3D-printed helical biodegradable anti-inflammatory vascular stent and preparation method thereof

Abstract

This invention discloses a 3D-printed helical biodegradable anti-inflammatory vascular stent and its preparation method, belonging to the field of vascular stents. The invention uses multiple helical support wires arranged into a tubular shape, with the ends connected in a serpentine transitional manner. The helical support wires are connected by connecting ribs, and the surface is coated. This invention is biodegradable after use, avoiding the harm caused by permanent retention in the body, and has a lower restenosis rate compared to metal stents. The surface of the vascular stent is coated with a spermidine-containing coating to prevent immune rejection of the implanted vascular stent, thereby addressing the problems of inflammation and intimal hyperplasia. The helical structure facilitates contraction and expansion, has good bending flexibility, and the added connecting ribs increase the radial support performance of the vascular stent, better achieving the effect of vascular remodeling. This invention has significant implications in terms of biodegradability, anti-immune rejection, and mechanical properties, and can be used for treatment in different locations such as peripheral and coronary vessels.

Description

Technical Field

[0001] This invention relates to vascular stents, specifically to a 3D-printed spiral biodegradable anti-inflammatory vascular stent and its preparation method. Background Technology

[0002] In recent years, the incidence of vascular diseases has been increasing year by year, resulting in a huge demand for vascular stents and a significant market potential. However, existing vascular stent materials and structures have many problems. In terms of materials, traditional metal stents remain permanently in the body, leading to problems such as late-stage in-stent restenosis and target lesion revascularization, which can harm human health. 3D printing technology has provided a new approach to the fabrication of vascular stents, and biodegradable vascular stents based on polymers have become a research hotspot. However, biodegradable materials can still trigger an immune rejection response in the human immune system, causing inflammation and significantly reducing the long-term patency rate in clinical practice.

[0003] Structurally, the polymers that make up biodegradable vascular stents provide insufficient radial strength for vascular remodeling and have poorer mechanical properties compared to metal stents, making them prone to complications such as acute stent collapse and late-stage rupture. Traditional stent structures, such as hexagonal or rhomboid pore structures, exhibit good shrinkage performance when fabricated as metal stents; however, their shrinkage performance is poor when fabricated as 3D-printed biodegradable vascular stents. Although 3D printing of vascular stents represents a cutting-edge development in medical implants and can meet patients' specific needs through personalized customization, the differences in mechanical properties between non-metallic and traditional metallic materials limit the available printable structures, making it difficult to meet all requirements.

[0004] Therefore, it is of great significance to develop a biodegradable vascular stent that can combine excellent mechanical properties with anti-inflammatory response. Summary of the Invention

[0005] To address the problems existing in the prior art, this invention proposes a 3D-printed spiral biodegradable anti-inflammatory vascular stent and its preparation method, which has excellent mechanical properties and anti-inflammatory characteristics.

[0006] One objective of this invention is to provide a 3D-printed spiral biodegradable anti-inflammatory vascular stent.

[0007] The 3D-printed spiral biodegradable anti-inflammatory vascular stent of the present invention comprises: a spiral support wire, a transition connecting arc, connecting ribs, and a coating; wherein, multiple parallel spiral support wires are arranged at equal intervals along the axial direction and uniformly distributed circumferentially to form a tubular shape, and the ends of two adjacent spiral support wires are connected sequentially by a transition connecting arc to form a complete closed spiral support body; the spiral support wires have an angle with the axis; two adjacent spiral support wires are connected by multiple uniformly distributed connecting ribs to form a set of connecting ribs; two adjacent sets of connecting ribs are staggered, with each set of connecting ribs closer to the end without a transition connecting arc and farther away from the end with a transition connecting arc; the spiral support body and the connecting ribs constitute a spiral support skeleton, and the surface of the spiral support skeleton is coated with a coating containing spermidine to form a vascular stent.

[0008] The helical support skeleton is immersed in a hydrogel solution containing spermidine to form a coating on its surface. The vascular stent is then placed in a cross-linking agent solution, and the coating is fixed to the surface of the helical support skeleton.

[0009] The spiral support skeleton is made of biodegradable polymer materials, which are one or more of polylactic acid (PLA), polyglycolic acid (PAG), polycaprolactone (PCL) and polylactic-glycolic acid copolymer (PLGA).

