A film material for a metal stent, a preparation method thereof, and a corresponding film-coated stent

Abstract

The application belongs to the technical field of biomedical new materials, and particularly relates to a film material for metal stents, a preparation method of the film material and a corresponding film stent. The film material for metal stents is composed of E-PLCL, a free radical inhibitor and a photoinitiator. The free radical inhibitor is added in an amount of 0.05% to 0.5% of the weight of the E-PLCL, and the photoinitiator is added in an amount of 0.2% to 2% of the weight of the E-PLCL. The E-PLCL is prepared by modifying PLCL diol by allyl isocyanate. In the application, allyl isocyanate is used as a modifier to modify the PLCL diol by reacting the hydroxyl end groups such as dihydric alcohol with the allyl isocyanate. The modification can be completed in only one step, and the mechanical property is higher than that of the conventional two-step modified polyurethane acrylate material. The photocuring material has low modulus and high elongation at break, and effectively solves the problem that the existing photocuring material library has a too high elastic modulus of the biodegradable printing material, and is difficult to match the human tissue.

Description

Technical Field

[0001] This invention relates to the field of new biomedical materials technology, specifically disclosing a coating material for metal scaffolds, its preparation method, and a corresponding coated scaffold. Background Technology

[0002] Covered stents are medical devices in which a polymer or biofilm is attached to the surface of a bare metal stent. They are widely used to treat diseases such as aneurysms, ruptured blood vessels, and stenosis of blood vessels, esophagus, trachea, and intestines. While traditional bare metal stents provide mechanical support, they are prone to intimal hyperplasia, leading to restenosis. To overcome this drawback, covered stents add a membrane material to the stent surface, effectively isolating blood flow from the vascular intima and reducing the risk of intimal hyperplasia. Existing covered stents typically use non-degradable polytetrafluoroethylene (PTFE), polyurethane, or polyester as the covering material. These materials have good biocompatibility and mechanical properties. However, several challenges remain with traditional non-degradable covering materials, mainly focusing on the long-term stability of the membrane material, the flexibility and compliance of the stent, and the risks of inflammation, hyperplasia, and thrombosis caused by long-term placement.

[0003] Currently, the demand for biodegradable covered stents is gradually increasing. Researchers have progressively developed biodegradable covered stents based on materials such as polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), and poly(L-lactide-co-ε-caprolactone) (PLCL). These materials can gradually degrade after fulfilling their therapeutic function, reducing complications associated with long-term implantation. However, due to the high melting point, high viscosity, and high elastic modulus of these materials, electrospinning technology is currently the most common method for stent covering. Although electrospinning technology has certain advantages in the preparation of covered stents, its processing method and material properties also bring some significant problems: First, because the fiber structure of the electrospun layer is relatively fragile, the covering layer is prone to tearing or detachment due to mechanical stress during stent installation and deployment, which greatly affects the stability and efficacy of the stent. Second, electrospinning technology is difficult to uniformly cover the surface of irregularly shaped stents, such as L-shaped and Y-shaped stents. This limitation not only affects the reliability of covered stents in clinical applications but also restricts their widespread use in more complex lesions. Therefore, there is an urgent need for a coating material that has high mechanical properties, is biodegradable, has a simple processing method, can be used to coat scaffolds of various shapes, and has drug loading function. Summary of the Invention

[0004] In view of the problems and shortcomings of the existing technology, the present invention aims to provide a UV-curable bioabsorbable elastomer resin suitable for covered scaffolds, and to design and prepare a fully covered tissue engineering scaffold based on the resin.

[0005] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0006] The first aspect of this invention provides a coating material for metal scaffolds, comprising E-PLCL, a free radical inhibitor, and a photoinitiator, wherein the amount of the free radical inhibitor added is 0.05% to 0.5% of the weight of E-PLCL, and the amount of the photoinitiator added is 0.2% to 2% of the weight of E-PLCL; wherein the E-PLCL is prepared by double bond modification of PLCL diol with allyl isocyanate.

[0007] The free radical inhibitor is 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxy radical or 2,2,6,6-tetramethylpiperidine oxide; the photoinitiator is 2,4,6-trimethylbenzoyl-diphenylphosphine oxide or ethyl 2,4,6-trimethylbenzoylphosphonate.

