Intelligent cerebrovascular stent based on polymer short fibers and preparation method of intelligent cerebrovascular stent

Abstract

The invention relates to an intelligent cerebrovascular stent based on polymer short fibers and a preparation method thereof. The method comprises the following steps: carrying out electrostatic spinning on a polymer spinning solution to obtain polymer long fibers, freezing the polymer long fibers in liquid nitrogen, and carrying out low-temperature shearing dispersion to obtain polymer short fibers; a polymer in the polymer spinning solution is at least one of polycaprolactone, polylactic acid, gelatin, cellulose, fibroin, collagen and chitosan; uniformly mixing the temperature response high-molecular polymer and the polymer short fiber to obtain a 4D printing raw material; and designing a 4D printing model of a spider-leg-imitating structure, and performing 4D printing on a 4D printing raw material to obtain the intelligent cerebrovascular stent. According to the preparation method, the intelligent cerebrovascular stent with the spider-leg-imitating structure is prepared, the spider-leg-imitating structure design and the introduction of the polymer short fibers can endow the cerebrovascular stent with better shape adaptability and intelligent responsiveness, and the mechanical property and the anti-skid property of the cerebrovascular stent are effectively improved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical device materials, and in particular to an intelligent cerebrovascular stent based on polymer short fibers and a preparation method thereof. Background Art

[0002] In the field of cerebrovascular and trigeminal nerve, existing medical stents mainly adopt traditional manufacturing technology and are usually made of traditional polymer materials. In clinical practice, traditional polymer planar structures are used and implanted into the lesion site through specific surgical instruments to support blood vessels or nerves. However, the existing cerebrovascular stents have certain mechanical properties and / or anti-slip properties under traditional structural design and traditional polymer materials. The surface of the traditional structure cerebrovascular stent is relatively smooth, and the contact area between the stent and the vascular wall or nerve tissue is limited. It is difficult to provide sufficient friction, which may cause the cerebrovascular stent to shift, requiring a second operation to cause economic pressure on the patient, and may even cause the patient to be in certain life-threatening situations. At the same time, although these traditional stents can meet clinical needs to a certain extent, they have some limitations, such as lack of intelligent characteristics, limited shape adaptability, etc., which make it difficult to meet the needs of complex cerebrovascular environments, difficult to enter the body with a small volume, and difficult to respond to changes in the vascular environment in a timely manner. Therefore, it is urgent to achieve minimally invasive delivery through 4D printing intelligent cerebrovascular stents, so as to break through the space limitations during surgery, and trigger the deformation of the stent under physiological conditions. Its functional shape deformation is of great significance for biomedical clinical applications.

[0003] In a high-stress environment, the fatigue strength of polymer materials is low, and long-term use may lead to deformation, breakage or material degradation, which will affect the stability of the stent. Similarly, the surface friction coefficient of the conventional polymer materials is low, which makes the cerebrovascular stent easy to shift or slide after implantation, especially in cerebral blood vessels with high blood flow pressure.

[0004] In summary, it is very necessary to provide an intelligent cerebrovascular stent based on polymer short fibers and a preparation method thereof. Summary of the invention

[0005] In order to solve one or more technical problems existing in the prior art, the present invention provides an intelligent cerebrovascular stent based on polymer short fibers and a preparation method thereof.

[0006] In a first aspect, the present invention provides a method for preparing an intelligent cerebrovascular stent based on polymer short fibers, the method comprising the following steps:

[0007] (1) electrospinning a polymer spinning solution to obtain polymer long fibers, then freezing the polymer long fibers under liquid nitrogen conditions and shearing and dispersing them under liquid nitrogen conditions to obtain polymer short fibers; the polymer in the polymer spinning solution is one or more of polycaprolactone, polylactic acid, gelatin, cellulose, silk protein, collagen, and chitosan;

[0008] (2) uniformly mixing the temperature-responsive polymer and the polymer short fibers to obtain a 4D printing material;

[0009] (3) Design a 4D printing model that mimics the structure of spider legs, use 4D printing materials for 4D printing, and obtain an intelligent cerebrovascular stent based on polymer short fibers.

