KR102418786B1 - PEEK implant with excellent osseointegration and method for manufacturing thereof - Google Patents

Abstract

The present invention relates to a peak implant and a method for manufacturing the same. According to this, the peak implant in which collagen is immobilized has excellent osseointegration ability, does not dissociate with the implant, can minimize the inflammatory reaction caused by metal or bacteria, accelerate bone formation, and at the same time, mineralized bone. All effects excellent in formability can be expressed. Accordingly, it can be widely used in clinics such as dentistry and orthopedic surgery.

Description

Peak implant with excellent osseointegration and manufacturing method thereof {PEEK implant with excellent osseointegration and method for manufacturing thereof}

The present invention relates to peak implants, and more specifically, by using salt-precipitated, compressed and concentrated liquid collagen, it is possible to immobilize a large amount of collagen by reacting with dopamine on the peak surface in a neutral aqueous solution without using acetic acid, thereby enabling osseointegration. It relates to a peak implant with excellent performance.

Bioimplants generally used for medical purposes are used to permanently implant spinal fixation prosthesis, interspecies correction prosthesis, artificial joint, etc., and must use a biocompatible material that is very stable for human tissue. In addition, there should be no side effects or other chemical and biochemical reactivity, and the mechanical strength should be very high so as not to be deformed and destroyed even when repeated loads and instantaneous pressures are applied, and for medical use, the bonding strength with biological tissues, especially bone tissues, is very high. it is an instrument

These implants are removed from the bone tissue after being placed in the bone tissue to function permanently or only for a period of time performing the intended function. It is common to perform processing. Examples of such processing include roughening processing to increase a specific surface area with bone tissue, or coating a component similar to bone tissue, for example, a component such as hydroxyapatite on the implant surface.

However, even when the surface of the implant is processed to have a high bonding strength with the bone tissue, the solution to side effects such as inflammation occurring in the surrounding tissue after the implant is placed is insufficient until now. In particular, the act of generating orthodontic force, such as pulling an orthodontic wire as a support for orthodontic implants after being placed like orthodontic micro-implants, forms a gap between the implant and the alveolar bone or surrounding tissues. The causative agent penetrates and causes inflammation, which can lead to the failure of the implant placement procedure.

In addition, conventional implant materials are generally implemented with biocompatible materials such as titanium to minimize in vivo side effects. In the case of commercially available titanium implants, tissue inflammation is induced, and such tissue inflammation is caused by implant and implanted bone and/or By creating a gap between the gums and making the gap more spaced apart, there was a problem that caused inflammation due to additional bacterial penetration. In addition, in the case of conventional implants, as the osseointegration ability is lowered, the phenomenon of detachment from the affected area after the procedure occurs, or in the case of surface-treated implants, there is a problem in that safety is reduced in terms of permanent implantation due to dissociation with the implant, etc.

Therefore, it has excellent osseointegration ability, does not dissociate with the implant, can minimize inflammatory reactions caused by metals or bacteria, accelerate bone formation, and exhibit all of the effects of mineralized bone formation. There is an urgent need for research on implants that can do this.

Laid-open Patent Publication No. 10-2014-0146512

The present invention was devised in consideration of the above points, and as a large amount of collagen can be immobilized on the surface of the peak implant, it has excellent osseointegration ability, does not dissociate with the implant, and is not caused by metal or bacteria. An object of the present invention is to provide a peak implant capable of minimizing an inflammatory response, accelerating bone formation, and exhibiting all of the excellent effects of mineralized bone formation, and a method for manufacturing the same.

In order to solve the above problems, the present invention has excellent osseointegration comprising a collagen layer fixed through poly-dopamine, well-known as a mussel adhesive, on at least part of the surface of a peak (poly ether ether ketone, PEEK) implant. Peak implants are provided.

According to an embodiment of the present invention, nitrogen (N) in the elemental composition of the surface measured according to the following measuring method may be 12 at% or more.

[How to measure]

The surface element composition was measured through the area of the peak formed by analyzing the surface of the peak implant with X-ray Photoelectron Spectroscopy (XPS).

In addition, the collagen layer may be formed through salt-precipitation compression-concentrated liquid collagen derived from pig skin.

