4D printed bamboo fiber lumen stent and preparation method thereof

Abstract

The invention relates to a 4D printed bamboo fiber lumen stent and a preparation method thereof, and belongs to the technical field of medical instruments. In order to solve the problems that an existing shape memory lumen stent is poor in mechanical durability and the interfacial compatibility of natural fibers and shape memory polymers is poor, the 4D printing bamboo fiber lumen stent is provided and is prepared from continuous bamboo fibers and the shape memory polymers, and the volume fraction of the continuous bamboo fibers is 15-60%. According to the method, the interface performance of the continuous bamboo fibers and the shape memory polymer is optimized through instantaneous heat treatment, and the mechanical durability of the lumen stent is remarkably improved. Due to the shape memory characteristic, the stent can be tightly attached to the inner wall of a lumen and can better adapt to a complex physiological environment, and stent displacement risks and complications are reduced. The composite coating is prepared on the surface of the lumen stent, so that the biocompatibility and the antibacterial property of the lumen stent are further improved, and an innovative and effective solution is provided for clinical treatment of diseases such as lumen stenosis or fistulous tracts.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical devices, and in particular relates to a 4D printed bamboo fiber luminal stent and a preparation method thereof. Background Art

[0002] Luminal stents are tubular prostheses made of high-performance medical materials, designed to solve the problems of stenosis, occlusion and dilatation of human vascular and non-vascular lumens, or to be used to insert new channels to maintain their patency, such as vascular stents, tracheal stents, biliary stents, etc.

[0003] Traditional metal stents are permanent foreign bodies that remain in the body for a long time, which is a major pain point of current stents. In contrast, degradable polymers can gradually degrade in the body, avoiding the risk of secondary surgery. However, for conventional polymer materials, standardized stents are difficult to fully match individuals, which is usually manifested in that stents with too large diameters are difficult to implant, while stents with too small diameters are prone to slippage in the body.

[0004] Shape memory polymers such as shape memory polylactic acid are degradable materials with functional properties such as shape memory and shape adaptation, which meet the requirements of biomedical implants for special material properties. Through 4D printing technology, personalized customization of luminal stents can be achieved, and the shape memory effect of shape memory polymers can be used for minimally invasive implantation in the body. Under stimulation, the shape memory polymers can be restored to their original shape and fit the adjacent tissues, thereby reducing the complexity and complications of the operation and solving the problem that traditional implants cannot perfectly adapt to individual differences in patients.

[0005] Although shape memory polymers have unique advantages in luminal stent applications, their brittleness and rapid degradation may lead to structural collapse, which is a problem that still needs to be solved in medical applications with high mechanical performance requirements.

[0006] The flexibility and strength of polymers are usually enhanced by adding continuous fibers such as carbon fibers, glass fibers, or aramid fibers. However, considering the biocompatibility issues in living organisms, biomass continuous fibers become ideal reinforcement materials that can improve the flexibility of polymers, delay degradation, and enhance biocompatibility.

[0007] Biomass continuous fibers have the advantages of being renewable, environmentally friendly and biodegradable. For example, silk fiber / PLA composites are used in bone repair and renewable scaffolds due to their high strength and biocompatibility, and hemp fibers and their composites are used in surgical implants and wound dressings. However, disadvantages such as poor interface compatibility, poor durability, weak impact resistance and production temperature restrictions limit the application of natural fibers in luminal scaffolds. Summary of the invention

[0008] In order to solve the problems of poor mechanical durability of existing shape memory tubular cavity stents and poor interface compatibility between natural fibers and shape memory polymers, the present invention provides a 4D printed bamboo fiber tubular cavity stent and a preparation method thereof.

[0009] The technical solution of the present invention:

[0010] A 4D printed bamboo fiber tubular cavity stent, the tubular cavity stent is a mesh tube structure with openings at both ends, the basic structural unit of the mesh tube structure is a rhombus, the preparation raw materials of the tubular cavity stent include a reinforcing phase and a matrix material, the reinforcing phase is continuous bamboo fiber, the matrix material is a shape memory polymer, and the volume fraction of the continuous bamboo fiber is 15-60%.

[0011] Furthermore, it also includes a composite coating covering the outer surface of the mesh tube structure, and the thickness of the composite coating is 50 to 200 μm.

[0012] Furthermore, the shape memory polymer is one or a combination of polylactic acid, polyvinyl alcohol, polyurethane, polycaprolactone, polystyrene, polyethylene oxide, and polydimethylsiloxane.

[0013] A method for preparing a 4D printed bamboo fiber luminal scaffold, the steps are as follows:

[0014] Step 1: Bamboo material processing;

[0015] The bamboo material is subjected to delignification treatment, drying and fiber separation in sequence to obtain single bamboo fiber;

[0016] Step 2, preparing continuous bamboo fibers;

[0017] The single bamboo fiber obtained in step 1 is twisted, knotted or glued to form continuous bamboo fiber;

[0018] Step 3: 4D printing to prepare the luminal stent;

[0019] The continuous bamboo fiber and shape memory polymer obtained in step 2 are used as printing materials, and a horizontal rotating shaft is set. During the printing process, the rotating shaft rotates in a circle around the axis. When the print head moves horizontally in the radial direction of the rotating shaft, the molten printing material is deposited on the rotating shaft. Through the horizontal reciprocating movement of the print head, a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft, and a 4D printed bamboo fiber tubular stent is obtained after molding.