[0010] Preferably, the temperature-responsive high molecular polymer is one or more of shape memory polyurethane, shape memory polyurea, and shape memory polyamide.

[0011] Preferably, the shape transition temperature of the temperature-responsive polymer is 36-42°C.

[0012] Preferably, the mass percentage of the temperature-responsive high molecular polymer in the 4D printing raw material is 60-80%; and / or the mass percentage of the polymer short fibers in the 4D printing raw material is 20-40%.

[0013] Preferably, during electrospinning: the concentration of the polymer spinning solution is 8 to 15 wt%; the solvent used for the polymer spinning solution is one or more of dichloromethane, methanol, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, water, and acetic acid solution; and / or the voltage of electrospinning is 15 to 20 kV, the receiving distance is 10 to 15 cm, and the flow rate of the polymer spinning solution is 0.5 to 2 mL / h.

[0014] Preferably, the freezing time under liquid nitrogen conditions is 10 to 20 minutes.

[0015] Preferably, the rotation speed of the shear dispersion is 3000-8000 rpm, and the shear dispersion time is 10-30 min.

[0016] Preferably, the temperature of the 4D printing is 150-260° C., the speed of the 4D printing is 10-20 mm / s, and the pressure of the 4D printing is 0.5-1 MPa.

[0017] Preferably, the intelligent cerebrovascular stent based on polymer short fibers can be shaped into a collapsed structure under external stimulation, and the collapsed structure can be restored to a spider-leg-like structure at 36-42°C.

[0018] In a second aspect, the present invention provides an intelligent cerebrovascular stent based on polymer short fibers prepared by the preparation method described in the first aspect of the present invention.

[0019] Compared with the prior art, the present invention has at least the following beneficial effects:

[0020] (1) Among medical devices, cerebrovascular stents play a key role in the treatment of cerebrovascular diseases. The present invention adopts the emerging 4D printing technology to provide a new idea and method for the manufacture of intelligent cerebrovascular stents. According to the requirements that the stent has a narrow space to enter the brain, needs to be fixed at the location of the trigeminal nerve, and is not easy to deviate or degrade, the structural design and material improvement of the cerebrovascular stent are carried out; the present invention combines polymer short fibers as 4D printing raw materials in temperature-responsive polymers and prints an intelligent cerebrovascular stent with a spider-leg-like structure through 4D printing technology. The spider-leg-like structure design in the present invention can give the cerebrovascular stent a better shape. The cerebrovascular stent with a spider-leg-like structure in the present invention can be shaped into a collapsed structure. Under external stimulation (shape recovery within the body temperature range), the collapsed structure can be restored to the original spider-leg-like structure. This shape memory property (deformation recovery property) allows the cerebrovascular stent in the present invention to be deformed into a small volume during implantation, making it easy to enter the brain blood vessels and reach the area adjacent to the trigeminal nerve. After reaching the target position, the cerebrovascular stent can be restored (recovered) to the spider-leg-like shape in the body, ensuring that it is firmly deployed and stably fixed in the blood vessels (target position), thereby achieving a three-dimensional support effect.

[0021] (2) The present invention combines polymer short fibers in temperature-responsive high molecular polymers as 4D printing raw materials and optimizes printing parameters (such as printing speed, printing temperature, and printing pressure-related parameters) to ensure the successful 4D printing of an intelligent cerebrovascular stent with a spider-leg-like structure. The new intelligent cerebrovascular stent prepared by the present invention not only has better biocompatibility, mechanical properties, and anti-slip properties, but also can achieve intelligent changes in shape (intelligent responsiveness to recovery at body temperature) through 4D printing technology to better adapt to the complex structure of the lesion site and better adapt to changes in the vascular environment, thereby meeting the use requirements of the cerebrovascular stent in a complex physiological environment and improving the effect and safety of the treatment of cerebrovascular diseases. The present invention improves the performance and applicability of the cerebrovascular stent, endows the cerebrovascular stent with intelligent characteristics, achieves real-time response to the vascular environment, and contributes to the development of medical technology in the field of cerebrovascular and trigeminal nerves.

