KR102131101B1 - Method for preparation of ePTFE-based artificial vessels with enhanced hemocompatibility via selective plasma etching - Google Patents

Abstract

The present invention is a method for manufacturing an artificial blood vessel comprising the step of injecting a bioactive metal without an interface to an expanded polytetrafluoroethylene (ePTFE) surface by performing plasma etching using a bioactive metal target. Accordingly, the present invention relates to an artificial blood vessel with improved blood compatibility.

Description

Method for preparation of ePTFE-based artificial vessels with enhanced hemocompatibility via selective plasma etching}

The present invention is a method for manufacturing an artificial blood vessel comprising the step of injecting a bioactive metal without an interface to an expanded polytetrafluoroethylene (ePTFE) surface by performing plasma etching using a bioactive metal target. Accordingly, the present invention relates to an artificial blood vessel with improved blood compatibility.

When blood vessels are narrowed and hardened due to the accumulation of cholesterol or fat on the inner wall of blood vessels such as arteries or veins in the body, it interferes with smooth blood circulation and causes various vascular diseases such as angina, myocardial infarction, and coronary artery disease. Today, the incidence of such vascular diseases is rapidly increasing as diabetes and obesity increase due to biased eating habits and static lifestyles, especially in developed countries. Once these blood vessel diseases become blocked, the blood flow becomes blocked. The fatality rate is also high, which has been reported as a very fatal disease. As a non-surgical treatment method for vascular disease, there is a method of suppressing further stenosis by taking anti-anginal medication, but these medications do not fundamentally solve the stenosis site, and pain from angina remains even after continued medication. . As a method of treating vascular diseases, surgical treatment methods such as vascular graft surgery and vascular bypass surgery have been emerging to remove hardened blood vessels through surgery and connect artificial blood vessels to the site.

In the surgical treatment method, initially, a donor's artery or vein was collected and transplanted, but the success rate was not high due to the occurrence of rejection or hardening. On the other hand, autograft, which replaces the damaged area by collecting the patient's healthy blood vessels, has the lowest immune response after transplantation, so the method has the highest success rate, but the number of blood vessels that can be secured at one time is limited. There is a disadvantage that the burden on the patient is increased because additional surgery is required. Therefore, in order to solve this, surgery to replace the existing damaged blood vessels using artificial vascular grafts made of synthetic polymers is currently underway. Synthetic polymers that can be selected for application to artificial blood vessels must first be harmless to the human body and be made of a material with high compatibility in vivo. In addition, when transplanted into the body, it should not be rejected by the immune system and must be able to be maintained in the body for a long time. Furthermore, in order to prevent stenosis and vascular stiffness that may occur after transplantation, it should be that there is no precipitation of proteins or lipids or formation of blood clots and inflammatory reactions.

The material currently commercialized and used as an artificial vascular material selected in consideration of the above conditions is expanded polytetrafluoroethylene (ePTFE), which is a fluorine-based polymer. This is a material modified to have a microporous structure in micro units by adding a stretching process to an existing polytetrafluoroethylene manufacturing process. The ePTFE composed of a fluorine-based polymer has a high surface hydrophobicity and is very stable in the body, and is not reactive with other substances, and thus can inhibit thrombus adhesion to the inner wall of blood vessels. At the same time, the microporous structure of ePTFE is known as a material suitable for artificial blood vessels by providing a passage between the inner and outer walls of blood vessels to promote the absorption of nutrients in the blood. In actual clinical results, a high success rate has been reported in large-diameter artificial vascular graft surgery with a diameter of 6 mm or more, and it has been applied as a relatively stable surgical method.

However, in small-diameter artificial vessels with a diameter of 6 mm or less, stenosis is still occurring at a high rate when an artificial blood vessel made of ePTFE material is implanted due to low blood flow rate. Therefore, research is being conducted to further improve blood compatibility by modifying the inner wall of the ePTFE artificial blood vessel. As a specific example, Korean Patent Registration No. 10-1483846 discloses a method of improving blood compatibility by imparting reactivity to an inner surface by treating the inner wall of a polymer tube with a microplasma, and US Patent No. 6,306,165 A method for inhibiting thrombus production by coating the anti-thrombotic protein heparin on the inner wall of an ePTFE artificial blood vessel is disclosed.