In addition, the present invention provides (1) preparing a peak (polyether ether ketone, PEEK) implant, (2) polymerizing and coating dopamine on the surface of the peak implant, and (3) polymerizing and coating dopamine for the peak implant. Provided is a method for producing a peak implant having excellent osseointegration, comprising reacting a liquid collagen composition on at least a portion of the surface.

According to an embodiment of the present invention, the liquid collagen composition may contain collagen in a concentration of 0.1 to 3.0 mg/ml.

The peak implant and its manufacturing method according to the present invention have excellent osseointegration ability, do not cause dissociation with the implant, can minimize the inflammatory reaction caused by metals or bacteria, and can accelerate bone formation and mineralization. All of the effects of excellent osteogenic properties can be expressed.

Accordingly, it can be widely used in clinics such as dentistry and orthopedic surgery.

1 is a schematic diagram of manufacturing a peak implant having excellent osseointegration according to an embodiment of the present invention.
2 is an epifluorescence image of a peak implant according to Example 1, Example 2, and Comparative Example 1 of the present invention.
3 to 6 are graphs analyzed by X-ray Photoelectron Spectroscopy (XPS) of the peak implant surfaces according to Comparative Example 1, Comparative Example 2, Example 2, and Example 1 of the present invention, respectively.
7 is an optical image of osteoblasts cultured for 2 days in Comparative Example 1, Comparative Example 2, and Example 1 of the present invention.
8 is a graph showing the activity of osteocytes cultured for 3 days in Comparative Example 1, Comparative Example 2, and Example 1 of the present invention.
9 is a graph showing a newly created bone volume among total bone volumes tested for peak implants according to Comparative Examples 1, 2, and 1 of the present invention.
10 is a graph showing the bone density volume tested for peak implants according to Comparative Example 1, Comparative Example 2, and Example 1 of the present invention.
11 is a photograph of Villanueva stained bone tissue tested for the peak implant (PEEK) according to Comparative Example 1 of the present invention.
12 is a photograph of Villanueva stained bone tissue tested for peak implant (PEEK-D-SCol) to which solid collagen is applied according to Example 2 of the present invention.
13 is a photograph of Villanueva stained bone tissue tested for peak implant (PEEK-D-LCol) to which liquid collagen according to Example 1 of the present invention is applied.

Hereinafter, embodiments of the present invention will be described in detail so that those of ordinary skill in the art can easily implement them. The present invention may be embodied in many different forms and is not limited to the embodiments described herein.

The peak implant with excellent osseointegration ability according to the present invention is implemented by including a collagen layer fixed through dopamine on at least a part of the peak (poly ether ether ketone, PEEK) implant surface.

First, the peak implant will be described.

The peak implant can be used without limitation in the case of implants placed in vivo, such as for fixing fractures, artificial spine, artificial prostheses, orthodontics.

In addition, since the implant according to the present invention is formed of polyether ether ketone, the problems of conventional metal-based (eg, titanium, etc.) implants can be solved, and the osseointegration ability is excellent, and bone formation can be accelerated at the same time. All of the excellent effects of mineralized bone formation can be expressed.

The polyether ether ketone is a thermoplastic plastic, and has excellent mechanical properties, chemical stability and biocompatibility showing a Young's modulus of about 3.6 GPa and tensile strength of 90 ~ 100 MPa, so it can replace a metal implant such as titanium. .

The polyether ether ketone is chemically very stable because it does not have -NH ₂ , -OH and -COOH structures that perform a chemical reaction in the molecule, so that it is difficult to bind other functional compounds to the surface. Accordingly, collagen, which will be described later, may be fixed to the peak surface through dopamine, which will be described later.

Meanwhile, the size of the peak implant may be, for example, a diameter of about 1 to 2 mm and a length of about 6 to 10 mm.

In addition, a collagen layer to be described later may be fixed on at least a portion of the peak implant surface, and preferably, a collagen layer to be described later may be fixed on all of the peak implant surface.