[0022] (3) The spider-leg structure of the intelligent cerebrovascular stent in the present invention is conducive to improving the anti-slip performance and fixation performance of the cerebrovascular stent, mainly because the spider-leg structure design can better adapt to the shape of the blood vessel through its unique multi-point support design, and provide uniform radial support force and a larger surface contact area, thereby enhancing the stability of the cerebrovascular stent and preventing displacement. The multiple "support feet" or branches of the cerebrovascular stent with the spider-leg structure can provide more contact points on the blood vessel wall. These contact points can increase the friction between the cerebrovascular stent and the blood vessel wall, thereby improving the anti-slip effect and fixation stability, and preventing The cerebrovascular stent is prevented from slipping during blood flow or vascular activity, and the cerebrovascular stent with a spider-leg-like structure can better conform to the shape of the blood vessel due to the flexibility of the "leg" shape, especially in curved or narrow vascular segments. The multiple branches of the cerebrovascular stent can be distributed at different contact points, so that the cerebrovascular stent is close to the vascular wall, reducing sliding caused by the inability of the cerebrovascular stent to fully fit the blood vessel, preventing displacement or deformation of the cerebrovascular stent caused by excessive local stress, reducing the risk of fatigue or fracture of the cerebrovascular stent due to excessive local stress, and further improving the fixation performance and long-term service life of the cerebrovascular stent in the cerebral blood vessels.

[0023] (4) The intelligent cerebrovascular stent in the present invention is prepared by using a temperature-responsive high molecular polymer and polymer short fibers. The present invention finds that the introduction of polymer short fibers into the intelligent cerebrovascular stent can effectively improve the mechanical properties and anti-slip properties of the cerebrovascular stent. This is because the polymer short fibers can form a reinforcing skeleton in the cerebrovascular stent, increase the strength and rigidity of the material, and the dispersion of the short fibers can share the force transmission under stress, slow down the fracture or deformation of the material, and make the cerebrovascular stent have better tensile strength and fatigue resistance under the action of external force. In addition, the addition of polymer short fibers forms a microscopic rough structure on the surface of the material. Such roughness When the surface contacts the inner wall of the blood vessel, it can increase friction and prevent the cerebrovascular stent from sliding inside the blood vessel; in addition, the "villi" structure of the polymer short fibers imitates the spider leg structure sensing performance and can provide richer surface textures at the microscopic level. These textures can enhance the adhesion ability of the material and inhibit cell proliferation. For cerebrovascular stents, this helps the stent to be tightly integrated with the inner wall of the blood vessel, thereby improving its stability and preventing displacement. In addition, because the villi-like surface of the polymer short fibers provides a rich microstructure, this rough surface imitates the spider leg structure and can provide more attachment points for the cerebrovascular stent, which is very beneficial for inhibiting cell proliferation. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The drawings of the present invention are provided for illustrative purposes only, and the proportions, sizes and quantities of the various parts in the drawings may not necessarily be consistent with the actual products.

[0025] Figure 1It is a schematic diagram of the structure of shaping and recovery of the smart cerebrovascular stent based on polymer short fibers in the present invention;

[0026] Figure 2 This is the infrared spectrum of the shape memory polyurea prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0028] In a first aspect, the present invention provides a method for preparing an intelligent cerebrovascular stent based on polymer short fibers, the method comprising the following steps:

[0029] (1) electrospinning a polymer spinning solution to obtain polymer long fibers, and then freezing the polymer long fibers under liquid nitrogen conditions and shearing and dispersing them under liquid nitrogen conditions to obtain polymer short fibers; the polymer in the polymer spinning solution is one or more of polycaprolactone, polylactic acid, gelatin, cellulose, silk protein, collagen, and chitosan; the present invention does not specifically limit the polymers such as polycaprolactone, polylactic acid, gelatin, cellulose, silk protein, collagen, and chitosan used in the polymer spinning solution, and those skilled in the art can routinely select and use products that can be directly purchased or products synthesized by existing technologies;

[0030] (2) uniformly mixing the temperature-responsive polymer and the polymer short fibers to obtain a 4D printing material;

[0031] (3) Designing a 4D printing model that mimics the structure of spider legs, using 4D printing materials for 4D printing, and obtaining an intelligent cerebrovascular stent based on polymer short fibers; in the present invention, 4D printing can be performed using, for example, a biological-grade printing device (i.e., a biological printer).