[0020] Furthermore, the bamboo material in step 1 is four-year-old natural bamboo material, and the delignification treatment is to immerse the cut bamboo material without bamboo nodes in a 20-60wt% peroxyformic acid solution at 40-60°C for 12-36 hours; the drying is freeze-drying, and the fiber separation is to obtain single bamboo fibers with a length of 50 cm and an average diameter of 50-200 μm by a mechanical separation method.

[0021] Furthermore, the twisting degree of the twisting in step 2 is 2 to 10 twists / cm; the diameter of the continuous bamboo fiber is 100 to 2000 μm, and the axial tensile performance of the continuous bamboo fiber is not less than 80 MPa.

[0022] Furthermore, during the printing process of step three, the angle of the rhombus basic structural unit is controlled by adjusting the ratio of the print head movement speed to the linear speed of the rotation axis around the axis, the acute angle of the rhombus basic structural unit is α, and the ratio of the print head movement speed to the linear speed of the rotation axis around the axis is the trigonometric function tanα. When the linear speed of the rotation axis around the axis is constant, the print head movement speed is the linear speed of the rotation axis around the axis × tanα.

[0023] Furthermore, in step three, the diameter of the rotating shaft is 0.1-20 mm, the rotation speed of the rotating shaft around the axis is 1-50 r / min, and the moving speed of the print head is 10-1000 mm / min.

[0024] Furthermore, in step 3, the temperature of the print head is 190-220° C., the printing thickness is 0.1-2 mm, and the print head reciprocates horizontally along the radial direction of the rotation axis for 2-10 cycles.

[0025] Furthermore, the deformation temperature of the 4D printed bamboo fiber luminal scaffold prepared in step three is 35-80°C.

[0026] A preparation method for a 4D printed bamboo fiber endoluminal stent, wherein the preparation method of the composite coating is as follows: the preparation method of the composite coating is as follows: preparing raw materials according to the mass volume ratio of silver nanoparticles, dichloromethane, N,N-dimethylformamide and polycaprolactone PCL of 0.096g:8mL:8mL:2.4g, ultrasonically dispersing the silver nanoparticles into an equal volume mixture of dichloromethane DCM and N,N-dimethylformamide DMF to obtain a suspension, and then dissolving polycaprolactone in the suspension to obtain a PCL / DCM / DMF@AgNPs spinning solution, using the obtained PCL / DCM / DMF@AgNPs spinning solution as a raw material to form a uniform composite coating on the outer surface of a mesh tube structure of a bamboo fiber endoluminal stent obtained by 4D printing through electrospinning.

[0027] Furthermore, the feed speed of the electrospinning is 0.05-0.09 mm / min, the rotation speed of the tubular stent receiving electrode is 50-200 r / min, the receiving distance between the nozzle and the tubular stent receiving electrode is 15 cm, the voltage is a positive voltage of 8-11 kV and a negative voltage of -4-0 kV, the electrospinning time is 0.2-2 h, the temperature is room temperature, and the relative humidity is 45%.

[0028] Beneficial effects of the present invention:

[0029] The present invention adds continuous bamboo fiber as a reinforcing phase to the shape memory polymer, and optimizes the interface performance of the continuous bamboo fiber and the shape memory polymer through instantaneous heat treatment, which significantly improves the mechanical durability of the luminal stent, can provide long-term support effects, and reduce the need for secondary surgery. After thousands of three-point bending cycles, the luminal stent prepared by the present invention still maintains excellent support performance; extreme load tests have proved that its flexibility far exceeds that of conventional polymer stents.

[0030] The present invention adopts 4D printing technology to prepare the luminal stent, which can design and manufacture personalized geometric structures based on the medical imaging data of the patient's specific luminal structure to meet different clinical needs. In addition, the shape memory property of the luminal stent enables it to actively adjust the shape and size of the mesh tube structure under temperature stimulation, closely fit the inner wall of the lumen, better adapt to the complex physiological environment of different lumens, and reduce the risk of stent displacement and complications.

[0031] The present invention further performs surface treatment on the luminal stent, prepares a composite coating on the outer surface of the mesh tube structure of the bamboo fiber luminal stent to improve its biocompatibility, and adds silver nanoparticles to the composite coating to improve its antibacterial properties. Cell and animal experiments have verified that the luminal stent provided by the present invention has good biocompatibility, can support the growth and differentiation of luminal epithelial cells, and provides an innovative and effective solution for the clinical treatment of diseases such as luminal stenosis or fistulas. It has important application value in improving the quality of life of patients and the treatment effect, showing its great potential in medical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is a schematic diagram of a diamond-shaped basic structural unit of a 4D printed bamboo fiber luminal stent according to the present invention;

[0033] Figure 2 The actual photos of the 4D printed bamboo fiber lumen prepared by the present invention according to different lumen structure designs;

[0034] Figure 3 This is a real photo of a 4D printed bamboo fiber lumen with a composite coating on the surface prepared according to different lumen structures designed by the present invention;

[0035] Figure 4 This is a macroscopic photograph of a single bamboo fiber separated in Example 1;

[0036] Figure 5 This is a microscopic photograph of a single bamboo fiber separated in Example 1;

[0037] Figure 6 This is a real photo of the continuous bamboo fiber obtained by twisting in Example 1;

[0038] Figure 7 The photographs are of the process of deformation and recovery of the original shape of the tracheal stent prepared in Example 1 at a temperature of 60°C;

