SURFACE-MODIFIED HYBRID SURFACE IMPLANT AND METHOD FOR MANUFACTURING THE SAME

Abstract

The present invention relates to an implant having a nanotube on a surface thereof and a method for manufacturing the same, and more particularly, to an implant having excellent stability and effectiveness because a nanotube is provided on the surface of the implant and a nanocapsule loaded with a medicine or the like is attached to the nanotube, thereby strengthening the adhesive force with the peripheral soft tissue and allowing to stably load factors related to osteogenesis and inflammation prevention and treatment or the like, thus not making them lost during an implant procedure and therefore not only having an increased lifespan but also preventing almost all occurrences of side effects caused by the implant.

Claims

1. A method for manufacturing an implant with a hybrid surface, comprising the steps of: (a) treating the surface of an implant fixture with sonication, and washing it with a solvent; (b1) preparing a SiO.sub.2 bead, and preparing a nano-sized capsule by using it as a template, wherein a biocompatible material is coated on the SiO.sub.2 template and then the SiO.sub.2 bead is removed to prepare a hollow capsule, or (b2) preparing a bead with a biocompatible material; and (c) attaching the hollow capsule prepared in step (b1) or the bead prepared in step (b2) to the implant fixture prepared in step (a) by dipping and stirring or centrifugation to prepare a first hybrid surface implant.

2. The method for manufacturing an implant with a hybrid surface according to claim 1, characterized in that the method further comprises, in step (b1), the step of loading a functional factor into the hollow capsule.

3. The method for manufacturing an implant with a hybrid surface according to claim 1, characterized in that the biocompatible material in step (b1) or step (b2) is selected from the group consisting of a titanium oxide selected from the group consisting of TiO.sub.2, Ti.sub.3O, Ti.sub.2O, Ti.sub.3O.sub.2, TiO, Ti.sub.2O.sub.3, Ti.sub.3O.sub.5 and titanium butoxide; tricalcium phosphate, calcium phosphate; apatite selected from the group consisting of hydroxyapatite, hydroxyapatite substituted with silicon and magnesium; calcium sulfate; zirconium dioxide; silicon dioxide; and combinations thereof.

4. The method for manufacturing an implant with a hybrid surface according to claim 1, characterized in that the biocompatible material in step (b1) or step (b2) is one or more selected from the group consisting of TiO.sub.2, hydroxyapatite and tricalcium phosphate.

5. The method for manufacturing an implant with a hybrid surface according to claim 1, characterized in that, in step (a), the diameter of the SiO.sub.2 bead is not less than 500 nm and not more than 1 m.

6. The method for manufacturing an implant with a hybrid surface according to claim 2, characterized in that the functional factor is selected from the group consisting of factors exhibiting the functions of promoting osteogenesis and enhancing antibacterial activity, anti-inflammatory activity and acidity, growth hormones, cell differentiation inducers, osteoblastic factors, and angiogenic factors.

7. The method for manufacturing an implant with a hybrid surface according to claim 2, characterized in that the functional factor is loaded into the hollow capsule by using one or more method selected from the group consisting of dipping, centrifugation and sonication.

8. An implant with a hybrid surface manufactured according to the method of claim 1.

9. The implant with a hybrid surface according to claim 8, characterized in that the implant is a dental implant.

10. An implant with a hybrid surface manufactured according to the method of claim 2.

11. An implant with a hybrid surface manufactured according to the method of claim 3

12. An implant with a hybrid surface manufactured according to the method of claim 4.

13. An implant with a hybrid surface manufactured according to the method of claim 5.

14. An implant with a hybrid surface manufactured according to the method of claim 6.

15. An implant with a hybrid surface manufactured according to the method of claim 7.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0014] FIG. 1 illustrates the development process of an implant surface.

[0015] FIG. 2 shows the shape of hollow nanocapsules of several properties.

[0016] FIG. 3 shows an electron micrograph of a cell which settled down onto the irregular shape of an implant surface.

[0017] FIG. 4 shows an electron micrograph of a cell which settled down onto the irregular shape of an implant surface.

[0018] FIG. 5 shows the experimental result indicating that when the surface is homogeneous, cells settle down rapidly.

[0019] FIG. 6 shows a photo of an irregular surface of an implant currently on the market.

