A method for preparing a composite material scaffold and the scaffold made therefrom

Abstract

This invention relates to the field of medical device manufacturing technology, and in particular to a method for preparing a composite material stent and the stent made therefrom. The method includes the following steps: Step S1, preparation of magnesium alloy tubing and initial processing of the skeleton; Step S2, surface pretreatment of the skeleton; Step S3, construction of an intermediate bonding layer; Step S4, coating with a PLLA outer layer; Step S5, molding and post-processing; Step S6, final inspection and sterilization. This invention achieves synergistically enhanced mechanical properties. The magnesium alloy core provides strong initial support, while the PLLA outer layer provides supplementary support. It also exhibits controllable degradation performance; the PLLA outer layer effectively delays the corrosion of the magnesium alloy by chloride ions and other substances in body fluids, extending the support time. The PLLA outer layer isolates the magnesium alloy from direct contact with blood, further reducing the risk of thrombosis. The specially designed intermediate bonding layer structure ensures the structural integrity of the stent during its service life.

Description

Technical Field

[0001] This invention relates to the field of medical device manufacturing technology, and in particular to a method for preparing a composite material stent and the stent made therefrom. Background Technology

[0002] In current technologies, stent implantation is frequently used to treat cardiovascular diseases, and it is a core technique in percutaneous coronary intervention (PCI). Traditional metallic stents (such as 316L stainless steel and cobalt-chromium alloys) pose long-term risks, including permanent placement in the body, potential late-stage thrombosis and restenosis, and impaired normal vascular function. To address these issues, absorbable stents have emerged, and current mainstream research directions in absorbable stents include: 1. Absorbable polymeric scaffolds: represented by poly-L-lactic acid. Their advantage is complete degradation in vivo with no permanent residue. However, their main disadvantages are insufficient mechanical support, weak radial support, and the potential for lumen loss due to rebound during the initial degradation phase, limiting their application in complex lesions.

[0003] 2. Absorbable alloy stents: Represented by magnesium alloys and iron alloys. Magnesium alloys have good biocompatibility and biodegradability, and their degradation products are elements needed by the human body. Their main advantage is strong initial support. However, their core drawback lies in the excessively rapid degradation rate; they typically lose their mechanical integrity before the blood vessel has completed remodeling. Furthermore, the hydrogen gas produced during degradation may form gas pockets, and the increased local pH may irritate the tissue.

[0004] As can be seen from the above, in the existing technology, absorbable stents made of a single material cannot simultaneously meet the clinical needs of "strong support in the early stage, controllable degradation in the middle stage, and good tissue compatibility in the later stage". The main reasons are: simple poly-L-lactic acid stents have insufficient support, while simple magnesium alloy stents degrade too quickly and have insufficient support time. Summary of the Invention

[0005] This invention addresses the problems of existing technologies by providing a method for preparing a composite material stent and the stent made therefrom, achieving synergistically enhanced mechanical properties. The magnesium alloy core provides strong initial support, while the outer PLLA structure provides supplementary support. It also exhibits controllable degradation performance; the outer PLLA structure effectively delays the corrosion of the magnesium alloy by chloride ions and other substances in body fluids, thus extending the support time. The outer PLLA structure isolates the magnesium alloy from direct contact with blood, further reducing the risk of thrombosis. Through the design of a specialized intermediate bonding layer structure, the structural integrity of the stent is ensured during its service life.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: This invention provides a method for preparing a composite material scaffold, which includes the following steps: Step S1, Magnesium alloy tube preparation and initial processing of the skeleton: Magnesium alloy thin-walled tubes are prepared using precision casting and drawing processes. A laser cutting machine is used to cut a mesh-like support shape on the magnesium alloy thin-walled tubes to form the primary skeleton of the support. Step S2, Surface pretreatment of the skeleton: Polish and clean the skeleton, and then perform micro-arc oxidation or acid etching to form micro-nano pores on its surface. Step S3: Constructing the intermediate bonding layer: Immerse the pretreated scaffold skeleton in the prepared bonding agent solution, keep it for a period of time, and then pull it out at a constant speed to ensure that the solution covers it evenly and reacts fully. Then dry and cure it. Step S4: Coating the outer layer of PLLA: Dissolve PLLA in an organic solvent to form a PLLA solution. Immerse the scaffold skeleton with the intermediate binding layer obtained in step S3 into the PLLA solution, or spray the PLLA solution onto the scaffold skeleton with the intermediate binding layer at a specific speed to uniformly cover its surface with a layer of PLLA outer layer. Step S5, Molding and Post-treatment: Place the coated bracket in a vacuum oven to remove residual solvent and perform annealing treatment; Step S6, Final Inspection and Sterilization: The finished stent is inspected for appearance, size and mechanical properties, and finally sterilized with ethylene oxide or electron beam.

