A vascular covered stent for emergency hemorrhage and a preparation method thereof

Abstract

The application belongs to the technical field of vascular covered stent, and relates to a vascular covered stent for emergency hemorrhage and a preparation method thereof. The vascular covered stent comprises a tubular stent framework and a double-layer composite fiber membrane covering the outer surface of the tubular stent framework. The double-layer composite fiber membrane is composed of an inner buffer layer and an outer structural layer. The inner buffer layer is a polyvinyl alcohol porous fiber membrane, and the outer structural layer is a biodegradable elastomer fiber membrane. In the preparation, the tubular stent framework subjected to surface activation treatment is first fixed on an electrospinning collector, and polyvinyl alcohol porous fiber membranes and biodegradable elastomer fiber membranes are spun on the outer surface of the tubular stent framework in sequence, and then the stent with the double-layer covering membranes is annealed to obtain the vascular covered stent. The product has excellent compression damage resistance, instant hemostasis function and good delivery. The preparation method is simple and easy to implement.

Description

Technical Field

[0001] This invention belongs to the field of vascular covered stent technology, and relates to a vascular covered stent for emergency bleeding and its preparation method. Background Technology

[0002] Vascular stent grafting has become a mainstream minimally invasive method for treating major vascular diseases such as aortic aneurysms and aortic dissections. This procedure involves inserting a balloon catheter, fitted with a tightly closed stent, into the narrowed lesion of a blood vessel using a guidewire and guide sheath. The balloon then expands the stent, restoring blood flow. However, rupture due to operational errors or other reasons is still unavoidable, especially when the catheter tip is passed through a tortuous iliac artery or a fragile aneurysm sac, where excessive force can cause rupture. In the field of interventional cardiovascular therapy, sudden rupture and bleeding of small blood vessels (such as coronary arteries) during the procedure is one of the most critical complications. This type of bleeding is sudden, rapid, and fatal; if it cannot be effectively sealed within a very short time, it will quickly lead to cardiac tamponade or increased intracranial pressure, resulting in an extremely high mortality rate.

[0003] The current "gold standard" strategy for dealing with intraoperative rupture is to either implant a standard covered stent after balloon occlusion or switch to open surgery. However, this approach has significant limitations: First, standard covered stents are not designed for emergency situations, and their preparation, delivery, and deployment procedures are too lengthy in critical moments where every second counts; second, switching to open surgery is extremely invasive, which is tantamount to a second blow to already high-risk patients, resulting in very poor postoperative healing.

[0004] Traditional pre-filled covered stent technology forms the basis of the current "gold standard" strategy. In this type of technology, the covering mainly serves to prevent blood from leaking out, and does not provide immediate hemostasis. It mainly falls into two categories: one involves weaving polyester yarn and nickel-titanium alloy wire into a tubular structure using a weaving process, such as braided / woven covered stents (CN104689379A, CN105105867A). However, the weaving gaps can lead to insufficient anti-permeability, allowing blood to easily leak through the fiber gaps. The second type uses ePTFE (expanded polytetrafluoroethylene) as the covering material, with the stent being a self-expanding nickel-titanium alloy or stainless steel structure, such as the vascular covered stent products from Bard Medical (National Medical Device Registration Certificates 20163132779, 20223130324, 20163462779, 20203130161). Traditional pre-filled covered stents primarily rely on physical barriers, resulting in poor applicability for emergency treatment, a lack of active intervention capabilities, and limited biocompatibility. Materials such as ePTFE and PET are bioinert, hindering the repair of vascular wall ruptures. Furthermore, there is a lack of sizes specifically designed for small vessels; traditional ePTFE covered stents (such as those from Bard) and braided stents have large outer diameters, primarily used for large vessel diseases, and cannot pass through small vessels of 2.5–4.5 mm.

[0005] The key to treating this type of emergency bleeding lies in whether a small-diameter covered stent can be immediately implanted that can quickly reach the lesion site and effectively seal the rupture. However, there are currently no suitable small-diameter covered stent products. Covered stents on the market (such as those based on ePTFE) are designed for large blood vessels such as the aorta. Their materials are rigid and their delivery diameter is large, making it impossible for them to pass through tortuous and delicate coronary or intracranial blood vessel pathways. Forcibly delivering them can easily cause secondary damage, and their covers are at risk of microstructural damage after being subjected to intense pressure, leading to closure failure.

[0006] The technological bottleneck of small-diameter vascular stent grafts is a systems engineering problem: it requires the graft material to be extremely flexible for smooth delivery, yet strong enough to withstand pressure damage; it must be dense enough to immediately prevent bleeding, while also possessing good biocompatibility to maintain long-term patency. Existing technologies struggle to meet these stringent clinical requirements. ePTFE, due to its rigidity and necessary thickness, results in a large outer diameter for the stent system, making it difficult to pass through tortuous and delicate blood vessels; PET woven grafts rely on post-treatment coatings to achieve bleeding prevention, but these coatings are easily damaged and fail during stent deformation.

[0007] To address the issue of immediacy, the industry has explored emergency hemostasis covered stent technology. For example, the in-situ rapid coating technology described in patent CN114159629A, while capable of forming a coating on the stent surface within tens of seconds, suffers from inherent defects in its single-layer dense membrane generated through phase inversion: insufficient toughness (limited elongation at break, typically <300%), making it prone to rupture during stent balloon expansion; weak damage resistance (the single-layer membrane structure cannot buffer the concentrated stress generated during the compression process of the metal stent skeleton, making the coating easily punctured by the skeleton, leading to failure during delivery); and limited functionality (difficult to balance flexibility, toughness, and biocompatibility). In addition, CN119367099A discloses a retrievable large vessel covered stent for medical emergency use. Under ultrasound guidance, the covered stent is quickly inserted into the aorta. The PTFE covering on the outer surface of the stent body temporarily seals the blood supply vessels to the ruptured or bleeding organs, thereby achieving rapid hemostasis. It is equipped with a retrieval traction mechanism, which can be used with the stent retrieval sheath to retrieve the temporary stent body from the blood vessel. However, its PTFE covering and design are still mainly used for emergency hemostasis in large vessels, and the core problem of delivery to small vessels has not been solved.