However, the conventional surface modification method using plasma may improve biocompatibility, but surface stability may be lowered due to high reactivity of radicals generated after plasma treatment, and aging treatment must be carried out to maintain it. There are limits. On the other hand, the method of coating a drug such as a natural polymer or an anticoagulant has a disadvantage that it is difficult to maintain the drug efficacy for a long time because it is released within a short time under the blood flow because the binding force with these drugs is weak due to the hydrophobicity of the surface. There is a risk of developing heparin-induced thrombocytopenia (HIT), which can cause serious secondary disease depending on the patient's age or health condition, because excessive release reduces platelets.

In the manufacture of artificial blood vessels based on ePTFE, the present inventors tried to find a surface modification method for improving blood compatibility of the surface so as not to cause stenosis even when used with a small diameter of 6 mm or less. By attaching a bioactive metal without an interface to the surface of the ePTFE using a selective plasma etching method, adhesion and/or proliferation of vascular endothelial cells is significantly increased, and adhesion and/or proliferation of activated platelets is suppressed, thereby providing a surface. It was confirmed that the present invention was completed.

The first aspect of the present invention is a step of injecting a bioactive metal without an interface to an expanded polytetrafluoroethylene (ePTFE) surface by performing plasma etching using a bioactive metal target under a predetermined reaction condition. At the same time, applying a negative voltage to the bioactive metal target in the presence of an inert gas, and applying a negative voltage for bias to the fixed plate on which the ePTFE specimen is placed, the bioactive metal cation is generated by a potential difference formed between the bioactive metal target and the ePTFE specimen. It provides a method of manufacturing an artificial blood vessel having a metallized surface comprising a bioactive metal injected without an interface to one surface of the ePTFE specimen, including the step of accelerating.

The second aspect of the present invention is an ePTFE substrate; And an bioactive metal injected without an interface on one surface of the ePTFE substrate.

Hereinafter, the present invention will be described in more detail.

The present invention is designed to improve the occurrence of a high rate of stenosis due to a low blood flow rate when the ePTFE tube currently used as an artificial blood vessel material is used with a small diameter within 6 mm. In order to solve this, when the inner diameter of the tube is treated with plasma, the surface stability is low due to the remaining highly reactive radicals, so there is a hassle accompanying aging treatment to improve it, and coating drugs such as natural polymers or anticoagulants If the coating is peeled off by the flow of blood or the drug is released quickly, it is difficult to continuously obtain the desired effect, and there is a possibility that secondary drugs may be caused by the released drug. However, artificial blood vessels having a metalized surface prepared by implanting bioactive metal ions into the surface of ePTFE by selective plasma etching according to the present invention significantly improve the adhesion and/or proliferation of vascular endothelial cells, and activated platelets In addition to suppressing the adhesion and/or proliferation of metals, metal ions are implanted to a certain depth from the polymer surface and the surface to a certain depth, unlike the substrate coated by simply depositing the metal, thereby forming a metal oxide, so that it is not easily peeled off or worn out and has structural stability. It is characterized by being able to remain stable for a long period of time even when transplanted into the body.

Plasma etching using a bioactive metal target under a predetermined reaction condition to inject a bioactive metal without an interface to the surface of the ePTFE, applying a negative voltage to the bioactive metal target in the presence of an inert gas and simultaneously positioning the ePTFE specimen. Comprising the step of accelerating the bioactive metal cation by the potential difference formed between the bioactive metal target and the ePTFE specimen by applying a negative voltage for bias to the fixed plate, the bioactive metal injected without an interface to the ePTFE specimen and one side thereof It provides a method of manufacturing an artificial blood vessel having a metallized surface containing.