[0010] The length of the vascular stent can be set from 6 to 200 mm according to clinical needs. The inner diameter of the vascular stent is 3 to 8 mm, which can meet the treatment needs of different sites such as peripheral blood vessels and coronary blood vessels.

[0011] The horizontal dimension of the connecting ribs and spiral support wires is 0.1~0.5mm, and the cross-sectional shape of the connecting ribs and spiral support wires is approximately circular, with the horizontal dimension of the circle being the diameter.

[0012] The number of helical support wires is 2N, corresponding to N transition connection arcs at each end of the vascular stent, where 3 ≤ N ≤ 8. The angle between the helical support wire and the axis is 15°~165°. The shape of the transition connection arc is a circular arc or an elliptical arc; if it is a circular arc, its radius is 0.5~2.5mm.

[0013] The number of connecting ribs in a group is determined by the number of spiral support wires. A group with 6 spiral support wires has 2-5 connecting ribs, a group with 8 spiral support wires has 2-7 connecting ribs, a group with 10 spiral support wires has 2-9 connecting ribs, and so on, with a group with 16 spiral support wires having 2-15 connecting ribs. The shape of the connecting ribs can be a straight line or an arc.

[0014] Biomechanical analysis is used to determine the length, inner diameter, diameter and number of helical support wires, and the angle between the helical support wires and the axis of the vascular stent. Biomechanical analysis of vascular stents can include: fluid-structure interaction finite element simulation analysis, three-point bending experiments, and radial compression experiments. Biomechanical analysis is used to assess the bending flexibility, radial support, and compliance of the vascular stent. Parameters that significantly affect mechanical properties include the diameter and number of helical support wires. A larger diameter enhances the radial support performance of the vascular stent but weakens its flexibility and contractility; a higher number of helical support wires enhances radial support but weakens flexibility and contractility. Therefore, a higher diameter and number of helical support wires are not necessarily better; these mechanical properties must be considered comprehensively. Simulating the state of the vascular stent in a blood vessel and measuring the deformation of the stent in a real blood environment assesses the stent's compliance in the blood vessel. The number of helical support wires is related to the amount of deformation; a higher number of helical support wires results in less stent deformation.

[0015] The vascular stent used in this invention is printed by a 3D bioprinting device. The 3D bioprinting device includes: an ink cartridge, a printhead, a temperature control module, a pressure control device, a rotation axis drive module, a rotating rod, a two-dimensional moving device, and a computer. The ink cartridge contains a biodegradable polymer material. The printhead is located at the bottom of the ink cartridge, and the temperature control module is located on the surface of the ink cartridge. The printhead is connected to the pressure control device. A rotating rod is mounted on the rotation axis of the rotation axis drive module, driving the rotating rod to rotate around the rotation axis. The ink cartridge is mounted on the two-dimensional moving device, which moves the ink cartridge in a two-dimensional direction, with the printhead positioned above the rotating rod. The temperature control module, pressure control device, rotation axis drive module, and two-dimensional moving device are all connected to the computer.

[0016] The two-dimensional moving device includes a linear module and a motor. A controller controls the motor's operation, driving the linear module to move up and down and left and right. The linear module includes a pair of horizontal slide rails and a pair of vertical slide rails. The ink cartridge is mounted on the pair of horizontal slide rails that move horizontally, parallel to the rotation axis. The pair of horizontal slide rails are mounted on the pair of vertical slide rails that move vertically. The diameter of the rotating rod matches the inner diameter of the vascular stent; the diameter of the printhead matches the diameter of the connecting ribs and the spiral support wire.

[0017] Another objective of this invention is to provide a method for preparing a 3D-printed spiral biodegradable anti-inflammatory vascular stent.

[0018] The method for preparing a 3D-printed helical biodegradable anti-inflammatory vascular stent of the present invention includes the following steps:

[0019] 1) Set the structure of the vascular stent in the computer; put the biodegradable polymer material into the ink cartridge; the temperature control module heats the temperature inside the ink cartridge to the set temperature to melt the biodegradable polymer material;

[0020] 2) The rotary shaft drive module drives the rotary rod to rotate, and the two-dimensional moving device controls the printing nozzle to translate along the axis. The pressure control device controls the extrusion pressure of the molten polymer material ejected from the printing nozzle. Polymer material is printed on the outer side of the rotating rod. Multiple spiral support filaments are connected end to end in a serpentine transition connection arc to form a complete closed spiral support body. Multiple evenly distributed connecting ribs are printed between two adjacent spiral support filaments to form a spiral support skeleton.

