nanosheets, thiol-type photoinitiator, and acrylamide monomer is 40-60 mg: 1-4 mg: 0.6-0.7 g.

[0016] In step 2, the near-infrared light wavelength is 808 nm, and the irradiation time is 10-20 min.

[0017] In step 2, the light curing light source is a xenon lamp equipped with a 420 nm cutoff filter. The curing time is 20-30 minutes.

[0018] The application of the core-shell structured hydrogel of this invention in the fabrication of magnetically controlled flexible microrobots.

[0019] Specifically, it includes:

[0020] A 3D printing device for fabricating flexible microrobots is constructed by assembling an air pump, a dispensing device, and a commercial 3D printer in a coordinated manner. The core-shell structured hydrogel is placed as ink in a dispensing syringe, and under the pressure of the air pump, it is extruded through a dispensing needle with a magnetic field. The resulting magnetically oriented flexible robot is then printed on a 3D printer platform along a pre-defined path.

[0021] The air pump delivers air at a pressure of 60-90 psi.

[0022] The applied magnetic field at the dispensing needle tip is 20-200 mT.

[0023] The printing speed is controlled between 1 and 10 mm / s.

[0024] This invention utilizes surface free radical initiation to construct a core-shell flexible microrobot in situ. A sulfur-rich defective vanadium disulfide, possessing both magnetic response and photoacoustic imaging capabilities, serves as the functional core, while polyacrylamide polymer chains form the flexible shell. Simple hydrogen bonding between amide bonds imparts 3D printability to the system. During printing, an external magnetic field is applied to achieve directional alignment of the core-shell structure, thereby achieving magnetic orientation alignment and endowing the flexible microrobot with magnetic orientation alignment and photoacoustic imaging navigation capabilities.

[0025] The beneficial effects of this invention are reflected in:

[0026] This invention provides a simple and easy-to-implement method for fabricating a photoacoustic imaging-guided magnetically controlled flexible microrobot. First, by adjusting the ratio of vanadium to sulfur sources, a simple hydrothermal method can enrich sulfur vacancy defects in VS2 nanosheets. The resulting defect states can introduce local electronic states and modulate the local electronic structure, thereby improving the magnetic response and photoacoustic imaging capabilities of the VS2 nanosheets. This novel nanomaterial successfully integrates magnetic response and photoacoustic imaging capabilities, overcoming the limitations of traditional magnetic response materials (which have limited properties for imaging and navigation) and traditional photoacoustic imaging materials (which cannot be driven). Second, this invention uses polyacrylamide polymer chains as a flexible substrate, which possesses good flexibility and biocompatibility. Simple hydrogen bonding between polyacrylamide molecules imparts good printability and shape retention to the system. During printing, an external magnetic field is applied to achieve the directional alignment of the "core-shell" structure, thereby achieving magnetic orientation alignment and endowing the flexible robot with controllable magnetic response and diverse motion capabilities. Furthermore, relying on the excellent photoacoustic imaging capabilities of the sulfur-rich defect-state vanadium disulfide nanosheets, the fabricated flexible microrobot can achieve real-time monitoring of its motion posture and spatial position, helping to expand its application prospects in drug delivery, minimally invasive surgery, and tissue therapy.

[0027] In summary, this invention achieves the integration of magnetic orientation alignment, magnetically controllable motion, and photoacoustic imaging navigation and positioning of flexible microrobots through defect manipulation, core-shell structure construction, and magnetic field-assisted printing, thus expanding the application of flexible microrobots in the field of medicine and biology. Attached Figure Description

[0028] Figure 1 SEM images of vanadium disulfide nanosheets prepared with different V:S ratios are shown, with the left image showing V:S=1:2 and the right image showing V:S=1:15. Figure 1 It can be seen that both samples have a two-dimensional sheet-like structure.

[0029] Figure 2 These are atomic force microscope images of the vanadium disulfide nanosheets prepared according to this invention. From Figure 2 As can be seen, the vanadium disulfide nanosheets are 20 nm thick, indicating that they have a thin sheet structure and belong to typical two-dimensional nanosheet materials.