[0039] Figure 8 A comparison chart of the compression performance of the tracheal stents prepared in Examples 1-4 and Comparative Example 1;

[0040] Fig. 9 A comparison chart of the three-point bending performance of the tracheal stents prepared in Examples 1-4 and Comparative Example 1;

[0041] Fig.10 This is a graph showing the results of 1000 three-point bending tests of the tracheal stent prepared in Example 1;

[0042] Fig.11 This is a graph showing the results of 1000 three-point bending tests of the tracheal stent prepared in Example 2;

[0043] Fig.12 This is a graph showing the results of 1000 three-point bending tests of the tracheal stent prepared in Example 3;

[0044] Fig.13 This is a graph showing the results of 1000 three-point bending tests of the tracheal stent prepared in Example 5;

[0045] Fig.14 This is a comparison of the results of using CCK8 to measure the cytotoxicity of the tracheal stents in Example 1 and Example 5;

[0046] Fig.15 This is a comparison of the tissue staining results of Example 1 and Example 5 after the tracheal stents were implanted in animals. DETAILED DESCRIPTION

[0047] The technical solution of the present invention is further described below in conjunction with the embodiments, but it is not limited thereto. Any modification or equivalent replacement of the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention shall be included in the protection scope of the present invention. The process equipment or devices not specifically noted in the following embodiments are all conventional equipment or devices in the art. If not specifically specified, the raw materials used in the embodiments of the present invention can be obtained commercially; if not specifically specified, the technical means used in the embodiments of the present invention are all conventional means well known to those skilled in the art.

[0048] Example 1

[0049] This embodiment provides an 8 mm diameter bamboo fiber luminal stent and a 4D printing preparation method thereof.

[0050] The tracheal stent prepared in this embodiment has a mesh tube structure with two open ends, and its basic structural unit is a diamond shape, such as Figure 1 shown.

[0051] The 4D printing preparation method of the tracheal stent in this embodiment includes the following preparation steps:

[0052] Step 1: Bamboo material processing;

[0053] Four-year-old natural bamboo was selected and cut into bamboo strips with a width of 8 cm and a length of 50 cm without bamboo nodes. The bamboo strips were immersed in a 45 wt % peroxyformic acid solution at 50°C for 12 h to remove the lignin in the bamboo, and then the surface of the bamboo was cleaned with deionized water.

[0054] The washed bamboo material was dried using a freeze drying device to remove moisture, and the dried bamboo material was separated into single bamboo fibers with a length of 50 cm and an average diameter of 200 μm by a mechanical separation device. Figure 4 and Figure 5 shown.

[0055] Step 2, preparing continuous bamboo fibers;

[0056] The single bamboo fiber separated in step 1 is twisted to form a continuous bamboo fiber, and the twist degree is 10 twists / cm; the diameter of the obtained continuous bamboo fiber is 1000μm, and the axial tensile property is 201MPa. Figure 6 shown.

[0057] Step 3: 4D printing to prepare the luminal stent;

[0058] The 4D printing equipment model used in this embodiment is COMBOT-200 desktop continuous fiber reinforced composite material 3D printer (Shaanxi Feibo Technology Development Co., Ltd.).

[0059] In this embodiment, a horizontal rotating shaft is provided. During the printing process, the rotating shaft rotates in a circle around the axis. When the print head moves horizontally in the radial direction of the rotating shaft, the molten printing material is deposited on the rotating shaft. Through the horizontal reciprocating movement of the print head, a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft.

[0060] (1) Structural design:

[0061] In this embodiment, the inner diameter of the tracheal stent is 8 mm, so the diameter of the rotating shaft in this embodiment is 8 mm.

[0062] To ensure that the tracheal stent fits perfectly with the patient's trachea, the 4D printing preparation method provided in this embodiment can also design the geometric structure of the tracheal stent based on the patient's tracheal structure medical imaging data to meet the needs of different anatomical structures.

[0063] (2) Print path settings:

[0064] The angle of the rhombus basic structural unit can be controlled by adjusting the ratio of the print head moving speed and the linear speed of the rotation axis around the axis, that is, the acute angle of the rhombus basic structural unit is 60°, and the ratio of the print head moving speed to the linear speed of the rotation axis around the axis is the trigonometric function tan60°. When the linear speed of the rotation axis around the axis is constant, the print head moving speed is the linear speed of the rotation axis around the axis × tan60°.

[0065] (3) Printing process:

[0066] The continuous bamboo fiber obtained in step 2 is used as the reinforcing phase, polylactic acid PLA is used as the shape memory polymer material, the print head temperature is set to 190°C, and the continuous bamboo fiber and PLA are mixed in the print head as printing materials through a dual-material printing system, wherein the volume fraction of the continuous bamboo fiber is 15%. The interface performance between the bamboo fiber and PLC can be optimized through instantaneous heat treatment, and the mechanical durability of the tracheal stent can be improved.

[0067] During the printing process, the rotation speed of the rotating shaft around the axis is 3r / min, the moving speed of the print head in the radial direction of the rotating shaft is 130.5936mm / min, the printing thickness is 1mm, and the print head moves horizontally in the radial direction of the rotating shaft for 4 cycles, and finally forms a mesh tube structure with a diamond-shaped basic structural unit on the rotating shaft, and obtains a 4D printed bamboo fiber endoluminal stent BF / SMP after molding. The deformation temperature of the tracheal stent prepared in this embodiment is 60°C.