[0021] 3) After the spiral support frame has cooled and solidified, peel it off from the rotating rod;

[0022] 4) Preparation of hydrogel solution: Dissolve gelatin and sodium alginate in water and stir at the set temperature until completely dissolved. Then add spermidine and stir evenly to form a hydrogel solution.

[0023] 5) The vascular stent is immersed in the hydrogel solution to ensure that the helical support skeleton is fully and evenly wrapped, forming a coating on the surface of the helical support skeleton. It is then quickly placed in the cross-linking agent solution to allow the coating to solidify on the surface of the helical support skeleton. After that, it is removed, the surface moisture is removed, and the vascular stent is obtained.

[0024] In step 1), the structure of the vascular stent includes: the length and inner diameter of the vascular stent, the diameter and number of spiral support wires, and the angle between the spiral support wires and the axis. The temperature control module controls the temperature of the ink cartridge to 60~380°C; the polymer material in the ink cartridge is a solid material, and the melting point of the polymer material used for 3D printing is not a fixed value, but varies significantly with the material, with an overall temperature range covering 60°C~380°C. Accelerated heating to above the melting point of the polymer material is required, so higher heating temperature and efficiency are necessary. To ensure it can withstand a high temperature of 380°C, the ink cartridge and printhead are made of heat-resistant metal with better heat transfer properties; the heating temperature is set not lower than the melting point of the corresponding biodegradable polymer material, and approximately 5~50°C higher than its melting point.

[0025] In step 2), the distance between the print head and the rotating shaft is adjusted to 0.1~1mm; the biodegradable polymer material is melted and then ejected by air pressure, with an extrusion pressure of 0.1~0.6MPa.

[0026] In step 3), the static cooling time of the spiral support frame is 1 to 5 minutes. After the spiral support frame has cooled and set, it can be removed.

[0027] In step 4), the concentration of gelatin is 1-5 wt%, the concentration of sodium alginate is 1-5 wt%, and the mixture is stirred evenly at 25-45°C; the concentration of spermidine is 50-250 μM; and the gelatin, sodium alginate, and spermidine are dissolved in water.

[0028] In step 5), the sample is immersed in the hydrogel solution for 2-10 minutes to ensure that the helical support framework is fully and uniformly encapsulated; then immersed in the crosslinking agent solution for 2-10 minutes; the crosslinking agent solution is a solution containing divalent or trivalent metal ions, wherein the divalent metal ion is Ca. 2+ Mg 2+ or Zn 2+ The trivalent metal ion is Fe 3+ Al 3+ or Cr 3+ Divalent and trivalent metal ions dissolve in water or buffers.

[0029] Advantages of this invention:

[0030] (1) 3D printed vascular stents can be degraded after meeting the requirements for use, avoiding the harm caused by the stent being permanently left in the body. At the same time, the restenosis rate is lower compared with metal stents.

[0031] (2) The surface of the vascular stent is coated with a coating containing spermidine, which can prevent the immune system from rejecting the implanted vascular stent, thereby solving the problems of inflammatory response and intimal hyperplasia.

[0032] (3) The spiral structure facilitates contraction and expansion, has good bending flexibility, and the addition of connecting ribs increases the radial support performance of the vascular stent, thus better achieving the effect of vascular remodeling.

[0033] Therefore, this invention is of great significance in terms of degradability, resistance to immune rejection, and mechanical properties. Attached Figure Description

[0034] Figure 1 This is a schematic diagram of one embodiment of the 3D bioprinting device of the present invention;

[0035] Figure 2 This is a perspective view of a first embodiment of the 3D-printed spiral biodegradable anti-inflammatory vascular stent of the present invention;

[0036] Figure 3 This is a plan view of a first embodiment of the 3D-printed spiral biodegradable anti-inflammatory vascular stent of the present invention;

[0037] Figure 4 This is a partial enlarged view of the end portion of a first embodiment of the 3D-printed spiral biodegradable anti-inflammatory vascular stent of the present invention.

[0038] Figure 5 This is a perspective view of a second embodiment of the 3D-printed spiral biodegradable anti-inflammatory vascular stent of the present invention;

[0039] Figure 6 This is a plan view of a second embodiment of the 3D-printed spiral biodegradable anti-inflammatory vascular stent of the present invention.