[0008] The double bond modification method of E-PLCL is as follows: PLCL diol is dissolved in toluene to form a solution with a concentration of 15wt% to 40wt%, then allyl isocyanate is added, and the reaction is carried out at 50 to 80°C for 0.5 to 1.5 h to obtain the product; the molar ratio of the terminal hydroxyl group of PLCL diol to allyl isocyanate is 1:(1.2 to 1.5).

[0009] The molecular weight of PLCL diol is 3000-10000;

[0010] A second aspect of the present invention provides a method for preparing the coating material for the metal stent described in the first aspect, comprising the following steps:

[0011] Step S1: Prepare PLCL diol;

[0012] Step S2: Dissolve PLCL diol in toluene to form a solution with a concentration of 15wt% to 40wt%, then add allyl isocyanate, and react at 50 to 80°C for 0.5 to 1.5 h to obtain E-PLCL;

[0013] Step S3: Mix E-PLCL with free radical inhibitors and photoinitiators, stir, and remove air bubbles by ultrasonication to obtain a bioabsorbable elastomer resin.

[0014] The specific method for preparing PLCL diol in step S1 is as follows: lactide, ε-caprolactone, diol and stannous octoate are added to a reaction vessel and stirred at 130-160°C under vacuum and oxygen-free conditions for 8-16 hours to obtain poly(L-lactide-co-ε-caprolactone) diol, which is PLCL diol.

[0015] The molar ratio of lactide, ε-caprolactone, and diol is 0.165:0.658:(0.01~0.0125);

[0016] The diol is selected from one or more of 1,6-hexanediol, ethylene glycol, or triethylene glycol.

[0017] A third aspect of this invention provides a coated stent, comprising a metal stent and a coating layer, wherein the coating layer is formed by impregnating or coating the metal stent with the coating material for metal stents as described in claim 1 or 2, followed by photocuring. The coating material prepared by this invention is a viscous liquid at around 40°C and can be directly used for impregnation or coating.

[0018] The coated scaffold also carries a drug, which is mixed into the coating material of the metal scaffold and photocured together with the coating material to complete the loading.

[0019] A fourth aspect of the present invention provides a method for preparing the covered scaffold described in the third aspect, comprising the following steps:

[0020] (1) Immerse the metal stent in the metal stent coating material and ultrasonically treat it at 40-50℃ for 25-35 minutes.

[0021] (2) Take out the metal bracket after step (1) and vacuum heat treat it at 40-50℃ for 15-25 minutes;

[0022] (3) The metal scaffold treated in step (2) is cured under a 365-406nm UV lamp for 10-15 minutes to obtain an E-PLCL fully coated scaffold.

[0023] The metal support is made of nickel-titanium alloy or magnesium alloy.

[0024] The vacuum heat treatment involves placing the object in a vacuum oven while it is suspended in mid-air.

[0025] In step (1), ultrasonic treatment is required to ensure that the E-PLCL fully wraps around the surface of the metal support and remove air bubbles.

[0026] Step (2) Vacuum heat treatment further removes air bubbles.

[0027] The mechanical properties of coating materials, such as elastic modulus, elongation at break, and ultimate tensile strength, are crucial for applications such as tracheal stent coatings. A low elastic modulus facilitates stent compression and placement, allowing for flexible expansion after implantation to accommodate respiratory movements. High elongation at break and tensile strength enable the coating to withstand significant deformation without cracking or failure, ensuring structural integrity. Furthermore, high elasticity allows the coating to recover rapidly under repeated stress. In summary, these properties ensure that the coated stent remains flexible, durable, and adaptable to dynamic deformation under physiological conditions. Current photopolymer biomaterials mainly consist of softer gel formulations (0.1–100 kPa) and harder, highly cross-linked resins (100 MPa), lacking elastomeric resins (low MPa, high elongation). Photocurable PLCLs not only possess the advantages of PLCLs, such as good biocompatibility, non-toxic degradation products, biodegradability, and drug permeability, but also overcome the slow degradation rate of poly(ε-caprolactone) (PCL). Furthermore, for the photocurable functional modification of resin materials, the functionalization of acrylates is considered the gold standard. However, despite the rapid crosslinking kinetics of acrylates, the resulting materials are inherently brittle, limiting their applicability and making them unsuitable as coating scaffold materials. While traditional polyurethane acrylate modification improves the mechanical properties of acrylate materials, the two-step modification process results in a low degree of functionalization. Furthermore, the low selectivity between the two isocyanate groups during modification often leads to the formation of repeating units within the central backbone, further limiting the improvement of mechanical properties.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0029] (1) In this invention, allyl isocyanate is used as a modifier to react the terminal hydroxyl groups of diol (or polyol) with allyl isocyanate to modify the double bond of PLCL diol. The modification can be completed in one step, and the functionalization degree can reach more than 95%. The mechanical properties are higher than those of polyurethane acrylate materials modified by the traditional two-step method.