[0007] In step S2, acetone, ethanol, and deionized water are used sequentially to perform ultrasonic cleaning on the scaffold skeleton.

[0008] In step S2, a dilute acid solution is used for controlled etching to form a rough structure with micro- and nano-sized pores on the surface of the magnesium alloy support skeleton.

[0009] In step S2, a porous ceramic oxide layer is grown on the surface of the magnesium alloy support frame in a high-voltage electrolyte.

[0010] In step S4, the organic solvent is dichloromethane, chloroform, or tetrahydrofuran, which is prepared into a PLLA solution by heating and magnetic stirring.

[0011] The step between step S5 and step S6 includes step S51, applying a drug coating: applying a polymer-free drug coating to the outer layer of the PLLA.

[0012] The present invention also provides a stent manufactured using the aforementioned preparation method, wherein the vascular stent has a tubular structure, the vascular stent's framework cross-section has a three-layer composite structure, and the vascular stent comprises: The inner structure, made of a biodegradable magnesium alloy, is used to provide the primary initial radial support force; The outer structure, made of biodegradable polymer material, is used to provide secondary radial support. An intermediate bonding layer structure, located between the inner and outer layers, is composed of a crosslinking agent or adhesive and is used to form a strong interfacial bond between the inner and outer layers.

[0013] The crosslinking agent or adhesive is at least one of silane coupling agent, polydopamine, or biodegradable polyurethane adhesive.

[0014] The outer layer structure is further provided with a surface coating, which is a polymer-free drug coating used to load anti-proliferative drugs.

[0015] The biodegradable polymer material is poly-L-lactic acid.

[0016] The beneficial effects of this invention are: 1. Synergistically Enhanced Mechanical Properties: The magnesium alloy core provides robust initial support beyond that of a pure polymer scaffold, while the PLLA shell provides supplemental support. The overall structure can be designed to be slimmer (reducing rod width) or use less magnesium metal to meet the same support requirements.

[0017] 2. Controllable degradation performance: The outer layer of PLLA effectively delays the corrosion of magnesium alloy by chloride ions and other substances in body fluids, thereby controlling the degradation rate of magnesium alloy and achieving the ideal degradation mode of "slow at first and then fast", thus extending the support time.

[0018] 3. Improved biocompatibility: The PLLA layer isolates the magnesium alloy from direct contact with blood, reducing the direct release of hydrogen gas in the early stages of degradation and the stimulation of vascular endothelium by local pH changes. At the same time, the smooth PLLA surface is less conducive to thrombus formation.

[0019] 4. Stable and reliable structure: Through a special intermediate bonding layer design, the technical problem of easy delamination between metal and polymer materials due to the large difference in elastic modulus is solved, ensuring the structural integrity of the stent during service.

[0020] 5. Comprehensive treatment function: Through the outer BIOlute coating, the anti-proliferative drugs are released in a controlled manner, effectively preventing restenosis and forming a triple effect of "mechanical support + barrier protection + drug therapy". Attached Figure Description

[0021] Figure 1 This is a schematic diagram of the overall three-dimensional structure of the composite material support of the present invention.

[0022] Figure 2 This is a cross-sectional view of the composite material support of the present invention.

[0023] exist Figures 1 to 2The reference numerals in the figures include: 101. Inner layer structure; 102. Intermediate bonding layer structure; 103. Outer layer structure; 104. Topcoat layer. Detailed Implementation

[0024] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to embodiments and accompanying drawings. The content mentioned in the embodiments is not intended to limit the present invention. The present invention will be described in detail below with reference to the accompanying drawings.