[0020] FIG. 7 and FIG. 8 show a very irregular surface of implants currently on the market.

[0021] FIG. 9 shows a photo of SiO.sub.2 templates.

[0022] FIG. 10 shows a photo of TiO.sub.2 nanocapsules.

[0023] FIG. 11 shows a photo of the first hybrid surface implant according to the present invention.

[0024] FIG. 12 to FIG. 14 shows a photo of the second hybrid surface implant according to the present invention.

[0025] FIG. 15 shows a photo of SiO.sub.2 beads.

DESCRIPTION OF EMBODIMENTS

[0026] The present invention provides an overall micro- and nano-scaled hybrid surface implant while ensuring the homogeneity of existing rough surfaced implants and also enabling the control of the degree thereof, by modifying existing micro-scaled rough surfaced implants into a nano-scaled implant.

[0027] According to the present invention, it is possible to obtain both the advantage of existing rough surfaced implants and that of implants with a homogeneous surface. Also, since the present invention allows to manufacture an implant with a homogeneous surface only by carrying out the process of surface modification on an existing implant, it enables to conveniently manufacture an implant with a hybrid surface.

[0028] The present invention also provides an implant to which nanocapsules loaded with functional factors exhibiting a DDS function are attached.

Embodiments

[0029] Hereinafter, the present invention will be described in more detail.

[0030] The present invention relates to a method for manufacturing an implant with a hybrid surface, comprising the steps of: (a) treating the surface of an implant fixture with sonication, and washing it with a solvent; (b1) preparing a SiO.sub.2 bead, and preparing a nano-sized capsule by using it as a template, wherein a biocompatible material is coated on the SiO.sub.2 template and then the SiO.sub.2 bead is removed to prepare a hollow nanocapsule, or (b2) preparing a nanocapsule with a biocompatible material; and (c) attaching the hollow capsule prepared in step (b1) or the bead prepared in step (b2) to the implant fixture prepared in step (a) by dipping, stirring or centrifugation to manufacture a first hybrid surface implant.

[0031] In one embodiment according to the present invention, step (b1) may further include the step of loading a functional factor into the hollow capsule.

[0032] In one embodiment according to the present invention, an implant manufactured according to the above method has an overall uniform surface due to the nanocapsules attached to the surface.

[0033] In one embodiment according to the present invention, the biocompatible material in step (b1) or step (b2) may be selected from the group consisting of a titanium oxide selected from the group consisting of TiO.sub.2, Ti.sub.3O, Ti.sub.2O, Ti.sub.3O.sub.2, TiO, Ti.sub.2O.sub.3, Ti.sub.3O.sub.5 and titanium butoxide; tricalcium phosphate, calcium phosphate; apatite selected from the group consisting of hydroxyapatite, hydroxyapatite substituted with silicon and magnesium; calcium sulfate; zirconium dioxide; silicon dioxide; and combinations thereof, and more specifically, selected from the group consisting of TiO.sub.2, hydroxyapatite and tricalcium phosphate.

[0034] In one embodiment according to the present invention, in step (b1), the diameter of the SiO.sub.2 nanocapsule may be not less than 500 nm and not more than 1 m, more specifically, 500 nm, 600 nm, 700 nm, 800 nm, 900 nm, 1 m.

[0035] In one embodiment according to the present invention, the functional factor may be selected from the group consisting of factors exhibiting the functions of promoting osteogenesis and enhancing antibacterial activity, anti-inflammatory activity and acidity, growth hormones, cell differentiation inducers, and angiogenic factors.

[0036] In one embodiment according to the present invention, the functional factor may be loaded into the hollow nanocapsule by using one or more method selected from the group consisting of dipping, centrifugation and sonication.

[0037] In another embodiment according to the present invention, an implant with a hybrid surface manufactured according to the above method is provided.

[0038] In one embodiment according to the present invention, the implant is characterized in that it is a dental implant.

[0039] The nanocapsule according to the present invention may be manufactured according to the following procedure:

(1) Preparation of a Silica Nanoparticles Dispersion

[0040] Silica nanoparticles with various sizes can be prepared by using the Stober method. In the sol-gel reaction, the type of solvent, amount of catalyst, amount of water, and the amount of tetraethylorthosilicate (TEOS), which is a precursor, etc. affect the size of particles. Ethanol and water are put into a reaction vessel and then catalyst is added, followed by stirring. Then, silica precursor is added and reacted with stirring to prepare a silica nanoparticles dispersion.

