3D-printed cuttlefish bone elastic hemostatic stent and construction method thereof

Abstract

This invention relates to a 3D-printed cuttlebone elastic hemostatic scaffold and its construction method. Existing hemostatic materials suffer from problems such as effectiveness only for mild to moderate bleeding, significant side effects, poor biocompatibility, and the need for compression and wound closure. This method involves dissolving a prepolymer of polyglycerol sebacate and polycaprolactone in tetrahydrofuran to prepare a polymer solution. Sodium chloride particles and cuttlebone powder are added and heated and stirred to obtain the 3D printing ink. This ink is then placed in a 3D printer to print sheet-like and block-like mesh scaffolds. The mesh scaffolds are then placed in a vacuum drying oven for vacuum thermal cross-linking. After cross-linking, they are immersed in distilled water for washing and desalting, and then freeze-dried to obtain the hemostatic scaffold. The hemostatic scaffold of this invention is particularly suitable for systemic lacunar wounds with deep bleeding sites that are difficult to control with compression. By combining a biodegradable elastic biopolymer with the traditional hemostatic drug cuttlebone powder, it possesses advantages such as porosity, elastic memory, rapid hemostasis, compressibility, and biodegradability.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, specifically to a 3D-printed cuttlebone elastic hemostatic stent and its construction method. Background Technology

[0002] Currently, in addition to gauze, bandages, gelatin sponges, and zeolite, commonly used hemostatic materials also include new materials such as fibrin glue, polysaccharides, and oxidized cellulose. These materials form a stable physical barrier at the bleeding site by enhancing the coagulation process, inhibiting blood clot degradation, or interacting with blood and tissues, thereby preventing blood from flowing out and promoting hemostasis.

[0003] Most hemostatic materials are only effective for mild to moderate bleeding, insufficient to control bleeding from large and uncontrollable vessels. They also have side effects such as high rebleeding rates, embolism, and tissue damage, severely limiting their widespread application. Furthermore, hemostatic materials containing animal-derived components such as collagen, fibrinogen, or thrombin may cause allergic reactions or immunogenicity when used in vivo, and excessive expansion can lead to nerve damage or tissue compression. Additionally, early hemostasis of general bleeding wounds is often achieved using tourniquets, hemostatic forceps, or covering the wound with hemostatic dressings, requiring compression and closure. This is unsuitable for wounds inside vital organs such as the heart, liver, and spleen, or for lacunar and deep wounds requiring no compression, such as gunshot wounds or shrapnel wounds. Inefficient hemostasis can lead to significant blood loss in a short time, causing hemorrhagic shock and resulting in secondary damage, local tissue necrosis, and infection. Therefore, a novel hemostatic material is needed to overcome the aforementioned clinical shortcomings of existing hemostatic materials. Summary of the Invention

[0004] The purpose of this invention is to provide a 3D-printed cuttlebone elastic hemostatic stent and its construction method, in order to solve the problems of existing hemostatic materials, such as being effective only for mild to moderate bleeding, having large side effects, poor biocompatibility, and requiring compression and wound closure.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0006] A method for constructing a 3D-printed cuttlebone elastic hemostatic stent, the method comprising:

[0007] Polyglycerol sebacate prepolymer and polycaprolactone were dissolved in tetrahydrofuran to prepare a polymer solution. Sodium chloride particles and cuttlebone powder were added and heated and stirred to obtain a light yellow clay-like solid, which is the 3D printing ink.

[0008] 3D printing ink is put into a 3D printer to print sheet-like and block-like mesh supports;

[0009] The mesh stent was placed in a vacuum drying oven for vacuum thermal cross-linking. After cross-linking, it was immersed in distilled water for washing and desalting, and then freeze-dried to obtain a hemostatic stent.

[0010] Further, a polymer solution was prepared by dissolving polyglycerol sebacate prepolymer and polycaprolactone in 500 mL of tetrahydrofuran at a mass ratio of 4:1.