[0030] Figure 3 The image shows the X-ray diffraction pattern of the vanadium disulfide nanosheets prepared in this invention. The obtained sample exhibits obvious characteristic diffraction peaks at the corresponding diffraction angles, and each diffraction peak is basically consistent with the standard diffraction peaks of vanadium disulfide, indicating that the prepared sample has good crystallinity. This proves that the vanadium disulfide nanosheets were successfully synthesized.

[0031] Figure 4 Hysteresis loops of vanadium disulfide nanosheets with different sulfur defect ratios. Figure 4 It is known that vanadium disulfide nanosheets possess remanence and coercivity, and the higher the proportion of sulfur defects, the greater the remanence magnetization, indicating that sulfur defects can enhance their magnetic response performance.

[0032] Figure 5 Photoacoustic signal intensity diagrams of vanadium disulfide nanosheets with different sulfur defect ratios. Figure 5 It can be seen that the prepared vanadium disulfide nanosheets have photoacoustic signal response, and the higher the proportion of sulfur defects, the greater the photoacoustic signal intensity, indicating that sulfur defects can enhance its photoacoustic imaging performance.

[0033] Figure 6 These are transmission electron microscope images of the core-shell structured material prepared in this invention. From... Figure 6 As can be seen, the obtained sample exhibits obvious core-shell structure characteristics, with the deeper internal region corresponding to the functional core and the shallower external region corresponding to the coating layer, indicating that the core-shell structure was successfully constructed in this invention.

[0034] Figure 7 This represents the response of a magnetically responsive flexible robot to an external magnetic field. From... Figure 7As can be seen, the prepared flexible robot has controllable directional motion under the action of an external magnetic field, indicating that it has good magnetic orientation alignment ability and magnetic response performance.

[0035] Figure 8 Photoacoustic imaging images of a magnetically responsive flexible robot during its motion, from Figure 8 As can be seen, the prepared flexible robot has a clearly visible photoacoustic imaging signal in its posture during movement, indicating that it has good photoacoustic imaging navigation capability.

[0036] Figure 9 These are photoacoustic images of a single hydrogel fiber at different depths in chicken tissue. The left image shows optical photographs of the hydrogel fiber placed at different depths within the chicken tissue, and the right image shows the corresponding photoacoustic images. Figure 9 It can be seen that the prepared hydrogel fiber can be clearly imaged at a depth of 30 mm, indicating that it has good depth photoacoustic imaging capability.

[0037] Figure 10 These are real-time photoacoustic images of an "H"-shaped flexible microrobot within chicken tissue ducts. The left image is an optical photograph of the chicken tissue ducts, and the right image shows the real-time photoacoustic imaging result of the flexible microrobot within the ducts. Figure 10 It can be seen that the prepared flexible microrobot can achieve real-time photoacoustic imaging in tissue channels, indicating that it has photoacoustic navigation and attitude feedback capabilities. Detailed Implementation

[0038] The present invention will be further described below with reference to specific embodiments, so that those skilled in the art can better understand and implement the present invention, but the embodiments are not intended to limit the present invention.

[0039] Example 1: Complete Synthesis Steps of Sulfur-Defective Vanadium Disulfide-Based Core-Shell Hydrogel Ink

[0040] 1. Synthesis of vanadium disulfide with sulfur-rich defects

[0041] 0.0936 g of ammonium metavanadate and 0.9132 g of thiourea were dissolved in 30 mL of deionized water and stirred thoroughly for 30 min. The resulting solution was then transferred to a polytetrafluoroethylene (PTFE) reactor and placed in an oven at 160 °C for 12 h. After the reaction was complete and the reactor cooled to room temperature, the precipitate at the bottom of the reactor was collected and repeatedly washed with ethanol and deionized water to remove unreacted solution and related impurities. Finally, the precipitate was dried in a vacuum oven at 40 °C for 8 h to obtain sulfur-rich defect vanadium disulfide nanosheet powder.