[0068] Example 2

[0069] This embodiment provides a 6 mm diameter bamboo fiber luminal stent and a 4D printing preparation method thereof.

[0070] The tracheal stent prepared in this embodiment is a mesh tube structure with openings at both ends, and its basic structural unit is a rhombus.

[0071] The 4D printing preparation method of the tracheal stent in this embodiment includes the following preparation steps:

[0072] Step 1: Bamboo material processing;

[0073] Four-year-old natural bamboo was selected and cut into bamboo strips with a width of 8 cm and a length of 50 cm without bamboo nodes. The bamboo strips were immersed in a 55 wt % peroxyformic acid solution at 50°C for 12 h to remove the lignin in the bamboo, and then the surface of the bamboo was cleaned with deionized water.

[0074] The washed bamboo material is dried using a freeze drying device to remove moisture, and the dried bamboo material is separated into single bamboo fibers with a length of 50 cm and an average diameter of 200 μm by a mechanical separation device.

[0075] Step 2, preparing continuous bamboo fibers;

[0076] The single bamboo fiber separated in step 1 is twisted to form continuous bamboo fiber, and the twist degree is 10 twists / cm; the diameter of the obtained continuous bamboo fiber is 1000 μm, and the axial tensile property is 204 MPa.

[0077] Step 3: 4D printing to prepare the luminal stent;

[0078] The 4D printing equipment model used in this embodiment is COMBOT-200 desktop continuous fiber reinforced composite material 3D printer (Shaanxi Feibo Technology Development Co., Ltd.).

[0079] In this embodiment, a horizontal rotating shaft is provided. During the printing process, the rotating shaft rotates in a circle around the axis. When the print head moves horizontally in the radial direction of the rotating shaft, the molten printing material is deposited on the rotating shaft. Through the horizontal reciprocating movement of the print head, a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft.

[0080] (1) Structural design:

[0081] In this embodiment, the inner diameter of the tracheal stent is 6 mm, so the diameter of the rotating shaft in this embodiment is 6 mm.

[0082] To ensure that the tracheal stent fits perfectly with the patient's trachea, the 4D printing preparation method provided in this embodiment can also design the geometric structure of the tracheal stent based on the patient's tracheal structure medical imaging data to meet the needs of different anatomical structures.

[0083] (2) Print path settings:

[0084] The angle of the rhombus basic structural unit can be controlled by adjusting the ratio of the print head moving speed and the linear speed of the rotation axis around the axis, that is, the acute angle of the rhombus basic structural unit is 60°, and the ratio of the print head moving speed to the linear speed of the rotation axis around the axis is the trigonometric function tan60°. When the linear speed of the rotation axis around the axis is constant, the print head moving speed is the linear speed of the rotation axis around the axis × tan60°.

[0085] (3) Printing process:

[0086] The continuous bamboo fiber obtained in step 2 is used as the reinforcing phase, polylactic acid PLA is used as the shape memory polymer material, the print head temperature is set to 190°C, and the continuous bamboo fiber and PLA are mixed in the print head as printing raw materials through a dual-material printing system, wherein the volume fraction of the continuous bamboo fiber is 30%.

[0087] During the printing process, the rotation speed of the rotating shaft around the axis is 3r / min, the moving speed of the print head in the radial direction of the rotating shaft is 97.9452mm / min, the printing thickness is 1mm, and the print head moves horizontally reciprocatingly in the radial direction of the rotating shaft for 4 cycles, and finally a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft. After molding, a 4D printed bamboo fiber luminal scaffold BF / SMP is obtained.

[0088] Example 3

[0089] This embodiment provides a 4 mm diameter bamboo fiber luminal stent and a 4D printing preparation method thereof.

[0090] The tracheal stent prepared in this embodiment is a mesh tube structure with openings at both ends, and its basic structural unit is a rhombus.

[0091] The 4D printing preparation method of the tracheal stent in this embodiment includes the following preparation steps:

[0092] Step 1: Bamboo material processing;

[0093] Four-year-old natural bamboo was selected and cut into bamboo strips with a width of 8 cm and a length of 50 cm without bamboo nodes. The bamboo strips were immersed in a 55 wt % peroxyformic acid solution at 50°C for 24 h to remove the lignin in the bamboo, and then the surface of the bamboo was cleaned with deionized water.

[0094] The washed bamboo material is dried using a freeze drying device to remove moisture, and the dried bamboo material is separated into single bamboo fibers with a length of 50 cm and an average diameter of 200 μm by a mechanical separation device.

[0095] Step 2, preparing continuous bamboo fibers;

[0096] The single bamboo fiber separated in step 1 is twisted to form continuous bamboo fiber, and the twist degree is 8 twists / cm; the diameter of the obtained continuous bamboo fiber is 800 μm, and the axial tensile property is 195 MPa.

[0097] Step 3: 4D printing to prepare the luminal stent;

[0098] The 4D printing equipment model used in this embodiment is COMBOT-200 desktop continuous fiber reinforced composite material 3D printer (Shaanxi Feibo Technology Development Co., Ltd.).

[0099] In this embodiment, a horizontal rotating shaft is provided. During the printing process, the rotating shaft rotates in a circle around the axis. When the print head moves horizontally in the radial direction of the rotating shaft, the molten printing material is deposited on the rotating shaft. Through the horizontal reciprocating movement of the print head, a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft.