[0025] Example 1

[0026] In Embodiment 1 of this application, a method for preparing a composite material scaffold includes the following steps: Step S1, Magnesium Alloy Tube Preparation and Initial Machining of the Skeleton: Magnesium alloy thin-walled tubes (e.g., outer diameter 1.6 mm, wall thickness 0.1 mm) are prepared using precision casting (e.g., vacuum / inert gas protected melting, continuous casting) combined with multi-pass cold / warm drawing processes. The magnesium alloy thin-walled tubes prepared in this manner have uniform composition, fine grains, and uniform wall thickness. Preferably, the magnesium content of the prepared magnesium alloy thin-walled tubes is ≥88%. Furthermore, the magnesium alloy tube is precisely cut using an ultrashort pulse laser (picosecond or femtosecond laser) with a laser cutting machine, and a mesh-like support shape is cut out on the aforementioned thin-walled magnesium alloy tube to form the primary skeleton of the support.

[0027] Step S2, Surface pretreatment of the framework: The framework is polished and cleaned, then subjected to micro-arc oxidation or acid etching to form micro- and nano-scale pores on its surface; the specific process is as follows: Basic cleaning: The support frame is ultrasonically cleaned in sequence with acetone, ethanol and deionized water to remove grease and particulate contaminants; Surface modification and activation: Controllable etching is performed using dilute acid solutions (such as nitric acid and phosphoric acid) to form a rough structure with micro- and nano-sized pores on the surface of the magnesium alloy support skeleton, which significantly increases the specific surface area and mechanical anchoring points. In step S2, micro-arc oxidation is used: a porous ceramic oxide layer is grown on the surface of the magnesium alloy support skeleton in a high-voltage electrolyte. This not only further enhances the adhesion to the bonding layer, but also acts as a degradation barrier to a certain extent, further regulating the initial degradation rate. Furthermore, in step S2, a plasma cleaning treatment is employed: oxygen or argon plasma treatment can be used, which can not only clean the surface but also introduce active functional groups (such as -OH) to increase the surface energy and make its reaction with the silane coupling agent more complete.

[0028] Step S3: Constructing the intermediate bonding layer: Immerse the pretreated scaffold skeleton in the prepared bonding agent solution (such as KH-550 in ethanol / water solution), keep it for a period of time, and then pull it out at a constant speed to ensure that the solution covers it evenly and reacts fully. Then dry and cure it at a low temperature (such as 80°C). The bonding agent can be a crosslinking agent or adhesive, which can be at least one of silane coupling agent, polydopamine or biodegradable polyurethane adhesive. Silane coupling agents: such as KH-550 (γ-aminopropyltriethoxysilane), whose alkoxy groups react with the hydroxyl groups on the metal surface after hydrolysis, and the amino group at the other end can react with the ester group of PLLA or form hydrogen bonds; Polydopamine: Through the self-polymerization of dopamine in a weakly alkaline solution, a highly adhesive film rich in active groups (catechol, amino) is formed on the surface of the pretreated magnesium alloy skeleton, which can form a very strong physical and chemical bond with PLLA. Biodegradable polyurethane adhesives: A polyurethane system with good biocompatibility and controllable degradation rate is selected, and an intermediate bonding layer is formed through solution coating or in-situ polymerization.

[0029] The intermediate bonding layer serves to form a strong and stable interfacial bond between the magnesium alloy and polymer layers through chemical bonding and physical anchoring, preventing delamination caused by degradation and blood flow shear forces in vivo; ensuring the integrity of the three-layer structure during stent expansion and degradation, and avoiding interlayer delamination.

[0030] Step S4, Coating the outer layer of PLLA: Dissolve PLLA in an organic solvent to form a PLLA solution. Immerse the scaffold skeleton with the intermediate binding layer obtained in step S3 into the PLLA solution, or spray the PLLA solution onto the scaffold skeleton with the intermediate binding layer at a specific speed to uniformly cover its surface with a layer of PLLA. Specifically, dissolve medical-grade PLLA particles in a suitable organic solvent (such as dichloromethane, chloroform, or tetrahydrofuran), and prepare a homogeneous solution with controllable viscosity by heating and magnetic stirring. The solution concentration (e.g., 3-10 wt.%) directly affects the thickness of the final coating.