[0008] Meanwhile, the development of functionalized covered stent technology has demonstrated more possibilities, but the core challenge of emergency hemostasis has not yet been overcome. For example, CN104490502A discloses a bioresorbable membrane covered stent, in which a membrane made of bioresorbable material is placed between the inner and outer stent layers. After the covered stent provides a temporary barrier for the blood vessel, the membrane can be absorbed by the body without any residue or accumulation, and has a good therapeutic effect on coronary artery perforation; however, its degradation behavior is difficult to control precisely, leading to premature or delayed absorption, affecting endothelialization; at the same time, the supporting force may decrease with degradation, causing collapse. CN120346023A discloses an electrospun membrane-coated stent, which uses electrospinning technology to prepare the membrane. The membrane covers the surface of the metal stent to form a tubular structure, which helps reduce the risk of stent displacement or instability. Furthermore, the micron-sized pores of the electrospun membrane effectively prevent blood permeation. However, the membrane structure of this patent is simple and lacks toughness, making it easily ruptured during stent expansion. The single-layer membrane cannot effectively buffer the concentrated stress on the membrane during stent scaffold compression, resulting in a high risk of the membrane being "punctured" by the scaffold. In addition, CN117731848A discloses a fiber-based directional drainage vascular membrane-coated stent. The fiber-based membrane has a gradient wetting structure formed by a gradual distribution of hydrophilic to hydrophobic fibers, guiding blood from the aneurysm cavity back to the maternal artery. However, its complex structure may increase the risk of thrombosis, and its fabrication process is difficult and costly. Electrospinning technology offers the possibility of preparing flexible nanofiber membranes, but their mechanical strength may be insufficient to withstand the long-term impact of intravascular blood flow, the periodic pulsation of the vessel wall, and the long-term radial stress of the stent itself. Electrospun fiber membranes are easily "punctured" by the framework after gripping and releasing, posing a risk to long-term durability. CN114176855A discloses a biodegradable polymer ultrathin film, its preparation method, applications, and a method for preparing covered vascular stents, using a copolymer of biodegradable polyester and polyethylene glycol as raw material to prepare the ultrathin film. However, the monolayer copolymer film is still a homogeneous structure in terms of physical topology and is a dense morphology. At the molecular scale, hydrophilic and hydrophobic segments coexist in the same membrane layer, and their hydrophilic function and mechanical support function are mutually restrictive and difficult to optimize simultaneously. Under stent gripping conditions, the normal stress generated by the rigid stent framework is directly transmitted to the interior of the membrane material; due to the lack of microscopic displacement tolerance and volume compression space in monolayer materials, molecular chain breakage easily occurs at stress concentration points.

[0009] Therefore, it is of great significance to study a vascular covered stent for emergency bleeding and its preparation method to solve the problems existing in the prior art. Summary of the Invention

[0010] The purpose of this invention is to solve the problems existing in the prior art and to provide a vascular covered stent for emergency bleeding and its preparation method.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0012] A vascular covered stent for emergency bleeding includes a tubular stent skeleton and a double-layer composite fiber membrane covering the outer surface of the tubular stent skeleton.

[0013] The bilayer composite fiber membrane is formed sequentially by electrospinning on the outer surface of a tubular scaffold. It is an interconnected micro-nano-scale fiber aggregate formed by electrospinning, consisting of an inner buffer layer and an outer structural layer. There is fiber interweaving and physical interlocking between the layers. The inner buffer layer is a polyvinyl alcohol porous fiber membrane, and the outer structural layer is a biodegradable elastomer fiber membrane.

[0014] The vascular covered stent of the present invention is used for emergency hemostasis during surgery, solving the problem that the covered stent in the prior art is easily damaged during the compression / delivery process after the rupture of small blood vessels during surgery, and cannot quickly and reliably seal the rupture.

[0015] The tubular scaffold framework is covered with a double-layer composite fiber membrane. The inner buffer layer is a porous polyvinyl alcohol (PVA) fiber membrane. During application, it is pressed and held above its dry glass transition temperature (PVA fibers annealed and cooled to room temperature, with a measured water content of 10-15% and a glass transition temperature of approximately 50°C). This layer directly contacts the scaffold framework. During the pressing process, the dry, highly elastic PVA inner layer, with its excellent flexibility and extensibility, deforms in tandem with the scaffold framework and disperses localized stress concentration, thus preventing the membrane from being punctured by the framework during pressing. After implantation, the PVA layer absorbs water and softens, transforming into a hydrogel state, further providing long-term dynamic stress buffering and excellent biocompatibility. Simultaneously, the softened PVA layer exhibits good biolubricity and anti-bleeding capabilities.

[0016] The outer structural layer is a biodegradable elastomer fiber membrane, which covers the PVA layer. Utilizing the inherent high elasticity and elongation at break (>300%) of the elastomer material, it withstands the main mechanical deformation during gripping and release, ensuring that the membrane can fully rebound to the preset shape after the stent is released, maintaining the overall structural integrity, and providing the main radial support force to adhere to the blood vessel wall.

[0017] This invention constructs a unique stress gradient dissipation system through a heterogeneous combination of an inner buffer layer and an outer structural layer. The inner polyvinyl alcohol porous fiber network possesses ultra-high porosity and extremely low compressive modulus. Under stress, it transforms point-concentrated stress into planar distributed stress through pore closure, thereby absorbing most of the deformation energy. The outer structural layer is responsible for maintaining overall mechanical strength. This specific structural design allows the coating to maintain high strength (outer layer) while achieving excellent resistance to compressive stress damage (inner layer), which cannot be achieved by simply altering the chemical composition of a single-layer coating.