[0042] 2. Adsorption of thiol-type photoinitiators

[0043] 2 mg of 2-methyl-1-[4-(methylthio)phenyl]-2-morpholino-1-propanone (Irgacure 907) and 60 mg of vanadium disulfide nanosheets prepared in step 1 were added to 5 ml of deionized water and sonicated for 3 min to ensure thorough dispersion. Under sealed conditions, an 808 nm near-infrared laser (2 W / cm²) was used for dispersion. 2 Irradiate for 20 minutes, ensuring continuous stirring of the solution during the irradiation process to guarantee uniform adsorption. After irradiation, allow the solution to cool to room temperature to obtain a vanadium disulfide nanosheet solution with adsorbed photoinitiator.

[0044] 3. Polymerization of core-shell hydrogel inks

[0045] 0.7 g of acrylamide monomer was added to the vanadium disulfide nanosheet solution containing the photoinitiator from step 2, and sonicated for 3 min to ensure complete dispersion. The resulting homogeneous solution was placed in a vacuum drying oven to remove dissolved oxygen, and then a glass slide was placed on top of the solution and irradiated with a xenon lamp (wavelength range: 420 nm to 780 nm) for 25 min. After cooling to room temperature, the core-shell hydrogel ink was obtained.

[0046] Example 2: Demonstration of magnetic drive for a magnetically responsive flexible robot

[0047] 1. Fabrication of magnetically oriented flexible robots

[0048] 10 g of core-shell hydrogel ink was loaded into a 30 cc dispensing syringe. A 34 G dispensing printing needle was attached to the front end of the syringe, and the rear end was connected to an air pump. The syringe was then fixed to a 3D printing device, and an external ring magnet was added to the dispensing needle. Following a pre-defined printing path, hydrogel fibers were deposited onto the 3D printing platform at a moving speed of 1 mm / s. After printing, the resulting flexible robot was removed from the printing platform and stored in a constant temperature and humidity chamber for later use.

[0049] 2. Demonstration of magnetic drive for magnetically oriented flexible robots

[0050] To simulate the viscosity environment of human blood plasma, the actuation demonstrations of the flexible robot were all conducted in liquid paraffin. By designing different printing paths, hydrogel monofilaments with a length of 2 mm and a diameter of 60 μm were printed. Due to the different printing paths, the orientation and arrangement of the magnetic nanosheets inside the resulting hydrogel monofilaments varied, thus leading to different magnetic actuation states for each hydrogel fiber. Subsequently, the hydrogel fibers printed using the different paths were placed in 60 mm plastic petri dishes filled with liquid paraffin, and a parallel magnetic field of 200 mT was applied to each. The macroscopic deformation of each hydrogel fiber was then observed.

[0051] 3. Demonstration of the motion patterns of a magnetically oriented flexible robot

[0052] A flexible microrobot in the shape of an "H" with a geometric dimension of 2×1 mm was printed using a pre-designed path. The hydrogel fibers of the "H"-shaped robot are all 60 μm in diameter, and the magnetic alignment of two parallel hydrogel fibers with a length of 2 mm is opposite. The flexible microrobot was placed in a 60 mm diameter plastic petri dish filled with liquid paraffin, and the direction of the applied magnetic field was periodically changed at a frequency of 2 Hz to observe its motion. The demonstration results are as follows: Figure 7 As shown.

[0053] Example 3: Photoacoustic Imaging Demonstration of a Magnetic Response Flexible Robot

[0054] 1. Preparation of agarose gel matrix

[0055] Weigh 0.75 g of agar powder and add it to 50 ml of deionized water. Place the resulting solution on a 120 ℃ hot platen and stir until it becomes homogeneous and transparent. Then pour the solution into a cylindrical mold with a length of 5 cm and a diameter of 2 cm, and allow it to cool to room temperature and solidify. Subsequently, insert a 5 cm long and 5 mm diameter transparent polypropylene plastic tube into the resulting solid agar to obtain the agar gel matrix for photoacoustic imaging.

