KR102179122B1 - Fabrication method of bioactive polymer-implant and bioacitve polymer-implant fabricated by the same - Google Patents

Abstract

The present invention comprises the steps of: a) preparing a body portion comprising a polymer material; b) implanting plasma ions of a bioactive material and plasma ions of a biocompatible material into the body by a plasma ion implantation method; And c) forming a deposition layer including a bioactive material and a biocompatible material on the surface of the body by a co-deposition method; including, a method of manufacturing a bioactive polymer implant and a bioactive polymer implant manufactured thereby It is about.

Description

TECHNICAL FIELD The manufacturing method of a bioactive polymer implant and the bioactive polymer implant manufactured thereby TECHNICAL FIELD [FABRICATION METHOD OF BIOACTIVE POLYMER-IMPLANT AND BIOACITVE POLYMER-IMPLANT FABRICATED BY THE SAME}

The present invention relates to a method of manufacturing a bioactive polymer implant and a bioactive polymer implant manufactured thereby, and more particularly, to a biological body having a deposition layer containing a material having high bioactivity on the surface of a body including a polymer material. It relates to a method of manufacturing an active polymer implant and a bioactive polymer implant manufactured thereby.

PEEK (poly(ether ether ketone)), a representative polymer material used as a biomaterial, has been used as an engineering plastic as a component of bearings, pistons, and pumps because of its excellent mechanical properties before being studied as a biomaterial. In recent years, titanium or its alloy, cobalt chromium alloy, and ceramic implants are stress shielding, a phenomenon in which the bone around the implant weakens due to the difference in modulus of elasticity between the implant and the bone. effect) is a problem. Accordingly, PEEK, which has an elastic modulus similar to that of human bones, is being studied as a biomaterial.

As a conventional technique, a method of making a complex by mixing PEEK with a powder of bioactive substances such as hydroxyapatite and β-TCP (β-tricalcium phosphate) to improve the bioactive properties of PEEK (Document 1. International patent WO 2012/110803) has been reported. However, in the case of such a method of making a composite, there is a problem in that the adhesion between PEEK and the bioactive material inside the PEEK is poor, resulting in a gap between the PEEK and the bioactive material, resulting in a decrease in durability, and an increase in the modulus of elasticity. .

In addition, a method of depositing a bioactive material on the surface of PEEK using various deposition methods (Document 2. Materials Science and Engineering C, July, 2015, Pages 58-66, “Enhancement of bioactivity on medical polymer surface using high power impulse. magnetron sputtered titanium dioxide film”, Document 3. Applied Surface Science May 2015, 283 6-11, “Osteoconductive hydroxyapatite coated PEEK for spinal fusion surgery”) has also been reported. However, in the case of using such a method, there is a problem that the thin film is peeled off due to the problem of adhesion between the coating layer and the PEEK.In addition to this adhesion problem, there may be a problem that the porous structure may collapse during the procedure of the implant on which the porous thin film is deposited. have.

An object of the present invention is to provide a method of manufacturing a bioactive polymer implant capable of solving the above-described problem of adhesion between a polymer material and a bioactive material and preventing collapse of a structure during a procedure, and a bioactive polymer implant manufactured thereby.

An exemplary embodiment of the present invention includes: a) preparing a body portion comprising a polymer material;

b) implanting plasma ions of a bioactive material and plasma ions of a biocompatible material into the body by a plasma ion implantation method; And

c) forming a deposition layer including a bioactive material and a biocompatible material on the surface of the body by a co-deposition method; comprising, a method of manufacturing a bioactive polymer implant.

According to the present invention, the bioactive material may include at least one of sodium, potassium, magnesium, calcium, hydroxyapatite, and β-tricalcium phosphate (β-TCP).

According to the present invention, the biocompatible material may include at least one of silicon, titanium, cobalt, chromium, zinc, tantalum, germanium, stainless steel, gold, platinum, alumina, and zirconia.

According to the present invention, the polymer material may be polyaryl ether ketone (PAEK).

According to the present invention, the co-deposition method may use sputtering or cathode arc deposition.

According to the present invention, steps b) and c) can be performed continuously in the same vacuum bath.

According to the present invention, prior to step b), it may further include a step of sanding the surface of the body portion.

According to the present invention, the thickness of the deposition layer may be 10 nm or more and 10 μm or less.

According to the present invention, the plasma ion implantation method and the co-deposition method may each use a target including the bioactive material and the biocompatible material.

According to the present invention, the atomic ratio of the bioactive material and the biocompatible material of the target may be 5:95 to 30:70.

