Dental implant having enhanced early stability and method for manufacturing same

Abstract

A dental implant and a method for manufacturing same which assure early stability and fixation power of an implant by suppressing early osteolysis after an implant procedure, and allowing better bone coherence of the implant surface during an osteogenic period by controlling the speed of bone remodeling.

Claims

1. A dental implant comprising: a hydrophilized roughened surface formed by plasma or ultraviolet treatment; and an osteoclast activity inhibitor coating film which is formed on the hydrophilized roughened surface of the dental implant to enhance initial stability of the implant and osseointegration at an implant-bone interface, wherein the osteoclast activity inhibitor comprises at least one selected from the group consisting of alendronate, zolendronate, and pharmaceutically acceptable salts, esters, and acids thereof, and wherein the osteoclast activity inhibitor coating film further comprises a bone growth factor.

2. A method for manufacturing a dental implant, the method comprising the steps of: roughening a surface of a dental implant to thereby form a roughened surface of the dental implant; subjecting the roughened surface of the dental implant to hydrophilization treatment performed by plasma or ultraviolet treatment to thereby form a hydrophilized roughened surface of the dental implant; and forming an osteoclast activity inhibitor coating film on the hydrophilized roughened surface of the dental implant, wherein the osteoclast activity inhibitor comprises at least one selected from the group consisting of alendronate, zolendronate, and pharmaceutically acceptable salts, esters, and acids thereof, and wherein the osteoclast activity inhibitor coating film further comprises a bone growth factor.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1A is a diagram showing the principle of decreased initial stability after implant procedure.

(2) FIG. 1B is a diagram showing the principle of increased initial stability after implant procedure according to the present discloser.

(3) FIG. 2 is a flowchart showing the preparation and implantation of an implant coated with an osteoclast activity inhibitor in accordance with an embodiment of the present discloser.

(4) FIGS. 3 and 4 show the results of evaluation of initial stability for 6 weeks after implantation of implants, coated with an osteoclast activity inhibitor in accordance with an embodiment of the present discloser, in the mandible and tibia of micropigs.

(5) FIG. 5 shows the measurement results of removal torque after 16 days for bone growth after implantation of implants, coated with an osteoclast activity inhibitor in accordance with an embodiment of the present discloser, in the tibia of micropigs.

(6) FIG. 6 shows the measurement results of removal torque after 16 days for bone growth after implantation of implants, coated with an osteoclast activity inhibitor and a bone growth factor in accordance with an embodiment of the present discloser, in the tibia of micropigs.

DETAILED DESCRIPTION OF THE INVENTION

(7) The present discloser provides a dental implant comprising a roughened surface and an osteoclast activity inhibitor coating film which is formed on the surface of the dental implant to enhance initial stability of the implant and osseointegration at an implant-bone interface.

(8) Moreover, the present discloser provides a method for manufacturing a dental implant, the method comprising the steps of: roughening a surface of a dental implant; subjecting the roughened surface of the dental implant to hydrophilization treatment; and forming an osteoclast activity inhibitor coating film on the surface of the hydrophilized surface of the dental implant.

(9) Meanwhile, the osteoclast activity inhibitor for application to alveolar bone can be applied to the surface of the alveolar bone, which is in contact with a dental implant, before implantation of the implant to inhibit bone resorption of the alveolar bone, thus enhancing initial stability of the implant and osseointegration at an implant-bone interface.

(10) The dental implant and the method for manufacturing the same in accordance with aspects of the present discloser will be described in detail with reference to the accompanying drawings.

(11) First, as used herein, the term implant refers to a substitute for restoring lost body tissue, and the term dental implant refers to a substitute intended to restore the original function of a tooth in a manner that a fixture is embedded and integrated in the alveolar bone, from which a natural dental root is removed, to replace the root of a missing tooth and then an artificial tooth is fixed onto the top of the fixture.

(12) In particular, in the present discloser, the surface of the dental implant refers to the surface of the fixture that can be integrated in the alveolar bone and may be made of titanium or a titanium alloy comprising titanium and at least one of aluminum, tantalum, niobium, vanadium, zirconium, platinum, magnesium, and sodium.

(13) As shown in FIG. 1A, when the implant is implanted in the alveolar bone, bone resorption to form new bone occurs first in the existing bone, which decreases the stability of the implant, and at the same time, new bone is formed around the implant, which in turn increases the stability of the implant due to osseointegration between the implant and the alveolar bone. Due to the nature of the process in which the stability of the implant is obtained, an area where the stability of the entire implant decreases is inevitably formed, and thus the time for which the implant is particularly vulnerable to external loads is present. Therefore, when an excessive load is applied to the implant with low initial stability, the osseointegration may be delayed due to minute vibrations.