At this time, as described above, the collagen layer may be fixed to the peak implant through dopamine, preferably by inducing mutual coupling between the peak implant and the collagen layer through dopamine, and more preferably, FIG. 1 As shown, the collagen layer can be fixed to the peak implant by chemical bonding with the amine group of dopamine.

On the other hand, when a collagen layer is used in combination with a peak implant in an untreated state, the amount of fixed collagen layer is greatly limited, so osseointegration is reduced, bone formation cannot be accelerated, and mineralized bone formation is reduced. and dissociation with the implant may occur. However, the peak implant according to the present invention can covalently bond collagen molecules to be described later through dopamine as a medium, and through this, it has excellent osseointegration ability, can accelerate bone formation, and has excellent mineralized osteogenic properties, and implantation. All effects in which dissociation with water does not occur can be simultaneously expressed.

Next, the collagen layer will be described.

The collagen layer has excellent osseointegration ability, can accelerate bone formation, and performs a function of expressing an excellent effect of mineralized bone formation. Collagen is a long fiber with a triple helix structure centered on glycine, proline, and hydroxyproline, and is hardly soluble in aqueous solution. In the case of the conventional solid collagen, it had to be dissolved in an aqueous acetic acid solution due to its remarkably low solubility in water, and thus there was a problem that it could not be introduced to a desired level on the surface of the material to be treated. In particular, in this case, the carboxyl group of acetic acid dissolved in the aqueous solution and the carboxyl group in the collagen molecule can be simultaneously activated by the EDC/NHS catalyst, which will be described later. In this case, the amino group of dopamine coated on PEEK can react with the carboxyl group of activated collagen, but also react with the carboxyl group of acetic acid at the same time, so it can act as a hindrance to the reaction with dopamine, so it is not suitable.

Accordingly, in the present invention, it is possible to introduce collagen to the surface of the peak implant at a high concentration by dissolving it in an aqueous solution without using acetic acid by using the salt-precipitated compressed and concentrated liquid collagen (LCol) derived from pigskin for the reaction.

Next, the dopamine will be described.

The dopamine is a monomolecular substance having a catechol and an amine functional group.

At this time, as described later, a polydopamine (PDA) coating layer can be formed by catechol oxidation on the surface of the peak implant through an aqueous dopamine solution of the same basic pH condition (pH 8.5) as in the marine environment.

On the other hand, in the peak implant according to an embodiment of the present invention, nitrogen (N) in the elemental composition of the surface measured according to the following measuring method may be 12 at% or more, preferably 13 at% or more, more preferably It may be 14 at% or more, and more preferably 14.5 at% or more.

[How to measure]

The surface element composition was measured through the area of the peak formed by analyzing the surface of the peak implant with X-ray Photoelectron Spectroscopy (XPS).

If nitrogen (N) in the elemental composition of the surface is less than 12at%, it may be difficult to express a desired level of mineralized bone formation.

The peak implant according to the present invention described above includes (1) preparing a peak (poly ether ether ketone, PEEK) implant, (2) polymerizing and coating dopamine on the surface of the peak implant, and (3) polymerizing dopamine. and reacting a liquid collagen composition onto at least a portion of the surface of the peak implant.

First, as step (1) of the present invention, a step of preparing a peak (poly ether ether ketone, PEEK) implant is performed.

Step (1) of preparing the peak implant is to mold the implant into a desired shape through the peak, and if it is a method that can be used for molding a molded body through a polymer resin conventionally in the art, it can be used without limitation, For example, a peak implant may be prepared through injection, etc., but is not limited thereto.

In addition, the step (2) may further include immersing the peak implant in a solution containing dopamine.

The solution may include without limitation as long as it is a known solvent capable of dissolving dopamine that can be commonly used in the art, and preferably, a Tris solution (Tris (hydroxymethyl) aminomethane buffer solution) may be used as the solvent, but in this It is not limited.

In this case, the solution may contain 0.0005 wt% or more of dopamine (Dopamine hydrochloride), preferably 0.001 wt% or more of dopamine (Dopamine hydrochloride) with respect to the total weight of the solution.

If dopamine is included in an amount of less than 0.0005% by weight based on the total weight of the solution, the collagen layer, which will be described later, cannot be fixed to the desired level in the peak implant through dopamine. Mineralized bone formation may be reduced, and dissociation with the implant may occur.