[0032] The present invention provides an intelligent cerebrovascular stent with excellent performance, which enables the cerebrovascular stent to have intelligent response capabilities, better adapt to changes in the vascular environment, and achieve real-time response to the vascular environment; and the present invention has the advantages of simple preparation process and low cost. This is because compared with traditional preparation methods, 4D printing technology can achieve fast and accurate production. At the same time, the automated printing process reduces manual intervention and improves production efficiency. Compared with traditional manufacturing methods, 4D printing technology is more environmentally friendly, reduces the waste of raw materials and the generation of waste, and is conducive to the control of environmental pollution.

[0033] The present invention combines polymer short fibers with temperature-responsive high molecular polymers as 4D printing materials and prints out an intelligent cerebrovascular stent with a spider-leg-like structure through 4D printing technology. The spider-leg-like structure design in the present invention can give the cerebrovascular stent better shape adaptability and intelligent responsiveness. The cerebrovascular stent with the spider-leg-like structure in the present invention can be shaped into a retracted structure. Under external stimulation (shape recovery within the body temperature range), the retracted structure can be restored to the original spider-leg-like structure. This shape memory property (deformation recovery property) allows the cerebrovascular stent in the present invention to be deformed into a small volume during implantation, making it convenient to enter the brain blood vessels and reach the area adjacent to the trigeminal nerve. After reaching the target position, the cerebrovascular stent can be restored (recovered) to the spider-leg-like shape in the body, ensuring that it is firmly deployed and stably fixed in the blood vessels (target position), thereby achieving a three-dimensional support effect.

[0034] The present invention uses 4D printing of a three-dimensional spider-leg structure and combines polymer chopped fibers to mimic the special adsorption capacity of spider legs, thereby increasing the contact area between the cerebrovascular stent and the vascular wall or nerve tissue, increasing friction to avoid displacement of the cerebrovascular stent, and realizing the application of a multifunctional cerebrovascular stent for minimally invasive delivery. The spider-leg structure of the intelligent cerebrovascular stent in the present invention is beneficial to improving the anti-slip and fixation performance of the stent, mainly because the spider-leg structure design can better adapt to the morphology of the blood vessels through its unique multi-point support design, and provide uniform radial support force and a larger surface contact area, thereby enhancing the stability of the cerebrovascular stent and preventing displacement. The multiple "support feet" or branches of the cerebrovascular stent with a spider-leg structure can provide more contact points on the vascular wall. These contact points can increase the friction between the cerebrovascular stent and the vascular wall, thereby improving the anti-slip effect and fixation stability, preventing the cerebrovascular stent from slipping during blood flow or vascular activity, and the spider-leg structure Due to the flexibility of the "leg" shape, the stent can better conform to the shape of the blood vessel, especially in curved or narrow blood vessel segments. The multiple branches of the cerebrovascular stent can be distributed at different contact points, so that the cerebrovascular stent is close to the blood vessel wall, reducing sliding caused by the inability of the cerebrovascular stent to fully fit the blood vessel, preventing displacement or deformation of the cerebrovascular stent caused by excessive local stress, reducing the risk of fatigue or fracture of the cerebrovascular stent due to excessive local stress, and further improving the fixation performance and long-term service life of the cerebrovascular stent in the cerebral blood vessels. If the anti-slip property of the cerebrovascular stent is poor, it will make the cerebrovascular stent difficult to fix, easily lead to secondary surgery and be detrimental to the patient's life safety.

[0035] The intelligent cerebrovascular stent in the present invention is prepared by using a temperature-responsive high molecular polymer and polymer short fibers. The present invention finds that the introduction of polymer short fibers into the intelligent cerebrovascular stent can effectively improve the mechanical properties and anti-slip properties of the cerebrovascular stent. This is because the polymer short fibers can form a reinforcing skeleton in the cerebrovascular stent, increase the strength and rigidity of the material, and the dispersion of the polymer short fibers can share the force transmission under stress, slow down the fracture or deformation of the material, so that the cerebrovascular stent has better tensile strength and fatigue resistance under external force, and the addition of the polymer short fibers forms a microscopic rough structure on the surface of the material. Such roughness When the surface contacts the inner wall of the blood vessel, it can increase friction and prevent the cerebrovascular stent from sliding inside the blood vessel; in addition, the "villi" structure of the polymer short fibers imitates the spider leg structure sensing performance and can provide richer surface textures at the microscopic level. These textures can enhance the adhesion ability of the material and inhibit cell proliferation. For cerebrovascular stents, this helps the stent to be tightly integrated with the inner wall of the blood vessel, thereby improving its stability and preventing displacement. In addition, because the villi-like surface of the polymer short fibers provides a rich microstructure, this rough surface imitates the spider leg structure and can provide more attachment points for the cerebrovascular stent, which is very beneficial for inhibiting cell proliferation.

