Method for making a silicone blood vessel model with a hydrophobic textured inner surface

Abstract

This invention belongs to the technical field of surgical medical simulators and provides a method for producing a silicone blood vessel model with a hydrophobic textured inner surface. Based on the hydrophobic biological surface, a silicone film with a biomimetic texture is fabricated using 3D printing technology and a replication method. The silicone film is then embedded in a 3D-printed soluble casting container, followed by casting, high-temperature curing, and water tank dissolution to produce the silicone blood vessel model with a hydrophobic inner surface texture. This method is suitable for customized customization of different biomimetic microstructures or textured surfaces, improving the blood compatibility of artificial blood vessels and achieving better uniformity and controllability of blood vessel thickness. Furthermore, the artificial blood vessels produced by this method have high transparency and can be used to simulate and observe thrombosis.

Description

Technical Field

[0001] The invention belongs to the technical field of surgical medical simulation equipment and relates to a method for manufacturing a silicone blood vessel with a hydrophobic texture on the inner surface. Background Art

[0002] Since the invention of vascular anastomosis in the early 20th century, vascular repair and replacement have been key to treating acute vascular injury and chronic atherosclerotic disease. Vascular replacement and repair remain common surgical procedures, and there is a significant clinical need for engineered arterial substitutes. However, in many of these procedures, without systemic anticoagulation, these artificial vessels can rapidly occlude due to thrombosis, which occurs when fibrin and platelets in the circulating blood adhere to the surfaces of these artificial materials. Consequently, the concomitant use of soluble anticoagulants, such as heparin, significantly reduces the safety of artificial vessels and hinders their effectiveness. Heparin contributes to morbidity and mortality through postoperative bleeding, thrombocytopenia, hypertriglyceridemia, hyperkalemia, and hypersensitivity, making its use contraindicated in some patient populations, and the majority of drug-related deaths resulting from adverse clinical events are attributable to systemic anticoagulation. Therefore, especially for small-caliber or low-flow arterial bypass applications, a suitable non-thrombotic luminal surface is required, which should prevent blood coagulation contact activation, platelet adhesion and activation, and thrombosis in the arterial system. At the same time, it faces equally huge challenges such as immune acceptance, necessary tissue mechanics, low thrombogenicity and immediate availability, making the widespread clinical application of engineered arteries very difficult.

[0003] The hemocompatibility of a biomaterial refers to its ability to inhibit thrombosis and its effects on blood physiological functions, such as hemolysis, decreased platelet function, transient leukopenia, decreased function, and complement activation. Implantable artificial blood vessels have saved countless lives, but these artificial blood vessels can become blocked due to thrombosis formed when fibrin and platelets in the circulating blood adhere to the artificial surface. Improving the hemocompatibility of material surfaces is a crucial step in biomaterial research, and surface modification of biomaterials is key to this process. Contact between materials and organisms occurs through the material surface, so surface modification is crucial to achieving good hemocompatibility. The material's surface structure and composition, surface morphology, surface energy, hydrophilicity, and charge all influence its interaction with the organism. By altering the material's surface characteristics through surface modification, the interaction between the material and blood can also be altered. The surface hydrophobicity and free energy are closely related to the adsorption and denaturation of blood components. By performing surface chemical treatment, surface physical modification and biological modification on traditional materials, the surface hydrophobicity of the materials can be improved, and the surface free energy can be reduced to a value close to the surface free energy of the vascular endothelium, thereby improving the blood compatibility of the materials. Research and preparation of biomedical materials that can meet people's needs.

[0004] Improving the biocompatibility of materials, especially their blood compatibility, is mainly achieved by changing the surface properties of the materials, and changing the wettability of the material surface is one of the effective ways. Generally speaking, materials with highly hydrophobic and highly hydrophilic surfaces have good blood compatibility. When the hydrophobicity of the material surface increases, the adsorption capacity of blood components decreases, resulting in better blood compatibility. In addition, the hydrophobicity and free energy of the material surface are closely related to the adsorption and denaturation of blood components. Increasing the hydrophobicity of the material surface can reduce the surface free energy to a value close to the surface free energy of the vascular endothelium, thereby achieving good anti-thrombotic properties. The wettability of the material surface is determined by the chemical composition and microscopic geometric structure of the surface. A superhydrophobic surface is generally achieved by reducing the surface free energy and constructing a suitable rough structure on the surface of the hydrophobic material. The chemical composition of the material surface determines its surface free energy and therefore has a significant influence on the wettability of the material. However, for solid smooth surfaces, even with the lowest surface free energy surface, its contact angle with water can only reach about 110 degrees. To achieve a high contact angle superhydrophobic surface, it is necessary to consider constructing a suitable rough structure on the surface of the hydrophobic material.