[0040] Figure 7 This is a partial enlarged view of the end portion of Embodiment 2 of the 3D-printed spiral biodegradable anti-inflammatory vascular stent of the present invention. Detailed Implementation

[0041] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0042] The 3D-printed helical biodegradable anti-inflammatory vascular stent comprises: helical support wires, transition connecting arcs, connecting ribs, and a coating. Multiple parallel helical support wires are arranged at equal intervals along the axial direction and uniformly distributed circumferentially, forming a tubular structure. The ends of adjacent helical support wires are connected sequentially by transition connecting arcs, forming a complete closed support body. The helical support wires form an angle with the axis. Adjacent helical support wires are connected by multiple evenly distributed connecting ribs, forming a set of connecting ribs. Adjacent sets of connecting ribs are staggered, with each set of connecting ribs closer to the end without a transition connecting arc and further away from the end with a transition connecting arc. The helical support body and connecting ribs constitute a helical support skeleton, and the surface of the helical support skeleton is coated with a spermidine-containing coating, forming the vascular stent.

[0043] like Figure 1 As shown, the 3D bioprinting device includes: an ink cartridge 1, a print head 3, a temperature control module 2, a pressure control device 4, a rotary axis drive module 5, a rotating rod 6, a two-dimensional moving device, and a computer. The ink cartridge 1 contains biodegradable polymer material. The print head 3 is located at the bottom of the ink cartridge 1, and the temperature control module 2 is located on the surface of the ink cartridge 1. The print head 3 is connected to the pressure control device 4. A rotating rod 6 is mounted on the rotary axis of the rotary axis drive module 5, driving the rotating rod 6 to rotate around the rotary axis. The ink cartridge 1 is mounted on the two-dimensional moving device, which moves the ink cartridge 1 in a two-dimensional direction. The print head 3 is located on the rotating rod 6. The temperature control module 2, pressure control device 4, rotary axis drive module 5, and two-dimensional moving device are all connected to the computer.

[0044] The two-dimensional moving device includes a linear module and a motor. The controller controls the rotation of the motor, which drives the linear module to move up and down and left and right. The linear module includes a pair of horizontal slide rails and a pair of vertical slide rails. The ink cartridges are located on the pair of horizontal slide rails that move in the horizontal direction, and the horizontal slide rails are parallel to the rotation axis. The pair of horizontal slide rails are located on the pair of vertical slide rails that move in the vertical direction.

[0045] Example 1

[0046] like Figures 2 to 4 As shown, the vascular stent of this embodiment includes eight helical support wires arranged at equal intervals along the axial direction and evenly distributed circumferentially. The ends are connected in a serpentine manner by transitional connecting arcs. Each end has four circumferentially evenly distributed transitional connecting arcs. The cross-sectional shape of the helical support wires and the transitional connecting arcs is circular with a diameter of 0.5 mm. The length of the vascular stent is 36 mm, the inner diameter is 6 mm, and the outer diameter is 6.5 mm. The angle between the helical support wires and the axis is 30°. The transitional connecting arcs are circular arcs with a radius of 0.94 mm. The connecting ribs and the material supporting the main body of the vascular stent are made of biodegradable polycaprolactone (PCL).

[0047] The connecting ribs are evenly distributed along the axial and circumferential directions, connecting two adjacent helical support wires. Four connecting ribs are distributed circumferentially, with two helical support wires spaced between each adjacent circumferential connecting rib; four connecting ribs are distributed axially, with four helical support wires spaced between each adjacent axial connecting rib. The diameter of the connecting ribs is consistent with the diameter of the helical support wires and the printhead, ensuring connection strength without affecting the overall flexibility of the support structure.

[0048] The method for preparing the 3D-printed spiral biodegradable anti-inflammatory vascular stent in this embodiment includes the following steps:

[0049] 1) Design vascular stents through biomechanical analysis. The design parameters of vascular stents include: the length, inner diameter, number of stents, diameter of the helical support wire, and the angle between the helical support wire and the axis.

[0050] Biodegradable polycaprolactone is placed inside the ink cartridge; the temperature control module heats the ink cartridge to 100°C, melting the biodegradable polymer material; the diameter of the rotating rod is 6mm, the diameter of the print head is 0.5mm, and the distance between the print head and the rotating shaft support is adjusted to 0.5mm.