[0011] Furthermore, the sodium chloride particles underwent grinding and screening before being added to the polymer solution, including:

[0012] Sodium chloride particles ground by a grinder are sieved through 400 mesh and 500 mesh. Sodium chloride particles that cannot pass through 500 mesh are collected and added to the polymer solution in an amount twice the total mass of polyglycerol sebacate prepolymer and polycaprolactone.

[0013] Furthermore, the cuttlebone powder underwent sterilization, grinding, and screening before being added to the polymer solution, including:

[0014] Cut the whole cuttlebone into several small pieces, wash it with water, soak it in 80% alcohol solution for 30 minutes, soak it in distilled water for 10 minutes, dry it and grind it thoroughly.

[0015] After sieving through a 500-mesh sieve, cuttlebone powder was obtained. The polymer solution was then added at a ratio of 17:3 between the total mass of polyglycerol sebacate prepolymer and polycaprolactone and the mass of cuttlebone powder.

[0016] Furthermore, sodium chloride granules and cuttlebone powder were added to the polymer solution, and the mixture was heated and stirred overnight using a heated magnetic stirrer at a temperature of 60°C and a speed of 450 rpm / min.

[0017] Furthermore, 3D printing ink is placed into a 3D printer to print sheet-like and block-like mesh supports, including:

[0018] Seal the 3D printing ink and place it in an environment at -20℃ to cool it down.

[0019] The cooled 3D printing ink was added to the 3D printing system, and the printing parameters were set as follows: temperature 65℃, air pressure 0.35Mpa, extruder diameter 0.4mm, and extrusion speed 8mm / s.

[0020] Printed block-shaped grid supports with fill rates of 20%, 30%, and 40% and interlayer angles of 60° × 2;

[0021] Printed sheet-like grid support with a fill rate of 40% and an interlayer angle of 60° × 3;

[0022] Let it air dry overnight.

[0023] Further, the mesh stent is placed in a vacuum drying oven for vacuum thermal cross-linking. After cross-linking, it is immersed in distilled water for washing and desalting, and then freeze-dried to obtain a hemostatic stent, comprising:

[0024] The mesh support was placed in a vacuum drying oven and thermally crosslinked at 120°C and 1.0 bar for 36 hours.

[0025] Remove the mesh stent, place it in distilled water to desalinate for 24 hours, wash it, freeze it at -20°C, and vacuum dry it to obtain a hemostatic stent.

[0026] On the other hand, a 3D-printed cuttlebone elastic hemostatic stent constructed as described by the method is provided, wherein the hemostatic stent is a sheet-like mesh structure, the sheet-like mesh structure comprising two layers of intersecting 3D-printed filaments forming a rhomboid, rectangular, or square mesh, or comprising three layers of intersecting 3D-printed filaments forming a triangular mesh.

[0027] On the other hand, a 3D-printed cuttlebone elastic hemostatic stent constructed as described in the method is provided. The hemostatic stent is a block-shaped mesh structure, which includes multiple layers of sheet-shaped mesh structures stacked on top of each other. The sheet-shaped mesh structure includes two layers of intersecting 3D-printed lines to form a rhomboid, rectangular, or square mesh, or includes three layers of intersecting 3D-printed lines to form a triangular mesh.

[0028] The 3D printing line of each layer of sheet-like mesh structure is interconnected.

[0029] On the other hand, the application of the 3D-printed cuttlebone elastic hemostatic stent as described above in the preparation of hemostatic materials for filling bleeding wounds is provided.

[0030] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0031] This invention provides a hemostatic stent constructed using 3D printing technology, which is particularly suitable for systemic lacunar wounds with deep bleeding sites that are difficult to control by compression. It combines biodegradable elastic biopolymer materials with the traditional hemostatic drug cuttlebone powder, which has the advantages of being porous, elastic, quick to stop bleeding, and compressible. After compression, the hemostatic stent can be inserted into the bleeding wound. After mixing with blood and rapidly expanding and rebounding, it can effectively compress the ruptured blood vessel. The 3D microchannels in the stent absorb blood and initiate a rapid coagulation process, activating a synergistic hemostatic mode of platelet concentration, physical expansion and compression, and calcium ion activation of the coagulation pathway, thus greatly improving the convenience of rescue operations.