[0030] (2) This invention synthesizes low molecular weight PLCL, and further modifies it to obtain E-PLCL, which retains the advantages of high molecular weight PLCL while successfully reducing the initial viscosity of PLCL. The resulting photocurable material has low modulus and high elongation at break, as well as good ductility and excellent fatigue resistance. It effectively solves the problem that the elastic modulus of existing biodegradable printing materials in the photocurable material library is too high and difficult to match with human tissue, filling the technological gap in photocurable biodegradable elastomer resin materials.

[0031] (3) The photocurable resin material of the present invention has the characteristics of low viscosity, low processing temperature, and good biocompatibility. It can be loaded with drugs and can also be mixed into cells for printing. The coating has sustained-release properties after loading drugs. By combining drugs with different properties, the advantages of the scaffold in local drug treatment can be further enhanced. The preparation method of the coated scaffold of the present invention is not limited by the shape of the scaffold and can quickly realize the coating of scaffolds of any shape.

[0032] (4) By adjusting the molecular weight, ratio and cross-linking network structure of the material, the photocurable biodegradable elastomer material of the present invention has excellent versatility and is suitable for applications in tissue repair, nerve conduit, artificial blood vessel, tracheal stent, artificial cartilage and drug sustained release system. In addition to being suitable for stent coating, it can also be used in ultraviolet curing 3D printers. Attached Figure Description

[0033] Figure 1 This is a schematic diagram of the preparation process of the photocurable biodegradable elastomer E-PLCL coated scaffold of the present invention;

[0034] Figure 2 The figures show the synthesis and modification routes of E-PLCL and the results of nuclear magnetic resonance and infrared spectroscopy analysis in Examples 1 to 4.

[0035] Figure 3 The following are DSC curves of Examples 1 to 4E-PLCL;

[0036] Figure 4 The figures show the degradation results of the E-PLCL fully covered scaffolds in Examples 1-4;

[0037] Figure 5 These are mechanical property test diagrams for Examples 1 to 4E-PLCL;

[0038] Figure 6 The figures show the results of in vitro biocompatibility experiments for Examples 1-4;

[0039] Figure 7 Viscosity test graphs for Examples 1-4E-PLCL;

[0040] Figure 8 E-PLCL coated scaffold and Y-type coated scaffold were prepared;

[0041] Figure 9 Figures showing cyclic tensile tests of E-8000 spline and cyclic compression tests of E-PLCL coated scaffold;

[0042] Figure 10 This is a diagram showing the compression and passage of the E-PLCL covered stent through the implantation catheter in this invention;

[0043] Figure 11This is a drug release experiment diagram of the E-PLCL / DOX drug-loaded coated stent in this invention;

[0044] Figure 12 This is an experimental diagram showing the inhibition of KYSE150 human esophageal cancer cells by the E-PLCL / DOX drug-loaded scaffold in this invention. Detailed Implementation

[0045] It should be noted that the following detailed description is exemplary and intended to provide further explanation of the present invention. Unless otherwise stated, all technical and scientific terms used herein should have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. For experimental methods in the following embodiments where specific conditions are not specified, conventional techniques in this art or operations performed according to the manufacturer's recommendations are employed; reagents or instruments used, unless otherwise specified, are conventional products available commercially.

[0046] To enable those skilled in the art to more clearly understand the technical solutions of the present invention, the present invention will now be further described in detail through specific embodiments, but these embodiments should not be regarded as limiting the scope of the present invention.