[0018] As a preferred technical solution:

[0019] As described above, a vascular stent graft for emergency bleeding has a tubular stent skeleton made of nickel-titanium alloy or biodegradable metal.

[0020] As described above, a vascular stent graft for emergency bleeding has an outer diameter of 2.5 to 5.0 mm, and the final diameter after balloon dilation is suitable for small-diameter vessels of 2.5 to 4.5 mm. For stents suitable for small-diameter vessels of 2.5 to 4.5 mm, their diameter should generally match or be slightly larger than the inner diameter of the target vessel to ensure that they can adhere to the vessel wall and provide sufficient radial support after deployment.

[0021] As described above, a vascular covered stent for emergency bleeding has an inner buffer layer with a thickness of 20-30 μm. If it is too thin, the buffering effect will be insufficient, and if it is too thick, it may affect the stent's flexibility and outer diameter. The outer structural layer has a thickness of 50-60 μm. This thickness setting ensures sufficient mechanical strength and resilience, while not affecting the overall outer diameter and delivery performance of the stent.

[0022] As described above, a vascular endothelial stent for emergency bleeding has a polyvinyl alcohol porous fiber membrane with a pore size of <2μm and a fiber diameter of 0.6~2μm; and a biodegradable elastomer fiber membrane with a pore size of <2μm and a fiber diameter of 0.8~2.5μm.

[0023] As described above, a vascular stent graft for emergency bleeding uses a biodegradable elastomer of one or more of polycaprolactone (PCL), polyethylene glycol-modified polyurethane (PEG-PU), poly(lactic-caprolactone) (PLCL), and poly(ethylene glycol-co-ε-caprolactone) (PGCL).

[0024] As described above, a vascular stent graft for emergency bleeding exhibits the following properties after three cycles of compression (to a diameter of 1.2 mm) and release: tensile strength retention rate ≥ 95%, elongation at break retention rate ≥ 95%, and graft integrity (no breakage rate) 100%.

[0025] The present invention also provides a method for preparing a vascular covered stent for emergency bleeding as described in any of the preceding claims. First, a surface-activated tubular stent skeleton is fixed on a high-speed rotating electrospinning collector. Polyvinyl alcohol porous fiber membrane and biodegradable elastomer fiber membrane are sequentially spun on the outer surface of the tubular stent skeleton. Then, the stent with double-layer covering is annealed (for example, for biodegradable elastomer PCL, the heat annealing temperature is 50~60℃ and the time is 1~3h) to obtain a vascular covered stent for emergency bleeding.

[0026] Polyvinyl alcohol (PVA) exhibits strong hydrophilicity and a high glass transition temperature, primarily demonstrating enhanced chain segment movement without significant melting during heating. In contrast, biodegradable elastomers typically possess lower glass transition temperatures and higher ductility, making them more prone to softening and even partial melting during heating. Therefore, heat treatment must simultaneously consider the structural stability and interfacial bonding requirements of both materials. Experiments show that when the annealing temperature is below the temperature required for sufficient elastomer chain movement, effective molecular chain entanglement is difficult to form at the interface, resulting in insufficient interlayer bonding and easy delamination during compression. Conversely, when the temperature approaches or exceeds the elastomer's melting point, the fiber structure collapses, disrupting the original porous network, leading to increased overall material rigidity and decreased elasticity, thus significantly reducing the coating's resistance to deformation. Therefore, the annealing temperature is set above the glass transition temperature of the biodegradable elastomer but below its melting point. This allows the biodegradable elastomer molecular chains to move, interdiffusion and entanglement with the inner PVA fibers at the interface, forming a robust interpenetrating network structure while maintaining the integrity of the fiber network. This process not only enhances the interfacial bonding but also preserves the stress buffering capacity provided by the porous structure.

[0027] This invention uses a biodegradable elastomer material as the outer layer, endowing the coating with extremely high elongation at break and resilience. This ensures that its mechanical properties do not significantly decrease after undergoing severe compression-release deformation, and it is less prone to permanent wrinkles or cracks. The tubular support framework provides radial support, ensures structural integrity and stability, and serves as the carrier and adhesion base for the coating. The elastomer in the outer structural layer provides high resilience and toughness, bearing the main deformation. The polyvinyl alcohol in the inner buffer layer softens after absorbing water, forming a hydrogel that buffers stress concentration and prevents the fiber membrane from being damaged from the inside. Simultaneously, the heat-annealed interface enhances interlayer bonding and prevents delamination.

[0028] As a preferred technical solution:

[0029] As described above, in the preparation method of a vascular covered stent for emergency bleeding, the surface activation treatment refers to ultrasonic cleaning followed by plasma activation treatment.

[0030] The ultrasonic cleaning time is 10~20 min, and the plasma activation treatment process parameters are: power 100~150W, time 5~10 min, argon flow rate 15~30 sccm.

[0031] Beneficial effects:

[0032] (1) The vascular covered stent of the present invention for emergency bleeding has excellent resistance to pressure injury, immediate hemostasis function and good delivery, which fundamentally solves the problem of easy damage to the covered stent during pressure and delivery of small-diameter covered stents, and achieves effective hemostasis.