(2) Preparation of Core-Shell Silica Particles with Single Mesopores

[0041] Silica nanoparticles dispersion is added to distilled water including ammonia solution, etc. in a reaction vessel, followed by stirring to prepare a solution A. Thereafter, a surfactant solution is stirred and added to the solution A, followed by stirring. Silica precursor is added with stirring, and heated to prepare a silica template.

(3) Preparation of a Capsule-Type Silica-Titania Composite

[0042] The silica template prepared in the above step is dispersed in a mixed solution of an organic solvent and water. TiO.sub.2 precursor can be prepared by adding titanium butoxide, etc. to a solvent such as ethylene glycol and then stirring it. The TiO.sub.2 precursor is added to the dispersed silica template, followed by stirring, washing with an organic solvent and then drying it. Then, the resultant is subjected to thermal treatment to prepare a capsule type silica composite on which a metal or metal oxide layer is formed.

(4) Preparation of a Porous Hollow Capsule

[0043] The prepared capsule type silica composite is dispersed in an organic solvent, and reacted appropriately, and then the silica template is removed to prepare a porous hollow capsule.

[0044] Hereinafter, the present invention will be described in more detail through the examples and preparation examples according to the present invention, but the scope of the present invention is not limited to the examples presented below.

EXAMPLES

Example 1

Preparation of an Implant Fixture with a Hybrid Surface

[0045] (1) SiO.sub.2 beads were prepared with a diameter not less than 100 nm and not more than 1 m. SiO.sub.2 nanocapsules were prepared according to the procedure below.

1) Preparation of Silica Nanoparticles Dispersion

[0046] Silica nanoparticles with various sizes were prepared by using the Stober method. In the sol-gel reaction, the type of solvent, amount of catalyst, amount of water, and the amount of tetraethylorthosilicate (TEOS), which is a precursor, etc. affect the size of particles. A more specific preparation procedure is as follows:

[0047] 1,000 mL of ethanol and 10 mL of deionized water were put into a reaction vessel and then 1 mol of 28 wt % ammonia solution as a catalyst was added, followed by stirring at room temperature for 1 hour. Then, 0.14 mol of TEOS as a silica precursor was added and reacted with stirring at room temperature for 3 hours to prepare a silica nanoparticles dispersion. The resultant silica particles were about 500 nm in diameter (see FIG. 1).

2) Preparation of Core-Shell Silica Particles with Single Mesopores

[0048] 10 mL of the silica nanoparticles dispersion prepared in step 1) was added to 20 mL of distilled water including ammonia solution (28 wt %, 0.1 mL) in a reaction vessel, followed by stirring for 30 minutes to prepare a solution A. 6.24 mL of a surfactant solution consisting of cetyltrimethylammonium bromide:1,3,5-trimethylbenzene:decane:distilled water:ethanol at the molar ratio of 1:1:1:113.99:17.77 was stirred at room temperature for 30 minutes and then added to the solution A, followed by stirring at room temperature for 30 minutes. Then, 0.43 mL of TEOS was added with stirring, followed by stirring for 10 minutes. After the stirring, the resultant was subjected to hydrothermal reaction in an oven set at 70 C. for 15 hours. The resultant sample was recovered by using a centrifuge, followed by drying at 70 C., gradual heating from room temperature up to 500 C. by using a tube furnace with oxygen blowing for 1 hour and 40 minutes, allowing it to stand at 500 C. for 5 hours, and then cooling it down back to room temperature to remove organic matter,

3) Preparation of a Capsule-Type Silica-Titania Composite

[0049] 0.1 g of the silica template prepared in the step 2) was put into a mixed solution of 50 mL of acetone and 0.1 mL of deionized water and then dispersed by using an ultrasonic machine. TiO.sub.2 precursor was prepared by adding 0.4 mL of titanium butoxide to 60 mL of ethylene glycol and stirring them for 12 hours. 10 mL of the TiO.sub.2 precursor was added to the dispersed silica template, followed by stirring for 3 hours, washing with ethanol and then drying it at 70 C. for 12 hours. Then, the resultant was subjected to thermal treatment at 450 C. for 5 hours by using a tube furnace with flowing oxygen to prepare a capsule type silica composite on which a metal or metal oxide layer is formed. The thickness of the resultant oxide layer was 25 nm.