[0047] (I) The Influence of Different Molecules on Material Properties

[0048] Example 1

[0049] A coating material for metal scaffolds, the preparation method includes the following steps:

[0050] Step S1: Synthesize PLCL-10000

[0051] First, the Schlenk reaction flask equipped with a magnetic stirrer was flame-dried. Then, 75.10 g (0.658 mol) of ε-caprolactone, 23.71 g (0.165 mol) of lactide, 1.18 g (0.01 mol) of 1,6-hexanediol, and 0.5 g (1.234 mmol) of Sn(Oct)₂ were added to the flask. The mixture was then purged with nitrogen for 30 minutes and evacuated for 30 minutes to create an oxygen-free environment. The reactants were then stirred at 150 °C for 16 hours to obtain the final product PLCL-10000.

[0052] Step S2: Olefin functionalization of PLCL (E-PLCL synthesis)

[0053] 10 g of PLCL-10000 diol was dissolved in toluene to form a 15 wt% solution, then allyl isocyanate (0.25 g, 0.003 mol) was added, and the reaction was carried out at 60 °C for 1 h. Precipitation was carried out in cold anhydrous ethanol to obtain the final product E-10000.

[0054] Step S3: Preparation of photocurable PLCL material

[0055] Using 5g of E-10000 as the quantitative basis, 0.1% Tempol and 1% TPO-L were added, mixed and stirred, and ultrasonicated for 30 minutes to remove air bubbles, thus obtaining the coating material for metal scaffolds.

[0056] A biodegradable tissue-engineered scaffold, the preparation process of which is as follows: Figure 1 As shown, the preparation method includes the following steps:

[0057] (1) Immerse the nickel-titanium alloy stent in the liquid of the coating material for metal stents and sonicate at 45°C for 30 minutes to fully coat the surface of the nickel-titanium alloy stent with E-PLCL and remove air bubbles.

[0058] (2) Remove the nickel-titanium alloy support after step (1) and suspend it in a vacuum oven at 45°C for 20 minutes to further remove air bubbles. E-PLCL forms a thin film on the support surface under the action of surface tension, while excess E-PLCL will drip off;

[0059] (3) The nickel-titanium alloy scaffold treated in step (2) is cured under a 365-406nm ultraviolet lamp for 15 minutes to obtain an E-PLCL fully coated scaffold.

[0060] The fabrication of coated stents is not limited by the shape of the stent, and stents of any shape can be coated quickly.

[0061] Example 2

[0062] Example 2 only completes steps S1, S2, and S3 of Example 1, and its content is basically the same as that of Example 1, except that:

[0063] In step S1, the amount of 1,6-hexanediol added was 3.94 g (0.033 mol), and the final product was PLCL-3000;

[0064] In step S2, the amount of allyl isocyanate added is 0.83g, and the final product is E-3000.

[0065] Example 3

[0066] Example 3 only completes steps S1, S2, and S3 of Example 1, and its content is basically the same as that of Example 1, except that:

[0067] In step S1, the amount of 1,6-hexanediol added was 1.97 g (0.0167 mol), and the final product was PLCL-6000;

[0068] In step S2, the amount of allyl isocyanate added is 0.42g, and the final product is E-6000.

[0069] Example 4

[0070] Example 4 only completes steps S1, S2, and S3 of Example 1, and its content is basically the same as that of Example 1, except that:

[0071] In step S1, the amount of 1,6-hexanediol added is 1.48 g (0.0125 mol), the stoichiometric ratio of initiator to monomer is 1:66.69, and the final product is PLCL-8000;

[0072] In step S2, the amount of allyl isocyanate added is 0.31g, and the final product is E-8000.

[0073] The E-PLCLs prepared in Examples 1-4 were characterized and their performance was tested.

[0074] (1) Characterization by proton nuclear magnetic resonance spectroscopy and infrared spectroscopy

[0075] The different molecular weight E-PLCLs in Examples 1-4 were analyzed by proton NMR and infrared spectroscopy, and the results are as follows: Figure 2 The 1H NMR spectroscopy results showed that a peak at 5.8 ppm corresponded to the introduced allylic olefin proton, marking the rapid transformation of the terminal hydroxyl functional group. Figure 2 b) In infrared spectroscopy analysis, at 3500 cm⁻¹ -1 (NH stretching of ethyl carbamate group), 1635cm -1 (C=C stretching of allyl groups) and 804 cm -1 The characteristic peak appearing at (Ch bending vibration of allyl group) further proves the success of the post-polymerization modification. Figure 2 c).