According to the present invention, the bioactive polymer implant can form a porous structure by dissolving the bioactive material in the body.

Another exemplary embodiment of the present invention provides a bioactive polymer implant manufactured by the above manufacturing method.

The bioactive polymer implant manufactured by the manufacturing method according to an exemplary embodiment of the present invention has an advantage of very excellent adhesion between a body including a polymer material and a deposition layer including a bioactive material. Further, since the bioactive polymer implant forms a porous structure after implantation in the body, problems such as collapse of the porous structure that may occur during implantation in the body can be solved. In addition, the bioactive polymer implant can achieve a high bone formation rate after implantation in the body.

1 is a measurement of element distribution in the depth direction of a bioactive polymer implant prepared according to an example using XPS (X-ray photoelectron spectroscopy).
2 is a measurement of element distribution in the depth direction of a bioactive polymer implant prepared according to a comparative example using XPS (X-ray photoelectron spectroscopy).
3 shows the results of pull-off tests of bioactive polymer implants according to Examples and Comparative Examples.
4 shows the results of X-ray diffraction (XRD) according to the hydroxyapatite formation test.
5 is an observation of the surface of a sample according to the porous structure formation test by SEM (Scanning electron microscopy).
6 is an observation of a cross section of a sample according to a porous structure formation test by SEM (Scanning electron microscopy).

When a member is referred to herein as being “on” another member, this includes not only the case where a member is in contact with another member, but also the case where another member exists between the two members.

In the present specification, when a part "includes" a certain component, it means that other components may be further included rather than excluding other components unless otherwise stated.

Hereinafter, the present invention will be described in detail.

An exemplary embodiment of the present invention includes: a) preparing a body portion comprising a polymer material;

b) implanting plasma ions of a bioactive material and plasma ions of a biocompatible material into the body by a plasma ion implantation method; And

c) forming a deposition layer including a bioactive material and a biocompatible material on the surface of the body by a co-deposition method; comprising, a method of manufacturing a bioactive polymer implant.

a) containing a polymer material Body part Steps to prepare

According to an exemplary embodiment of the present invention, the polymer material may be polyaryl ether ketone (PAEK). Specific examples of the polyaryl ether ketone (PAEK) include polyether ether ketone (PEEK), polyether ketone (PEK), polyether ketone ketone (PEKK), polyether ether ketone ketone (PEEKK), and polyether ketone ether It may be a ketone ketone (PEKEKK). However, the polymer material is not limited thereto, and a polymer material applicable to an animal or human implant may be used. In addition, the body portion may be manufactured by adding various additives or filler materials in addition to the polymer material.

The body portion is a portion that becomes a basic frame of the bioactive polymer implant, and may be prepared in various shapes according to the application of the bioactive polymer implant. For example, the body portion may be prepared in the form of an implant used in a procedure that requires bone regeneration, such as a dental implant, an implant for a spinal procedure, an implant for a skull procedure, an implant for a joint procedure, etc.

When the above-described polymeric material is applied to an animal or human body using only itself, it may be difficult for cells to proliferate because the biological activity is not high. Therefore, by applying a bioactive material and a biocompatible material to the body portion through steps b) and c) below, it is possible to improve the bioactivity of the implant.

According to an exemplary embodiment of the present invention, prior to step b), a step of sanding the surface of the body portion may be further included. Specifically, the body portion may be sanded using a polishing paper or the like to facilitate formation of a deposition layer through plasma ion implantation and co-deposition in a later step.

b) plasma By ion implantation, the bioactive material plasma Of ionic and biocompatible substances plasma Remind ions Body part Step of injecting

The step b) may be a means to solve the problem of low adhesion between a body including a conventional polymer material and a deposition layer including a bioactive material and a biocompatible material. Specifically, through step b), plasma ions of the same material as that of the deposition layer are implanted into the body, thereby improving adhesion between the body and the deposition layer.

According to an exemplary embodiment of the present invention, the bioactive material may include at least one of sodium, potassium, magnesium, calcium, hydroxyapatite, and β-tricalcium phosphate (β-TCP). Specifically, the bioactive material may be calcium or magnesium, and more specifically, magnesium.

The bioactive material is dissolved when the bioactive polymer implant is inserted into the body, so that the bioactive polymer implant can have a porous structure. Furthermore, since the bioactive material remains undissolved before being inserted into the body, the bioactive polymer implant does not have a porous structure before the procedure. Accordingly, the bioactive polymer implant can prevent the problem of being broken during the procedure due to the weak physical properties of the porous structure, and can activate the proliferation of cells by forming a porous structure after the procedure.