In the bioactive metal used in the manufacturing method of the present invention, ions formed when plasma is generated etch the surface of a polymer substrate having a relatively low specific gravity to cause shape change on the surface while atoms formed together are deposited on the surface and remain on the surface. It can be a substance that can change the chemical composition. Non-limiting examples of such bioactive metals include tantalum, niobium, tungsten, renum, osmium, iridium, hafnium, platinum or gold. Preferably, the bioactive metal may be tantalum, but is not limited thereto. The tantalum is a highly anti-corrosion and abrasion-resistant material, and thus is a biocompatible material that is used in various ways for corrosion-resistant materials such as batteries and electronic devices, implants for insertion into the body, or coatings thereof. .

In the manufacturing method according to the present invention, the voltage applied to the bioactive metal target may be a negative voltage equal to or higher than a threshold voltage at which metal cations are released from the bioactive metal target. For example, when using tantalum as a target, a negative voltage in the range of 10 to 500 V may be applied, but is not limited thereto, and may be selected in consideration of the type of bioactive metal used and the possibility of ion generation.

Furthermore, the negative voltage for bias applied to the fixed plate on which the ePTFE specimen is placed may apply a negative voltage greater than the negative voltage applied to the bioactive metal target, for example, a negative voltage in the range of 500 to 2000 V.

Thus, by applying a negative voltage for bias to the fixed plate on which the ePTFE specimen is placed, that is, a negative voltage higher than the voltage applied to the bioactive metal, the bioactive metal cation generated from the bioactive metal target is accelerated toward the ePTFE specimen. Metal ion implantation to the surface of the ePTFE specimen can be induced.

In the manufacturing method of the present invention, in order to maximize the content of the bioactive metal injected into the surface of the ePTFE specimen, the distance between the bioactive metal target and the fixed plate on which the ePTFE specimen is placed can be adjusted, and the target and the specimen are 5 to 15 It can be spaced apart in cm, but is not limited thereto.

For example, the manufacturing method of the present invention can be performed using a magnetron sputtering device having a DC power supply connected to a fixed plate on which a bioactive metal target and an ePTFE specimen are positioned, but is not limited thereto.

Preferably, the plasma etching includes a vacuum chamber including a bioactive metal target and ePTFE specimens spaced apart from each other inside; And a direct current power supply connected to the bioactive metal target and the ePTFE specimen, respectively. Preferably, a negative voltage is respectively applied to the bioactive metal target and the ePTFE specimen located spaced apart from each other, but the bioactive metal ion generated by the voltage gradient is applied to the ePTFE specimen by applying a larger negative voltage than the bioactive metal target, and Atoms can be accelerated toward the ePTFE specimen.

In order to provide a predetermined pressure required for the plasma process, an inert gas may be injected into the vacuum chamber to maintain a predetermined pressure. Argon gas may be used as the inert gas, but is not limited thereto. The pressure may be 0.5×10 ^-2 to 5×10 ^-2 torr, but is not limited thereto, and may be appropriately selected by those skilled in the art.

Bioactive metal ions can be implanted from the surface of the ePTFE and from the surface to a specific depth, for example, 1 to 100 nm, without an interface with the polymer by selective plasma etching under the above conditions.

The ePTFE specimen used in the manufacturing method of the present invention may have a thickness equal to the thickness of an artificial blood vessel to be finally provided, and the width and length may be a specimen having a plane greater than the inner diameter and length of the artificial blood vessel to be provided, respectively.

Thus, the manufacturing method of the present invention, after the step of injecting the bio-active metal, may further include the step of bending or suturing or bent in a blood vessel shape so that the surface into which the bio-active metal is injected faces inward. Specifically, it is preferable that the ePTFE specimen to be injected is planar due to the characteristics of the manufacturing method of the present invention in which the surface of the ePTFE to be modified and the bioactive metal target to be injected are spaced apart at predetermined intervals. For example, the ePTFE tube of the desired size and/or length is cut open in a cylindrical direction, and then the bioactive metal is injected into the inner surface, and then sealed or adhered in the form of a tube to restore the tube shape, or the bioactive metal is placed on a flat ePTFE substrate. After the injection, the metal may be manufactured by bending or sealing it by bending it into a blood vessel shape so that the surface on which it is injected faces, but is not limited thereto. At this time, the thickness of the artificial blood vessel to be produced may be 0.01 to 0.2 mm, but is not limited thereto. More specifically, the thickness and/or diameter of the artificial blood vessel may be adjusted in consideration of blood flow, blood pressure, and blood vessel thickness of the vascular defect to be transplanted.