In addition, in the method of manufacturing a peak implant according to an embodiment of the present invention, between the steps (1) and (2), the peak implant is washed through any one or more of a Piranha solution and deionized water. It may include further steps.

At this time, as described above, the peak implant can be washed with at least one of Piranha solution and deionized water, and preferably, the peak implant can be washed with Piranha solution and further washed with deionized water. can In this case, the peak implant can be washed 1 to 3 times, preferably 1 to 2 times, with Piranha solution, and then washed 2 to 4 times, preferably 3 to 4 times with deionized water. have.

On the other hand, the pirana solution may include sulfuric acid and hydrogen peroxide solution in a ratio of 4:1 to 8:1, preferably sulfuric acid and hydrogen peroxide solution in a ratio of 5:1 to 7:1, but is limited thereto not.

Next, as step (3) of the present invention, a step of reacting the liquid collagen composition on at least a portion of the surface of the peak implant coated with dopamine is performed.

Step (3) may be performed by immersing the peak implant in a liquid collagen composition containing liquid collagen. Accordingly, it is possible to immobilize a high-concentration collagen layer on at least a portion of the surface of the peak implant, preferably on the entire surface of the peak implant.

The liquid collagen composition can be used without limitation as long as it is a solvent that can be commonly used in the art, and preferably 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide [1-ethyl-3-(3- An aqueous solution containing dimethyl aminopropyl)carbodiimide, EDC] and N-hydroxysuccinimide [N-hydroxysuccinimide, NHS] may be used as a solvent. At this time, in the conventional case, the pH was adjusted through an acid component for dissolution of the solid collagen, but the liquid collagen composition according to the present invention is directly dissolved in an aqueous solution containing EDC/NHS without using a separate acid component and reacted with an acid. Disturbances from components such as acetic acid were removed.

Meanwhile, the liquid collagen composition may contain collagen at a concentration of 0.1 to 3 mg/ml, preferably at a concentration of 0.7 to 1.5 mg/ml. If the concentration of the collagen is less than 0.1 mg/ml, the desired level of effect cannot be expressed because the amount of collagen to be immobilized is significantly low, and if the concentration exceeds 3 mg/ml, undissolved collagen is generated. By interfering with the chemical reaction, the amount of collagen introduced can be reduced.

The present invention will be described in more detail through the following examples, but the following examples are not intended to limit the scope of the present invention, which should be construed to aid understanding of the present invention.

[Example]

<Example 1: PEEK-D-LCol>

Among the peak implants, a spinal cage for intervertebral body fusion prosthesis was prepared. After that, the peak implant was washed once with a solution of Piranha (Piranha, sulfuric acid: hydrogen peroxide = 6:1 by weight) and then washed three more times with deionized water. Then, the peak implant washed in a tris solution (Tris (hydroxymethyl) aminomethane buffer solution, pH 8.5) in which dopamine hydrochloride was dissolved at 0.002% by weight as a dopamine solution was placed in the solution and left at room temperature for 24 hours. After that, as a liquid collagen composition, salt-precipitated and concentrated liquid collagen derived from pork skin was dissolved in an aqueous solution of EDC and NHS with a pH of 5.6 at a concentration of 1 mg/ml, and the peak implant obtained by immersion in a dopamine solution and leaving it alone was added thereto for 48 hours. stirred for a while. Then, by washing with deionized water and drying, a peak implant with a collagen layer fixed as shown in FIG. 1 was prepared.

<Example 2: PEEK-D-SCol>

In the same manner as in Example 1, but without using a liquid collagen composition, a collagen layer was fixed Peak implants were prepared.

<Comparative Example 1: PEEK>

Among the peak implants, a spinal cage for intervertebral body fusion prosthesis was prepared.

<Comparative Example 2: PEEK-D>

A peak implant coated with only dopamine on the surface was prepared in the same manner as in Example 1, but without adding and stirring the liquid collagen composition.

<Experimental Example 1>

For the peak implants according to Example 1 (PEEK-D-LCol), Example 2 (PEEK-D-SCol) and Comparative Example 1 (PEEK), FITC staining reagent reacting with dopamine and collagen amino groups was used for each peak The implant was reacted and observed through a confocal fluorescence microscope, as shown in FIG. 2 .