[0032] Meanwhile, the material can be naturally degraded in the body without the need for later removal, which would cause secondary damage and rebleeding. All raw materials used have excellent biocompatibility, and potential risks of biosafety and side effects have been eliminated during the experimental verification process. All raw materials used have excellent blood compatibility, will not cause hemolytic reactions, and will not affect intrinsic or extrinsic coagulation pathways.

[0033] The hemostatic stent construction method of the present invention is characterized by standardization, commercialization, and proceduralization, and has broad prospects for military and civilian applications. Attached Figure Description

[0034] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other embodiments can be obtained from these drawings without creative effort.

[0035] Figure 1 This is a flowchart of the method of the present invention.

[0036] Figure 2 These are powder electron micrographs comparing the hemostatic stent of this invention.

[0037] Figure 3 These are MicroCT 3D reconstruction comparison images of the hemostatic stent of this invention.

[0038] Figure 4 This is a comparison diagram of the tensile deformation-stress curves of the hemostatic stent of the present invention.

[0039] Figure 5 This is a comparison diagram of the compression deformation-stress curves of the hemostatic stent of the present invention.

[0040] Figure 6 This is a comparison of in vitro coagulation experiments and BCI index diagrams of the hemostatic stent of this invention.

[0041] Figure 7 These are electron microscope images comparing blood clots magnified at different magnifications using different hemostatic materials.

[0042] Figure 8 This is a diagram demonstrating the hemostatic effect of the hemostatic stent of the present invention applied to a rat liver injury model, and a quantitative comparison of blood loss and hemostasis time.

[0043] Figure 9 This is a demonstration of the application of the block-shaped hemostatic stent of the present invention in a rabbit carotid artery bleeding model, along with a quantitative comparison of blood loss and hemostasis time.

[0044] Figure 10 This is an in vivo degradation diagram of the hemostatic stent of the present invention.

[0045] Figure 11 This is a schematic diagram of the hemostatic stent of the present invention being loaded in a capsule.

[0046] Figure 12 This is a structural diagram of a triangular-hole plate-shaped hemostatic stent.

[0047] Figure 13 This is a structural diagram of a diamond-shaped perforated block-shaped hemostatic stent.

[0048] Figure 14 This is a structural diagram of a rectangular-hole curved block hemostatic stent.

[0049] Figure 15 This is a structural diagram of a triangular-hole strip-shaped block hemostatic stent.

[0050] Figure 16 This is a diagram illustrating the compression deformation of the block-shaped hemostatic stent of the present invention.

[0051] Figure 17 This is a comparison diagram of the deformation ratio of the block-shaped hemostatic stent of the present invention.

[0052] Figure 18 This is a comparison chart of the deformation recovery ratio of the block-shaped hemostatic stent of the present invention.

[0053] Figure 19 This is a comparison chart of the deformation recovery time of the block-shaped hemostatic stent of the present invention. Detailed Implementation

[0054] To facilitate understanding of the present invention, a more complete description will be given below with reference to the accompanying drawings. Preferred embodiments of the invention are shown in the drawings. However, the invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the invention.

[0055] In the description of this patent, it should be understood that all technical and scientific terms used have the same meaning as commonly understood by one of ordinary skill in the art to which this patent pertains. In case of any contradiction, the definitions in this specification shall prevail. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art, the reagents used in the embodiments are commercially available products, and the devices used in the embodiments are existing devices. The limitation on the means, reagents, or devices shall not be construed as a limitation on this patent, and means, reagents, or devices of the same type that solve the same technical problem are all within the protection scope of this patent.