[0036] According to some preferred embodiments, the temperature-responsive polymer is one or more of shape memory polyurethane, shape memory polyurea, and shape memory polyamide; the temperature-responsive polymers such as shape memory polyurethane, shape memory polyurea, and shape memory polyamide preferably used in the present invention also have the characteristic of not being easily degraded.

[0037] According to some preferred embodiments, the shape transition temperature of the temperature-responsive polymer is 36 to 42°C; in the present invention, for example, by synthesizing different polyurea, polyurethane or polyamide molecular structures and controlling the soft and hard segments of the molecular chain segments, the shape memory of the material can be achieved in the range of 36 to 42°C.

[0038] According to some specific embodiments, the preparation of the shape memory polyurea is as follows: isophorone diisocyanate and N,N-dimethylformamide are stirred evenly, and then polyetheramine is added to react at room temperature for 3 to 5 hours, and then isophthalic acid hydrazide is added to react at 40 to 50°C for more than 24 hours, thereby obtaining a liquid shape memory polyurea; wherein the molar ratio of isophorone diisocyanate, polyetheramine, and isophthalic acid hydrazide is (10 to 14):(3.5 to 4.5):1, and the amount ratio of isophorone diisocyanate to N,N-dimethylformamide is (10 to 14) mmol:10 mL, that is, the amount of isophorone diisocyanate corresponding to each 10 mL of N,N-dimethylformamide is 10 to 14 mmol; in the present invention, the polyetheramine can, for example, be a polyetheramine with a molecular weight of 1000 to 1500; in the present invention, the room temperature refers to a room temperature of 15 to 35°C.

[0039] According to some preferred embodiments, the mass percentage of the temperature-responsive high molecular polymer in the 4D printing raw material is 60-80% (for example, 60%, 65%, 70%, 75% or 80%); and / or the mass percentage of the polymer short fibers in the 4D printing raw material is 20-40% (for example, 20%, 25%, 30%, 35% or 40%).

[0040] According to some preferred embodiments, during electrospinning: the concentration of the polymer spinning solution is 8 to 15 wt% (e.g., 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt% or 15 wt%); the solvent used in the polymer spinning solution is one or more of dichloromethane, methanol, tetrahydrofuran, N, N-dimethylformamide, N, N-dimethylacetamide, water, and acetic acid solution; in the present invention, The acetic acid solution is an aqueous acetic acid solution, preferably, the mass percentage of acetic acid in the aqueous acetic acid solution is 20-40%; and / or the voltage of electrospinning is 15-20 kV (for example, 15, 16, 17, 18, 19 or 20 kV), the receiving distance is 10-15 cm (for example, 10, 11, 12, 13, 14 or 15 cm), and the flow rate of the polymer spinning solution is 0.5-2 mL / h (for example, 0.5, 1, 1.5 or 2 mL / h).

[0041] According to some preferred embodiments, the freezing time under liquid nitrogen conditions is 10 to 20 min (e.g., 10, 15 or 20 min); and / or the shear dispersion rotation speed is 3000 to 8000 rpm (e.g., 3000, 4000, 5000, 6000, 7000 or 8000 rpm), and the shear dispersion time is 10 to 30 min (e.g., 10, 15, 20, 25 or 30 min).

