KR20040032297A - Biodegradable Coating-Implant For Bone Fixation - Google Patents

Abstract

PURPOSE: Provided is a biodegradable coating implant coated with an adhesion- stimulating material, which improves the bonding force of the implant to a tissue around the implant. CONSTITUTION: The biodegradable implant for bone connection comprises a coating layer formed of an adhesion-stimulating material, which stimulates the adhesion between the implant inserted into a living body and a tissue around the implant, on the surface of the implant. Particularly, the adhesion-stimulating material is selected from the group consisting of proteins, extracellular materials, cytokine, hormones, pigments and mixtures thereof.

Description

Biodegradable Coating-Implant For Bone Fixation

The present invention relates to a coating implant for bone bonding using a biodegradable polymer that can be degraded and absorbed in vivo, and more particularly, a protein, an extracellular substance, a cytokine, a cytokine, Coatings using biodegradable polymers coated with adhesion promoters such as hormones and pigments, and in particular, coatings having a color as an identification mark to facilitate identification of the specifications of the implants varying according to the site of use, depth of use and lesions used. It relates to an implant.

A method of joining broken or cracked bones is taping using bandages to restrain the movement of the fractured part. Taping method. Apply bone binder directly to the fractured or cracked part. And bonding to form a bonding hole or a groove in the broken bone and inserting an implant into the bonding hole or the groove.

At this time, the type of implant used in the fixing method includes a wire, a pin, a screw, a fracture plate, a rivet, an intervertebral insertion device, and a spinal fixation device. The implant for bone bonding inserted into the surgical site is a tissue. Since it is not an external tissue or an external substance, the chemical composition of the inserted implant is not compatible with the living body, or the biorejection reaction may occur due to corrosion / wear, and thus necrosis or carcinogenesis of the internal tissue may occur. .

In this case, when the material of the implant is a metal, it is possible to easily make a sophisticated product, and mass production is possible, and there is an advantage of low cost, but after the procedure, when the load of the human body is transferred to the inserted metal implant, the stress shielding Symptoms (stress shielding) may cause sequelae in the future, such as osteoporosis, there is a disadvantage that the second procedure to remove the metal implant inserted after the fractured bone is completed.

Because of these drawbacks, in recent years, the use of implants using biodegradable polymers that degrade in the body has been increasing. Implants of biodegradable polymer materials have a number of advantages and disadvantages when compared to the metal implants. In particular, the implants using the biodegradable polymers have a weaker binding strength with tissues than the metal implants. .

That is, since the implant using the biodegradable polymer is inserted into the body and it takes a long time to be adhered to a certain degree or more through the binding with the surrounding biological tissue, it has a certain or more binding force between the implant and the biological tissue Decomposition of the implant has already proceeded before adhesion occurs, which causes a problem that adhesion is inhibited.

Therefore, before the decomposition of the implant occurs, there is a need for a method in which the biological tissue is more rapidly adhered and bonded with the implant of the inserted biodegradable polymer material so that the holes in the biological tissue formed by the insertion of the implant can be filled. It is becoming.

In addition, since there are many types of such implants having a small difference in form and specification, it is possible to identify an implant having a precise shape and specification suitable for a site, a depth of use, and a lesion used in an urgent procedure. There was a problem that it is not easy to do.

Therefore, there is a need for a simple identification method for immediately identifying and selecting an implant suitable for a specific purpose among a plurality of implants according to various forms and specifications.

The present invention has been made to solve the above problems, proteins, extracellular substances, cytokines, hormones and natural to promote the adhesion between the implant using the biodegradable polymer inserted into the body and the biological tissue surrounding the implant Or it is an object of the present invention to provide a coating implant for biodegradable bone bonding is coated on the surface of the implant adhesion promoting material such as artificial pigments.

In addition, there is an additional object to provide a coating coating for biodegradable bone joints having a color as an identification mark to facilitate identification of the specifications of the implant that depends on the site of use, depth of use and lesions used.

1 is a cross-sectional view of one embodiment of a coating implant for biodegradable bone joints according to the present invention.

Figure 2 is an embodiment photograph of a coating implant for biodegradable bone joints having a color according to the present invention.

Figure 3a to Figure 3b is a photograph showing the results of cell adhesion experiments of the coating coating for biodegradable bone joints according to the present invention.

Figures 4a to 4b is a photograph showing the results of cell adhesion experiments of conventional biodegradable bone bonding implants.

* Explanation of symbols for the main parts of the drawings

100: head 200: rod

300: coating layer

In the present invention for achieving the above object, in the biodegradable bone joint implant, the adhesion promoting material for promoting adhesion between the implant inserted in the body and the living tissue surrounding the implant is coated on the surface of the implant It is characterized by that.