The process of bending the ePTFE substrate of the plane into which the bioactive metal is injected can be performed using a medical device for blood vessels such as a plastic cannula, but is not limited thereto. At this time, the size of the plastic cannula can be selected in consideration of the diameter of an artificial blood vessel to be manufactured.

In order to prevent blood from leaking, so that the side surfaces can be provided in the form of a closed tube, the substrates bent in a blood vessel shape may seal or bond portions that come into contact with each other. The suture may be performed using any method and/or means capable of suturing artificial blood vessels, such as suture using a suture. The suture used for the suture is ligation of blood vessels to bring about the hemostatic effect or to support the tissue until the damaged tissue is healed, so it must be inactive that does not react with the tissue, should be flexible, and damage the tissue It does not give, and there should be no foreign body action. As the suture, one or more selected from the group consisting of silk, nylon, Vicryl, Prolin, and Dacron may be used. Since the silk is not slippery, the knot is hardly loosened if tied only 3 to 4 times during sealing, and is inexpensive, and is used for skin suture, intestinal suture, and extensive fascial suture. In addition, nylon is a polyamide polymer, and there are two types of monofilament and multifilament. Mainly, nylon made of monofilament is often used. The larger the first number, the thinner the thickness. The suture may use nylon made of 6-0 to 10-0 monofilament, but is not limited thereto. Meanwhile, the adhesion may be performed using any method and/or means capable of adhering an artificial blood vessel using an adhesive for biological tissues. As an adhesive for biological tissues, materials used for the purpose of fixing tissue, sealing wounds, preventing hemostasis, and preventing air leakage in various medical fields such as microsurgery, vascular surgery, lung surgery and plastic surgery, orthopedics, and dentistry are not limited. Can be used. Because it is used in vivo, it must be biodegradable and free from toxicity and risk. In addition, since it is intended to be inserted into the body as an artificial blood vessel, it is difficult to obtain sufficient adhesion since it is exposed to the wet state by body fluids or blood after transplantation, and it must have properties such as fast adhesion and biocompatibility, so only limited materials can be used. Can. One or more selected from the group consisting of fibrin glue, gelatin glue, polyurethane-based adhesive, and cyanoacrylate-based adhesive may be used as the adhesive for biological tissues.

Furthermore, the present invention is based on ePTFE; And an bioactive metal injected without an interface on one surface of the ePTFE substrate.

Artificial blood vessels having a metalized surface of the present invention can be prepared by a selective plasma etching method, but are not limited thereto.

Specifically, the artificial blood vessel of the present invention may be manufactured by the above-described manufacturing method, but is not limited thereto.

The artificial blood vessel prepared as described above may be one in which a bioactive metal is injected from the surface of the ePTFE to a depth of 1 to 100 nm. When the thickness of the bioactive metal injection layer is thinner than 1 nm, it may be difficult to achieve a desired degree of blood compatibility improvement effect, whereas when it is deeply formed to exceed 100 nm, the intensity increases to increase blood pressure as a blood vessel that requires flexibility. It can be difficult to use.

As described above, the artificial blood vessel of the present invention is characterized in that a bioactive metal ion is implanted on the surface of ePTFE without an interface. At this time, the content of the bioactive metal contained within 10 nm from the surface of the ePTFE is on average from 1 to 50 atomic%, and is characterized by exhibiting a pattern of a tendency for the content of the bioactive metal to decrease with depth from the surface of the ePTFE. As described above, the artificial blood vessel of the present invention contains metal ions in the ePTFE substrate without an interface with a content gradient of a pattern in which the metal content decreases as the depth increases from the outermost surface, so it is wet by external stimulation or in vivo insertion. Even when exposed to conditions and blood flow, the metal layer is not peeled off and maintains a constant content, so it is structurally stable and can maintain improved properties even after a long period of time.