[0005] Currently, creating textures or microstructures on the inside of artificial blood vessels is technically difficult, inefficient, and ineffective. Therefore, we introduce a method for fabricating silicone blood vessels with a hydrophobic textured inner surface. This relatively simple fabrication process is suitable for creating silicone blood vessel models with small calibers and varying wall thicknesses. It allows for personalized customization of the biomimetic microstructure inside the vessels. By replicating the hydrophobic textured inner surface of silicone blood vessels, blood compatibility is improved. This method can be used experimentally to simulate and observe thrombosis in artificial blood vessels, providing a theoretical basis for clinical vascular replacement surgery.

[0006] Patent application: Three-layer bionic artificial blood vessel with anti-thrombotic and tissue regeneration-promoting properties and its preparation method, application number CN202210888742.7. The main problem with this three-layer bionic artificial blood vessel is that the inner layer of the blood vessel uses an anticoagulant, which may cause side effects such as anticoagulant shedding or abnormal coagulation function.

[0007] Patent application: Method for preparing electrospun artificial blood vessels with micro-nano biomimetic intima structures, application number CN201210287469.9. The artificial blood vessels produced by this method have an oriented microstructure that mimics the vascular intima, ensuring that the blood compatibility of the artificial blood vessels meets clinical anticoagulant performance requirements. However, this method is costly, complex, and difficult to create with varying microstructures.

[0008] Patent application: "An apparatus and method for preparing an artificial blood vessel with a microstructure on the inner surface," application number CN202210738869.0. The main issues with this method are the high requirements for the size of the blood vessels, the difficulty in producing small-caliber vessels, the lack of specific details on the process for producing microstructured columns, and the difficulty in creating personalized microstructures. Summary of the Invention

[0009] The technical problem to be solved by the present invention is to propose a method for producing silicone blood vessels with inner surface texture or microstructure. This method can produce silicone blood vessel models with hydrophobic texture on the inner wall, and has a certain degree of versatility for personalized textured or microstructured blood vessel models. This solves the problem that existing methods require special processing equipment or complex process steps. The overall production process of this patent is simple and does not require any special processing equipment, which improves the applicability of the method.

[0010] The technical solution of the present invention:

[0011] A method for making a silicone blood vessel model with a hydrophobic textured inner surface, because the feathers of animals and the surfaces of plant leaves in nature mostly have texture characteristics with different wettability. Public experimental data show that the textures of bird feathers such as magpie feathers and swan feathers, plant leaves such as ginkgo leaves and lotus leaves, and the surfaces of marine organisms such as shark skin and shellfish all have high hydrophobicity. This patent mainly takes the texture of magpie feathers as an example, and uses a replication method to replicate the hydrophobic feather texture onto the silicone surface. The replication method for other textured surfaces is the same. A 3D printer is used to print and produce a replication mold based on a soluble material, and a silicone gel with a certain proportion of curing agent is added. Fill the mold with silicone gel, stick the feather flatly to a flat plate and cover it upside down on the mold. After the silicone gel completely soaks the feather, heat the mold to solidify the silicone gel, and then dissolve it in a water bath. After removing the feather, a silicone membrane with a feather texture is obtained.

[0012] A casting mold is printed using a 3D printer using a soluble material. The surface of the printed model is smoothed to eliminate the stair-stepping problem caused by layer-by-layer printing. The textured side of a silicone membrane is wrapped around the shaft and then inserted into the casting container. Silicone is slowly poured in from the inlet, allowing it to flow down along the seams on both sides of the silicone membrane. When the silicone stops sinking, the mold is heated to solidify the silicone, which is then dissolved in a water bath to produce a silicone blood vessel model with a textured inner surface.

[0013] To create a personalized microstructured vascular model, one must first obtain a personalized microstructure model, and then use the method provided in this patent to replicate the microstructure on the inner wall of the silicone blood vessel. The microstructure model can be created through processes such as mechanical micromachining, soft lithography, and photolithography, and existing technologies and methods are relatively mature.