[0056] In the description of this patent, it should be understood that when a quantity, concentration, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pair of any upper or preferred value with any lower or preferred value, regardless of whether the range is disclosed individually. When numerical ranges are described herein, unless otherwise stated, the range is intended to include its endpoints and all integers and fractions within that range.

[0057] In the description of this patent, it should be understood that the method involves multiple steps, which should not be interpreted as a limitation on the order of the steps. Technical solutions obtained by changing the order of steps when solving the same technical problem are also within the scope of protection of this patent.

[0058] 3D printing technology, with its advantages of personalization and precision, is widely used in tissue engineering and biomaterials. However, research on 3D printing of hemostatic materials is currently limited, mainly focusing on hydrogel applications. Hydrogel materials, however, exhibit poor mechanical properties such as strength and elasticity, restricting the practical application of gel-based hemostatic materials.

[0059] To achieve rapid hemostasis in clinical practice, ideal hemostatic materials need to meet the following requirements: a) excellent fluid absorption capacity; b) suitable mechanical properties to withstand blood pressure and compressive contact with surrounding tissues; c) maintaining structural stability under stress and not causing damage to wound tissue; d) good biocompatibility; and e) simple and quick operation. For controlling bleeding and treating specific wounds, especially for deep bleeding types that are difficult to stop by pressure, the requirements are even higher.

[0060] This invention provides a method for constructing a 3D-printed cuttlebone elastic hemostatic stent. The constructed hemostatic stent is particularly suitable for systemic lacunar wounds with deep bleeding sites that are difficult to control with compression. The method includes:

[0061] S1: Preparing 3D printing ink:

[0062] Polyglycerol sebacate prepolymer and polycaprolactone were dissolved in tetrahydrofuran to prepare a polymer solution. Sodium chloride granules and cuttlebone powder were added, and the solution was heated and stirred to obtain a light yellow, clay-like solid, which is the 3D printing ink. The specific steps include:

[0063] S101: Polyglycerol sebacate prepolymer and polycaprolactone are dissolved in 500 mL of tetrahydrofuran at a mass ratio of 4:1 to prepare a polymer solution. The commonly chosen mass ratio is 4 g of polyglycerol sebacate prepolymer and 1 g of polycaprolactone.

[0064] S102: Sodium chloride particles were ground and screened before being added to the polymer solution, including:

[0065] Sodium chloride particles ground by a grinder are sieved through 400 mesh and 500 mesh. Sodium chloride particles that cannot pass through 500 mesh are collected, i.e., those with a diameter of 30-38 micrometers. Sodium chloride particles in this diameter range are added to the polymer solution in an amount twice the total mass of polyglycerol sebacate prepolymer and polycaprolactone.

[0066] S103: The cuttlebone powder underwent sterilization, grinding, and screening before being added to the polymer solution, including:

[0067] The whole cuttlebone is made from fresh, adult needleless squid caught between April and August, with a length of 15cm, a width of more than 3cm, and a thickness of more than 1cm at its thickest point. The whole cuttlebone is cut into several small pieces, washed with water, soaked in 80% alcohol solution for 30 minutes, soaked in distilled water for 10 minutes, dried, and thoroughly ground.

[0068] After sieving through a 500-mesh sieve, cuttlebone powder with a particle size of less than 30 μm was obtained. The polymer solution was added at a ratio of 17:3 (15% of total mass) of the total mass of polyglycerol sebacate prepolymer and polycaprolactone to the cuttlebone powder.

[0069] S104: After adding sodium chloride granules and cuttlebone powder to the polymer solution, heat and stir with a heated magnetic stirrer at 60°C and 450 rpm / min overnight to fully volatilize tetrahydrofuran.

[0070] S2: 3D printed mesh support structure

[0071] 3D printing ink is placed into a 3D printer to print sheet-like or block-like mesh supports, including:

[0072] S201: The 3D printing ink is sealed and placed in an environment of -20℃ to cool down, which reduces the surface viscosity and makes it easier to transfer to the printing barrel;

[0073] S202: Add the cooled 3D printing ink to the 3D printing system. Set the printing parameters as follows: temperature 65℃, air pressure 0.35Mpa, extruder diameter 0.4mm, and extrusion speed 8mm / s.