As a result, from the fact that significantly many green spots were observed in the peak implant according to Example 1, it was found that Example 1 prepared by using salt-precipitated compression-concentrated liquid collagen introduced significantly more collagen.

<Experimental Example 2>

For the surface of the peak implant according to Comparative Example 1 (PEEK), Comparative Example 2 (PEEK-D), Example 2 (PEEK-D-SCol) and Example 1 (PEEK-D-LCol), X-ray photoelectron spectroscopy (X-ray Photoelectron Spectroscopy, XPS) was analyzed.

As a result, as shown in FIG. 3 , in Comparative Example 1 (PEEK), a C1s peak appeared at 284.6 eV, an O1s peak appeared at 536.1 eV, and as it did not contain dopamine and collagen, the N1s peak did not appear. can be checked In addition, as shown in FIG. 4 , in Comparative Example 2 (PEEK-D), an N1s peak was additionally displayed at 397.7 eV, thereby confirming that dopamine was introduced. In addition, as shown in FIG. 5 , in Example 2 (PEEK-D-SCol), it was confirmed that collagen was introduced in a small amount through an increase in the size of the N1s peak. In addition, as shown in FIG. 6 , in Example 1 (PEEK-D-LCol), it can be confirmed that collagen was significantly introduced as the size of the N1s peak significantly increased.

And, the element composition of the peak implant surface was measured from the peak area of FIGS. 3 to 6 and shown in Table 1 below.

division Elemental composition (at%) C O N S Comparative Example 1 84.8 15.2 < 0.1 < 0.1 Comparative Example 2 74.7 18.6 6.7 < 0.1 Example 2 70.2 19.6 10.2 < 0.1 Example 1 66.0 18.5 15.5 < 0.1

As can be seen in Table 1, in the case of Example 2 using solid collagen, nitrogen (N) was 10.2%, and compared to 15.5% of Example 1 using liquid collagen, 51.9% of nitrogen was significantly less. , Accordingly, it can be confirmed that a significant amount of collagen was introduced in Example 1.

<Experimental Example 3>

For the peak implants according to Comparative Example 1 (PEEK), Comparative Example 2 (PEEK-D), and Example 1 (PEEK-D-LCol), after culturing osteocytes in each peak implant for 2 days, the following items were evaluated.

1. Surface Analysis

The surface of each peak implant in which osteocytes were cultured for 2 days was observed with an optical microscope.

As a result, as shown in FIG. 7 , in Example 1 using liquid collagen, it can be confirmed that cells adhere well to the surface and proliferate.

2. Evaluation of osteocytic activity

For each peak implant in which osteocytes were cultured for 2 days, cell activation was evaluated.

As a result, as shown in FIG. 8, Example 1 using liquid collagen was significantly superior in cell activity by 31.8% or more compared to Comparative Example 1, and it was confirmed that the cell activity was significantly superior to that of Comparative Example 2 by 16% or more. have.

<Experimental Example 4>

For the implants according to Examples 1 and 2 and Comparative Example 1, using an 8-month-old male Beagle dog as a clinical trial, micro-CT scans were performed 5 and 10 weeks after implantation to evaluate the results related to bone formation. did The animal testing procedure is described in more detail as follows.

First, ketamine hydrochloride (Ketamine, Yuhan Corporation, Korea, 5mg/kg) and medetomidine hydrochloride (Domitor, zoetis, USA, 40ug/kg) were injected intramuscularly to anesthetize, followed by isoflurane (isoflurane, 1.5 to 2%) was maintained under anesthesia. After the anesthetized test animal was corrected in a supine position, both hind legs were removed, and the surgical site was disinfected with alcohol and povidone solution. After incision of the skin and muscle of the inner part of the tibia of the test animal, the periosteum was removed to expose the tibia, and a total of 4 defects were made, 2 on each side, 2 cm apart, using an electric surgical drill. The diameter was 4 mm. After that, after putting each peak implant sample to fit the defect, the muscles and skin were sutured sequentially, and disinfected and dressing with povidone solution.