[0033] (2) The present invention provides a method for preparing a vascular covered stent for emergency bleeding. By precisely controlling the fiber diameter and spinning structure, the pore size of the covered stent is ensured to be small enough (<2μm), which can effectively seal the vascular rupture and prevent blood leakage; and the preparation method is simple. Attached Figure Description

[0034] Figure 1 This is a structural diagram of the vascular covered stent of the present invention;

[0035] Among them, 1-tubular scaffold framework, 2-polyvinyl alcohol porous fiber membrane, and 3-biodegradable elastomer fiber membrane. Detailed Implementation

[0036] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0037] The test methods involved in the performance indicators in the embodiments and comparative examples of this invention are as follows:

[0038] Compression-Release Cycle Test: The radial loading principle for stent fatigue testing was adapted to YY / T 0663.2-2024 "Vascular Stents Part 2: Standard for Extracorporeal Pulsivity Durability Testing of Vascular Stents". A heavy-duty stent compression machine (model: RXSC-YWJD26L100Y10H) equipped with a customized radial compression clamp was used. The stent sample was compressed to a diameter of 1.2 mm, held for 30 seconds, and then completely released, which was recorded as one cycle. This process was repeated a total of 3 times.

[0039] Compression modulus: Referring to YY / T 1660-2019 "Radial Load Test Method for Balloon-Expandable and Self-Expanding Vascular Stents", pure PVA and pure biodegradable elastomer electrospun fiber tubes of the same thickness were prepared according to the thickness of the inner and outer fiber membranes of the vascular graft stent. Radial compression tests were performed on them using a multi-functional tensile strength tester for medical textiles (model: YG(B) 026G-500) until the diameter of the fiber tube was reduced by 50%. Calculation of compression modulus: The radial compression modulus E=Δσ / Δε was calculated from the elastic deformation stage of the stress-strain curve. Where, σ: stress (unit: Pa) ε: strain (dimensionless).

[0040] Porosity: Referring to GB / T 1033.1-2008 "Determination of density of non-foamed plastics - Part 1: Impregnation method", the porosity of the inner and outer fiber membranes was determined by gravimetric method. Fiber membrane samples were cut into 10 mm × 10 mm pieces, and the dry weight (Wd) was recorded. The samples were immersed in anhydrous ethanol and degassed under vacuum for 30 min to ensure complete impregnation. After removal, excess ethanol was absorbed with filter paper, and the wet weight (Ww) was recorded. Porosity was calculated using the following formula:

[0041] ;

[0042] Where, ρ 乙醇 The density of ethanol (0.789 g / cm³) is ρ. 聚合物 The density is the density of the fiber membrane material.

[0043] Tensile strength retention rate: Refer to GB / T 1040.3-2006 "Determination of tensile properties of plastics - Part 3: Test conditions for films and sheets". Using a film tensile clamp, the tensile strength of the coated samples before and after the grip-release cycle was tested on a multi-functional tensile strength tester for medical textiles (model: YG(B) 026G-500). Tensile strength retention rate (%) = (Tensile strength after cycle / Tensile strength before cycle) × 100%. The test speed was set to 10 mm / min.

[0044] Elongation at break retention: Refer to GB / T 1040.3-2006 "Determination of tensile properties of plastics - Part 3: Test conditions for films and sheets". A film tensile fixture was used, and a multi-functional tensile strength tester for medical textiles (model: YG(B)026G-500) was employed. The test was conducted simultaneously with the tensile strength test. The elongation at break was recorded. Elongation at break retention (%) = (Elongation at break after cycles / Elongation at break before cycles) × 100%.

[0045] Coating integrity: After completing three grip-release cycles, the coating surface and edge areas were observed using a scanning electron microscope (model: FLEX1000) at magnification of 500x or higher. The presence of cracks, perforations, or separation from the scaffold skeleton was checked. Coating integrity was measured as the percentage of undamaged samples out of the total number of tested samples.

[0046] Example 1

[0047] A method for preparing a vascular covered stent for emergency bleeding, comprising the following steps:

[0048] (1) Surface activation treatment of tubular scaffold framework:

[0049] The 2.5mm outer diameter nickel-titanium alloy tubular support skeleton was placed in anhydrous ethanol, ultrasonically cleaned for 15 minutes, removed and dried with nitrogen gas, and then subjected to plasma activation treatment.

[0050] The process parameters for plasma activation treatment are: power 100W, time 5min, argon flow rate 20sccm;

[0051] (2) Preparation of polyvinyl alcohol spinning solution:

[0052] Polyvinyl alcohol (PVA, molecular weight 1750±50) was added to deionized water, stirred in a water bath at 90℃ for 4 hours, and then allowed to stand for 2 hours to remove bubbles, thus preparing a polyvinyl alcohol spinning solution with a mass concentration of 10%.

[0053] (3) The surface-activated tubular scaffold skeleton is fixed on a high-speed rotating electrospinning collector, and a polyvinyl alcohol spinning solution is used to spin a 20 μm thick polyvinyl alcohol porous fiber membrane on the outer surface of the tubular scaffold skeleton.

[0054] The spinning process parameters are as follows: needle diameter 21G, receiving distance 15cm; positive voltage 18kV, negative voltage 2kV; spinning solution flow rate 0.8mL / h; collector rotation speed 800r / min; spinning time 30min.

[0055] The obtained polyvinyl alcohol porous fiber membrane has a pore size of 1.2 μm and a fiber diameter of 1 μm;

[0056] (4) Polycaprolactone (manufacturer Sigma-Aldrich, brand name: 440744, Mn=80,000) was added to a dichloromethane / acetone mixed solvent with a volume ratio of 7:3, stirred at room temperature for 6 hours, and then allowed to stand for 3 hours to degas, so as to prepare a polycaprolactone spinning solution with a mass concentration of 8%.

[0057] (5) Using polycaprolactone spinning solution, continue spinning on the surface of the polyvinyl alcohol porous fiber membrane in step (3) to form a polycaprolactone fiber membrane with a thickness of 50 μm, and obtain a scaffold with a double-layer coating.