According to an exemplary embodiment of the present invention, the biocompatible material may include at least one of silicon, titanium, cobalt, chromium, zinc, tantalum, germanium, stainless steel, gold, platinum, alumina, and zirconia. Specifically, the biocompatible material may be titanium, or a titanium alloy formed with at least one of silicon, titanium, cobalt, chromium, zinc, tantalum, germanium, stainless steel, gold, platinum, alumina, and zirconia. .

The bioactive material may serve to improve the bioactivity of the polymer implant by supplementing the low bioactivity of the polymer material constituting the body part.

By step b), the bioactive material and the biocompatible material may be implanted into the body in the form of plasma ions, respectively, so that the bioactive material and the biocompatible material may be provided in the matrix of the polymer material.

c) by co-deposition method, Body part Comprising the bioactive material and the biocompatible material on the surface Deposited layer Forming steps

The bioactive material and biocompatible material in step c) may be the same as the bioactive material and biocompatible material in step b) described above, respectively.

According to an exemplary embodiment of the present invention, the co-deposition method may use sputtering or cathode arc deposition. By the co-deposition method, the biocompatible material together with the bioactive material is deposited on the surface of the body to form a deposition layer.

According to an exemplary embodiment of the present invention, the thickness of the deposition layer may be 10 nm or more and 10 μm or less. However, the present invention is not limited thereto, and the thickness of the deposition layer may be appropriately adjusted according to the use of the bioactive polymer implant.

According to an exemplary embodiment of the present invention, steps b) and c) may be continuously performed in the same vacuum bath. Through this, it is possible to quickly and effectively manufacture the bioactive polymer implant.

According to an exemplary embodiment of the present invention, the plasma ion implantation method and the co-deposition method may use targets including the bioactive material and the biocompatible material, respectively. Specifically, the plasma ion implantation method and the co-deposition method may be performed by ionizing the target in the vacuum chamber by a magnetron deposition source. In addition, the plasma ion implantation method and the co-deposition method may be continuously performed using one of the targets.

The atomic ratio of the bioactive material and the biocompatible material of the target may be 5:95 to 30:70. Specifically, by adjusting the content of the bioactive material in the target, the porosity of the bioactive polymer implant inserted into the body can be adjusted. Specifically, when the bioactive polymer implant is inserted into the body, the bioactive material is dissolved to form a porous structure, so by adjusting the content of the bioactive material of the target, the bioactive polymer implant in the human body Porosity can be adjusted.

According to an exemplary embodiment of the present invention, the plasma ion implantation method and the co-deposition method may be performed in a vacuum chamber provided with a magnetron deposition source supplied with pulsed DC power and a sample mounting table supplied with a negative high voltage pulse, respectively. have

For the plasma ion implantation, the power supplied to the magnetron deposition source may use a pulsed DC power capable of supplying high power at the moment when a pulse is supplied while maintaining a low average power. Specifically, the pulsed DC power supplied to the magnetron deposition source is a density of 10 W/cm 2 to 10 kW/cm 2, a frequency of 1 Hz to 10 kHz, and a pulse width of 10 μsec to 1 msec. Can have

The negative high voltage pulse supplied to the sample mount may accelerate plasma ions toward the sample and inject plasma ions into the body. The negative high voltage pulse may be used in synchronization with the pulsed DC power supplied to the magnetron deposition source at the same frequency. Specifically, the negative high voltage pulse has a frequency of 1 Hz to 10 kHz synchronized with the pulsed DC power supplied to the magnetron deposition source, and further, a pulse voltage of -1 kV to -100 kV and a pulse voltage of 1 μsec to It may have a pulse width of 200 μsec.

For the co-deposition that proceeds continuously after the plasma ion implantation, the DC power density applied to the magnetron deposition source may be 1 W/cm 2 to 50 W/cm 2. However, it is not limited thereto, and may be appropriately adjusted as necessary. When the DC power density applied for the co-deposition is less than 1 W/㎠, the speed of sputtering from the target mounted on the magnetron evaporation source is very slow, so it takes a lot of processing time, so there is a problem that the economic value of this technology is reduced. . In addition, when the DC power density applied for the co-deposition is greater than 50 W/cm 2, there is a problem in that it is very difficult to manufacture a magnetron deposition source in reality due to the difficulty of cooling.

The gas pressure inside the vacuum tank may be 0.5 mTorr to 20 mTorr. When the gas pressure inside the vacuum chamber is within the above range, it is possible to easily generate plasma and minimize energy loss of accelerated plasma ions. Specifically, plasma generation is difficult when the gas pressure inside the vacuum chamber is less than 0.5 mTorr, whereas plasma accelerated due to frequent collisions between plasma ions and surrounding gas particles accelerated when plasma ions are implanted when it exceeds 20 mTorr. The energy loss of ions can be very severe.