[0074] S203: Printed block grid support, with fill rates of 20%, 30%, and 40% and interlayer angles of 60° × 2;

[0075] S204: Printed sheet-like grid support, 40% fill rate, 60°×3 interlayer angle;

[0076] S205: Air dry overnight to further volatilize residual tetrahydrofuran.

[0077] The 3D printer can be the PCPrinterBR151S printing system from Particle Cloud Biotechnology Co., Ltd.

[0078] S3: Fabrication and preparation of hemostatic stents:

[0079] The mesh scaffold obtained in S2 was placed in a vacuum drying oven for vacuum thermal crosslinking. After crosslinking, it was immersed in distilled water for washing and desalting, and then freeze-dried to obtain a hemostatic scaffold, comprising:

[0080] S301: Place the mesh support in a vacuum drying oven and thermally crosslink it for 36 hours at 120°C and 1.0 bar.

[0081] S302: Remove the mesh stent, place it in distilled water to desalinate for 24 hours, wash it, freeze it at -20℃, and vacuum dry it to obtain a hemostatic stent.

[0082] This method combines traditional Chinese medicine cuttlebone powder, rich in calcium ions, chitosan, and chitin, with 3D printing technology. It utilizes biocompatible PGS (polyglycerol sebacate) / PCL (polycaprolactone) printing materials to reconstruct an elastic 3D sponge scaffold for hemostasis, possessing shape memory properties and an ordered pore structure. Based on this material, the physical compression and shaping of the elastic scaffold can be achieved by optimizing the printed structure, enabling the development of ballistic expansion compression and hypercoagulable hemostatic materials. In this invention, the cuttlebone powder is loaded into the hemostatic scaffold not on the surface or in the micropores of the 3D structure, but directly added to the 3D printing ink, where it is thoroughly mixed and cross-linked with other 3D printing materials. This significantly enhances the superior spatial structure of the final hemostatic scaffold.

[0083] The above methods can be used to construct hemostatic stents with different structural forms. The shape, thickness, length, width, and hole shape of the hemostatic stent can be flexibly adjusted according to specific clinical needs and wound conditions. It can be designed and printed in real time, or existing printed products can be cut to obtain the desired structural form. The specific implementation describes two structural limitations: block-shaped and sheet-shaped, but it is not limited to these as needed.

[0084] The 3D-printed cuttlebone elastic hemostatic scaffold of the present invention can be a block-shaped mesh structure, used as a hemostatic sponge to fill bleeding wounds. The block-shaped mesh structure includes multiple layers of sheet-like mesh structures stacked vertically, with the 3D-printed filaments of each layer interconnected. The sheet-like mesh structure includes two layers of intersecting 3D-printed filaments forming a rhomboid, rectangular, or square mesh, or includes three layers of intersecting 3D-printed filaments forming a triangular mesh. Figure 13This hemostatic stent is a rhomboid-shaped block hemostatic stent, comprising a multi-layered sheet-like mesh structure. Each layer of the sheet-like mesh structure includes two layers of intersecting 3D-printed filaments with an interlayer angle of 60° × 2. The holes are rhomboid, making it suitable for deep wounds where pressure is not possible for hemostasis. Figure 14 This hemostatic stent is a rectangular-hole curved block hemostatic stent, comprising a multi-layered sheet-like mesh structure. Each sheet-like mesh structure includes two layers of intersecting 3D-printed filaments. The holes are rectangular or square, and it has relatively low compressibility, making it suitable for deep, large wounds on the body surface. Figure 15 This hemostatic stent is a triangular-hole strip-shaped stent with a relatively low compressibility, suitable for narrow wounds on the body surface. It includes a multi-layered sheet-like mesh structure, with each layer consisting of three intersecting 3D-printed lines at an angle of 60° x 3. The holes are triangular. Depending on specific needs, the number of layers and the shape of the holes can be combined to obtain various design schemes, forming different types of hemostatic stents.