[0100] (1) Structural design:

[0101] In this embodiment, the inner diameter of the tracheal stent is 4 mm, so the diameter of the rotating shaft in this embodiment is 4 mm.

[0102] To ensure that the tracheal stent fits perfectly with the patient's trachea, the 4D printing preparation method provided in this embodiment can also design the geometric structure of the tracheal stent based on the patient's tracheal structure medical imaging data to meet the needs of different anatomical structures.

[0103] (2) Print path settings:

[0104] The angle of the rhombus basic structural unit can be controlled by adjusting the ratio of the print head moving speed and the linear speed of the rotation axis around the axis, that is, the acute angle of the rhombus basic structural unit is 60°, and the ratio of the print head moving speed to the linear speed of the rotation axis around the axis is the trigonometric function tan60°. When the linear speed of the rotation axis around the axis is constant, the print head moving speed is the linear speed of the rotation axis around the axis × tan60°.

[0105] (3) Printing process:

[0106] The continuous bamboo fiber obtained in step 2 is used as the reinforcing phase, polylactic acid PLA is used as the shape memory polymer material, the print head temperature is set to 190°C, and the continuous bamboo fiber and PLA are mixed in the print head as printing raw materials through a dual-material printing system, wherein the volume fraction of the continuous bamboo fiber is 45%.

[0107] During the printing process, the rotation speed of the rotating shaft around the axis is 3r / min, the moving speed of the print head in the radial direction of the rotating shaft is 65.2968mm / min, the printing thickness is 0.9mm, and the print head moves horizontally reciprocatingly in the radial direction of the rotating shaft for 4 cycles, and finally a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft. After molding, a 4D printed bamboo fiber luminal scaffold BF / SMP is obtained.

[0108] Example 4

[0109] This embodiment provides a bamboo fiber luminal stent with a diameter of 2.5 mm and a 4D printing preparation method thereof.

[0110] The tracheal stent prepared in this embodiment is a mesh tube structure with openings at both ends, and its basic structural unit is a rhombus.

[0111] The 4D printing preparation method of the tracheal stent in this embodiment includes the following preparation steps:

[0112] Step 1: Bamboo material processing;

[0113] Four-year-old natural bamboo was selected and cut into bamboo strips with a width of 8 cm and a length of 50 cm without bamboo nodes. The bamboo strips were immersed in a 45 wt % peroxyformic acid solution at 50°C for 24 h to remove the lignin in the bamboo, and then the surface of the bamboo was cleaned with deionized water.

[0114] The washed bamboo material is dried using a freeze drying device to remove moisture, and the dried bamboo material is separated into single bamboo fibers with a length of 50 cm and an average diameter of 200 μm by a mechanical separation device.

[0115] Step 2, preparing continuous bamboo fibers;

[0116] The single bamboo fiber separated in step 1 is twisted to form continuous bamboo fiber, and the twist degree is 2 twists / cm; the diameter of the obtained continuous bamboo fiber is 200 μm, and the axial tensile property is 205 MPa.

[0117] Step 3: 4D printing to prepare the luminal stent;

[0118] The 4D printing equipment model used in this embodiment is COMBOT-200 desktop continuous fiber reinforced composite material 3D printer (Shaanxi Feibo Technology Development Co., Ltd.).

[0119] In this embodiment, a horizontal rotating shaft is provided. During the printing process, the rotating shaft rotates in a circle around the axis. When the print head moves horizontally in the radial direction of the rotating shaft, the molten printing material is deposited on the rotating shaft. Through the horizontal reciprocating movement of the print head, a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft.

[0120] (1) Structural design:

[0121] In this embodiment, the inner diameter of the tracheal stent is 2.5 mm, so the diameter of the rotation axis in this embodiment is 2.5 mm.

[0122] To ensure that the tracheal stent fits perfectly with the patient's trachea, the 4D printing preparation method provided in this embodiment can also design the geometric structure of the tracheal stent based on the patient's tracheal structure medical imaging data to meet the needs of different anatomical structures.

[0123] (2) Print path settings:

[0124] The angle of the rhombus basic structural unit can be controlled by adjusting the ratio of the print head moving speed and the linear speed of the rotation axis around the axis, that is, the acute angle of the rhombus basic structural unit is 60°, and the ratio of the print head moving speed to the linear speed of the rotation axis around the axis is the trigonometric function tan60°. When the linear speed of the rotation axis around the axis is constant, the print head moving speed is the linear speed of the rotation axis around the axis × tan60°.

[0125] (3) Printing process:

[0126] The continuous bamboo fiber obtained in step 2 is used as the reinforcing phase, polylactic acid PLA is used as the shape memory polymer material, the print head temperature is set to 190°C, and the continuous bamboo fiber and PLA are mixed in the print head as printing raw materials through a dual-material printing system, wherein the volume fraction of the continuous bamboo fiber is 15%.

[0127] During the printing process, the rotation speed of the rotating shaft around the axis is 3r / min, the moving speed of the print head in the radial direction of the rotating shaft is 40.8105mm / min, the printing thickness is 0.2mm, and the print head moves horizontally in the radial direction of the rotating shaft for 4 cycles, and finally a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft. After molding, a 4D printed bamboo fiber luminal scaffold BF / SMP is obtained.

[0128] Example 5

[0129] This embodiment provides a bamboo fiber luminal stent with a surface composite coating and a preparation method thereof.