Cefazolin sodium (Cefazolin, Chong Kun Dang Pharm, Korea, 20 mg/kg) and Meloxicam (Metacam, Boehringer Ingelheim, Germany, 0.2 mg/kg) were administered for 3 days after surgery. The suture site was checked for 7 days after surgery, and the suture was removed since it was confirmed that there was no abnormality. Ketamine hydrochloride (Ketamine, Yuhan Corporation, Korea, 7 mg/kg) and Medetomidine hydrochloride (Domitor, zoetis, USA, 40 ug/kg) in 3 mice at 5 and 10 weeks postoperatively After anesthesia by intramuscular injection, euthanasia was performed by intravenous injection of potassium chloride (KCl). The euthanized test animals were excised from the tibia of the test animals to which the test substance was applied using an electric surgical drill, and micro-CT was taken and evaluated. Micro-CT (Quantum FX uCT, Perkin Elmer, USA) was evaluated under 90kV, 160uA, FOV 20mm, scan time 2min conditions, and analyzed using the Analyze 12.0 (Analyze Direct, USA) program.

BV/TV (Bone Volume/Total Bone Volume) and vBMD (Volume Bone Mineral Density) were measured by setting the periphery of the test substance as ROI (Region of Interest). For tissue staining for histological evaluation, a slide with a thickness of 10 μm was prepared after embedding with resin, and Villanueva staining was performed. After the staining was completed, an X100 magnification image was acquired with a microscope (Axio Imager A2, Carl Zeiss), and the degree of bone formation was analyzed using the Image J program.

1. Measurement of bone volume (BV/TV, Bone Volume/Total Volume) out of total bone volume

First, for the peak implants according to Examples 1 and 2 and Comparative Example 1, the bone volume (BV/TV, Bone Volume/Total Volume) generated among the total bone volume was measured. As a result, as shown in FIG. 9 , Likewise, compared to the peak implant according to Comparative Example 1, the peak implants according to Examples 1 and 2 in which collagen was introduced showed a greater volume of generated bone among the total bone volume. This can be seen as an increase in bone volume due to increased affinity for osteocytes as collagen is immobilized. In addition, there was no significant difference between Example 2 using solid collagen and Example 1 using liquid collagen at week 5, but at week 10, it can be seen that the bone volume significantly increased in the peak implant according to Example 1. This is because, as shown in Table 1 above, Example 1 was able to introduce significantly more collagen than Example 2.

2. Measurement of Volume Bone Mineral Density (vBMD)

Next, first, the bone density volume (vBMD, Volume Bone Mineral Density) was measured for the peak implants according to Examples 1 to 2 and Comparative Example 1. As a result, as shown in FIG. 10 , according to Comparative Example 1 Compared to the implant, the peak implants according to Examples 1 and 2 in which collagen was introduced had higher bone density and volume. In addition, there was no significant difference between Example 2 using solid collagen and Example 1 using liquid collagen at week 5, but at week 10, it can be seen that the bone density volume in the peak implant according to Example 1 was significantly high.

3. Villanueva stained bone tissue photograph evaluation

And, for the implants according to Examples 1 to 2 and Comparative Example 1, Villanueva-stained bone tissue photos were taken. The results are shown in FIGS. 11 (Comparative Example 1), 12 (Example 2), and 13 (Example 1), respectively, and B and D indicated in each figure enlarge the red rectangle area of A and C 20 times. it's one picture

In the bone tissue analysis method through Villanueva staining, as new bone is formed and mineralized, it appears in pink, indigo, purple, and apricot, gray and white.

At this time, the blue arrow head indicated in FIGS. 11, 12 and 13 indicates the bone before mineralization (Osteoid), and the red arrow head indicates the mineralized bone (osteoblast cell). , Red star indicates immature bone, and blue star indicates lamellar bone.