[0085] The 3D-printed cuttlebone elastic hemostatic scaffold of this invention can also be a sheet-like mesh structure, which can be directly applied as a hemostatic membrane. The sheet-like mesh structure consists of three intersecting 3D-printed membrane-like scaffolds forming a triangular mesh. For example... Figure 12 The hemostatic stent is a triangular-hole plate-shaped hemostatic stent, consisting of three intersecting 3D printed lines with an interlayer angle of 60°×3 and triangular holes.

[0086] 3D printed lines can be straight or curved, but when curved, the overall elasticity is better.

[0087] The block grid structure can be regular or irregular in shape, and the edges can be straight or curved. It can be flexibly adjusted to adapt to the shape and depth of the wound, and multiple structures can even be used in combination.

[0088] like Figure 11 The hemostatic stent of the present invention can be constructed in the shape of a windmill. After being loaded into the shell of a gelatin capsule, it forms a capsule-type hemostatic stent with a regular shape and size. The capsule is more convenient to carry, the manufacturing process is more procedural, and it can play a better role in expansion, compression, blood absorption and coagulation.

[0089] The hemostatic stent constructed in this invention exhibits excellent performance in terms of elasticity, compressibility, biocompatibility, and biodegradability, and shows particular advantages in the treatment of deep bleeding wounds. Specific performance test results are analyzed below:

[0090] 1. Sample preparation:

[0091] For block-shaped, elastic, compressible sponge scaffolds, a rhomboid hole structure was selected and cut to a size of X:5mm × Y:1.2cm × Z:5mm. Compression along the Y-axis at -20℃ yielded a stable, foldable cubic scaffold, reducing its volume to 1 / 4 of its original size, serving as a block-shaped sample. For sheet-shaped hemostatic scaffolds, an 8mm diameter circumferential cutter was used to cut a large-area printed product, obtaining a circular sheet-shaped hemostatic scaffold, serving as a sheet-shaped sample. Flowcharts and views of various scaffold shapes are shown below. Figure 1 As shown.

[0092] 2. Observation of Cuttlebone Powder Loading:

[0093] Based on the content of cuttlefish bone (CB) powder, samples were divided into 0% CB (no CB powder loaded) and 15% CB groups. The surface morphology and morphology of the cuttlefish bone powder in different sheet-like samples were observed using scanning electron microscopy. MicroCT was used to scan and reconstruct the sheet-like samples with and without CB powder to verify the loading status of the CB powder. Results are as follows: Figure 2 and Figure 3 As shown in the figure, the content and distribution of cuttlebone powder under microscopic structure are as follows: In the 0% CB group, the sheet-like samples show densely packed micro-connected pores of 30-50 μm. In the 15% CB group, under high magnification, a large amount of cuttlebone powder is visible densely distributed on the surface of the scaffold within the pores; the addition of cuttlebone powder does not affect the size and distribution of the pores. Three-dimensional reconstruction of the scaffold using Micro-CT scanning can display the loading content of cuttlebone powder, as shown... Figure 3 As shown, the sheet-like samples in the 0% CB group showed no high-density development. With the increase of cuttlebone powder content, the development degree also increased significantly. At the same time, the cuttlebone powder can be seen to be evenly distributed throughout the printed support grid.

[0094] 3. Mechanical properties:

[0095] Tensile and compression tests were performed on sheet-like samples, and fatigue resistance tests were conducted on block-shaped elastic compressible sponge scaffold samples under cyclic compression. Figure 4 , 5 and Figure 9 As shown in the figure, the tensile and compressive results show that with the addition of cuttlebone powder, both tensile strength and compressive strength increase significantly (the following section illustrates elasticity and compressibility).