For example, the artificial blood vessel of the present invention is characterized by improved blood compatibility compared to an ePTFE substrate that is not injected with a bioactive metal. Specifically, the artificial blood vessel of the present invention can increase the adhesion, proliferation, or both of vascular endothelial cells, and decrease the adhesion, proliferation, or both of activated platelets, compared to the ePTFE substrate without bioactive metal injection. In a specific embodiment of the present invention, it was confirmed that the adhesion and proliferation rate of cells were significantly increased when vascular endothelial cells were cultured on the surface of the ePTFE in which tantalum ions were implanted on the surface by selective plasma etching of the present invention compared to the untreated ePTFE. When platelets were cultured by dispensing, activated platelets widely attached through filopods were found to adhere and proliferate with high density on the untreated ePTFE surface within the same time, but the surface was obtained by selective plasma etching of the present invention. To the surface of the ePTFE implanted with tantalum ions, a markedly small number of platelets were observed, and these platelets were identified as inactive platelets maintaining a disc shape (FIGS. 5 and 6).

As described above, the artificial blood vessel of the present invention can be implanted by suturing or adhering to a defective vascular site in vivo. For example, the artificial blood vessel of the present invention is a non-limiting sealing method known in the art, using a suture, a non-limiting sealing method known in the art, sealing with a vascular defect, or using an adhesive for biological tissue. As a result, it can be adhered to the vascular defect. At this time, the types of sutures and/or adhesives for biological tissues that can be used are as described above.

The artificial blood vessel according to the present invention may further include an antithrombotic component. The antithrombotic component can be used commercially without limitation, for example, immersed in a solution containing an antithrombotic component such as 4-hexylresorcinol to support the antithrombotic component in the pores of ePTFE. However, it is not limited thereto.

Artificial blood vessel having a metalized surface containing a bioactive metal injected without an interface on one surface of an ePTFE specimen by the selective plasma etching method of the present invention

1 is a view showing a scanning electron microscope (SEM) image of an ePTFE surface before and after surface treatment by selective plasma etching.
2 is a view showing the results of analyzing the chemical bonding state of the atoms on the surface of the ePTFE before and after surface treatment by selective plasma etching by X-ray photoelectron spectroscopy (XPS).
3 is a view showing the water contact angle (contact angle) of the surface of the ePTFE before and after surface treatment by selective plasma etching.
4 is a view showing an attached image of vascular endothelial cells cultured for 1 day and 7 days on the surface of the ePTFE before and after surface treatment by selective plasma etching, observed with a confocal microscope.
FIG. 5 is a view showing attached images of platelets cultured for 1 day on the surface of ePTFE before and after surface treatment by selective plasma etching, observed according to magnification using SEM.
FIG. 6 is a diagram showing the adhesion density of platelets cultured for 1 day on the surface of ePTFE before and after surface treatment by selective plasma etching to the surface of ePTFE.

Hereinafter, the present invention will be described in more detail through examples. These examples are intended to illustrate the present invention more specifically, but the scope of the present invention is not limited by these examples.

Comparative example One: Untreated ePTFE Preparations

The medical ePTFE artificial blood vessel (GORE-TEX, Stretchable Vascular Grafts) commercially available from Gore was purchased and processed to a size of 10 mm×10 mm to facilitate subsequent experiments.

Example 1: optional plasma By etching Surface-treated ePTFE Produce

In order to inject bioactive metal tantalum ions using a selective plasma etching method on the surface of the ePTFE specimen prepared in a size of 10 mm×10 mm according to Comparative Example 1, the ePTFE specimen and the tantalum target were magnetron sputtered (DC magnetron sputter). After being positioned about 15 cm away from the vacuum chamber, argon gas was introduced as a sputtering gas to form a plasma in the chamber to form a vacuum degree of about 10 ^-2 torr. Thereafter, a negative voltage was applied to the tantalum target (purity of 99.99%) to form a plasma inside the vacuum chamber, and a higher negative voltage was applied to the fixed plate on which the ePTFE specimen was placed to form a potential difference between the target and the fixed plate. The tantalum ions accelerated to the stationary plate by the electric attraction due to the potential difference were impinged on the surface of the ePTFE specimen, and finally, ePTFE having a metallized surface in which tantalum ions were implanted on the surface was obtained. At this time, the voltage applied to the tantalum target was 500 V or less, and the processing time was completed within 1 minute in total.