[0042] The present invention finds that after preparing polymer long fibers by electrospinning, polymer fibers of a certain hardness are obtained by suitable liquid nitrogen freezing, and short fibers are obtained by shear dispersion under liquid nitrogen, which is beneficial for making the polymer short fibers have a rich "fluff structure". This is because liquid nitrogen puts the polymer at an extremely low temperature, and the fibers become more fragile. Since the molecular chains of the polymer cannot move at low temperatures, the fibers are prone to breakage, especially when subjected to shear force. By controlling the magnitude of the shear force and the shear time, the long fibers can be effectively broken into short fibers, and shearing at low temperatures helps to reduce the thermoplastic deformation of the polymer fibers, so that the fiber fracture mode is more inclined to brittle fracture rather than ductile deformation, which is beneficial for obtaining polymer short fibers with rich villi structure in the mechanical dispersion process. In the freezing environment of liquid nitrogen, the heat effect on the electrospun fibers is significantly reduced, which means that during the processing, the surface microstructure of the polymer long fibers is not easy to collapse or deform. This feature provides favorable conditions for obtaining a rich villi structure.

[0043] According to some preferred embodiments, the temperature of the 4D printing is 150-260°C (e.g., 150°C, 160°C, 170°C, 180°C, 190°C, 200°C, 210°C, 220°C, 230°C, 240°C, 250°C or 260°C), the speed of the 4D printing (the speed at which the print head moves on the printing path) is 10-20 mm / s (e.g., 10, 12, 15, 18 or 20 mm / s), and the pressure of the 4D printing is 0.5-1 MPa (e.g., 0.5, 0.6, 0.7, 0.8, 0.9 or 1 MPa); in the present invention, the diameter of the print head is, for example, 1.5-2.0 mm; the present invention combines polymer short fibers as 4D printing raw materials in temperature-responsive polymers and controls the printing parameters ( The 4D printing technology of the present invention can optimize the parameters related to the printing speed, printing temperature and printing pressure, thereby ensuring the successful 4D printing of the intelligent cerebrovascular stent with the spider-leg-like structure. The new intelligent cerebrovascular stent prepared by the present invention not only has better biocompatibility, mechanical properties and anti-slip properties, but also can realize the intelligent change of shape (intelligent responsiveness of recovery at body temperature) through 4D printing technology, so as to better adapt to the complex structure of the lesion site and the changes in the vascular environment, thereby meeting the use requirements of the cerebrovascular stent in a complex physiological environment and improving the effect and safety of the treatment of cerebrovascular diseases. The present invention improves the performance and applicability of the cerebrovascular stent, endows the cerebrovascular stent with intelligent characteristics, realizes real-time response to the vascular environment, and contributes to the development of medical technology in the field of cerebrovascular and trigeminal nerve. In the present invention, it is preferred to optimize the 4D printing temperature, 4D printing speed and 4D printing pressure. If the printing temperature is too low, the print head is easily blocked. If the printing temperature is too high, it is difficult to print and form. The control of printing speed and printing pressure will affect the uniformity and accuracy of material deposition, improve the accuracy of shape control, and help to ensure the structure and performance of the intelligent cerebrovascular stent, and facilitate the precise preparation of high-quality intelligent cerebrovascular stents with spider leg-like structures.

[0044] According to some preferred embodiments, the smart cerebrovascular stent based on polymer short fibers can be shaped into a collapsed structure under external stimulation, and the collapsed structure can be restored to a spider-leg-like structure at 36 to 42° C. The structural schematic diagram of the shaping and restoration of the smart cerebrovascular stent based on polymer short fibers in the present invention is as shown in FIG. Figure 1 As shown; in the present invention, the external stimulus is, for example, artificial contraction within the range of 55 to 75°C; specifically, the intelligent cerebrovascular stent based on polymer short fibers can obtain a contracted structure by artificial contraction at, for example, 55 to 75°C.

[0045] In a second aspect, the present invention provides an intelligent cerebrovascular stent based on polymer short fibers prepared by the preparation method described in the first aspect of the present invention.

[0046] According to some preferred embodiments, the dynamic friction coefficient of the smart cerebrovascular stent based on polymer short fibers is 0.4 to 0.5.

[0047] The technical scheme in the embodiment of the present invention will be clearly and completely described below. Obviously, the described embodiment is only a part of the embodiment of the present invention, rather than all the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the art without making creative work are within the scope of protection of the present invention. Unless otherwise specified, each raw material used in the embodiments of the present invention and the comparative examples can be obtained by commercial purchase or synthesized by existing methods. The experimental methods used in the following embodiments and comparative examples are conventional methods unless otherwise specified.