[0076] (2) Thermal analysis characterization

[0077] Differential scanning calorimetry (DSC) was used to test E-PLCLs of different molecular weights in Examples 1-4, and the results are as follows: Figure 3 As shown. Figure 3 Differential scanning calorimetry (DSC) analysis showed that the melting point of E-10000 was significantly higher than that of other samples, at around 37°C.

[0078] (3) Degradability test

[0079] To evaluate the degradation behavior of E-PLCL, accelerated degradation experiments with 0.05M NaOH and degradation experiments with PBS were conducted on the E-PLCL prepared in Examples 1-4 and thermoplastic PLCL (300,000 g / mol). The experimental results are as follows: Figure 4 As shown in the figure, the experimental results demonstrate that E-PLCL exhibits good biodegradability. In particular, the degradation time significantly increases with increasing E-PLCL molecular weight, indicating that the degradation time of the scaffold can be controlled by selecting E-PLCLs with different molecular weights to meet the requirements of different scaffold coatings.

[0080] (4) Mechanical property testing

[0081] The mechanical properties of coating materials, such as elastic modulus, elongation at break, and ultimate tensile strength, are crucial for scaffold coatings. A low elastic modulus facilitates scaffold compression and placement, and allows for flexible expansion after implantation to accommodate respiratory movements. High elongation at break and tensile strength enable the coating to withstand significant deformation without cracking or failure, ensuring structural integrity. Furthermore, high elasticity allows the coating to recover rapidly under repeated stress.

[0082] The E-PLCLs prepared in Examples 1-4 were subjected to tensile tests and elastic modulus tests, and the results are as follows: Figure 5 As shown in Table 1, the mechanical properties of E-PLCL vary with different precursor molecular weights: elongation at break 588%–1595%, ultimate tensile stress 2.67–14.86 MPa, and elastic modulus 0.96 MPa–2.16 MPa. Higher precursor molecular weights lead to lower Young's modulus but higher ultimate tensile strength and elongation at break. The increased Young's modulus of E-10000 can be attributed to its semi-crystalline nature. Thermal analysis shows that the melting point of E-10000 is significantly higher than other samples. This semi-crystalline structure masks the expected contribution of crosslinking density, becoming the main factor controlling Young's modulus under tensile conditions.

[0083] Table 1 Mechanical properties of Examples 1-4E-PLCL

[0084]

[0085] (5) Biocompatibility testing

[0086] 1. Transwell cell co-culture

[0087] To verify the biocompatibility of E-PLCL, we co-cultured E-PLCL with L929 cells using the Transwell system, and performed live / dead cell staining and CCK-8 assays at 1, 3, and 7 days. Figure 6 a, Figure 6 b、 Figure 6c). The results showed that there was no significant difference in cell growth between the E-PLCL groups with different molecular weights and the pure PLCL group. This indicates that E-PLCL exhibits good biocompatibility in the cell culture environment, and its molecular weight does not significantly affect cell growth and proliferation.

[0088] 2. Subcutaneous implantation experiment in mice

[0089] Subcutaneous implantation experiments were conducted on mice with E-PLCL samples of different molecular weights at 1-week and 4-week intervals. Figure 6 d、 Figure 6 e). Specifically, 6-8 week old female Bcl-2 mice were used. A 3D-printed 4×2×1mm implant was placed in a pouch through an abdominal incision, and the incision was sutured. Three mice were operated on per group, with two implants placed on each side. The control group underwent the same procedure using high-molecular-weight PLCL. Mice behavior and weight were observed during the study. Mice were euthanized and autopsied at 1 week and 4 weeks post-implantation. The implants were fixed together with surrounding tissues for histopathological evaluation. Results showed that mild acute inflammation appeared around the implant tissue one week after implantation of all components, and the inflammation subsided at 4 weeks, with no signs of host immune response. This further validates the biocompatibility of E-PLCL in vivo, demonstrating its safety and reliability in biomedical applications.

[0090] (6) Viscosity test

[0091] Viscosity tests were performed on the E-PLCLs prepared in Examples 1-4. It was observed that the viscosity of all E-PLCL components decreased significantly with increasing temperature. Figure 7 Considering the uniformity of coating during the dip-coating process, E-8000 exhibits a good balance between low viscosity and mechanical properties at moderate temperatures (50℃), making E-8000 the optimal choice as the substrate coating material.