[0130] In this embodiment, the outer surface of the mesh tube structure of the bamboo fiber endoluminal stent prepared in Example 1 is covered with a composite coating with a thickness of 100 μm.

[0131] The preparation method of the composite coating in this embodiment is as follows:

[0132] 0.096 g of silver nanoparticles AgNPs were ultrasonically dispersed into 16 mL of an equal volume mixture of dichloromethane DCM and N,N-dimethylformamide DMF to obtain a suspension, and then 2.4 g of polycaprolactone PCL with a molecular weight of 80,000 was dissolved in the suspension to obtain a PCL / DCM / DMF@AgNPs spinning solution. The obtained PCL / DCM / DMF@AgNPs spinning solution was used as raw material for electrospinning.

[0133] The feed speed of electrospinning is 0.08 mm / min, the rotation speed of the luminal stent receiving electrode is 150 r / min, the receiving distance between the nozzle and the luminal stent receiving electrode is 15 cm, the voltages are 8.9 kV and -2.3 kV respectively, the electrospinning temperature is room temperature, the relative humidity is 45%, and after 1 hour of electrospinning, a uniform composite coating is formed on the outer surface of the mesh tube structure of the bamboo fiber luminal stent obtained by 4D printing prepared in Example 1, and the obtained stent is recorded as BF / SMP@AgNPs / PCL.

[0134] Example 6

[0135] This embodiment provides a bamboo fiber luminal stent with a surface composite coating and a preparation method thereof.

[0136] In this embodiment, the outer surface of the mesh tube structure of the bamboo fiber endoluminal stent prepared in Example 2 is covered with a composite coating with a thickness of 100 μm.

[0137] The preparation method of the composite coating in this embodiment is as follows:

[0138] 0.096 g of silver nanoparticles AgNPs were ultrasonically dispersed into 16 mL of an equal volume mixture of dichloromethane DCM and N,N-dimethylformamide DMF to obtain a suspension, and then 2.4 g of polycaprolactone PCL with a molecular weight of 80,000 was dissolved in the suspension to obtain a PCL / DCM / DMF@AgNPs spinning solution. The obtained PCL / DCM / DMF@AgNPs spinning solution was used as raw material for electrospinning.

[0139] The feed speed of electrospinning is 0.08 mm / min, the rotation speed of the tubular cavity stent receiving electrode is 80 r / min, the receiving distance between the nozzle and the tubular cavity stent receiving electrode is 15 cm, the voltages are 9.2 kV and -1 kV respectively, the electrospinning temperature is room temperature, the relative humidity is 45%, and a uniform composite coating is formed on the outer surface of the bamboo fiber tubular cavity stent mesh tube structure obtained by 4D printing prepared in Example 2 after 1 hour of electrospinning.

[0140] Example 7

[0141] This embodiment provides a bamboo fiber luminal stent with a surface composite coating and a preparation method thereof.

[0142] In this embodiment, the outer surface of the mesh tube structure of the bamboo fiber endoluminal stent prepared in Example 3 is covered with a composite coating with a thickness of 50 μm.

[0143] The preparation method of the composite coating in this embodiment is as follows:

[0144] 0.096 g of silver nanoparticles AgNPs were ultrasonically dispersed into 16 mL of an equal volume mixture of dichloromethane DCM and N,N-dimethylformamide DMF to obtain a suspension, and then 2.4 g of polycaprolactone PCL with a molecular weight of 80,000 was dissolved in the suspension to obtain a PCL / DCM / DMF@AgNPs spinning solution. The obtained PCL / DCM / DMF@AgNPs spinning solution was used as raw material for electrospinning.

[0145] The feed speed of electrospinning was 0.06 mm / min, the rotation speed of the luminal stent receiving electrode was 100 r / min, the receiving distance between the nozzle and the luminal stent receiving electrode was 15 cm, the voltages were 8.9 kV and -1 kV, respectively, the electrospinning temperature was room temperature, the relative humidity was 45%, and after 0.5 h of electrospinning, a uniform composite coating was formed on the outer surface of the 4D-printed bamboo fiber luminal stent mesh tube structure prepared in Example 3. The actual photo is shown in FIG. Figure 6 As shown, the scaffold with composite coating is BF / SMP@AgNPs / PCL.

[0146] Example 8

[0147] This embodiment provides a bamboo fiber luminal stent with a surface composite coating and a preparation method thereof.

[0148] In this embodiment, the outer surface of the mesh tube structure of the bamboo fiber endoluminal stent prepared in Example 4 is covered with a composite coating with a thickness of 40 μm.

[0149] The preparation method of the composite coating in this embodiment is as follows:

[0150] 0.096 g of silver nanoparticles AgNPs were ultrasonically dispersed into 16 mL of an equal volume mixture of dichloromethane DCM and N,N-dimethylformamide DMF to obtain a suspension, and then 2.4 g of polycaprolactone PCL with a molecular weight of 80,000 was dissolved in the suspension to obtain a PCL / DCM / DMF@AgNPs spinning solution. The obtained PCL / DCM / DMF@AgNPs spinning solution was used as raw material for electrospinning.