[0014] The specific steps are as follows:

[0015] Step 1: Cut the cleaned magpie feathers into regular shapes and fix the back of the feathers on the acrylic board;

[0016] Step 2: Use a 3D printer and dissolvable printing materials to print out a square container, shaft column, and pouring container;

[0017] Step 3: Use water or printing material dissolving agent solution to evenly wipe the surface of the printed device to remove the rough texture of the printed device surface. After multiple wiping and drying, a printed device with a smooth surface is obtained;

[0018] Step 4: Prepare a two-component silicone AB mixed solution, mix the two-component silicone AB mixed solution and the curing agent in a certain proportion to obtain a silicone solution; use a vacuum pump to remove bubbles mixed in due to stirring to obtain a clear and transparent silicone mixed solution.

[0019] Step 5: Pour the silicone mixture into the square container until it overflows, place the acrylic sheet with feathers on top of the square container, and press it down with a heavy object;

[0020] Step 6: Dry the entire model obtained in step 5. After the silicone is solidified, remove the acrylic plate and feathers, immerse the entire model in water, and wait until the square container is completely dissolved to obtain a silicone film with feather texture.

[0021] Step 7: Wrap the shaft with the textured side of the silicone film and insert it into the casting container. Slowly inject the silicone mixture from the inlet of the casting container until the silicone mixture at the inlet no longer sinks.

[0022] Step 8: Dry the entire silicone blood vessel model obtained in step 5. After the silicone solidifies, immerse the entire silicone blood vessel model in water. After the casting container and the shaft column are completely dissolved, a silicone blood vessel model with an inner surface texture is obtained.

[0023] In step 1, the magpie feathers can be replaced by feathers of other birds, plant leaves or surfaces of marine organisms.

[0024] In step 2, the soluble printing consumables are: PVA (polyvinyl alcohol), water-soluble gypsum, HIPS (high-impact polystyrene) or ABS (acrylonitrile butadiene styrene), wherein PVA is soluble in water, HIPS is soluble in limonene, and ABS is soluble in organic solvents such as acetone.

[0025] In step 3, the mass ratio of PVA to water in the printing material dissolving agent solution is 1:10 to 1:5.

[0026] In step 4, a two-component silica gel of model 7055 is used to prepare a two-component silica gel AB mixed solution in a mass ratio of A:B=1:1, and a vulcanizing agent is added in an amount of 1% of the total mass of the two-component silica gel AB mixed solution to obtain a silica gel solution; after stirring the solution evenly, the solution is placed in a vacuum machine and evacuated for 0.5-1 hour to obtain a clear and transparent silica gel mixed solution.

[0027] In step 6, the curing conditions are: curing in a constant temperature drying oven at 60° C.-90° C. for more than 2 hours.

[0028] In step 6, the dissolution process is as follows: Place the solidified model in a water tank until the square container is completely dissolved. To accelerate the dissolution of the square container, fill the water tank with 60-100°C hot water, changing the hot water every 1-3 hours. Use a constant temperature oven to control the water temperature at 60-100°C. Change the water 2-10 times until the square container is completely dissolved.

[0029] In step 8, the curing conditions are: curing in a constant temperature drying oven at 60° C.-90° C. for more than 6 hours.

[0030] In step 8, the dissolution process is as follows: the solidified silicone blood vessel model is placed in a water tank, 60-100°C hot water is injected into the water tank, the hot water is replaced every 1-3 hours, and the water temperature is controlled at 60-100°C in a constant temperature oven for dissolution. After 10-25 water changes, the casting container and the internal shaft column are completely dissolved.

[0031] Beneficial results of the present invention:

[0032] (1) This method is low-cost, simple, and reproducible in producing silicone blood vessels;

[0033] (2) This method does not use anticoagulants, but only improves the blood compatibility of silicone blood vessels through the hydrophobicity of the surface microstructure;

[0034] (3) This method is suitable for personalized customization of different biomimetic microstructures or textured surfaces, and can produce blood vessel models with different diameters and wall thicknesses;

[0035] (4) The silicone blood vessel model with textured inner wall produced by this method can be used in experiments to simulate and observe the thrombosis of artificial blood vessels, providing a theoretical basis for clinical vascular replacement surgery. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 It is an acrylic plate with feathers glued on it.