[0056] 2. Photoacoustic imaging of flexible microrobots of different shapes

[0057] Flexible microrobots of different shapes were prepared according to Example 2. These microrobots were placed inside polypropylene tubes coated with agar gel, and liquid paraffin was slowly injected into the tubes to ensure no air bubbles were present. The ends of the plastic tubes were then sealed with glue. The materials were placed in the laser chamber of a photoacoustic imaging instrument for photoacoustic testing. After the first photoacoustic imaging was completed, a magnetic field was applied to change the shape of the robot, and the photoacoustic test was performed again. This yielded photoacoustic images of the flexible microrobots of different shapes, as shown in the image below. Figure 8 As shown.

[0058] 3. Photoacoustic imaging tests at different depths

[0059] Single hydrogel fibers were prepared according to Example 2, with geometric dimensions of 2 mm in length and 60 μm in diameter. Two chicken tissue samples, each with geometric dimensions of 42 mm in length, 42 mm in width, and 5 mm in thickness, were taken. The single hydrogel fibers were evenly arranged on the surface of one of the chicken samples, with a total of 8 fibers and a spacing of 5 mm between fibers. The other chicken sample was then placed on top to construct embedding samples at different depths. Finally, the resulting chicken pieces were fixed in a photoacoustic imaging chamber, with the laser direction perpendicular to the thickness direction of the chicken tissue, and the relevant photoacoustic imaging signals were acquired. The test results are as follows: Figure 9 As shown.

[0060] 4. Photoacoustic real-time monitoring and imaging of magnetically responsive flexible robots

[0061] An "H"-shaped flexible microrobot was prepared according to Example 2. A piece of chicken meat, 40 mm long, 40 mm wide, and 5 mm thick, was repeatedly pierced through its interior with a fine filament along a predetermined direction to form a channel required for magnetically driven movement. The "H"-shaped flexible microrobot was then placed in the internal channel, and both ends of the channel were sealed with glue. The chicken meat was then placed in a photoacoustic imaging chamber, with a laser beam incident perpendicular to the thickness of the chicken meat. A 2 Hz parallel magnetic field was applied outside the chamber to drive the movement of the internal flexible microrobot. Finally, a photoacoustic imaging test was performed on the chicken meat sample every 10 seconds, and the test results are as follows: Figure 10 As shown.

[0062] In summary, this invention provides a method for fabricating a magnetically driven flexible microrobot capable of photoacoustic imaging navigation. First, vanadium disulfide nanosheets with sulfur-rich defects were prepared using an excess sulfur source-inhibited crystallization method. These defect states can introduce localized electronic states and modulate the local electronic structure, thereby improving the magnetic response and photoacoustic imaging capabilities of the vanadium disulfide nanosheets. Subsequently, a "core-shell" hydrogel ink was prepared, with vanadium disulfide with sulfur-rich defects as the functional core and polyacrylamide polymer chains as the flexible shell. The magnetic orientation of the flexible microrobot was achieved by modifying the 3D printing device and applying an external magnetic field during the printing process, thus enabling controllable and precise magnetically driven motion. Finally, a photoacoustic imaging system was used to achieve real-time monitoring, positioning, and navigation of the magnetic flexible microrobot. This contributes to expanding the application of flexible microrobots in the pharmaceutical and biotechnology fields.

[0063] Comparative Example 1:

[0064] 1. Synthesis of vanadium disulfide with low sulfur defects

[0065] Vanadium disulfide nanosheets were prepared according to the method described in step 1 of Example 1, wherein the amount of thiourea added was changed to 0.1218 g, and the amount of ammonium metavanadate added, the volume of deionized water, the hydrothermal reaction temperature, the hydrothermal reaction time, the washing conditions and the drying conditions were kept consistent with those in Example 1, thus obtaining low-sulfur defect vanadium disulfide powder.

[0066] 2. Adsorption of thiol-type photoinitiators

[0067] The low-sulfur defect vanadium disulfide powder obtained in step 1 was used to replace the sulfur-rich defect vanadium disulfide powder in Example 1, and the adsorption of the mercapto-type photoinitiator was carried out using the method described in step 2 of Example 1.