4) Preparation of a Porous Hollow Capsule

[0050] 0.1 g of the resultant capsule type silica composite was dispersed in 3 mL of ethanol, and the dispersion was put into 5 mL of NaOH aqueous solution. The resultant was reacted in a reaction oven set at 70 C. for 3 to 5 hours to remove the silica template and thereby to prepare a porous hollow capsule. The resultant porous hollow capsule was separated by means of centrifugation, washed with ethanol, and dried at 70 C. for 12 hours.

[0051] (2) TiO.sub.2, HA or TCP was coated onto SiO.sub.2 bead templates using SiO.sub.2 beads having the respective diameters as a template, and the SiO.sub.2 beads template was removed (dissolved) to prepare TiO.sub.2, HA or TCP hollow capsule. In order to prepare a capsule type silica-titania composite, the silica template prepared in the above step was put into a mixed solution of an organic solvent and water and then dispersed. Titania precursor was added to a mixed solution of an organic solvent such as ethylene glycol and water and then stirred to disperse the precursor uniformly into the solution. Here, when the precursor solution is added dropwise to the dispersed silica template, followed by vigorous stirring to proceed with reaction, coating starts with deposition of the precursor on the surface of the silica template through hydrolysis. The coating thickness is determined by the concentration and drop time of the precursor solution. After addition and stirring for a sufficient time of 30 minutes or more is completed, the coated capsule type silica-titania composite was centrifuged by using a centrifuge. Impurities adhered to these particles were washed with an organic solvent and air drying was performed. When thermal drying at 60 C. or higher is performed, a pure capsule type silica composite from which solvent and impurities have been completely removed can be prepared. Thereafter, a porous hollow capsule was prepared as follows: The prepared capsule type silica composite was uniformly dispersed in a solvent in which water and an organic solvent is mixed, and silica and strong base were appropriately diluted in an aqueous solution, followed by heating and stirring for 30 minutes or more. During this process, the silica template in the core reacts with the base ion of the aqueous solution which penetrated thereinto to release silica gradually, resulting in the preparation of a porous hollow capsule from which the core has been removed.

[0052] (3) The fixture surface of an implant (Osstem Implant Co., Ltd., RBM type, SLA type or Laser type) was sonicated for 5 to 10 minutes and then washed with alcohol. After the washing was completed, it was treated with silane and dried.

[0053] (4) The silica nanocapsule and hollow nanocapsule prepared through the steps (1) and (2) were put into the implant fixture prepared through the step (3), and then attached thereto by dipping and stirring or centrifugation. Thereafter, sonication was carried out to detach and remove an excess remnant of nanocapsules and hollow nanocapsules or those bonded with weak bonds. Thereby, an implant with a first hybrid surface, that is, an implant with a nano- and micro-scaled hybrid surface was prepared.

[0054] (5) It was shown that the hollow capsule prepared through the step (2) was not a closed capsule, but a spherical capsule with irregular pores of various sizes having a diameter 1/100 to 1/10 that of the capsule.

[0055] (6) The hollow nanocapsule attached to an implant with the first hybrid surface prepared through the step (4) exhibited pores not less than 20 nm and not more than 100 nm. Functional factors, such as peptide involved in promotion of osteogenesis, factors enhancing acidity, e.g., citric acid, ascorbic acid, medicines such as antibiotics, antibacterials, and anti-inflammatory drugs may be loaded within the hollow nanocapsule by a method(s) of dipping, centrifugation, sonication. Thereby, it is possible to prepare an implant with a hybrid surface having a drug delivery system (DDS) allowing a sustained release of functional factors (an implant with a second hybrid surface, that is, an implant with a hybrid surface having a DDS function).

INDUSTRIAL APPLICABILITY

[0056] The implant according to the present invention induces rapid settling down of cells involved in osteogenesis and thereby inducing rapid wound healing and regeneration of solid bony tissue, and can also serve as a drug delivery system by virtue of the nanocapsules loaded therein. Therefore, the implant according to the present invention is very useful industrially.