[0048] Example 1

[0049] ① Polycaprolactone is prepared into a polycaprolactone dispersion with a mass percentage of 12% by tetrahydrofuran, gelatin is prepared into a gelatin dispersion with a mass percentage of 9% by acetic acid aqueous solution (the mass percentage of acetic acid in the acetic acid aqueous solution is 30%) and tetrahydrofuran in a volume ratio of 4:1, the polycaprolactone dispersion and the gelatin dispersion are uniformly mixed in a volume ratio of 1:1 to obtain a polymer spinning solution, and then the polymer spinning solution is electrospun to obtain polymer long fibers, and then the polymer long fibers are placed in liquid nitrogen conditions for freezing for 15 minutes and shear dispersion is performed under liquid nitrogen conditions for 20 minutes, the shear dispersion speed is 5000rpm, and a polymer short fiber with a length of 2 to 5 mm is obtained; wherein, the electrospinning is carried out at room temperature of 25°C and a relative humidity of 35%, the electrospinning voltage is 18kV, the receiving distance is 12cm, and the flow rate of the polymer spinning solution is 1mL / h.

[0050] ② The temperature-responsive polymer and the polymer short fibers (polymer chopped fibers) obtained in step ① are mixed uniformly in a mass ratio of 6:4 to obtain a 4D printing raw material; wherein the temperature-responsive polymer is a shape memory polyurea; the shape memory polyurea is prepared by: stirring isophorone diisocyanate and N,N-dimethylformamide uniformly, then adding polyetheramine to react at room temperature for 4 hours, and then adding isophthalic acid hydrazide to react at 45°C for 24 hours, thereby obtaining a liquid shape memory polyurea; wherein the molar ratio of isophorone diisocyanate, polyetheramine, and isophthalic acid hydrazide is 12:4:1, and the ratio of isophorone diisocyanate to N,N-dimethylformamide is 12mmol:10mL; the infrared spectrum of the shape memory polyurea prepared in this embodiment is as follows Figure 2 As shown, from Figure 2 The results can demonstrate the successful synthesis of shape memory polyurea.

[0051] ③ Design a 4D printing model that imitates the structure of spider legs, such as Figure 1 The spider leg-like structure shown is 4D printed using the 4D printing material obtained in step ② to obtain an intelligent cerebrovascular stent based on polymer short fibers. The obtained intelligent cerebrovascular stent based on polymer short fibers can be shaped into a collapsed structure by artificial collapse in the range of 55 to 75° C., and the collapsed structure can be restored to the spider leg-like structure at 36 to 42° C., with a shape recovery rate of 95%. The 4D printing temperature is 150° C., the 4D printing speed is 10 mm / s, the 4D printing pressure is 0.5 MPa, and the diameter of the print head is 1.8 mm.

[0052] Comparative Example 1

[0053] Comparative Example 1 is substantially the same as Example 1, except that:

[0054] ③ Design a 4D printing model with a grid structure, and use the 4D printing material obtained in step ② to perform 4D printing to obtain an intelligent cerebrovascular stent; wherein the 4D printing temperature is 150° C., the 4D printing speed is 10 mm / s, the 4D printing pressure is 0.5 MPa, and the diameter of the print head is 1.8 mm.

[0055] Comparative Example 2

[0056] Comparative Example 2 is substantially the same as Example 1, except that:

[0057] ③ Design a 4D printing model of a tubular structure, and use the 4D printing material obtained in step ② to perform 4D printing to obtain an intelligent cerebrovascular stent; wherein the 4D printing temperature is 150° C., the 4D printing speed is 10 mm / s, the 4D printing pressure is 0.5 MPa, and the diameter of the print head is 1.8 mm.