[0031] The methods for coating the outer layer of PLLA include dip coating-spin coating or electrospinning: 1. Dip-coating-spin-coating method: Dip coating: The support with the intermediate layer is fixed to the mandrel and immersed in PLLA solution; Spin coating / lift coating: After the solution is lifted out at a uniform speed, the support rotates at high speed under the drive of the mandrel. Centrifugal force is used to spread the solution evenly and throw off excess liquid, thereby obtaining a coating with uniform thickness. Multi-axis spin coating: To overcome the problem of uneven axial coating of long tubular supports, a composite motion mechanism can be used to make the support move axially while being dipped and rotated, ensuring the uniformity of the coating along the entire length. 2. Electrospinning method: The PLLA solution is placed in a spinneret with high voltage electrostatic discharge. The solution jet is stretched and refined under the action of electric field force, and deposited into continuous nano / micro fibers on the support skeleton (grounded or negatively charged) that serves as the receiving electrode. The PLLA layer formed by this method is a porous nonwoven fabric structure, which is conducive to cell and tissue ingrowth (long-term endothelialization) and provides additional flexibility through fiber interweaving. By controlling the spinning parameters (voltage, flow rate, distance, solution properties), the fiber diameter, porosity and coating thickness can be precisely controlled.

[0032] Step S5, Molding and Post-treatment: Place the coated substrate in a vacuum oven and perform staged low-temperature (e.g., 30-40°C) and high-vacuum drying to thoroughly remove residual solvents and prevent blistering or cracking of the coating. Annealing is then performed to eliminate internal stress and increase the crystallinity of PLLA, thereby regulating its degradation rate. Higher crystallinity generally results in a slower degradation rate and a longer retention time of mechanical properties for PLLA.

[0033] Step S6, Final Inspection and Sterilization: The finished stent is inspected for appearance, size and mechanical properties, and finally sterilized with ethylene oxide or electron beam.

[0034] Mechanical testing: The radial support force of the bracket (120 μm wide) of this application was measured by a radial compression tester and was significantly higher than that of a pure PLLA bracket with the same wide rod, and close to that of a pure magnesium alloy bracket with a wider rod (e.g., 150 μm).

[0035] In vitro degradation test: Immersion experiments were conducted in simulated body fluid. The results showed that the stent of this application could still maintain more than 80% of its original support force within 4 weeks, while the support force of the pure magnesium alloy stent decreased by more than 50% within 2 weeks. At the same time, the increase in solution pH and the amount of hydrogen produced were much lower than those of the pure magnesium alloy stent group.

[0036] In Embodiment 1 of this application, step S51, applying a drug coating, is further included between step S5 and step S6: applying a polymer-free drug coating to the outer layer of the PLLA. Specifically, ultrasonic spraying technology can be used to uniformly spray a sirolimus-loaded BIOlute coating solution onto the surface of the PLLA outer layer. The BIOlute coating is essentially an ultrathin layer composed of a drug (sirolimus, everolimus, etc.) and an absorbable carrier (such as polylactic acid-glycolic acid copolymer microcrystals or lipids). Ultrasonic spraying technology atomizes the drug-carrier solution into extremely fine and uniform droplets, which are then sprayed onto the rotating stent surface under controlled airflow. Ultrasonic atomization reduces droplet size, achieving submicron-level precision coating thickness control, ensuring uniform drug distribution and controllable release rate on the stent surface. This coating is loaded with an anti-proliferative drug to inhibit excessive proliferation of vascular smooth muscle cells and prevent restenosis. Due to its polymer-free nature, it can further reduce inflammatory responses.

[0037] This application's first embodiment possesses the following core technical features: 1. The core of the three-layer composite structure is the specific layered configuration of "magnesium alloy inner layer - crosslinking agent intermediate layer - poly-L-lactic acid outer layer".

[0038] 2. Material combination: A specific combination of biodegradable magnesium alloy and biodegradable polymer (PLLA).

[0039] 3. Functional synergy: Complementary mechanical properties and regulation of degradation rate are achieved through structural design.

[0040] 4. Interface bonding process: A stable and strong interlayer bonding is achieved by using a specific biocompatible crosslinking agent.

[0041] 5. Optional drug coating system: BIOlute polymer-free drug coating combined with the above composite structure.