[0037] Figure 2 It is a square container printed by a 3D printer using soluble material PVA.

[0038] Figure 3 It is a silicone membrane with a feather texture.

[0039] Figure 4 It is a casting container and shaft column printed by a 3D printer using soluble material PVA.

[0040] Figure 5 It is a mold with a textured silicone membrane that wraps around the shaft.

[0041] Figure 6 This is a silicone blood vessel model with a feather texture on the inner surface.

[0042] Figure 7 Schematic diagram of the mold with the textured silicone membrane wrapped around the shaft.

[0043] In the figure, 1 is the casting container A; 2 is the casting container B; 3 is the shaft column; 4 is the silicone membrane with replica texture embedded in the mold; 5 is the casting inlet. DETAILED DESCRIPTION

[0044] The present invention is further illustrated by examples below in conjunction with the accompanying drawings, but is not intended to limit the present invention. The specific materials used in the embodiments of the present invention and their sources are provided below. However, it should be understood that these are merely exemplary and are not intended to limit the present invention. Materials identical or similar to the types, models, qualities, properties or functions of the following reagents and instruments can be used to implement the present invention. The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources.

[0045] Taking the super-hydrophobic magpie feather as an example, first clean the magpie feather with clean water, dry it at room temperature, and then cut the feather into a regular shape with a width of 15mm and a length of 50mm. Use double-sided tape to stick the back of the feather to a square acrylic plate with a length of 80mm. Figure 1 shown.

[0046] Use a 3D printer to print the model and 3D print a PVA container with a depth of 1.5mm, a width of 20mm and a length of 50mm. Figure 2 As shown. Water was evenly applied to the printed component surface to remove any rough texture. After four applications and drying, a smooth surface was obtained. Model 7055 two-component silicone was used for modeling. The silicone was prepared in a mass ratio of A:B = 1:1, and a curing agent was added at 1% of the total mass of the AB mixture. The mixture was stirred evenly and placed in a vacuum machine to evacuate for half an hour to obtain a silicone mixture.

[0047] Fill the square container with the silica gel mixture until it overflows, place the acrylic plate with feathers on the square PVA container filled with silica gel, press the cover with a heavy object, and place it in a 60℃ constant temperature drying oven to cure for 2 hours. After the silica gel is completely cured, remove the acrylic plate and feathers, and place the silica gel film with feather microstructure on the surface into a water tank. Fill the water tank with hot water, change the hot water every three hours, and use a constant temperature oven to control the water temperature at 60℃ to dissolve it. After 6 hours and 2 water changes, the soluble PVA container is completely dissolved, and a 1.5mm thick silica gel film with feather texture is obtained. Figure 3 shown.

[0048] Use a 3D printer to print out a 70mm long, 5mm diameter shaft column and an 8mm inner diameter casting container made of PVA material. Figure 4 As shown. PVA aqueous solution is prepared by mixing PVA material and water in a mass ratio of 1:10. The PVA aqueous solution is evenly applied on the surface of the model. After four coats and drying, the surface of the entire model becomes smoother. The textured side of the silicone film is wrapped around the shaft column and then embedded in the casting container, as shown. Figure 5As shown, silica gel is slowly injected from the inlet until the silica gel at the inlet no longer sinks, and then the entire mold is placed in a constant temperature drying oven at 60°C for curing for 6 hours.

[0049] Place the PVA casting container model after silicone solidification into a water tank, inject hot water into the water tank, change the hot water every three hours, use a constant temperature oven to control the water temperature at 60℃, and perform the dissolution operation. After 48 hours and 16 water changes, the soluble container and the internal shaft column are completely dissolved, and a silicone blood vessel model with a feather texture is obtained. Figure 6 shown.

[0050] Compared with existing artificial silicone blood vessels, the preparation process of the present invention is very simple and has low dependence on processing equipment. It can achieve personalized customization of the inner surface microstructure and the production of blood vessel models with controllable thickness.