[0151] The feed speed of electrospinning was 0.07 mm / min, the rotation speed of the luminal stent receiving electrode was 150 r / min, the receiving distance between the nozzle and the luminal stent receiving electrode was 15 cm, the voltages were 9.2 kV and -2.5 kV, respectively, the electrospinning temperature was room temperature, the relative humidity was 45%, and after 0.3 h of electrospinning, a uniform composite coating was formed on the outer surface of the 4D-printed bamboo fiber luminal stent mesh tube structure prepared in Example 4. The actual photo is shown in FIG. Figure 6 As shown, the scaffold with composite coating is BF / SMP@AgNPs / PCL.

[0152] Comparative Example 1

[0153] This comparative example provides a shape memory luminal stent and a 4D printing preparation method thereof.

[0154] The tracheal stent prepared in this comparative example is a mesh tube structure with openings at both ends, and its basic structural unit is a rhombus.

[0155] The 4D printing preparation method of the tracheal stent in this comparative example includes the following preparation steps:

[0156] Step 1: 4D printing to prepare the luminal stent;

[0157] The 4D printing equipment model used in this comparative example is the COMBOT-200 desktop continuous fiber reinforced composite material 3D printer (Shaanxi Feibo Technology Development Co., Ltd.).

[0158] In this comparative example, a horizontal rotating shaft is set up. During the printing process, the rotating shaft rotates in a circle around the axis. When the print head moves horizontally in the radial direction of the rotating shaft, the molten printing material is deposited on the rotating shaft. Through the horizontal reciprocating movement of the print head, a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft.

[0159] In this comparative example, the inner diameter of the tracheal stent is 8 mm, so the diameter of the rotation axis is 8 mm.

[0160] Polylactic acid PLC was used as the shape memory polymer material, and the temperature of the print head was set to 190°C. During the printing process, the rotation speed of the rotating shaft around the axis was 3r / min, the moving speed of the print head along the radial direction of the rotating shaft was 130mm / min, the printing thickness was 0.3mm, and the print head moved horizontally along the radial direction of the rotating shaft for 4 cycles, and finally formed a mesh tube structure with a diamond-shaped basic structural unit on the rotating shaft, and obtained the 4D printed luminal stent SMP after molding.

[0161] Performance verification test:

[0162] 1. Shape memory performance test

[0163] Test method:

[0164] The shape memory performance of the tracheal stent prepared in Example 1 was tested. Figure 7 As shown, the stent is heated to 60°C to soften and deform. After cooling, the deformed state is maintained. A metal rod is built into the stent to provide instantaneous temperature. The stent is reheated to 60°C and the stent is observed to return to its original shape, proving that it can actively adjust the shape and size of the mesh tube structure under temperature excitation and has good shape memory properties.

[0165] 2. Mechanical properties test

[0166] The mechanical properties of the tracheal stents prepared in Examples 1-4 and Comparative Example 1 were tested by compression test and three-point bending test.

[0167] Compression test method: completed by a universal mechanical testing machine, with a loading rate of 1mm / min.

[0168] Three-point bending test method: the test span is 25 mm, the loading speed is 5 mm / min. All mechanical test samples of three-point bending are brackets with a diameter of 8 mm and a length of 50 mm.

[0169] The results are as follows Figure 8-Figure 13 As shown, the mechanical properties of the tracheal stents prepared in Examples 1-4 are better than those of the tracheal stent prepared in Comparative Example 1. After thousands of three-point bending cycles, the trachea prepared in Examples 1-4 still maintain excellent airway support performance. The extreme load test proves that the flexibility of the tracheal stent with continuous bamboo fiber as the reinforcement phase far exceeds that of conventional polymer stents. This shows that the preparation method provided by the present invention optimizes the interface performance of continuous bamboo fiber and shape memory polymer through instantaneous heat treatment, thereby significantly improving the mechanical durability of the luminal stent and providing long-term support effect.

[0170] 3. Biocompatibility testing

[0171] The cytotoxicity of the tracheal stent prepared by the present invention was evaluated using CCK8 assay.

[0172] Test method:

[0173] Bronchial epithelial cells (HBEC) were inoculated on 96-well plates containing the tracheal scaffold BF / SMP prepared in Example 1 and 96-well plates containing the tracheal scaffold BF / SMP@AgNPs / PCL prepared in Example 5, respectively. A blank control group was set up at the same time. Each well of the 96-well plate contained 2×10 3HBEC cells were observed on days 1, 3, 5 and 7. At each time point, the cell culture medium was replaced with 10% (v / v) CCK-8 reagent in fresh culture medium and cultured at 37°C for 2 hours. The absorbance value was measured at 450nm using a spectrophotometer (Bio-Rad 680, Berkeley, USA) for cell viability and proliferation tests. Each group was measured 3 times at each time point, and the results were expressed as mean ± SD.

[0174] The results are as follows Fig.14 As shown, compared with the blank control group, the cells in Example 1 and Example 5 groups still maintained a high vitality, which indicates that the two groups of tracheal stents have good biocompatibility and cell support capabilities, can support the growth and differentiation of bronchial epithelial cells, and the tracheal stent with a composite coating prepared in Example 5 has a better effect.

[0175] 4. Animal Experiments

[0176] The biocompatibility of the tracheal stent prepared by the present invention was tested by a New Zealand rabbit tracheal implantation experiment. All animal experiments were approved by the Experimental Animal Ethics Committee of Guangxi Medical University and followed the NIH guidelines.