[0058] Comparative Example 3

[0059] Comparative Example 3 is substantially the same as Example 1, except that:

[0060] ① Polycaprolactone is prepared into a polycaprolactone dispersion with a mass percentage of 12% by tetrahydrofuran, gelatin is prepared into a gelatin dispersion with a mass percentage of 9% by acetic acid aqueous solution (the mass percentage of acetic acid in the acetic acid aqueous solution is 30%) and tetrahydrofuran in a volume ratio of 4:1, the polycaprolactone dispersion and the gelatin dispersion are uniformly mixed in a volume ratio of 1:1 to obtain a polymer spinning solution, and then the polymer spinning solution is electrospun to obtain polymer long fibers, and then the polymer long fibers are directly cut into polymer short fibers with a length of 2 to 5 mm; wherein the electrospinning is carried out at room temperature of 25°C and a relative humidity of 35%, the electrospinning voltage is 18 kV, the receiving distance is 12 cm, and the flow rate of the polymer spinning solution is 1 mL / h.

[0061] The present invention tested the anti-slip performance of the smart cerebrovascular stent based on polymer short fibers prepared in Example 1 and the smart cerebrovascular stents finally prepared in Comparative Examples 1 to 3. The results are shown in Table 1.

[0062] Table 1

[0063]

[0064]

[0065] Parts of the present invention that are not described in detail are well known to those skilled in the art.

[0066] Finally, it should be noted that: the above is a detailed introduction to the intelligent cerebrovascular stent based on polymer short fibers and the preparation method thereof disclosed in the embodiments of the present invention. Specific examples are used in this article to illustrate the implementation methods of the present invention. The description of the above embodiments is only used to help understand the method of the present invention and its core idea. At the same time, for those skilled in the art, according to the idea of ​​the present invention, there will be changes in the specific implementation methods and application scopes. In summary, the content of this specification should not be understood as limiting the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions recorded in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. These modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing an intelligent cerebrovascular stent based on polymer short fibers, characterized in that: The method comprises the following steps: (1) electrospinning a polymer spinning solution to obtain polymer long fibers, then freezing the polymer long fibers under liquid nitrogen conditions and shearing and dispersing them under liquid nitrogen conditions to obtain polymer short fibers; the polymer in the polymer spinning solution is one or more of polycaprolactone, polylactic acid, gelatin, cellulose, silk protein, collagen, and chitosan; (2) uniformly mixing the temperature-responsive polymer and the polymer short fibers to obtain a 4D printing material; (3) Design a 4D printing model that mimics the structure of spider legs, use 4D printing materials for 4D printing, and obtain an intelligent cerebrovascular stent based on polymer short fibers.

2. The preparation method according to claim 1, characterized in that: The temperature responsive high molecular polymer is one or more of shape memory polyurethane, shape memory polyurea, and shape memory polyamide.

3. The preparation method according to claim 2, characterized in that: The shape transition temperature of the temperature-responsive high molecular polymer is 36-42°C.

4. The preparation method according to claim 1, characterized in that: The mass percentage of the temperature-responsive polymer in the 4D printing raw material is 60-80%; and / or The mass percentage of polymer short fibers in the 4D printing raw material is 20-40%.

5. The preparation method according to claim 1, characterized in that: During electrospinning: The concentration of the polymer spinning solution is 8 to 15 wt %; The solvent used in the polymer spinning solution is one or more of dichloromethane, methanol, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, water, and acetic acid solution; and / or The voltage of electrospinning is 15-20 kV, the receiving distance is 10-15 cm, and the flow rate of the polymer spinning solution is 0.5-2 mL / h.

6. The preparation method according to claim 1, characterized in that: The freezing time under liquid nitrogen conditions is 10 to 20 minutes.

7. The preparation method according to claim 1, characterized in that: The rotation speed of shear dispersion is 3000-8000 rpm, and the time of shear dispersion is 10-30 min.

8. The preparation method according to claim 1, characterized in that: The temperature of the 4D printing is 150-260° C., the speed of the 4D printing is 10-20 mm / s, and the pressure of the 4D printing is 0.5-1 MPa.

9. The preparation method according to claim 1, characterized in that: The intelligent cerebrovascular stent based on polymer short fibers can be shaped into a collapsed structure under external stimulation, and the collapsed structure can be restored to a spider-leg-like structure at 36-42°C. 10 . An intelligent cerebrovascular stent based on polymer short fibers prepared by the preparation method according to any one of claims 1 to 9 .

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