[0058] The spinning process parameters are as follows: needle diameter 22G, receiving distance 18cm; positive voltage 20kV, negative voltage 2kV; spinning solution flow rate 1mL / h; collector rotation speed 800r / min; spinning time 20min.

[0059] The obtained polycaprolactone fiber membrane has a pore size of 1.5 μm and a fiber diameter of 1.2 μm;

[0060] (6) The stent with double-layer coating was annealed at 55°C for 2 hours and cooled to room temperature to obtain a vascular covered stent for emergency bleeding.

[0061] like Figure 1 As shown, the final vascular endothelial stent for emergency bleeding consists of a tubular stent framework 1 and a double-layer composite fiber membrane covering the outer surface of the tubular stent framework 1. The double-layer composite fiber membrane consists of an inner buffer layer and an outer structural layer. The inner buffer layer is a polyvinyl alcohol porous fiber membrane 2 with a compressive modulus of 65 kPa and a porosity of 85%. The outer structural layer is a polycaprolactone fiber membrane (i.e., a biodegradable elastomer fiber membrane 3) with a compressive modulus of 1.5 MPa and a porosity of 70%. After three compression-release cycles at 55°C, the vascular endothelial stent retains 98% of its tensile strength, 99% of its elongation at break, and 100% of its endothelial integrity.

[0062] Comparative Example 1

[0063] A method for preparing a vascular covered stent is basically the same as in Example 1, except that steps (4) to (5) are omitted, i.e., the polycaprolactone fiber membrane is not included, while the total thickness of the fiber membrane is kept constant.

[0064] After three cycles of grip-release, the final fabricated vascular stent retained 72% of its tensile strength, 68% of its elongation at break, and 60% of its vascular graft integrity.

[0065] Comparing Comparative Example 1 and Example 1, it can be found that the mechanical property retention rate and structural integrity of the scaffold coating are significantly reduced after the outer PCL structural layer is missing. This is because although the single-layer PVA film is hydrophilic and buffering, it lacks the support of highly elastic materials and cannot effectively rebound in the violent deformation of the compression release, which easily produces permanent wrinkles and micro-cracks, resulting in loss of mechanical properties and coating damage.

[0066] Comparative Example 2

[0067] A method for preparing a vascular covered stent is basically the same as in Example 1, except that steps (2) to (3) are omitted, that is, the polyvinyl alcohol porous fiber membrane is not included, while the total thickness of the fiber membrane is kept constant.

[0068] After three cycles of grip-release, the tensile strength of the fabricated vascular stent remained at 88%, the elongation at break remained at 85%, and the integrity of the vascular stent cover was 75%.

[0069] Comparing Comparative Example 2 and Example 1, it can be found that without the inner PVA buffer layer, the coating's resistance to pressure-grinding damage, especially its integrity, is significantly worse. This is because the single-layer PCL membrane is in direct contact with the rigid support skeleton, and during the pressure-grinding process, the lack of a buffer layer to disperse the concentrated stress at the skeleton nodes makes the coating more susceptible to being "punctured," resulting in a decrease in integrity.

[0070] Comparative Example 3

[0071] A method for preparing a vascular covered stent is basically the same as in Example 1, except that step (6) does not involve annealing.

[0072] After three cycles of grip-release, the final fabricated vascular stent retained 90% of its tensile strength, 87% of its elongation at break, and 80% of its vascular graft integrity.

[0073] Comparing Comparative Example 3 and Example 1, it can be found that after omitting the thermal annealing process, the interlayer bonding force of the double-layer coating is insufficient, and the overall performance is somewhat reduced. This is because the interfacial interpenetrating network structure induced by thermal annealing is lacking, the bonding between the PVA layer and the PCL layer is weak, and interlayer slippage or even separation is prone to occur during mechanical deformation, thereby affecting the overall mechanical performance and barrier integrity of the composite film.

[0074] Comparative Example 4

[0075] A method for preparing a vascular covered stent is basically the same as in Example 1, except that the annealing temperature in step (1) is 65°C.

[0076] After three cycles of grip-release, the final fabricated vascular stent retained 82% of its tensile strength, 80% of its elongation at break, and 65% of its vascular graft integrity.

[0077] Comparing Comparative Example 4 and Example 1, it can be found that excessively high annealing temperature (exceeding the melting point of PCL) leads to a serious deterioration in the coating performance. This is because excessively high temperature causes PCL fibers to melt excessively, destroying their inherent porous fiber structure, resulting in the film becoming hard, brittle, and losing its elasticity. At the same time, it may affect the cross-linking structure of the PVA layer, thereby seriously impairing its resistance to deformation and integrity.

[0078] Comparative Example 5

[0079] A method for preparing a vascular covered stent is basically the same as in Example 1, except that in steps (2) to (5), the spinning material is only poly(ethylene glycol-co-ε-caprolactone) copolymer. The preparation process of the copolymer ultrafilm is as follows: the poly(ethylene glycol-co-ε-caprolactone) copolymer is dissolved in dichloromethane to prepare a spinning solution with a mass fraction of 10%; the surface-activated tubular stent skeleton is fixed on a high-speed rotating electrospinning collector, and a 70μm thick polyvinyl alcohol porous fiber membrane is formed by spinning the spinning solution on the outer surface of the tubular stent skeleton. Then, the vascular covered stent is prepared by the original method (6).

[0080] After three cycles of grip-release, the tensile strength of the fabricated vascular stent remained at 58%, the elongation at break remained at 52%, and the integrity of the vascular stent cover was 55%.

[0081] Comparing Comparative Example 5 and Example 1, it can be found that after the single-layer coated stent of Comparative Example 5 was placed at 55°C for 3 compression-release cycles, its mechanical properties decreased and the integrity of the coating could not be maintained. This is because the single-layer membrane structure cannot effectively buffer the local stress concentration generated by the metal stent skeleton during the compression process, lacks a stress buffer barrier, and its mechanical properties are significantly degraded, resulting in microcracks or even damage to the coating after multiple compression-release cycles.