Experimental Example 1: optional plasma By etching Surface-treated , Tantalum ion implanted Confirm the change of surface structure of ePTFE

In order to confirm the change in the surface structure of the ePTFE before (comparative) and after (example) surface treatment by the selective plasma etching method according to the present invention, a field emission-scanning electron microscope (FE-SEM) was used. Observation and the results are shown in FIG. 1. As shown in FIG. 1, it was confirmed that the high magnification images of Comparative Examples and Examples stably maintain the porous pore structure of the untreated ePTFE without any surface structure change by surface treatment by selective plasma etching.

Experimental Example 2: optional plasma By etching Surface-treated , Tantalum ion implanted Identification of chemical structures on the surface of ePTFE

Comparative Example 1 and Example by X-ray photoelectron spectroscopy (XPS) to identify chemical species change on the surface by implantation of tantalum ions by selective plasma etching identified in Experimental Example 1 The chemical bonding state and composition of the surface atoms of the specimen prepared according to 1 were confirmed, and the results are shown in FIG. 2. As shown in FIG. 2, in the comparative example, which is an untreated ePTFE specimen, no atoms except carbon, oxygen, and fluorine were detected, but in the embodiment, which is an ePTFE specimen in which tantalum ions were injected by selective plasma etching, tantalum atoms were additionally detected ( 4.04%).

Experimental Example 3: optional plasma By etching Surface-treated , Tantalum ion implanted Check the hydrophilicity of ePTFE surface

In order to confirm the change in the properties of the surface of the ePTFE according to the surface treatment by the selective plasma etching method, the hydrophilicity, which is the surface property of a representative polymer substrate, was confirmed. Specifically, the water contact angle was measured for the tantalum injection surfaces of the samples of Comparative Example 1 and Example 1, and the results are shown in FIG. 3. As shown in FIG. 3, the comparative example, which is an untreated ePTFE specimen, was confirmed to be highly hydrophobic with a very high water contact angle of about 133°, but an example of an injected ePTFE specimen of tantalum ions by selective plasma etching was about 96 It showed a markedly reduced water contact angle in °. This indicates that hydrophilicity was imparted to the surface of the hydrophobic ePTFE by surface treatment by selective plasma etching.

Experimental Example 4: optional plasma By etching Surface-treated , Tantalum ion implanted Evaluation of adhesion and proliferation of vascular endothelial cells on the surface of ePTFE

In order to confirm the effect of surface treatment by selective plasma etching on the blood compatibility of the ePTFE surface, endothelial cells were dispensed on the specimens of Comparative Examples 1 and 1 and cultured by a known method, The degree of adhesion and proliferation of the cells on the substrate was confirmed by a confocal microscope. Specifically, vascular endothelial cells (ATCC, CRL-1730) are cultured by dispensing and culturing the surfaces treated with the non-treated and selective plasma etching methods of Comparative Examples and Examples, respectively, and the form of cells attached to the surfaces on Days 1 and 7, respectively. It was observed, and the results are shown in FIG. 4. As shown in Fig. 4, the degree of proliferation was weak even when cultured for up to 7 days on untreated ePTFE specimens (comparative example), and this is considered to be due to the high hydrophobicity of the untreated ePTFE surface. On the other hand, markedly increased proliferation of vascular endothelial cells was observed after 7 days of culture on the surface of the ePTFE treated with the selective plasma etching method, and these cells spread evenly over the entire surface and adhered. This may be due to the hydrophilicity of the surface imparted by the surface treatment by a selective plasma etching method.