[0051] 2) The rotary shaft drive module drives the rotating rod to rotate, and the two-dimensional moving device controls the printing nozzle to translate axially. The pressure control device controls the extrusion pressure of the molten polymer material ejected from the printing nozzle to be 0.2MPa. Polymer material is printed on the outer side of the rotating rod to form a spiral support filament. A transition connecting arc is printed at the end of the spiral support filament. The two-dimensional moving device controls the printing nozzle to translate in the opposite direction axially, and the rotary shaft drive module drives the rotating rod to rotate in the same direction. The transition connecting arc is connected to continue printing the next spiral support filament. The above steps are repeated until the last spiral support filament is printed. The last spiral support filament is connected to the first spiral support filament by a transition connecting arc printed on the same side, forming a complete closed spiral support body. Multiple evenly distributed connecting ribs are printed between adjacent spiral support filaments to form a spiral support skeleton.

[0052] 3) After standing for 2 minutes to cool and solidify, peel the spiral support frame off the rotating rod;

[0053] 4) Preparation of hydrogel solution: Gelatin and sodium alginate were dissolved in a water-containing culture medium with a gelatin concentration of 3 wt% and a sodium alginate concentration of 1 wt%. The mixture was stirred at 37°C until completely dissolved. Then, spermidine was added and stirred until homogeneous to form a hydrogel solution with a spermidine concentration of 200 μM. Anhydrous calcium chloride was weighed quantitatively, dissolved in pure water, and stirred until completely dissolved to prepare a 100 mM calcium chloride solution as a crosslinking agent solution.

[0054] 5) After immersing the vascular stent in the hydrogel solution for 5 minutes, remove it to ensure that the spiral support skeleton is fully and evenly wrapped and a coating is formed on the surface of the spiral support skeleton; quickly place it in the calcium chloride solution to allow the coating to solidify on the surface of the spiral support skeleton, remove it after 2 minutes, remove the surface moisture, and obtain the vascular stent.

[0055] Example 2

[0056] like Figures 4 to 6 As shown, the vascular stent of this embodiment includes 10 helical support wires arranged at equal intervals along the axial direction and uniformly distributed circumferentially, each end having 5 circumferentially evenly distributed transition connecting arcs; the vascular stent has a length of 36 mm, an inner diameter of 6 mm, and an outer diameter of 6.5 mm; the angle between the helical support wires and the axis is 30°; the transition connecting arcs are circular arcs with a radius of 0.8 mm. The connecting ribs and the supporting body of the vascular stent are made of biodegradable polylactic acid (PLA).

[0057] The method for preparing the 3D-printed spiral biodegradable anti-inflammatory vascular stent in this embodiment includes the following steps:

[0058] 1) Place biodegradable polylactic acid into the ink cartridge; the temperature control module heats the ink cartridge to 180°C, and adjusts the distance between the print head and the rotating shaft support to 1mm, otherwise the same as in Example 1;

[0059] 2) The extrusion pressure of the molten polymer material ejected from the printhead is 0.18 MPa, and other parameters are the same as in Example 1;

[0060] 3) After standing for 1 minute to cool and solidify, peel the spiral support frame off the rotating rod;

[0061] 4) The concentration of gelatin is 5 wt%, the concentration of spermidine is 100 μM, and the rest is the same as in Example 1; anhydrous calcium chloride is weighed quantitatively, dissolved in pure water, and stirred until completely dissolved to prepare a calcium chloride solution with a concentration of 120 mM as a crosslinking agent solution.

[0062] 5) After immersing the helical support skeleton in the hydrogel solution for 5 minutes, remove it to ensure that the helical support skeleton is fully and evenly wrapped and a coating is formed on the surface of the helical support skeleton; quickly put it into the calcium chloride solution to allow the coating to solidify on the surface of the helical support skeleton. After 5 minutes, remove it, remove the surface moisture, and obtain the vascular stent.

[0063] The contractile performance of the vascular stent is obtained by twisting its two ends in opposite directions. The contractile performance is related to the diameter and number of helical support wires; the larger the diameter of the helical support wire, the worse the contractile performance, and the more helical support wires, the worse the contractile performance.

[0064] Finally, it should be noted that the purpose of disclosing the embodiments is to help further understand the present invention. However, those skilled in the art will understand that various substitutions and modifications are possible without departing from the spirit and scope of the present invention and the appended claims. Therefore, the present invention should not be limited to the content disclosed in the embodiments, and the scope of protection of the present invention is defined by the claims.