[0096] 4. Shape memory capability of the support:

[0097] Figure 16This demonstrates the compression deformation of a block-shaped, elastic, compressible sponge grid support. At low temperatures (4°C), the large-volume support can extend its axis for volume compression and maintain its shape at room temperature. Upon contact with liquids (water, blood, etc.), it expands rapidly (within 4 seconds) by absorbing the liquid. Figure 17-19 For different filling rates, quantitative analyses were performed on deformation capacity (deformation ratio), deformation recovery time, and deformation recovery ratio, all of which showed excellent performance.

[0098] 5. Hemostatic effect:

[0099] Flake-shaped samples were used for in vitro coagulation assays, including dynamic whole blood agglutination tests and electron microscopic observation of stent clots, such as... Figure 6 and Figure 7 The results showed that the sheet-like sample could effectively absorb blood and induce the aggregation of red blood cells in the blood, and promote the production of a large amount of thrombin by platelets, thereby inducing the production of fibrin, accelerating the aggregation and adhesion of blood cells, forming blood clots, and thus having a strong hemostatic ability.

[0100] Sheet-shaped samples and block-shaped elastic compressible sponge scaffold samples were used in animal hemostasis models. Sheet-shaped samples were applied to an SD rat liver injury model, and the results are shown below. Figure 8 The hemostatic effect of compressed, elastic, compressible sponge stents injected into a New Zealand rabbit carotid artery hemorrhage model was demonstrated, as shown in the results. Figure 9 Both achieved better hemostatic effects compared to the commercially available gauze control group.

[0101] 5. Biocompatibility and degradability:

[0102] In vivo degradation and biosafety experiments used sheet-like samples, which were further cut into 5mm × 2mm pieces and embedded in the middle lobe of the liver of SD rats. Samples were collected and analyzed at different time points. Histological staining results are as follows: Figure 10 As shown in the figure. The results indicate that the scaffold material can be naturally degraded in vivo, and the liver and kidney function tests showed that it does not produce biotoxicity.

[0103] This invention combines biodegradable biopolymer materials with excellent elastic memory function with traditional Chinese medicine hemostatic agents, and uses 3D printing technology to prepare expandable plug-type hemostatic materials, which are a better choice for emergency hemostasis of wounds that are difficult to stop with pressure. Relying on artificially designed and manufactured compressible structures, a large-volume elastic scaffold sponge is formed, which can be filled into the bleeding wound when compressed. While expanding and compressing the bleeding site, it quickly absorbs blood and activates the coagulation pathway to form a blood clot. The polymer material with excellent mechanical properties and good biocompatibility can be degraded in vivo without the need for secondary removal, reducing patient pain and the risk of rebleeding.

[0104] This printed scaffold incorporates cuttlebone powder, known for its high hemostatic properties, into the printing material, resulting in a highly effective procoagulant effect. The guiding bone regeneration membrane, designed to shield connective tissue, has a high filling rate and a dense membrane structure that hinders blood penetration, limiting the contact between the loaded procoagulant components and the blood. In contrast, the target scaffold's printing filling rate is controlled between 30% and 40%, with appropriate pore size allowing blood flow while maintaining sufficient contact with the loaded cuttlebone powder, further enhancing hemostasis. Simultaneously, the scaffold's internal ordered pore structure allows for rapid fluid absorption, achieving local shape recovery. Furthermore, the temperature during thermal cross-linking is reduced to 120 degrees Celsius, and the time is adjusted to 36 hours. This aims to protect the organic matter (chitosan, chitin, etc.) in the cuttlebone powder while ensuring the target scaffold achieves sufficient mechanical strength and shape memory properties.

[0105] The above examples illustrate the present invention only to aid in understanding it and are not intended to limit the scope of the invention. Those skilled in the art can make various simple deductions, modifications, or substitutions based on the principles of this invention.