[0092] Referring to Example 1, a coated scaffold was prepared using the E-PLCL obtained in Example 4, and its performance was tested.

[0093] Figure 8 a(i) shows the before and after effects of coating the bare NiTi alloy scaffold with E-8000, where Figure 8 a(i) The leftmost image shows the bare stent, and the middle image shows the E-PLCL covered stent (E-8000). Figure 8 The scanning electron microscope image of a(ii) shows that the prepared coated scaffold has a uniform coating and a smooth surface. Furthermore, the E-PLCL coating method was successfully applied to the fabrication of coated Y-type scaffolds, demonstrating its adaptability to scaffolds with complex geometries. Figure 8b). After 1000 cycles of stretching to 500% strain, E-8000 fully recovered its shape, demonstrating excellent elasticity and adaptability to the dynamic environment of the trachea. Figure 9 a). Cyclic compression tests further verified the mechanical properties of the E-PLCL covered scaffold. Figure 9 (b) Compared to bare NiTi alloy scaffolds, E-PLCL-coated scaffolds exhibit smaller hysteresis loops and less residual deformation, indicating stronger fatigue resistance and energy absorption capacity. Over 1000 compression cycles, the E-PLCL-coated scaffolds maintained unchanged mechanical properties and exhibited minimal deformation recovery loss, as evidenced by stable force-displacement curves. Figure 10 a and Figure 10 b. This visually demonstrates the E-PLCL covered stent's ability to completely recover its original shape after cyclic compression. Furthermore, the E-PLCL covered stent can be easily compressed and successfully delivered via a delivery catheter, confirming its implantability. Figure 10 c). These findings highlight the effectiveness of the E-PLCL coating in providing durability and flexibility, making it well-suited for tracheal stent applications.

[0094] (II) Differences in the effects of one-step and traditional two-step methods on the mechanical properties of PLCL diols

[0095] Examples 1-4 use the one-step method provided by this invention to modify PLCL diol. Comparative Examples 1-4 are set up below, using the traditional two-step method to modify PLCL diol. The mechanical properties of the two groups of samples are observed to investigate the influence of different processes on the mechanical properties of modified PLCL diol.

[0096] Comparative Example 1

[0097] Step S1 of Comparative Example 1 is the same as that of Example 1;

[0098] Step S2: Olefin functionalization of PLCL (PE-PLCL synthesis)

[0099] 10 g of PLCL-10000 diol was dissolved in toluene to form a 15 wt% solution. Then, L-lysine ethyl ester diisocyanate (LDI, 0.9 g, 0.004 mol) was added, along with stannous octoate at a comonomer molar ratio of 1%. The reaction was carried out at 40 °C for 6 h under a dry argon atmosphere. Subsequently, 2-hydroxyethyl acrylate (HEA, 0.46 g, 0.004 mol) was added dropwise to the reaction mixture, and the reaction was continued at room temperature for 24 h. The polymer was concentrated under reduced pressure and precipitated in cold anhydrous ethanol to obtain the final product PEUA-10000.

[0100] Comparative Example 2

[0101] Comparative Example 2 completes steps S1 and S2 of Comparative Example 1. Its content is basically the same as Comparative Example 1, except that:

[0102] In step S1, the PLCL-3000 obtained in step S1 of Example 2 is used;

[0103] In step S2, 3.02 g of L-lysine ethyl ester diisocyanate and 1.51 g of 2-hydroxyethyl acrylate were added, and the final product was PEUA-3000.

[0104] Comparative Example 3

[0105] Comparative Example 3 completes steps S1 and S2 of Comparative Example 1. Its content is basically the same as Comparative Example 1, except that:

[0106] In step S1, the PLCL-6000 obtained in step S1 of Example 3 is used;

[0107] In step S2, 1.51 g of L-lysine ethyl diisocyanate and 0.75 g of 2-hydroxyethyl acrylate were added, and the final product was PEUA-6000.

[0108] Comparative Example 4

[0109] Comparative Example 4 completes steps S1 and S2 of Comparative Example 1. Its content is basically the same as Comparative Example 1, except that:

[0110] In step S1, the PLCL-8000 obtained in step S1 of Example 4 is used;

[0111] In step S2, 1.13 g of L-lysine ethyl diisocyanate and 0.58 g of 2-hydroxyethyl acrylate were added, and the final product was PEUA-8000.