Experimental Example 5: optional plasma By etching Surface-treated , Tantalum ion implanted Evaluation of platelet adhesion tendency and density on ePTFE surface

To confirm the effect of surface treatment by selective plasma etching on the blood compatibility of the ePTFE surface, the tendency and density of platelet adhesion on the specimens of Comparative Example 1 and Example 1 were confirmed by FE-SEM, and the results are shown. 5 and 6. Specifically, platelets extracted from healthy human blood were dispensed on a surface treated with an untreated and selective plasma etching method, and cultured for 1 hour, and then platelets attached to the surface were observed. As shown in FIG. 5, platelets evenly attached to the entire area were observed on the untreated ePTFE specimen (comparative example), and the attached morphology of these platelets was observed with a high magnification image to activate strongly adhered to the surface of the substrate. Platelets were confirmed. On the other hand, the number of attached platelets observed on the surface of the ePTFE treated with the selective plasma etching method was remarkably small, and these attached platelets were observed with a high magnification image, confirming that they were inactivated platelets. As shown in Fig. 6, as a result of quantitatively calculating the density of platelets attached from these images, the density of platelets attached to the substrate of the present invention surface-treated by selective plasma etching method compared to untreated ePTFE is almost 1/6. Level. This indicates that ePTFE surface-treated by the selective plasma etching method according to the present invention can significantly reduce thrombus formation and/or blood clotting compared to untreated ePTFE.

Claims (15)

Plasma etching using a bioactive metals target under a predetermined reaction condition to inject a bioactive metal without an interface to an expanded polytetrafluoroethylene (ePTFE) surface, which is bioactive in the presence of an inert gas. By applying a negative voltage to the metal target and simultaneously applying a negative voltage for bias to the fixed plate on which the stretched polytetrafluoroethylene specimen is placed, the bioactive metal cation is caused by a potential difference formed between the bioactive metal target and the stretched polytetrafluoroethylene specimen. A method of manufacturing an artificial blood vessel having a metallized surface comprising a stretched polytetrafluoroethylene specimen and a bioactive metal injected without an interface on one surface thereof, comprising:
The artificial blood vessel produced by the above manufacturing method is characterized in that the attachment, proliferation or both of vascular endothelial cells is increased, and the adhesion, proliferation or both of activated platelets is decreased, and both are reduced.
According to claim 1,
The bioactive metal is tantalum, niobium, tungsten, renum, osmium, iridium, hafnium, platinum or gold, the manufacturing method.
According to claim 1,
The voltage applied to the bioactive metal target is a negative voltage equal to or higher than a threshold voltage at which metal cations are released from the bioactive metal target.
According to claim 3,
The voltage applied to the bioactive metal target is a negative voltage in the range of 10 to 500 V, the manufacturing method.
According to claim 1,
The voltage applied to the fixed plate on which the stretched polytetrafluoroethylene specimen is placed is a negative voltage greater than the negative voltage applied to the bioactive metal target.
The method of claim 5,
The voltage applied to the fixed plate on which the stretched polytetrafluoroethylene specimen is placed is a negative voltage in the range of 500 to 2000 V.
According to claim 1,
The bioactive metal target and the fixed plate on which the stretched polytetrafluoroethylene specimen is placed are spaced apart at intervals of 5 to 15 cm.
According to claim 1,
The method is performed using a magnetron sputtering device having a direct current power supply connected to a fixed plate on which a bioactive metal target and a stretched polytetrafluoroethylene specimen are positioned.
Stretched polytetrafluoroethylene base; And an bioactive metal injected without an interface on one surface of the stretched polytetrafluoroethylene substrate, as an artificial blood vessel having a metalized surface,
An artificial blood vessel characterized in that the adhesion, proliferation or both of vascular endothelial cells is increased, and the adhesion, proliferation or both of activated platelets is decreased.
The method of claim 9,
Artificial blood vessels prepared by a selective plasma etching method.
The method of claim 9,
The artificial blood vessel is characterized in that produced by the method of any one of claims 1 to 8, artificial blood vessels.
The method of claim 9,
The bioactive metal is injected from a stretched polytetrafluoroethylene surface to a depth of 1 to 100 nm, artificial blood vessel.
The method of claim 9,
The content of the bioactive metal contained within 10 nm from the stretched polytetrafluoroethylene surface is on average from 1 to 50 atomic%, showing a pattern of a tendency for the content of the bioactive metal to decrease with depth from the stretched polytetrafluoroethylene surface. Phosphorus, artificial blood vessels.
The method of claim 9,
Artificial blood vessels with improved blood compatibility compared to stretched polytetrafluoroethylene substrates without injection of bioactive metals.
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