Another exemplary embodiment of the present invention provides a bioactive polymer implant manufactured by the above manufacturing method.

According to an exemplary embodiment of the present invention, the bioactive polymer implant may be one in which the bioactive material is dissolved in the body to form a porous structure. As described above, when the bioactive polymer implant is inserted into the body, since the bioactive material is dissolved and formed into a porous structure, cell proliferation can be performed smoothly. Furthermore, since the bioactive polymer implant is not a porous structure during a procedure, there is an advantage of preventing the risk of collapse of the porous structure during the procedure. Further, the porosity of the bioactive polymer implant can be simply adjusted by adjusting the content of the bioactive material of the target used in steps b) and c) as described above.

Hereinafter, examples will be described in detail to illustrate the present invention in detail. However, the embodiments according to the present invention may be modified in various other forms, and the scope of the present invention is not construed as being limited to the embodiments described below. The embodiments of the present specification are provided to more completely describe the present invention to those of ordinary skill in the art.

[ Example ]

As a body part, a PEEK having a diameter of 40 mm and a height of 10 mm was prepared, sanded with abrasive paper having a particle size of about 68 μm, and ultrasonically washed for use. Then, a titanium/magnesium alloy (85/15 at%) target having a diameter of 76.2 mm, a thickness of 3.18 mm, and a purity of 99.9% was used as a magnetron evaporation source.

The PEEK body was mounted on a sample mount in the vacuum tank, and the gas pressure inside the vacuum tank was exhausted to 10 ^-6 Torr, and then argon gas was introduced and the gas pressure inside the vacuum tank was adjusted to 2 mTorr.

For the plasma ion implantation of titanium-magnesium, the magnetron deposition source is supplied with pulsed DC power of frequency 350 Hz, pulse width 20 μsec, voltage -1 kV, average current 120 mA, and average power 2.6 W/㎠ to the magnetron deposition source. Turned on. The average power is a power that makes it difficult for the elements of the target to be ionized, but the pulsed DC power can be sufficiently ionized by adjusting to about 3.2 kW/cm 2.

About 40 μsec after supplying the pulsed DC power, a pulse voltage of -10 kV, a pulse width of 20 μsec, and a negative high voltage pulse of 350 Hz, which is the same frequency as the pulsed DC power, were applied to the sample mount to the sample mount. , In a state where the density of titanium-magnesium plasma ions was sufficiently high, plasma ions were implanted into the PEEK body.

After the plasma ion implantation was performed, a titanium-magnesium deposition layer was continuously formed. Specifically, the gas pressure inside the vacuum tank was maintained at 2 mTorr, the same magnetron evaporation source was used, and an average of 350 W of direct current (DC) was applied to the magnetron evaporation source to provide a 500 nm-thick titanium-magnesium deposition layer. To form a bioactive polymer implant.

[ Comparative example ]

Without going through the plasma ion implantation step, a 500 nm-thick titanium-magnesium deposited layer was formed directly on the PEEK body in the same manner as in the above example, thereby manufacturing a bioactive polymer implant.

1 is a measurement of element distribution in the depth direction of a bioactive polymer implant prepared according to an example using XPS (X-ray photoelectron spectroscopy). In addition, FIG. 2 is a measurement of element distribution in the depth direction of a bioactive polymer implant prepared according to a comparative example using XPS (X-ray photoelectron spectroscopy). According to Figs. 1 and 2, it can be seen that a lot of oxygen is deposited and/or plasma ions are injected together even though oxygen gas is not introduced, which is the deposition and/or plasma ion implantation of oxygen attached to the inner wall of the vacuum chamber. Is expected. Further, compared to the comparative example in which the deposition layer was formed without plasma ion implantation, in the example in which the deposition layer was formed after plasma ion implantation, it was confirmed that titamune and magnesium penetrated deeper into the PEEK body. It can be seen that plasma ion implantation was effectively performed.

Adhesion test

The same method as in the above embodiment was used, but the voltage of the negative high voltage pulse applied to the sample mount during plasma ion implantation was adjusted to -5 kV or -10 kV, and the plasma ion implantation time was changed from 0 minutes to 60 minutes. The bioactive polymer implant was manufactured, and the adhesion between the PEEK body and the deposition layer was tested. Specifically, the prepared bioactive polymer implant was tested for adhesion between the PEEK body and the deposition layer by a pull-off test method using a universal testing machine. The diameter of the dolly used at this time was 15 mm, the adhesive was 3M's DP-460 adhesive, and the pulling speed was 1 mm/min.