[0082] Example 2

[0083] A method for preparing a vascular covered stent for emergency bleeding, comprising the following steps:

[0084] (1) Surface activation treatment of tubular scaffold framework:

[0085] A magnesium alloy tubular support frame with an outer diameter of 3 mm was placed in anhydrous ethanol, ultrasonically cleaned for 10 min, removed and dried with nitrogen gas, and then subjected to plasma activation treatment.

[0086] The process parameters for plasma activation treatment are: power 110W, time 10min, argon flow rate 15sccm;

[0087] (2) Preparation of polyvinyl alcohol spinning solution:

[0088] Polyvinyl alcohol (PVA, molecular weight 1750±50) was added to deionized water, stirred in a water bath at 90℃ for 4 hours, and then allowed to stand for 2 hours to remove bubbles, thus preparing a polyvinyl alcohol spinning solution with a mass concentration of 9%.

[0089] (3) The surface-activated tubular scaffold skeleton is fixed on a high-speed rotating electrospinning collector, and a polyvinyl alcohol spinning solution is used to spin a 25 μm thick polyvinyl alcohol porous fiber membrane on the outer surface of the tubular scaffold skeleton.

[0090] The spinning process parameters are as follows: needle diameter 20G, receiving distance 16cm; positive voltage 15kV, negative voltage 1kV; spinning solution flow rate 0.5mL / h; collector rotation speed 500r / min; spinning time 20min.

[0091] The obtained polyvinyl alcohol porous fiber membrane has a pore size of 1.5 μm and a fiber diameter of 0.8 μm;

[0092] (4) Polyethylene glycol modified polyurethane (manufacturer: Bayer, brand name: Tecophilic™ SP-93A-100) was added to a dichloromethane / acetone mixed solvent with a volume ratio of 7:3, stirred at room temperature for 6 hours, and then allowed to stand for 3 hours to degas, so as to prepare a 9% (w / w) polyethylene glycol modified polyurethane spinning solution.

[0093] (5) Using polyethylene glycol modified polyurethane spinning solution, continue spinning on the surface of the polyvinyl alcohol porous fiber membrane in step (3) to form a polyethylene glycol modified polyurethane fiber membrane with a thickness of 55 μm, and obtain a scaffold with double-layer coating.

[0094] The spinning process parameters are as follows: needle diameter 21G, receiving distance 15cm; positive voltage 15kV, negative voltage 1kV; spinning solution flow rate 0.5mL / h; collector rotation speed 500r / min; spinning time 25min.

[0095] The obtained polyethylene glycol modified polyurethane fiber membrane has a pore size of 1.2 μm and a fiber diameter of 1 μm;

[0096] (6) The stent with double-layer coating was annealed at 52°C for 1 hour and cooled to room temperature to obtain a vascular covered stent for emergency bleeding.

[0097] The final vascular stent graft for emergency bleeding consists of a tubular stent framework and a double-layer composite fiber membrane covering the outer surface of the tubular stent framework. The double-layer composite fiber membrane is composed of an inner buffer layer and an outer structural layer. The inner buffer layer is a polyvinyl alcohol porous fiber membrane with a compressive modulus of 60 kPa and a porosity of 87%. The outer structural layer is a polyethylene glycol modified polyurethane fiber membrane with a compressive modulus of 1.2 MPa and a porosity of 74%. After three compression-release cycles at 55°C, the vascular stent graft retains 96% of its tensile strength, 97% of its elongation at break, and 100% of its graft integrity.

[0098] Example 3

[0099] A method for preparing a vascular covered stent for emergency bleeding, comprising the following steps:

[0100] (1) Surface activation treatment of tubular scaffold framework:

[0101] A zinc alloy tubular support frame with an outer diameter of 3.5 mm was placed in anhydrous ethanol, ultrasonically cleaned for 12 minutes, removed and dried with nitrogen gas, and then subjected to plasma activation treatment.

[0102] The process parameters for plasma activation treatment are: power 120W, time 8min, argon flow rate 25sccm;

[0103] (2) Preparation of polyvinyl alcohol spinning solution:

[0104] Polyvinyl alcohol (PVA, molecular weight 1750±50) was added to deionized water, stirred in a water bath at 90℃ for 4 hours, and then allowed to stand for 2 hours to remove bubbles, thus preparing a polyvinyl alcohol spinning solution with a mass concentration of 8%.

[0105] (3) The surface-activated tubular scaffold skeleton is fixed on a high-speed rotating electrospinning collector, and a polyvinyl alcohol spinning solution is used to spin a 30 μm thick polyvinyl alcohol porous fiber membrane on the outer surface of the tubular scaffold skeleton.

[0106] The spinning process parameters are as follows: needle diameter 21G, receiving distance 17cm; positive voltage 16kV, negative voltage 1.5kV; spinning solution flow rate 0.6mL / h; collector rotation speed 600r / min; spinning time 25min.

[0107] The obtained polyvinyl alcohol porous fiber membrane has a pore size of 1.8 μm and a fiber diameter of 1.5 μm;

[0108] (4) Poly(lactic acid-caprolactone) (manufacturer: Corbion, brand: PURASORB PLC 7015) (LA:CL=70:30) was added to a dichloromethane / acetone mixed solvent with a volume ratio of 7:3, stirred at room temperature for 6 hours, and then allowed to stand for 3 hours to remove bubbles, so as to prepare a poly(lactic acid-caprolactone) spinning solution with a mass concentration of 10%.