(14) In the present discloser, in order to solve these problems, the osteoclast activity inhibitor coating film, which can inhibit early bone resorption of the alveolar bone, is formed on the implant surface. When the implant is coated with the osteoclast activity inhibitor and then implanted in the alveolar bone, the osteoclast activity inhibitor coated on the implant surface is released from the alveolar bone to the surrounding bone. The released osteoclast activity inhibitor is adsorbed onto the surrounding bone to inhibit the activity of osteoclasts, which delays bone remodeling at an implant-bone interface fixed to the alveolar bone to alleviate the decrease in primary stability of the implant, thus increasing the initial stability of the implant as shown in FIG. 1B. Moreover, the implant coated with the osteoclast activity inhibitor of the present discloser maintains the increase in the initial stability due to an increased osseointegration period, thus enhancing the osseointegration at the implant-bone interface.

(15) That is, the implantation of the implant coated with the osteoclast activity inhibitor according to the present discloser can ensure the initial stability and fixation of the implant by minimizing the area where the stability of the implant decreases and, at the same time, enable early loading of the implant, thus preventing delay in osseointegration due to minute vibrations and reducing the osseointegration period.

(16) Moreover, as shown in FIG. 2, the osteoclast activity inhibitor may not be coated directly on the implant, but may be applied directly to the surface of the alveolar bone, which is in contact with the implant, before implantation of the implant, thus obtaining the same effect. Moreover, the osteoclast activity inhibitor may be applied in the form of a solution or in a dried state to the implant surface or the alveolar bone surface to facilitate its release and absorption.

(17) The osteoclast activity inhibitor may comprise alendronate, zolendronate, and pharmaceutically acceptable salts, esters, and acids thereof.

(18) Furthermore, the osteoclast activity inhibitor coating film may further comprise a bone growth factor such as (rh)BMP-2 to promote osseointegration of the implant.

(19) Meanwhile, before the step of coating the osteoclast activity inhibitor on the implant surface, the implant surface may be further subjected to the step of roughening the surface and the step of hydrophilization treatment so as to further enhance the osseointegration. The roughening may be performed by various methods such as blasting, resorbable blasting media, acid etching, alkali etching, titanium plasma spray, sandblasting with large grit and acid treatment, anodizing, laser surface processing, etc., and the roughened implant surface has an increased surface area, which enhances the osseointegration of the implant.

(20) Moreover, the hydrophilization treatment of the implant surface may be performed by various methods that can remove organic contaminants from the surface, and as an example, plasma treatment such as RFGD, O.sub.2, and room temperature plasma or ultraviolet treatment may be used.

(21) Next, the effect of the present discloser will be described in detail with reference to the following Examples. However, the following Examples are merely illustrative of one or more detailed examples, and the scope of the present discloser is not limited to the following Examples.

Example 1: Preparation of Dental Implant Subjected to Hydrophilization Treatment and Coated with Osteoclast Activity Inhibitor

(22) Machined titanium implants were blasted with Al.sub.2O.sub.3 powder with a particle size of 1 mm or less at a blast pressure of 1 to 10 atm for 1 to 60 seconds. Macro- & micro-morphology was given to the implant surface by acid treatment using a mixed acid solution, and then the acid-etched dental titanium implant was washed with ethanol for 30 minutes and with distilled water by ultrasonication for 30 minutes and then dried.

(23) In order to impart hydrophilicity to the implants which were subjected to the above processes, the titanium surface was hydrophilized by plasma treatment (RFGD, O.sub.2, etc.) for 1 minutes and light radiation (ultraviolet rays, ultraviolet-ozone, etc.) for 5 minutes. Then, a 10 ml solution of 40 g Alendronate, 40 g Zolendronate, 1 g BMP-2, and 40 g Alendronate+1 g BMP-2 was uniformly applied to the surface, and the prepared implants, in which the solution was not dried, were used in the following Examples 2, 3 and 4.

Example 2: Animal Experiments for Measurement of Implant Stability Quotients to Evaluate Initial Stability of Dental Implants Coated with Osteoclast Activity Inhibitor

(24) In order to determine implant stability quotients (ISQs), the dental implants coated with alendronate prepared in Example 1 were implanted in the mandible and tibia of micropigs, and then the resonance frequency analysis (RFA) values were measured for ISQs using Osstell Mentor (Integration Diagnostics Ltd., Goteborg, Sweden) and Smartpeg (Integration Diagnostics Ltd., Goteborg, Sweden) at 0, 0.5, 1, 1.5, 2, 4, and 6 weeks, respectively. At this time, implants that were not coated with the osteoclast activity inhibitor were used as the negative control group, and implants that were subjected to pre-treatment for hydrophilizing the titanium surface and coated with alendronate were used as the experimental group.