Implants using biodegradable polymers used in the present invention have various shapes and shapes according to their use and purpose of use. In the material, a porous structure in which many holes are formed on the surface and a continuum structure are not. can be divided into (continuum structure). In this case, in the case of the implant of the porous structure, a part of the adhesion promoting material coating layer according to the present invention may be formed therein due to the characteristics of the structure, and in this specification, the expression of the coating treatment on the surface of the implant is included. Used.

When an appropriate coating is applied to the surface of the implant using a biodegradable polymer, after the implant is inserted into the body, cells or tissues around the implant are rapidly adhered to the surface of the implant, so that decomposition of the implant occurs. The implant and bone tissue will be firmly combined before doing so.

Therefore, at the interface between the implant and the bone, the phenomenon in which the implant is slowly detached from the insertion site due to pressure (micro-motion) due to the growth of the bone tissue is prevented, and the loss of the bone tissue due to the biodegradation of the implant is prevented. Expansion by growth is harmonized to enable desirable bone regeneration.

The coating material having an adhesion promoting function according to the present invention may be any material having a good coating on the biodegradable polymer, the coating is maintained for a long time, and compatible with biological tissues. , Purified proteins such as gelatin and pronectin, unrefined proteins such as extracellular matrix, and hormones such as cytokines.

Here, the extracellular substance is a basic substance constituting cells or tissues, and examples thereof include fibronectin, collagen, laminin, elastin, and the like. They make cell adhesion easier and help tissue regeneration.

In addition, among the adhesion promoting substances, in particular, cytokines and other hormones, in addition to the action of promoting adhesion between the implanted bone tissue around the implant and the implant, there is a function of promoting the regeneration and growth of biological tissues, Prompt bone union and wound healing. In other words, after the inserted biodegradable implant is decomposed, the insertion hole formed for insertion of the implant can be quickly filled by bone growth in response to the absorption rate of the implant.

Representative substances having such a function include cytokines such as Interleukin 4 (IL-4), Interleukin 6 (IL-6), and Interleukin 10 (IL-10) and BMP-1 (BMP-1, Bone Morphogenetic). Protein 1), BMP-2 and Epidermal Growth Factor (EGF).

In addition to the materials mentioned above, as described above, any material that can promote adhesion between the tissue and the implant that is harmless to the human body, including natural or artificial pigments, which is harmless to the human body, can be coated. The specific method for coating the implant surface of the biodegradable polymer material may also be applied to any method used in the related art.

As a method used in the related art, for example, protein coating method using photooxidization of UV light, collagen coating and protein coating method by ozone treatment, biodegradable polymer material for implant and Mixing in an appropriate ratio and then injection molding.

In addition, the present invention for achieving the above additional object, in order to facilitate identification of the specifications of the implant that varies depending on the site of use, depth of use and lesions, etc., the biodegradable bone joint coating implant coated with the adhesion promoting material It is characterized in that the color as an identification mark formed on the.

That is, the color of each of the biodegradable bone joint coating implants are different according to the specifications, thereby facilitating the identification of many types of implants having a small difference in form and specification, and thus making the implants in an urgent procedure. Allow the operator to immediately select the correct size of implant suitable for the site of use, depth of use and lesion used.

In this case, the coloring of the color may be formed over the entirety of the implant, but may be formed only in a specific part such as a head or a rod, and various kinds as well as a single color. It is also possible to use the colors together.

"Implant" in the present invention, ① as an internal fixation for the treatment of fractures, pins, screws, fracture plates, washers, wires, rivets, intervertebral inserts, spinal fixation devices, etc .; and ② for cruciate ligament reconstruction Interference screws and the like as fixtures; And ③ suture anchors for fixing sutures, and the like, which are completely inserted into the human body and used as an artificial internal fixation for fixing and bonding hard tissues or soft tissues.

Hereinafter, detailed features or functions of the various methods will be described in detail.

The coating method and the coloring method described in the following is only one exemplary embodiment according to the present invention, and thus the technical spirit of the present invention is not limited or changed by those skilled in the art. It will be obvious to you.

Example 1 Coating Method (1)

A biodegradable implant coated with profectin (or albumin) was used as an adhesion promoter.

Implant produced by injection molding from PLLA (Poly-L-Lactide), a biodegradable polymer, is called 'PLLA', and is made of 1M sodium hydroxide (NaOH) at room temperature. 10 minutes to 1 hour, then washed with phosphate buffer (PBS: phosphate buffered solution, hereinafter 'PBS') and soaked in 0.1% nectin (or 0.1% albumin) solution for 1 hour. The implant was removed, washed with PBS and dried at room temperature to complete the implant coated with profectin (or albumin).

Example 2 coating method (2)

Gelatin-coated biodegradable implants were prepared as adhesion promoters.