Claims

1. A 3D-printed spiral biodegradable anti-inflammatory vascular stent, characterized in that, The vascular stent comprises: helical support wires, transition connecting arcs, connecting ribs, and a coating; wherein, multiple parallel helical support wires are arranged at equal intervals along the axial direction and uniformly distributed circumferentially, forming a tubular shape, and the ends of two adjacent helical support wires are connected sequentially by transition connecting arcs to form a complete closed helical support body; the helical support wires have an angle with the axis; two adjacent helical support wires are connected by multiple uniformly distributed connecting ribs to form a set of connecting ribs; two adjacent sets of connecting ribs are staggered, with each set of connecting ribs closer to the end without a transition connecting arc and farther away from the end with a transition connecting arc; the helical support body and connecting ribs constitute a helical support skeleton, and the surface of the helical support skeleton is coated with a coating containing spermidine, thus forming the vascular stent.

2. The vascular stent according to claim 1, characterized in that, The material of the spiral support skeleton is a biodegradable polymer material, which is one or more of polylactic acid, polyglycolic acid, polycaprolactone and polylactic acid-glycolic acid copolymer.

3. The vascular stent according to claim 1, characterized in that, The length of the vascular stent is 6-200 mm; the inner diameter of the vascular stent is 3-8 mm.

4. The vascular stent according to claim 1, characterized in that, The number of spiral support wires is 2N, and the number of transition connection arcs at each end of the corresponding vascular stent is N, where 3≤N≤8; the angle between the spiral support wire and the axis is 15°~165°.

5. The vascular stent according to claim 1, characterized in that, The shape of the transition connection arc is a circular arc or an elliptical arc.

6. A method for preparing a 3D-printed spiral biodegradable anti-inflammatory vascular stent according to any one of claims 1 to 5, characterized in that, The preparation method includes the following steps: 1) Set the structure of the vascular stent in the computer; put the biodegradable polymer material into the ink cartridge; the temperature control module heats the temperature inside the ink cartridge to the set temperature to melt the biodegradable polymer material; 2) The rotary shaft drive module drives the rotary rod to rotate, and the two-dimensional moving device controls the printing nozzle to translate along the axis. The pressure control device controls the extrusion pressure of the molten polymer material ejected from the printing nozzle. Polymer material is printed on the outer side of the rotating rod. Multiple spiral support filaments are connected end to end in a serpentine transition connection arc to form a complete closed spiral support body. Multiple evenly distributed connecting ribs are printed between two adjacent spiral support filaments to form a spiral support skeleton. 3) After the spiral support frame has cooled and solidified, peel it off from the rotating rod; 4) Preparation of hydrogel solution: Dissolve gelatin and sodium alginate in water and stir at the set temperature until completely dissolved. Then add spermidine and stir evenly to form a hydrogel solution. 5) The vascular stent is immersed in the hydrogel solution to ensure that the helical support skeleton is fully and evenly wrapped, and a coating is formed on the surface of the helical support skeleton; it is then placed in a cross-linking agent solution to allow the coating to solidify on the surface of the helical support skeleton, and then removed to remove surface moisture, thus obtaining the vascular stent.

7. The preparation method according to claim 6, characterized in that, In step 1), the structure of the vascular stent includes: the length of the vascular stent, the inner diameter, the diameter and number of spiral support wires, and the angle between the spiral support wire and the axis.

8. The preparation method according to claim 6, characterized in that, In step 2), the distance between the print head and the rotating shaft is adjusted to 0.1~1mm; the extrusion pressure of the polymer material is 0.1~0.6MPa.

9. The preparation method according to claim 6, characterized in that, In step 4), the concentration of gelatin is 1-5 wt%, the concentration of sodium alginate is 1-5 wt%, and the mixture is stirred evenly at 25-45°C; the concentration of spermidine is 50-250 μM.

10. The preparation method according to claim 6, characterized in that, In step 5), the sample is immersed in a hydrogel solution for 2-10 minutes; then immersed in a crosslinking agent solution for 2-10 minutes; the crosslinking agent solution is a solution containing divalent or trivalent metal ions, wherein the divalent metal ion is Ca. 2+ Mg 2+ or Zn 2+ The trivalent metal ion is Fe. 3+ Al 3+ or Cr 3+ .

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