3 shows the results of pull-off tests of bioactive polymer implants according to Examples and Comparative Examples. Specifically, the case where the plasma ion implantation time of FIG. 3 is 0 corresponds to a comparative example in which plasma ion implantation is not performed. According to FIG. 3, it can be seen that the best adhesion is exhibited when the plasma ion implantation time is 40 minutes and the voltage of the negative high voltage pulse applied to the sample mounting table is -10 kV. For reference, in the case of the comparative example in which plasma ion implantation was not performed (the plasma ion implantation time was 0 minutes), the adhesion was significantly lower than that of the example.

Hydroxy Apatite formation test

When the bioactive polymer implant prepared according to the example was inserted into the body, the following experiment was performed to confirm whether the formation of hydroxyapatite, which helps cell proliferation, is smoothly performed.

The bioactive polymer implant prepared according to the example was immersed in a simulated body fluid (SBF) at 37° C. for 7 days, and then the surface was analyzed using X-ray diffraction (XRD). As a comparative group, a PEEK sample, which was not separately treated, was immersed in a simulated body fluid (SBF) at 37° C. for 7 days, and then the surface was analyzed using X-ray diffraction (XRD).

4 shows the results of X-ray diffraction (XRD) according to the hydroxyapatite formation test. Referring to FIG. 4, it can be seen that the bioactive polymer implant according to the embodiment has hydroxyapatite (HA), unlike the PEEK sample. Therefore, when the bioactive polymer implant according to the embodiment is inserted into the body, it can be expected that cells such as bone cells can be formed smoothly.

Porous structure formation test

In order to predict whether a porous structure is formed when the bioactive polymer implant according to Examples and Comparative Examples is inserted into the body, a deposition layer is formed on a Si wafer under the same conditions as in Example, but the magnesium of the titanium/magnesium alloy target After forming a deposition layer by variously adjusting the content (at%) (0 at% to 78 at%), it was immersed in physiological saline for 7 days. Furthermore, the surface and cross section of the prepared sample were observed through SEM (Scanning electron microscopy).

5 is an observation of a surface of a sample according to a porous structure formation test by SEM (Scanning electron microscopy). In addition, FIG. 6 is a cross-section of a sample according to the porous structure formation test observed by SEM (Scanning electron microscopy). 5 and 6, it can be seen that the porosity increases as the magnesium content (at%) of the titanium/magnesium alloy target increases. Through this, when the bioactive polymer implant according to the embodiment is inserted into the human body, it can be expected that magnesium can be dissolved to form a porous structure, and further, the porosity can be easily adjusted by adjusting the magnesium content of the alloy target. You can see that you can.

Claims (11)

a) preparing a body portion comprising a polymer material;
b) implanting plasma ions of a bioactive material and plasma ions of a biocompatible material into the body by a plasma ion implantation method using pulsed DC power having a density of 10 W/cm 2 to 10 kW/cm 2; And
c) forming a deposition layer including a bioactive material and a biocompatible material on the surface of the body by a co-deposition method using direct current power having a density of 1 W/cm 2 to 50 W/cm 2;
The plasma ion implantation method and the co-deposition method each use a target including the bioactive material and the biocompatible material in an atomic ratio of 5:95 to 30:70,
The bioactive material includes at least one of sodium, potassium, magnesium, calcium, hydroxyapatite, and β-tricalcium phosphate (β-TCP),
The biocompatible material comprises at least one of silicon, titanium, cobalt, chromium, zinc, tantalum, germanium, stainless steel, gold, platinum, alumina, and zirconia. delete delete The method according to claim 1,
The method of manufacturing a bioactive polymer implant, characterized in that the polymer material is polyaryl ether ketone (PAEK). The method according to claim 1,
The co-deposition method is a method for producing a bioactive polymer implant, characterized in that using sputtering or cathode arc deposition. The method according to claim 1,
Before step b), the method of manufacturing a bioactive polymer implant, further comprising the step of sanding the surface of the body portion. The method according to claim 1,
The method of manufacturing a bioactive polymer implant, characterized in that the thickness of the deposition layer is 10 nm or more and 10 μm or less. delete delete The method according to claim 1,
The bioactive polymer implant is characterized in that the bioactive material is dissolved in the body to form a porous structure, a method of manufacturing a bioactive polymer implant. A bioactive polymer implant prepared by the manufacturing method according to any one of claims 1, 4 to 7, and 10.

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