The implant produced by injection molding the biodegradable polymer PLLA into a product shape was immersed in 0.1M NaOH solution for 10 minutes, washed with PBS and immersed in 0.1 wt% gelatin solution for 1 hour. The implant was removed, washed with PBS, and dried at room temperature to complete a gelatin-coated implant.

Example 3 Coating Method (3)

Using photooxidation of ultraviolet light, a biodegradable implant coated with an adhesion promoter was prepared.

Implants were immersed in 40 ml of a 30% solution of hydrogen peroxide and then photooxidized by UV light generated from a 250 W high-pressure mercury lamp at 50 ° C. for 40 minutes, and then the mineralized implants were washed in neutral water for 4 hours to remove residual hydrogen peroxide. Dried under vacuum. The thus dried implant was coated by immersing it in a protein solution having a predetermined concentration contained in a nitrogen-washed Pyrex glass tube. At this time, the coating was carried out for 1 hour at a distance of 12.5cm from the ultraviolet light source and 50 ℃, the implant is completed, in 70 ℃ neutral water to remove the unreacted protein or homopolymer (homopolymer) Complete by washing for 24 hours.

Example 4 Coloring Method (1)

The biodegradable polymer material PLLA 1Kg was mixed with 0.1% by weight of artificial pigment (FD & C Red No. 4), which is harmless to the human body, to produce a biodegradable implant having a color expression by a conventional injection molding method.

Example 5 coloring coating method (1)

A colorless fenectin was coated on the surface of the red biodegradable implant prepared in <Example 4> to prepare an implant having both an identification mark and adhesion promoting function by coloring.

The red implant prepared in <Example 4> was immersed in 1M NaOH solution at room temperature for 1 hour at 10 minutes, washed with PBS and immersed in colorless 0.1% nectinine solution for 1 hour. The implant was removed, washed with PBS, and dried at room temperature to complete a procectin-coated red implant.

Example 6: coloring coating method (2)

Using blue pectin as a method of <Example 1>, a blue implant coated with nectin was prepared as an adhesion promoting material.

The implant produced by injection molding from PLLA, a biodegradable polymer, was molded into a product shape at room temperature for 10 minutes to 1 hour, then washed with PBS and washed in blue 0.1% nectinine solution. Immerse for 1 hour. The implant was taken out, washed with PBS, and dried at room temperature to complete a blue implant coated with profectin.

Example 7: coloring coating method (3)

By re-coating green gelatin on the protein-coated implant by the method of <Example 3>, a green implant coated with protein and gelatin as an adhesion promoting material was prepared.

The coated implant prepared by the method of <Example 3> was immersed in 0.1M NaOH solution for 10 minutes, washed with PBS and immersed in green 0.1 wt% gelatin solution for 1 hour. The implant was taken out, washed with PBS and dried at room temperature to complete a protein-coated green implant.

The above objects, features and advantages will become more apparent from the following detailed description taken in conjunction with the accompanying drawings. Hereinafter, with reference to the accompanying drawings and embodiments will be described the present invention in detail. The drawings and the embodiments are only examples of the present invention, and the technical spirit of the present invention is not limited thereto or changed by this.

1 is a cross-sectional view of an embodiment of a coating implant for biodegradable bone joints according to the present invention.

As shown in FIG. 1, the biodegradable bone joint coating implant according to the present invention is formed by coating an adhesion promoting material on the surface of a conventional biodegradable implant (300), wherein the adhesion promoting material is coated. , Gelatin, protein, such as nectin, extracellular substance, and cytokines and other hormones can be used.

In this case, the coating layer 300 may be formed only on the rod 200 directly inserted into the body, and may be integrally formed up to the head 100.

Figure 2 is a photograph of one embodiment of a coating implant for biodegradable bone bonding having a color according to the present invention.

As shown in Figure 2, the biodegradable bone joint coating implant having a color according to the present invention, in order to enable the operator to easily identify the specifications of the implant that varies depending on the site of use, depth of use and lesions used, etc. By forming a color on the surface of the implant, which differs according to the specifications of the implant.

Methods for producing such a coated coating implant include the following.

First, injection molding is performed by mixing a dye in a biodegradable polymer raw material in the manufacturing process of an implant, and coating the adhesion promoting material on the thus manufactured implant. A detailed example of the manufacturing process for this is described above in Example 5.

Secondly, it uses the color of the adhesion promoting material for coating the surface of the implant. In this case, a color unique to the adhesion promoting material may be used, but when the distinction of the color falls, it is also possible to use a single color dye or two or more mixed dyes in the adhesion promoting material. A detailed example of the manufacturing process for this is described above in Example 6.

Thirdly, the implant coated with the colorless adhesion promoting material is coated with the colored adhesion promoting material again. A detailed example of the manufacturing process for this has been described in <Example 7>.