(25) As can be seen from FIGS. 3 and 4, there was little decrease in ISQ values or the degree of the decrease was very lower in the experimental group than in the negative control group, from which it was confirmed that the initial stability of the implant increased.

Example 3: Animal Experiments for Measurement of Osseointegration at Implant-Bone Interface to Evaluate Initial Stability of Dental Implants Coated with Osteoclast Activity Inhibitor

(26) In order to determine the osseointegration at the implant-bone interface, the dental implants coated with alendronate and zolendronate prepared in Example 1 were implanted in the tibia of micropigs, and then the removal torques were measured after 16 days for bone growth. At this time, implants that were not coated with the osteoclast activity inhibitor were used as the negative control group, and implants that were subjected to pre-treatment for hydrophilizing the titanium surface and coated with alendronate and zolendronate were used as the experimental group.

(27) As shown in FIG. 5, the removal torque was increased by about 6 to 13% in the experimental group compared to the negative control group, from which it was confirmed that the osseointegration at the implant-bone interface increased in the implants coated with the osteoclast activity inhibitor.

Example 4: Animal Experiments for Measurement of Osseointegration at Implant-Bone Interface to Evaluate Initial Stability of Dental Implants Coated with Osteogenic Protein and Osteoclast Activity Inhibitor

(28) In order to determine the osseointegration at the implant-bone interface, the dental implants coated with rhBMP-2 and alendronate prepared in Example 1 were implanted in the tibia of micropigs, and then the removal torques were measured after 16 days for bone growth. At this time, implants that were coated only with rhBMP-2, an osteogenic protein, were used as the negative control group, and implants that were subjected to pre-treatment for hydrophilizing the titanium surface and coated with rhBMP-2 and alendronate were used as the experimental group.

(29) As shown in FIG. 6, the removal torque was increased by about 23% in the experimental group compared to the negative control group, from which it was confirmed that the osseointegration at the implant-bone interface was increased by the use of the osteoclast activity inhibitor in combination with the osteogenic protein.

Example 5: Measurement of Osseointegration at Implant-Bone Interface for Long-Time Storage

(30) In order to confirm the long-time storage stabilities of implant, osseointegration at implant-bone interface were measured via removal torque.

(31) Each dental implant was coated with various bisphosphonates as described example 1 and its removal torque was measured just after coating step and 3-year self-storage, respectively.

(32) TABLE-US-00001 TABLE 1 Removal torque measurement results for coated implant with various bisphosphonates Storage Bare implant Implants coated with 10 ml solution of 40 g bisphosphonate Period Ctrl Alendronate Zolendronate Resendronate Pamindronate Ibandronate 0 year 82.4 10.2 100.2 8.4 104.4 11.1 103.5 9.3 99.6 7.9 98.4 12.1 3 year 81.8 8.6 99.4 11.8 103.8 8.9 83.2 9.3 84.1 11.4 85.4 12.5

(33) According to the results of table 1, implants coated with alendronate or zolendronate showed higher removal torque than other bisphosphonates and bare one (control).

(34) Similarly, osseointegration at implant-bone interface were measured via removal torque for dental implants wherein the osteoclast activity inhibitor coating film further comprises a bone growth factor (BMP-2) as shown in Table 2.

(35) TABLE-US-00002 TABLE 2 Removal torque measurement results for coated implant with various bisphosphonates and bone growth factor Storage Bare implant 1 g Implants coated with 10 ml solution of 40 g bisphosphonate and 1 g rhBMP-2 Period Ctrl rhBMP-2 Alendronate Zolendronate Resendronate Pamindronate Ibandronate 0 year 79.4 10.5 108.2 10.6 130.1 9.7 134.4 11.9 128.1 11.6 127.5 12.2 128.8 13.4 3 year 80.3 12.9 104.9 11.4 129.8 13.1 132.5 10.7 108.1 11.6 109.7 12.2 110.8 13.4

(36) As shown in Table 2, the implants coated with both rhBMP-2 and alendronate or zolendronate, showed higher removal torque value than other dental implants.

(37) The present discloser is not limited to the above-described specific embodiments and description, and it will be appreciated by those skilled in the art that changes may be made in these embodiments without departing from the principles and spirit of the discloser, the scope of which is defined in the appended claims and their equivalents.