[0112] The PEUA-PLCLs prepared in Comparative Examples 1-4 were subjected to the above-mentioned mechanical property tests, and their mechanical properties were compared with those of the E-PLCLs prepared in Examples 1-4. The results are shown in Table 2.

[0113] Table 2 Mechanical Properties of E-PLCL and PEUA-PLCL

[0114]

[0115] As shown in Table 2, compared with PEUA-PLCL, E-PLCL with different molecular weights has a lower elastic modulus, higher ultimate tensile stress and elongation at break, and better mechanical properties. This indicates that the E-PLCL obtained by reacting terminal hydroxyl groups of diols (or polyols) with allyl isocyanate to modify the double bonds of PLCL diol has higher mechanical properties than polyurethane acrylate materials modified by the traditional two-step method.

[0116] (III) Examples of E-PLCL / DOX covered stents used in the treatment of esophageal / tracheal cancer

[0117] Example 5

[0118] Example 5 is basically the same as Example 1, except that in step S3, 2% doxorubicin hydrochloride is added to the E-PLCL to obtain the E-PLCL / DOX coated scaffold, as shown in the photograph. Figure 8 As shown in the right-hand side of a(i), it appears orange-red.

[0119] Example 5 describes the preparation of an E-PLCL / DOX-coated stent loaded with the thermosensitive chemotherapeutic drug doxorubicin (DOX), which can provide mechanical support for the trachea and local chemotherapy for patients with tracheal cancer.

[0120] (1) Drug release behavior of E-PLCL / DOX covered stent

[0121] To investigate the drug release behavior of the E-PLCL / DOX-coated scaffold, we immersed the E-PLCL / DOX membrane in 5 mL of PBS solution and maintained it at a constant temperature of 37°C in a shaker. Every two days, 3 mL of PBS was removed, and the drug concentration was measured using a UV spectrophotometer. Simultaneously, an equal volume of fresh PBS was added. The experiment continued for 60 days. The drug release results of the E-PLCL / DOX drug-loaded scaffold are shown below. Figure 11 As shown in Figure a, the cumulative release curve of DOX indicates that the release of DOX from the E-PLCL reaches 38% after 60 days. To further elucidate the sustained release mechanism of DOX, we investigated the relationship between drug release and E-PLCL coating degradation, and observed the surface morphology changes of the samples during drug release using SEM and EDS. The results are shown in Figure a. Figure 11 As shown in b and 11c, Figure 11 b shows the EDS analysis results, indicating that doxorubicin hydrochloride formed a uniform distribution in the system. Figure 11SEM images of the E-PLCL coating showed that on day 1, crystalline DOX was uniformly distributed on the surface, indicating that initial release was primarily driven by dissolution and diffusion processes. After 30 days, the surface of the E-PLCL coating gradually degraded, exposing DOX crystals embedded deeper within the coating, thus promoting sustained drug release. By day 60, significant erosion of the E-PLCL coating was observed, allowing the release of DOX from deeper layers. These results indicate that the drug release behavior of the E-PLCL / DOX-coated scaffold is controlled by a dual mechanism: initially, DOX is released from the coating surface through dissolution and diffusion; as the E-PLCL coating gradually degrades, deeply embedded DOX crystals are gradually exposed and released, thus achieving sustained release. This dual mechanism of dissolution-diffusion combined with material degradation ensures the controllability and continuity of drug release.