[0042] Compared with the prior art, Embodiment 1 of this application has the following significant advantages: 1. Synergistically Enhanced Mechanical Properties: The magnesium alloy core provides robust initial support beyond that of a pure polymer scaffold, while the PLLA shell provides supplemental support. The overall structure can be designed to be slimmer (reducing rod width) or use less magnesium metal to meet the same support requirements.

[0043] 2. Controllable degradation performance: The outer layer of PLLA effectively delays the corrosion of magnesium alloy by chloride ions and other substances in body fluids, thereby controlling the degradation rate of magnesium alloy and achieving the ideal degradation mode of "slow at first and then fast", thus extending the support time.

[0044] 3. Improved biocompatibility: The PLLA layer isolates the magnesium alloy from direct contact with blood, reducing the direct release of hydrogen gas in the early stages of degradation and the stimulation of vascular endothelium by local pH changes. At the same time, the smooth PLLA surface is less conducive to thrombus formation.

[0045] 4. Stable and reliable structure: Through a special intermediate bonding layer design, the technical problem of easy delamination between metal and polymer materials due to the large difference in elastic modulus is solved, ensuring the structural integrity of the stent during service.

[0046] 5. Comprehensive treatment function: Through the outer BIOlute coating, the anti-proliferative drugs are released in a controlled manner, effectively preventing restenosis and forming a triple effect of "mechanical support + barrier protection + drug therapy".

[0047] Example 2

[0048] In Embodiment 2 of this application, a stent prepared using the aforementioned method is provided. The vascular stent has a tubular structure, and the cross-section of the stent's framework is a three-layer composite structure. The vascular stent comprises: The inner structure 101, made of a biodegradable magnesium alloy, is used to provide the primary initial radial support force; The outer structure 103 is made of a biodegradable polymer material and is used to provide secondary radial support; wherein the biodegradable polymer material is poly-L-lactic acid; An intermediate bonding layer structure 102, located between the inner layer structure and the outer layer structure, is composed of a crosslinking agent or adhesive and is used to form a strong interfacial bond between the inner layer structure and the outer layer structure; wherein the crosslinking agent or adhesive is at least one of a silane coupling agent, polydopamine, or a biodegradable polyurethane adhesive.

[0049] Specifically, Embodiment 2 of this application features a novel and ingenious structure, providing a composite stent. The inner magnesium alloy layer provides the primary initial radial support, ensuring the stent can effectively open blood vessels after implantation. The outer poly-L-lactic acid layer provides secondary support during the initial degradation phase and works synergistically with the magnesium alloy, resulting in an overall support strength superior to that of a pure poly-L-lactic acid stent of the same strut width. The poly-L-lactic acid layer forms a physical barrier on the magnesium alloy, slowing down the erosion of the magnesium alloy by body fluids, thereby effectively delaying the degradation rate of the magnesium alloy and extending the overall support time of the stent. A robust intermediate bonding layer ensures the structural integrity and stability of the composite material in the dynamic environment within the body.

[0050] Embodiment 2 of this application achieves synergistically enhanced mechanical properties. The magnesium alloy core provides stronger initial support than pure polymer stents, while the outer PLLA structure provides supplementary support. Under the same support force requirements, the overall structure can be designed to be thinner (reducing the rod width) or using less magnesium metal. Embodiment 2 of this application has controllable degradation performance: the outer PLLA structure effectively delays the corrosion of magnesium alloy by chloride ions in body fluids, thereby controlling the degradation rate of magnesium alloy and achieving the ideal degradation mode of "slow at first and then fast", thus extending the support time. The outer PLLA structure isolates the magnesium alloy from direct contact with blood, reducing the direct release of hydrogen gas and the stimulation of vascular endothelium by local pH changes in the early stage of degradation. At the same time, the smooth PLLA surface is less conducive to thrombus formation. Through the design of a special intermediate bonding layer structure, the technical problem of easy delamination between metal and polymer materials due to the large difference in elastic modulus is solved, ensuring the structural integrity of the stent during service.

[0051] In Embodiment 2 of this application, the magnesium alloy thin-walled tube with inner structure, through structural design, reduces the amount of magnesium alloy used while ensuring the same support performance, thereby reducing the risk of excessive hydrogen and other byproducts generated due to the rapid degradation of magnesium.