In addition, there is a method of coloring the surface of the implant coated with the adhesion promoting material, and in addition to the above-described method, it is possible to identify the specifications of the implant, harmless to the human body and does not interfere with the action of the adhesion promoting material. Any method can be used if the method of coloring the color is not allowed.

At this time, the coloring of the color may be formed over the whole of the implant, may be formed only in a portion of the head 100, the rod 200, etc., only a single color may be used, two or more colors Can also be used together.

In this case, as described above, all the dyes mixed in the injection molding process or colored on the surface are dyes harmless to the human body, such as food dyes.

3A to 4B show the results of adhesion experiments with tissues of implants using biodegradable polymers coated on adhesion surfaces.

Application example: Analysis of effect of adhesion promoter coating

According to the present invention, cell adhesion experiments were carried out using an implant coated with an adhesion promoting substance and a conventional non-coated implant.

A biodegradable bone joint implant having a diameter of 3.5 mm and a length of 40 mm was used, and a testectin-coated implant as an adhesion promoting material, according to the present invention, manufactured according to the method of <Example 2> as a test group Five were used as control, five implants of PLLA, a biodegradable polymer without coating treatment.

3A to 4B show photographs showing the degree of adhesion between the surface of the implant and the body tissue in the test group and the control group. FIGS. 3A and 3B show the test group, and FIGS. 4A and 4B show the control group, respectively.

As a result of the experiment, as shown in Figures 3a and 3b, the test group implants coated with nectin, smoothly induced cell adhesion on the surface (Fig. 3a), the adhesion is maintained even if the implant is washed with PBS The result was shown (FIG. 3B).

On the other hand, as shown in FIGS. 4A and 4B, uncoated control implants were observed to adhere a small amount of cells to the surface thereof (FIG. 4A), but no adhered cells were observed when the implant was washed with PBS. (FIG. 4B).

Therefore, in the case of the control group not coated, cell adhesion is not achieved, whereas in the test group coated with the adhesion promoting substance according to the present invention, cell adhesion is smoothly achieved, and adhesion and growth of cells and bone tissues when applied to the actual procedure ( It was confirmed that it may contribute to bone in-growth.

The present invention described above is not limited to the above-described embodiments and drawings, and it is common in the art that various substitutions, modifications, and changes can be made without departing from the technical spirit of the present invention. It will be apparent to those who have knowledge.

The present invention as described above, by coating the adhesion promoting material such as protein to the implant using a biodegradable polymer, the biodegradable implant is inserted into the body, it is required to be decomposed and adhered to the surrounding biological tissues with a certain degree of binding force It is possible to greatly shorten the time it takes, eventually increasing the binding force of the biodegradable implant.

In addition, by using the color as an identification marker for easy identification of the specification of the coating implant that varies depending on the site of use, depth of use and lesions used, there is an additional effect that can increase the safety of the procedure.

Claims (10)

In biodegradable bone joint implant, A coating implant for biodegradable bone joints, characterized in that the adhesion promoting material for promoting adhesion between the implant inserted into the body and the biological tissue surrounding the implant is coated on the surface of the implant. The method of claim 1, The adhesion promoting material, Biodegradable bone joint coating implant, characterized in that any one or a mixture of two or more selected from the group consisting of proteins, extracellular substances, cytokines, hormones and pigments. The method of claim 2, The protein is, Biodegradable bone joint coating implant, characterized in that gelatin (gelatin) or pronectin (pronectin). The method of claim 2, Said cytokine, Interleukin 4 (IL-4), Interleukin 6 (IL-6), or Interleukin 10 (IL-10), which promotes bone tissue growth, characterized in that the biodegradable bone joint coating implant. The method of claim 2, The hormone is BMP-1 (Bone Morphogenetic Protein 1), BMP-2 (BMP-2) or EGF (EGF, Epidermal Growth Factor), which promotes bone tissue growth. . The method of claim 2, The pigment, A biodegradable bone joint coating implant, characterized in that the dye is a single color or a mixture of two or more dyes, which is harmless to the human body. The method according to claim 1 or 2, The implant, The biodegradable bone joint coating implant, characterized in that it has a color that makes it possible to identify the specifications of the implant that depends on the site of use, depth of use and lesions used. The method according to claim 1 or 2, The adhesion promoting material, The biodegradable bone joint coating implant, characterized in that it has a color that makes it possible to identify the specifications of the implant that depends on the site of use, depth of use and lesions used. The method of claim 8, The color is A biodegradable bone joint coating implant, which is formed by a dye of a single color or a mixture of two or more dyes, which is harmless to the human body. The method of claim 8, The color is A biodegradable osteoconjugate coating implant formed by a single color adhesion promoting material or a mixture of two or more colored adhesion promoting materials.