As a result of the experiment, the 5 weeks and 10 weeks staining results of the peak implant implantation site of FIG. 11 using Comparative Example 1 (PEEK) showed the phenomenon before mineralization of new bone and mineralization above a certain level, but immature bone (Woven bone) It can be seen that the form of

The 5 weeks and 10 weeks staining results of the peak implant implantation site of FIG. 12 using Example 2 (using solid collagen) confirmed the form of lamellar bone in which mineralization was sufficiently advanced, and Comparative Example 1 (PEEK) Compared with the staining results, it can be seen that bone regeneration is accelerated.

The 5 week and 10 week staining results of the peak implant implantation site of FIG. 13 using Example 1 (using liquid collagen) showed sufficient mineralization of the implanted site similar to FIG. 12 of Example 2 to form lamellar bone It can be seen that appears.

In addition, in the 10th week D picture, it can be seen that the density of mineralized mature bone is significantly higher compared to the 12 and 10 week D pictures of Example 2 (using solid collagen), which indicates that more mineralization has progressed. .

Through these results, Example 1 (using liquid collagen) showed significantly better mineralized bone formation than Example 2 (using solid collagen) and Comparative Example 1 (peak implant alone), so that a large amount of mineralized bone was confirmed. Able to know. This is because a much larger amount of collagen was immobilized in the case of immobilization on the PEEK surface using liquid collagen than in the case of using solid collagen.

<Example 3 ~ Example 6>

The same procedure as in Example 1 was performed, except that the concentration of liquid collagen in the liquid collagen composition was changed to prepare peak implants as shown in Table 2 below.

<Experimental Example 5>

The surfaces of the peak implants according to Example 1 and Examples 3 to 6 were analyzed by X-ray Photoelectron Spectroscopy (XPS).

As a result, the elemental composition of the peak implant surface was measured from the measured peak area and is shown in Table 2 below.

division liquid collagen composition Elemental composition (at%) Liquid Collagen Concentration (mg/ml) C O N S Example 1 One 66.0 18.5 15.5 < 0.1 Example 3 0.05 69.7 19.6 10.7 < 0.1 Example 4 0.7 66.3 18.6 15.1 < 0.1 Example 5 1.5 65.9 18.5 15.6 < 0.1 Example 6 3.5 68.2 19.0 12.8 < 0.1

As can be seen in Table 2, Examples 1, 4, and 5 satisfying the concentration range of liquid collagen had significantly more nitrogen (N) than Examples 3 and 6, which did not satisfy this. As a result, it can be indirectly confirmed that Examples 1, 4, and 5 are significantly superior in mineralized bone formation compared to Examples 3 and 6.

Although one embodiment of the present invention has been described above, the spirit of the present invention is not limited to the embodiments presented herein, and those skilled in the art who understand the spirit of the present invention can add components within the scope of the same spirit. , changes, deletions, additions, etc. may easily suggest other embodiments, but this will also fall within the scope of the present invention.

Claims (5)

peak (poly ether ether ketone, PEEK) comprising a collagen layer immobilized via dopamine on at least a portion of the implant surface;
The collagen layer is formed through salt precipitation compression and concentrated liquid collagen derived from pork skin,
Peak implant having osseointegration ability containing 12 to 15.6 at% of nitrogen (N) in the elemental composition of the surface measured according to the following measurement method:
[How to measure]
The surface element composition was measured through the area of the peak formed by analyzing the surface of the peak implant on which the collagen layer was formed by X-ray Photoelectron Spectroscopy (XPS). delete delete (1) preparing a peak (poly ether ether ketone, PEEK) implant;
(2) polymerizing coating of dopamine on the surface of the peak implant; and
(3) forming a collagen layer by reacting a liquid collagen composition containing a salt-precipitated compression-concentrated liquid collagen derived from pigskin but not containing acetic acid on at least a portion of the surface of the peak implant coated with dopamine; Manufactured including,
Method for producing a peak implant having osseointegration ability containing 12 to 15.6 at% of nitrogen (N) in the elemental composition of the surface measured according to the following measurement method:
[How to measure]
The surface element composition was measured through the area of the peak formed by analyzing the surface of the peak implant on which the collagen layer was formed by X-ray Photoelectron Spectroscopy (XPS). 5. The method of claim 4,
The liquid collagen composition is a method for producing a peak implant having an osseointegration ability comprising collagen in a concentration of 0.7 to 1.5 mg/ml.

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