[0109] (5) Using poly(lactic acid-caprolactone) spinning solution, continue spinning on the surface of the polyvinyl alcohol porous fiber membrane in step (3) to form a poly(lactic acid-caprolactone) fiber membrane with a thickness of 60 μm, and obtain a scaffold with a double-layer coating.

[0110] The spinning process parameters are as follows: needle diameter 20G, receiving distance 16cm; positive voltage 16kV, negative voltage 2kV; spinning solution flow rate 0.6mL / h; collector rotation speed 600r / min; spinning time 30min.

[0111] The poly(lactic acid-caprolactone) fiber membrane obtained has a pore size of 1.8 μm and a fiber diameter of 2 μm;

[0112] (6) The stent with double-layer coating was annealed at 58°C for 2 hours and cooled to room temperature to obtain a vascular covered stent for emergency bleeding.

[0113] The final vascular stent graft for emergency bleeding consists of a tubular stent framework and a double-layer composite fiber membrane covering the outer surface of the tubular stent framework. The double-layer composite fiber membrane is composed of an inner buffer layer and an outer structural layer. The inner buffer layer is a polyvinyl alcohol porous fiber membrane with a compressive modulus of 70 kPa and a porosity of 82%. The outer structural layer is a poly(lactic acid-caprolactone) fiber membrane with a compressive modulus of 1.9 MPa and a porosity of 65%. After three compression-release cycles at 55°C, the vascular stent graft retains 97% of its tensile strength, 98% of its elongation at break, and 100% of its graft integrity.

[0114] Example 4

[0115] A method for preparing a vascular covered stent for emergency bleeding, comprising the following steps:

[0116] (1) Surface activation treatment of tubular scaffold framework:

[0117] A nickel-titanium alloy tubular support skeleton with an outer diameter of 4 mm was placed in anhydrous ethanol, ultrasonically cleaned for 16 min, removed and dried with nitrogen gas, and then subjected to plasma activation treatment.

[0118] The process parameters for plasma activation treatment are: power 130W, time 6min, argon flow rate 30sccm;

[0119] (2) Preparation of polyvinyl alcohol spinning solution:

[0120] Polyvinyl alcohol (PVA, molecular weight 1750±50) was added to deionized water, stirred in a water bath at 90℃ for 4 hours, and then allowed to stand for 2 hours to remove bubbles, thus preparing a polyvinyl alcohol spinning solution with a mass concentration of 9%.

[0121] (3) The surface-activated tubular scaffold skeleton is fixed on a high-speed rotating electrospinning collector, and a polyvinyl alcohol spinning solution is used to spin a 22 μm thick polyvinyl alcohol porous fiber membrane on the outer surface of the tubular scaffold skeleton.

[0122] The spinning process parameters are as follows: needle diameter 22G, receiving distance 18cm; positive voltage 17kV, negative voltage 2.5kV; spinning solution flow rate 0.7mL / h; collector rotation speed 800r / min; spinning time 28min.

[0123] The obtained polyvinyl alcohol porous fiber membrane has a pore size of 1 μm and a fiber diameter of 0.7 μm;

[0124] (4) Poly(ethylene glycol-co-ε-caprolactone) (manufacturer: ALADDIN, brand name: P665308, PEG: MW2000 & PCL: MW 3000) was added to a dichloromethane / acetone mixed solvent with a volume ratio of 7:3, stirred at room temperature for 6 hours, and then allowed to stand for 3 hours to remove bubbles, so as to prepare a poly(ethylene glycol-co-ε-caprolactone) spinning solution with a mass concentration of 9%;

[0125] (5) Using poly(ethylene glycol-co-ε-caprolactone) spinning solution, continue spinning on the surface of the polyvinyl alcohol porous fiber membrane in step (3) to form a poly(ethylene glycol-co-ε-caprolactone) fiber membrane with a thickness of 52 μm, and obtain a scaffold with a double-layer coating.

[0126] The spinning process parameters are as follows: needle diameter 22G, receiving distance 17cm; positive voltage 17kV, negative voltage 3kV; spinning solution flow rate 0.8mL / h; collector rotation speed 800r / min; spinning time 20min.

[0127] The obtained poly(ethylene glycol-co-ε-caprolactone) fiber membrane has a pore size of 1 μm and a fiber diameter of 0.9 μm;

[0128] (6) The stent with double-layer coating was annealed at 50°C for 3 hours and cooled to room temperature to obtain a vascular covered stent for emergency bleeding.

[0129] The final vascular stent graft for emergency bleeding consists of a tubular stent framework and a double-layer composite fiber membrane covering the outer surface of the tubular stent framework. The double-layer composite fiber membrane is composed of an inner buffer layer and an outer structural layer. The inner buffer layer is a polyvinyl alcohol porous fiber membrane with a compressive modulus of 65 kPa and a porosity of 85%. The outer structural layer is a poly(ethylene glycol-co-ε-caprolactone) fiber membrane with a compressive modulus of 1.4 MPa and a porosity of 72%. After three compression-release cycles at 55°C, the vascular stent graft retains 95% of its tensile strength, 96% of its elongation at break, and 100% of its graft integrity.

[0130] Example 5

[0131] A method for preparing a vascular covered stent for emergency bleeding, comprising the following steps:

[0132] (1) Surface activation treatment of tubular scaffold framework:

[0133] A nickel-titanium alloy tubular support frame with an outer diameter of 5 mm was placed in anhydrous ethanol, ultrasonically cleaned for 20 min, removed and dried with nitrogen gas, and then subjected to plasma activation treatment.

[0134] The process parameters for plasma activation treatment are: power 150W, time 5min, argon flow rate 15sccm;

[0135] (2) Preparation of polyvinyl alcohol spinning solution:

[0136] Polyvinyl alcohol (PVA, molecular weight 1750±50) was added to deionized water, stirred in a water bath at 90℃ for 4 hours, and then allowed to stand for 2 hours to remove bubbles, thus preparing a polyvinyl alcohol spinning solution with a mass concentration of 10%.