[0068] 3. Polymerization of core-shell hydrogel inks

[0069] The low-sulfur defect vanadium disulfide nanosheet solution with adsorbed photoinitiator obtained in step 2 was used to replace the vanadium disulfide nanosheet solution with adsorbed photoinitiator in Example 1, and the core-shell hydrogel ink was polymerized using the method described in step 3 of Example 1.

[0070] The above embodiments are only used to illustrate the technical solutions of the present invention and do not constitute a limitation on the scope of protection of the present invention. Equivalent changes or substitutions made within the scope of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing a core-shell structured hydrogel, characterized in that: First, vanadium disulfide nanosheets rich in sulfur defects are synthesized by an excess sulfur source-inhibited crystallization method. The vanadium disulfide nanosheets rich in sulfur defects are then dispersed in an aqueous solution containing a thiol-type photoinitiator. The adsorption of the thiol-type photoinitiator on the vanadium disulfide nanosheets is promoted by photothermal response, thereby obtaining a vanadium disulfide nanosheet precursor solution with a surface-loaded photoinitiator. Subsequently, acrylamide monomer is added to the precursor solution, and free radical initiation on the surface of vanadium disulfide is carried out by light irradiation to synthesize a hydrogel with a core-shell structure.

2. The preparation method according to claim 1, characterized in that... Includes the following steps: Step 1: Synthesis of vanadium disulfide nanosheets rich in sulfur defects The vanadium source and sulfur source are added to deionized water and mixed evenly. The mixture is then transferred to a stainless steel reactor lined with polytetrafluoroethylene, sealed, and placed in an oven for hydrothermal reaction. After the reaction is completed and cooled to room temperature, the product is removed, washed with ethanol and deionized water, and dried in a vacuum drying oven to obtain vanadium disulfide nanosheets rich in sulfur defects. Step 2: Synthesis of core-shell hydrogels The vanadium disulfide nanosheets rich in sulfur defects were placed in deionized water with a thiol-type photoinitiator, and the adsorption of the initiator on the surface of the nanosheets was promoted by near-infrared light irradiation to obtain a precursor solution. Acrylamide monomer was then added to the precursor solution and dissolved completely by ultrasonic treatment. Finally, the mixture was placed in a photocuring chamber for photocuring to obtain a core-shell structured hydrogel.

3. The preparation method according to claim 2, characterized in that: In step 1, the vanadium source is ammonium metavanadate, the sulfur source is thiourea, and the molar ratio of the vanadium source to the sulfur source is 1:

15.

4. The preparation method according to claim 2, characterized in that: In step 1, the hydrothermal reaction temperature is 160 ℃ and the reaction time is 12 h.

5. The preparation method according to claim 2, characterized in that: In step 2, the structural formula of the thiol-type photoinitiator is as follows: 。 6. The preparation method according to claim 5, characterized in that: In step 2, the mass ratio of sulfur-defect-rich vanadium disulfide nanosheets, thiol-type photoinitiator, and acrylamide monomer is 40-60 mg: 1-4 mg: 0.6-0.7 g.

7. The preparation method according to claim 2, characterized in that: In step 2, the near-infrared light wavelength is 808 nm, and the irradiation time is 10-20 min.

8. The preparation method according to claim 2, characterized in that: In step 2, the light curing light source is a xenon lamp equipped with a 420 nm cutoff filter, and the light curing time is 20-30 min.

9. The application of the core-shell structured hydrogel prepared by any one of claims 1-8 in the preparation of magnetically controlled flexible microrobots, characterized in that: The core-shell structured hydrogel is placed as ink in a dispensing syringe. Under the pressure of an air pump, it is extruded through a dispensing needle with a magnetic field and printed on a 3D printer platform through a preset path to obtain a magnetically oriented flexible robot.

10. The application according to claim 9, characterized in that: The applied magnetic field at the dispensing needle tip is 20-200 mT.

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