[0051] The descriptions presented in the above exemplary embodiments are only intended to illustrate the technical solutions of the present invention and are not intended to be exhaustive or to limit the present invention to the precise forms described. Obviously, it is possible for a person of ordinary skill in the art to make many changes and variations based on the above examples. The exemplary embodiments are selected and described in order to explain the specific principles of the present invention and its practical applications, so that other persons of ordinary skill in the art can easily understand, implement and utilize the various exemplary embodiments of the present invention and its various selected forms and modified forms. The scope of protection of the present invention is intended to be defined by the appended claims and their equivalents.

Claims

1. A method for making a silicone blood vessel model with a hydrophobic textured inner surface, characterized in that: The specific steps are as follows: Step 1: Cut the cleaned magpie feathers into regular shapes and fix the back of the feathers on the acrylic board; Step 2: Use a 3D printer and dissolvable printing materials to print out a square container, shaft column, and pouring container; Step 3: Use water or printing material dissolving agent solution to evenly wipe the surface of the printed device to remove the rough texture of the printed device surface. After multiple wiping and drying, a printed device with a smooth surface is obtained; Step 4: Prepare a two-component silicone AB mixed solution, mix the two-component silicone AB mixed solution and the curing agent in a certain proportion to obtain a silicone solution; use a vacuum pump to remove bubbles mixed in due to stirring to obtain a clear and transparent silicone mixed solution; use model 7055 two-component silicone, prepare the two-component silicone AB mixed solution in a mass ratio of A:B=1:1, add 1% of the total mass of the two-component silicone AB mixed solution to obtain a silicone solution; stir it evenly and place it in a vacuum machine to evacuate for 0.5-1 hour to obtain a clear and transparent silicone mixed solution; Step 5: Pour the silicone mixture into the square container until it overflows, place the acrylic sheet with feathers on top of the square container, and press it down with a heavy object; Step 6: Dry the entire model obtained in step 5. After the silicone is solidified, remove the acrylic plate and feathers, immerse the entire model in water, and wait until the square container is completely dissolved to obtain a silicone film with feather texture. Step 7: Wrap the shaft with the textured side of the silicone film and insert it into the casting container. Slowly inject the silicone mixture from the inlet of the casting container until the silicone mixture at the inlet no longer sinks. Step 8: Dry the entire silicone blood vessel model obtained in step 5. After the silicone solidifies, immerse the entire silicone blood vessel model in water. After the casting container and the shaft column are completely dissolved, a silicone blood vessel model with an inner surface texture is obtained.

2. The method for making a silicone blood vessel model with a hydrophobic textured inner surface according to claim 1, characterized in that: In step 1, the magpie feathers can be replaced by feathers of other birds, plant leaves or surfaces of marine organisms.

3. The method for making a silicone blood vessel model with a hydrophobic textured inner surface according to claim 1, characterized in that: In step 2, the soluble printing consumables are: PVA, water-soluble gypsum, HIPS or ABS.

4. The method for making a silicone blood vessel model with a hydrophobic textured inner surface according to claim 1, characterized in that: In step 3, the mass ratio of PVA to water in the printing material dissolving agent solution is 1:10 to 1:

5.

5. The method for making a silicone blood vessel model with a hydrophobic textured inner surface according to claim 1, characterized in that: In step 6, the curing conditions are: curing in a constant temperature drying oven at 60° C.-90° C. for more than 2 hours.

6. The method for making a silicone blood vessel model with a hydrophobic textured inner surface according to claim 1, characterized in that: In step 6, the dissolution process is as follows: the solidified whole model is placed in a water tank until the square container is completely dissolved; to accelerate the dissolution of the square container, 60-100°C hot water can be injected into the water tank, and the hot water can be replaced every 1-3 hours. The water temperature is controlled at 60-100°C in a constant temperature oven, and the water is changed 2-10 times until the square container is completely dissolved.

7. The method for making a silicone blood vessel model with a hydrophobic textured inner surface according to claim 1, characterized in that: In step 8, the curing conditions are: curing in a constant temperature drying oven at 60° C.-90° C. for more than 6 hours.

8. The method for making a silicone blood vessel model with a hydrophobic textured inner surface according to claim 1, characterized in that: In step 8, the dissolution process is as follows: the solidified silicone blood vessel model is placed in a water tank, 60-100°C hot water is injected into the water tank, the hot water is replaced every 1-3 hours, and the water temperature is controlled at 60-100°C in a constant temperature oven for dissolution. After 10-25 water changes, the casting container and the internal shaft column are completely dissolved.

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