[0137] (3) The surface-activated tubular scaffold skeleton is fixed on a high-speed rotating electrospinning collector, and a polyvinyl alcohol spinning solution is used to spin a 28 μm thick polyvinyl alcohol porous fiber membrane on the outer surface of the tubular scaffold skeleton.

[0138] The spinning process parameters are as follows: needle diameter 20G, receiving distance 15cm; positive voltage 20kV, negative voltage 3kV; spinning solution flow rate 1mL / h; collector rotation speed 1000r / min; spinning time 30min.

[0139] The obtained polyvinyl alcohol porous fiber membrane has a pore size of 1.3 μm and a fiber diameter of 1.8 μm;

[0140] (4) Polycaprolactone (manufacturer: Sigma-Aldrich, grade: 440744, Mn=80,000) and poly(lactic acid-caprolactone) (manufacturer: Corbion, grade: PURASORB PLC 7015) with a mass ratio of 1:1 were added to a dichloromethane / acetone mixed solvent with a volume ratio of 7:3. The mixture was stirred at room temperature for 6 hours and then allowed to stand for 3 hours to remove bubbles, thus preparing a polycaprolactone and poly(lactic acid-caprolactone) mixed spinning solution with a mass ratio of 1:1 and a mass concentration of 8%.

[0141] (5) Using a polycaprolactone and poly(lactic acid-caprolactone) mixed spinning solution with a mass ratio of 1:1, continue spinning on the surface of the polyvinyl alcohol porous fiber membrane in step (3) to form a polycaprolactone and poly(lactic acid-caprolactone) fiber membrane with a mass ratio of 1:1 and a thickness of 58 μm, to obtain a scaffold with a double-layer coating.

[0142] The spinning process parameters are as follows: needle diameter 21G, receiving distance 18cm; positive voltage 19kV, negative voltage 2kV; spinning solution flow rate 1mL / h; collector rotation speed 1000r / min; spinning time 25min.

[0143] The obtained polycaprolactone (and poly(lactic acid-caprolactone) fiber membrane with a mass ratio of 1:1 had a pore size of 1.6 μm and a fiber diameter of 1.8 μm.

[0144] (6) The stent with double-layer coating was annealed at 60°C for 1 hour and cooled to room temperature to obtain a vascular covered stent for emergency bleeding.

[0145] The final vascular stent graft for emergency bleeding consists of a tubular stent framework and a double-layer composite fiber membrane covering the outer surface of the tubular stent framework. The double-layer composite fiber membrane is composed of an inner buffer layer and an outer structural layer. The inner buffer layer is a polyvinyl alcohol porous fiber membrane with a compressive modulus of 80 kPa and a porosity of 78%. The outer structural layer is a polycaprolactone and poly(lactic acid-caprolactone) fiber membrane in a 1:1 mass ratio with a compressive modulus of 1.8 MPa and a porosity of 68%. After three compression-release cycles at 55°C, the vascular stent graft retains 98% of its tensile strength, 99% of its elongation at break, and 100% of its graft integrity.

Claims

1. A vascular stent graft for emergency bleeding, characterized in that: It includes a tubular scaffold framework and a double-layer composite fiber membrane covering the outer surface of the tubular scaffold framework; The double-layer composite fiber membrane is formed sequentially by electrospinning on the outer surface of a tubular scaffold framework. It consists of an inner buffer layer and an outer structural layer. The inner buffer layer is a polyvinyl alcohol porous fiber membrane, and the outer structural layer is a biodegradable elastomer fiber membrane.

2. A vascular covered stent for emergency bleeding according to claim 1, characterized in that, The tubular scaffold framework is made of nickel-titanium alloy or biodegradable metal.

3. A vascular stent graft for emergency bleeding according to claim 1, characterized in that, The outer diameter of the vascular covered stent is 2.5~5.0mm.

4. A vascular covered stent for emergency bleeding according to claim 1, characterized in that, The thickness of the inner buffer layer is 20~30μm, and the thickness of the outer structural layer is 50~60μm.

5. A vascular covered stent for emergency bleeding according to claim 1, characterized in that, Polyvinyl alcohol porous fiber membranes have a pore size of <2μm and a fiber diameter of 0.6~2μm; biodegradable elastomer fiber membranes have a pore size of <2μm and a fiber diameter of 0.8~2.5μm.

6. A vascular stent graft for emergency bleeding according to claim 1, characterized in that, The biodegradable elastomer is one or more of polycaprolactone, polyethylene glycol modified polyurethane, poly(lactic acid-caprolactone), and poly(ethylene glycol-co-ε-caprolactone).

7. A vascular covered stent for emergency bleeding according to claim 1, characterized in that, After three cycles of grip-release, the vascular stent graft maintained a tensile strength of ≥95%, an elongation at break of ≥95%, and a graft integrity of 100%.

8. A method for preparing a vascular stent graft for emergency bleeding as described in any one of claims 1 to 7, characterized in that: First, the surface-activated tubular stent skeleton is fixed on an electrospinning collector. Polyvinyl alcohol porous fiber membrane and biodegradable elastomer fiber membrane are sequentially spun on the outer surface of the tubular stent skeleton. Then, the stent with double-layer coating is annealed to obtain a vascular covered stent for emergency bleeding. The annealing temperature is higher than the glass transition temperature of biodegradable elastomers but lower than their melting point.

9. A method for preparing a vascular stent graft for emergency bleeding according to claim 8, characterized in that, Surface activation treatment refers to ultrasonic cleaning followed by plasma activation treatment; The ultrasonic cleaning time is 10~20 min, and the plasma activation treatment process parameters are: power 100~150W, time 5~10 min, argon flow rate 15~30 sccm.

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