[0122] (2) Anti-cancer effect of E-PLCL / DOX covered scaffold

[0123] The anticancer effect of the E-PLCL / DOX covered scaffold was evaluated using KYSE 150 human esophageal squamous cell carcinoma cell activity assay, cell migration assay, and apoptosis analysis. Figure 12 First, E-PLCL / DOX films were prepared and co-incubated with tumor cells for 3 days. The effects of different treatment groups on cell viability were detected using the CCK-8 assay. Figure 12 a). The results showed that the E-PLCL / DOX group significantly reduced tumor cell activity, with significant differences compared to the control group (Control, E-PLCL-coated scaffold, unloaded) and the E-PLCL group prepared in Example 1. Simultaneously, the inhibitory effects of different groups on tumor cell migration ability were investigated using scratch assays. Figure 12 (b) Microscopic images showed that after 1 day (1D) and 3 days (3D) of culture, the E-PLCL / DOX group had the lowest scratch closure and significantly inhibited cell migration. In contrast, the Control and E-PLCL groups showed stronger cell migration and rapid scratch closure. Furthermore, Annexin V-FITC / PI double staining flow cytometry analysis... Figure 12 c) Apoptosis of KYSE150 tumor cells cultured for 3 days. Results showed that the E-PLCL / DOX group induced the highest proportion of tumor cell apoptosis, especially a significant increase in late-stage apoptosis, with a more pronounced apoptotic effect compared to the Control and E-PLCL groups. These results demonstrate the significant effects of the E-PLCL / DOX covered scaffold in inhibiting tumor cell proliferation and migration and promoting apoptosis, providing a highly efficient and controllable solution for the local treatment of tracheal tumors.

Claims

1. A coating material for metal supports, characterized in that, It is composed of E-PLCL, free radical inhibitor and photoinitiator, wherein the amount of free radical inhibitor added is 0.05% to 0.5% of the weight of E-PLCL, and the amount of photoinitiator added is 0.2% to 2% of the weight of E-PLCL; The E-PLCL is prepared by double bond modification of PLCL diol with allyl isocyanate. The double bond modification method is as follows: PLCL diol is dissolved in toluene to form a solution with a concentration of 15wt% to 40wt%, then allyl isocyanate is added, and the reaction is carried out at 50 to 80°C for 0.5 to 1.5 h. The molar ratio of the terminal hydroxyl group of PLCL diol to allyl isocyanate is 1:(1.2 to 1.5). The preparation method of PLCL diol is as follows: lactide, ε-caprolactone, diol and stannous octoate are added to a reaction vessel and stirred at 130-160℃ for 8-16 h under vacuum and oxygen-free conditions to obtain poly(L-lactide-co-ε-caprolactone) diol, i.e. PLCL diol.

2. The coating material for metal supports as described in claim 1, characterized in that, The free radical inhibitor is 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxy radical or 2,2,6,6-tetramethylpiperidine oxide; the photoinitiator is 2,4,6-trimethylbenzoyl-diphenylphosphine oxide or ethyl 2,4,6-trimethylbenzoylphosphonate.

3. The coating material for metal supports as described in claim 1, characterized in that, The molar ratio of lactide, ε-caprolactone, and diol is 0.165:0.658:(0.01~0.0125); the diol is selected from one or more of 1,6-hexanediol, ethylene glycol, or triethylene glycol.

4. The coating material for metal supports as described in claim 1, characterized in that, The molecular weight of PLCL diol is 3000-10000.

5. The method for preparing the coating material for the metal scaffold as described in claim 1 or 2, characterized in that, Includes the following steps: Step S1: Dissolve the PLCL diol of claim 1 in toluene to form a solution with a concentration of 15wt% to 40wt%, then add allyl isocyanate, and react at 50 to 80°C for 0.5 to 1.5 h to obtain E-PLCL; Step S2: Mix E-PLCL with free radical inhibitors and photoinitiators, stir, and remove air bubbles by ultrasonication to obtain a coating material for metal scaffolds.

6. A covered stent, characterized in that, It includes a metal support and a coating layer, wherein the coating layer is formed by impregnating or coating the metal support with the coating material of claim 1 or 2, and then photocuring it to form a fully coated support.

7. The covered stent as described in claim 6, characterized in that, The coated scaffold also carries a drug, which is mixed into the coating material of the metal scaffold and photocured together with the coating material to complete the loading.

8. The method for preparing the covered scaffold as described in claim 6, characterized in that, Includes the following steps: (1) Immerse the metal stent in the metal stent coating material and sonicate at 40-50°C for 25-35 min; (2) Take out the metal bracket after step (1) and vacuum heat treat it at 40-50℃ for 15-25 min; (3) The metal scaffold treated in step (2) is cured under a 365-406 nm UV lamp for 10-15 min to obtain an E-PLCL fully coated scaffold.

9. The method for preparing the covered scaffold as described in claim 8, characterized in that, The metal support is made of nickel-titanium alloy or magnesium alloy.

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