Claims

1. A method for constructing a 3D-printed cuttlebone elastic hemostatic stent, characterized in that: The method includes: Polyglycerol sebacate prepolymer and polycaprolactone were dissolved in tetrahydrofuran to prepare a polymer solution. Sodium chloride granules and cuttlebone powder were added and heated and stirred to obtain a light yellow, clay-like solid, which is the 3D printing ink. The cuttlebone powder underwent sterilization, grinding and screening before being added to the polymer solution, including: cutting the whole cuttlebone into several small pieces, washing with water, soaking in 80% alcohol solution for 30 minutes, soaking in distilled water for 10 minutes, drying and grinding thoroughly; after sieving through a 500-mesh sieve, the cuttlebone powder was obtained and added to the polymer solution at a ratio of 17:3 between the total mass of polyglycerol sebacate prepolymer and polycaprolactone and the mass of cuttlebone powder. The process involves placing 3D printing ink into a 3D printer to print sheet-like and block-like mesh supports, including: sealing the 3D printing ink in an environment of -20°C to cool it down; adding the cooled 3D printing ink to the 3D printing system, setting the printing parameters to: temperature 65°C, air pressure 0.35 MPa, extruder diameter 0.4 mm, and extrusion speed 8 mm / s; printing block-like mesh supports with infill rates of 20%, 30%, and 40% and interlayer angles of 60° × 2; printing sheet-like mesh supports with an infill rate of 40% and interlayer angles of 60° × 3; and allowing them to dry overnight. The process involves placing the mesh scaffold in a vacuum drying oven for vacuum thermal cross-linking, followed by immersion in distilled water for washing and desalting, and then freeze-drying to obtain a hemostatic stent. The process includes: placing the mesh scaffold in a vacuum drying oven for thermal cross-linking at 120°C and 1.0 bar for 36 hours; removing the mesh scaffold, placing it in distilled water for desalting for 24 hours, washing, freezing at -20°C, and then vacuum-drying to obtain a hemostatic stent. The hemostatic stent has shape memory properties, and when compressed and placed in a bleeding wound, it can rapidly expand and recover its original shape within 4 seconds by absorbing liquid.

2. The method for constructing a 3D-printed cuttlebone elastic hemostatic stent according to claim 1, characterized in that: Polyglycerol sebacate prepolymer and polycaprolactone were dissolved in 500 mL of tetrahydrofuran at a mass ratio of 4:1 to prepare a polymer solution.

3. The method for constructing a 3D-printed cuttlebone elastic hemostatic stent according to claim 2, characterized in that: Sodium chloride particles were ground and screened before being added to the polymer solution, including: Sodium chloride particles ground by a grinder are sieved through 400 mesh and 500 mesh. Sodium chloride particles that cannot pass through 500 mesh are collected and added to the polymer solution in an amount twice the total mass of polyglycerol sebacate prepolymer and polycaprolactone.

4. The method for constructing a 3D-printed cuttlebone elastic hemostatic stent according to claim 3, characterized in that: Sodium chloride granules and cuttlebone powder were added to the polymer solution, and the mixture was heated and stirred overnight using a heated magnetic stirrer at a temperature of 60°C and a speed of 450 rpm / min.

5. The 3D-printed cuttlebone elastic hemostatic stent constructed by the method described in claim 4, characterized in that: The hemostatic stent is a sheet-like mesh structure, which includes two layers of intersecting 3D printed lines to form a rhomboid, rectangular, or square mesh, or includes three layers of intersecting 3D printed lines to form a triangular mesh.

6. The 3D-printed cuttlebone elastic hemostatic stent constructed by the method described in claim 4, characterized in that: The hemostatic stent is a block-shaped mesh structure, which includes multiple layers of sheet-shaped mesh structures stacked on top of each other. The sheet-shaped mesh structure includes two layers of intersecting 3D printed lines to form a rhomboid, rectangular, or square mesh, or includes three layers of intersecting 3D printed lines to form a triangular mesh. The 3D printing line of each layer of sheet-like mesh structure is interconnected.

7. The application of the 3D-printed cuttlebone elastic hemostatic stent as described in claim 5 or 6 in the preparation of hemostatic materials for filling systemic lacunar, deep, non-compressible bleeding wounds.

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