[0177] Test method:

[0178] New Zealand rabbits (3-3.5 kg body weight) were purchased from the Experimental Animal Center of Guangxi Medical University. Rabbits were provided with a standard diet and maintained at 21°C. Sodium pentobarbital (40 mg kg -1 ) anesthetized rabbits. Then the anterior neck area was shaved and disinfected. The experimental rabbits (n=3) were divided into 3 groups, and the tracheal stent BF / SMP prepared in Example 1, the tracheal stent BF / SMP@AgNPs / PCL prepared in Example 5 and the sham operation group were implanted in the corresponding trachea.

[0179] Two weeks after implantation, the rabbits were sacrificed and then stained with hematoxylin and eosin (H&E) and Masson's trichrome. The tissue reaction was observed under an optical microscope. Fig.15 As shown, both groups of stents were well integrated with the surrounding tissues without obvious inflammatory response, proving their safety and effectiveness in vivo.

Claims

1. A 4D printed bamboo fiber luminal stent, the luminal stent is a mesh tube structure with openings at both ends, the basic structural unit of the mesh tube structure is a rhombus, characterized in that: The raw materials for preparing the luminal support include a reinforcing phase and a matrix material. The reinforcing phase is continuous bamboo fiber, the matrix material is a shape memory polymer, and the volume fraction of the continuous bamboo fiber is 15-60%.

2. According to claim 1, a 4D printed bamboo fiber luminal stent is characterized in that: It also includes a composite coating covering the outer surface of the mesh tube structure, wherein the thickness of the composite coating is 50 to 200 μm.

3. A method for preparing a 4D printed bamboo fiber luminal scaffold as claimed in claim 1, characterized in that: Here are the steps: Step 1: Bamboo material processing; The bamboo material is subjected to delignification treatment, drying and fiber separation in sequence to obtain single bamboo fiber; Step 2, preparing continuous bamboo fibers; The single bamboo fiber obtained in step 1 is twisted, knotted or glued to form continuous bamboo fiber; Step 3: 4D printing to prepare the luminal stent; The continuous bamboo fiber and shape memory polymer obtained in step 2 are used as printing materials, and a horizontal rotating shaft is set. During the printing process, the rotating shaft rotates in a circle around the axis. When the print head moves horizontally in the radial direction of the rotating shaft, the molten printing material is deposited on the rotating shaft. Through the horizontal reciprocating movement of the print head, a mesh tube structure with a diamond-shaped basic structural unit is formed on the rotating shaft, and a 4D printed bamboo fiber tubular stent is obtained after molding.

4. The method for preparing the 4D printed bamboo fiber luminal scaffold according to claim 3, characterized in that: The bamboo material in step 1 is four-year-old natural bamboo material. The delignification treatment is to soak the bamboo material without bamboo nodes after cutting in a 20-60wt% peroxyformic acid solution at 40-60°C for 12-36 hours. The drying is freeze-drying, and the fiber separation is to obtain single bamboo fibers with a length of 50 cm and an average diameter of 50-200 μm by a mechanical separation method.

5. The method for preparing the 4D printed bamboo fiber luminal scaffold according to claim 3 or 4, characterized in that: The twisting degree of the twisting in step 2 is 2 to 10 twists / cm; the diameter of the continuous bamboo fiber is 100 to 2000 μm, and the axial tensile performance of the continuous bamboo fiber is not less than 80 MPa.

6. The method for preparing the 4D printed bamboo fiber luminal scaffold according to claim 5, characterized in that: During the printing process of step three, the angle of the rhombus basic structural unit is controlled by adjusting the ratio of the print head movement speed to the linear speed of the rotation axis around the axis, the acute angle of the rhombus basic structural unit is α, and the ratio of the print head movement speed to the linear speed of the rotation axis around the axis is the trigonometric function tanα. When the linear speed of the rotation axis around the axis is constant, the print head movement speed is the linear speed of the rotation axis around the axis × tanα.

7. The method for preparing the 4D printed bamboo fiber luminal scaffold according to claim 6, characterized in that: Step 3: The diameter of the rotating shaft is 0.1-20 mm, the rotation speed of the rotating shaft around the axis is 1-50 r / min, and the moving speed of the print head is 10-1000 mm / min.

8. The method for preparing the 4D printed bamboo fiber luminal scaffold according to claim 7, characterized in that: In step 3, the temperature of the print head is 190-220° C., the printing thickness is 0.1-2 mm, and the print head moves horizontally back and forth along the radial direction of the rotation axis for 2-10 cycles.

9. The method for preparing the 4D printed bamboo fiber luminal scaffold according to claim 8, characterized in that: The deformation temperature of the 4D printed bamboo fiber luminal scaffold prepared in step three is 35-80°C.

10. A method for preparing a 4D printed bamboo fiber luminal scaffold as claimed in claim 2, characterized in that: The preparation method of the composite coating is as follows: prepare the raw materials according to the mass volume ratio of silver nanoparticles, dichloromethane, N,N-dimethylformamide and polycaprolactone PCL of 0.096g:8mL:8mL:2.4g, ultrasonically disperse the silver nanoparticles into equal volumes of mixed dichloromethane DCM and N,N-dimethylformamide DMF to obtain a suspension, and then dissolve polycaprolactone in the suspension to obtain a PCL / DCM / DMF@AgNPs spinning solution, and use the obtained PCL / DCM / DMF@AgNPs spinning solution as a raw material to form a uniform composite coating on the outer surface of the mesh tube structure of the bamboo fiber luminal stent obtained by 4D printing through electrospinning.

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