[0052] In Embodiment 2 of this application, the outer layer structure is further provided with a surface coating 104, which is a polymer-free drug coating used to load antiproliferative drugs. Specifically, the polymer-free drug coating can be achieved by uniformly spraying a sirolimus-loaded BIOlute coating solution onto the surface of the PLLA outer layer, realizing the controlled release of antiproliferative drugs, effectively preventing restenosis, and forming a triple effect of "mechanical support + barrier protection + drug therapy".

[0053] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some changes or modifications to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and modifications made to the above embodiments based on the present invention without departing from the scope of the present invention are within the scope of the present invention.

Claims

1. A method for preparing a composite material scaffold, characterized in that, Includes the following steps: Step S1, Magnesium alloy tube preparation and initial processing of the skeleton: Magnesium alloy thin-walled tubes are prepared using precision casting and drawing processes. A laser cutting machine is used to cut a mesh-like support shape on the magnesium alloy thin-walled tubes to form the primary skeleton of the support. Step S2, Surface pretreatment of the skeleton: Polish and clean the skeleton, and then perform micro-arc oxidation or acid etching to form micro-nano pores on its surface. Step S3: Constructing the intermediate bonding layer: Immerse the pretreated scaffold skeleton in the prepared bonding agent solution, keep it for a period of time, and then pull it out at a constant speed to ensure that the solution covers it evenly and reacts fully. Then dry and cure it. Step S4: Coating the outer layer of PLLA: Dissolve PLLA in an organic solvent to form a PLLA solution. Immerse the scaffold skeleton with the intermediate binding layer obtained in step S3 into the PLLA solution, or spray the PLLA solution onto the scaffold skeleton with the intermediate binding layer at a specific speed to uniformly cover its surface with a layer of PLLA outer layer. Step S5, Molding and Post-treatment: Place the coated bracket in a vacuum oven to remove residual solvent and perform annealing treatment; Step S6, Final Inspection and Sterilization: The finished stent is inspected for appearance, size and mechanical properties, and finally sterilized with ethylene oxide or electron beam.

2. The method for preparing a composite material scaffold according to claim 1, characterized in that, In step S2, the scaffold skeleton is ultrasonically cleaned sequentially using acetone, ethanol, and deionized water.

3. The method for preparing a composite material scaffold according to claim 1, characterized in that, In step S2, a dilute acid solution is used for controlled etching to form a rough structure with micro- and nano-sized pores on the surface of the magnesium alloy support skeleton.

4. The method for preparing a composite material scaffold according to claim 1, characterized in that, In step S2, a porous ceramic oxide layer is grown on the surface of the magnesium alloy support frame in a high-voltage electrolyte.

5. The method for preparing a composite material scaffold according to claim 1, characterized in that, In step S4, the organic solvent is dichloromethane, chloroform, or tetrahydrofuran, which is prepared into a PLLA solution by heating and magnetic stirring.

6. The method for preparing a composite material scaffold according to claim 1, characterized in that, Between step S5 and step S6, there is also step S51, coating a drug coating: coating a polymer-free drug coating on the outer layer of PLLA.

7. A stent manufactured using the preparation method according to any one of claims 1-6, characterized in that: The vascular stent is a tubular structure, and the cross-section of the stent's framework has a three-layer composite structure. The vascular stent includes: The inner structure, made of a biodegradable magnesium alloy, is used to provide the primary initial radial support force; The outer structure, made of biodegradable polymer material, is used to provide secondary radial support. An intermediate bonding layer structure, located between the inner and outer layers, is composed of a crosslinking agent or adhesive and is used to form a strong interfacial bond between the inner and outer layers.

8. The absorbable composite vascular stent according to claim 1, characterized in that: The crosslinking agent or adhesive is at least one of silane coupling agents, polydopamine, or biodegradable polyurethane adhesives.

9. The absorbable composite vascular stent according to claim 1, characterized in that: The outer layer structure is also provided with a surface coating, which is a polymer-free drug coating used to load anti-proliferative drugs.

10. The absorbable composite vascular stent according to claim 1, characterized in that: The biodegradable polymer material is poly-L-lactic acid.

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