KR20130117899A - Implant coated with nano titania by anodic oxidation and the method for coating thereof - Google Patents

Abstract

PURPOSE: An implant coated with nanotitania and a coating method thereof are provided to improve the adhesion of bone to the implant. CONSTITUTION: A method for coating an implant with nanotitania includes the following steps: immersing implants in an electrolyte which is formed by mixing acid and nanotitania powder with calcium acetate and beta-glycerol phosphate electrolyte; and forming a nanotitania coating on the surface of the implants by applying an electric current to the immersed implants. The implant includes a base formed with Ca-P and Ti oxide and nanotitania coating particles coated on the surface of the base through anodizing. [Reference numerals] (A) Matrix part; (AA) Surface shape; (B) Particle part; (BB) Content analysis result

Description

Implanted implants coated with nano titania by anodization and its coating method {IMPLANT COATED WITH NANO TITANIA BY ANODIC OXIDATION AND THE METHOD FOR COATING THEREOF}

The present invention relates to an implantable implant coated with nano titania by an anodizing method and a coating method thereof.

Dental implants (hereinafter referred to as implants) are implantable medical devices that reinforce the loss part when there is a tooth loss due to trauma or internal injury. In terms of functional and practical aspects, a method for minimizing adjacent tooth loss in dental restoration to be. Most intraosseous implant systems based on the osteointegration presented by Branemark and its researchers in the early 1980s are currently in use. Osteogenesis is based on direct bone fixation of the implant fixture. Important factors affecting bone adhesion include biocompatibility of the implant material, implant design or surface condition, bone condition of the surgical site, surgical technique, and loading conditions. Typically, the root implant has a mandible of 3 ?? 4 months, the maxilla is buried in the bone for 6 months to cause bone adhesion, and then the procedure to produce the upper prosthesis is common. Therefore, during the period of bone adhesion, patients suffer from the use of temporary dentures or temporary crowns, and sometimes have to undergo a second operation when repairing the final prosthesis. In addition, there is a disadvantage that discomfort and dissatisfaction for the patient for non-aesthetic reasons such as discoloration due to long-term use of the temporary tooth.

Implants have been developed with a focus on implant stability and ease of treatment, but it is difficult to expect stability without improving the ability to bond with the bone. Since the 1990s, many studies have been conducted to minimize the absorption of peri-implant bones while increasing the adhesion rate to the bones, and to improve the affinity and adhesion to the surrounding soft tissues. In order to improve bone adhesion, research on structures or materials having good affinity with bone, increasing surface area, and surface treatment research for changing the surface shape have been conducted. In general, titanium implants are first generation by simple processing, second generation such as calcium phosphate or HA coating, titanium plasma spray (TPS) coating, third generation with particle spray, acid treatment, and anodized surface treatment. This can be divided into 4th generation implants applied. In addition, there is a lot of interest and research on the method of directly coating a biomaterial (ceramic, bioactive polymer, protein) or a field using nanomaterial.

Titanium implant surface treatment, which is being carried out worldwide, is a trend that SLA, RBM, and anodization occupy a large market share. Anodic Oxidation, one of the surface treatment methods, is an electrochemical method that forms an oxide film on the surface of titanium. As a result, the overall rough surface including pores is formed to improve bonding to bone. Release can be suppressed. To date, TiO ₂ oxides have been formed by anodic oxidation with sulfuric acid, hydrogen peroxide and hydrochloric acid, phosphoric acid, or calcium-glycerol phosphate.

It is an object of the present invention to provide an implantable implant and a coating method of the implantable implant having improved bone adhesion of the implantable implant by coating nano titania.

The present invention provides an implantable implant in which nano titania is coated by anodic oxidation, comprising nano-titania coated particles coated on the entire surface of a matrix by a matrix formed of Ca-P and Ti oxides.

The present invention also provides an implantable implant in which nano titania is coated by anodizing by depositing 0.5 to 5 wt% of nano titania (TiO ₂ ) powder in an electrolyte solution.

In another embodiment of the present invention, the electrolytic solution provides an implantable implant coated with nano titania by anodizing, characterized in that 0.1 to 1.0 vol% of acid is mixed with Calcium Acetate and β-Glycerol Phosphate electrolyte. do.

In another aspect, the present invention is the first step of depositing the implant type implant in the electrolyte solution of 0.1 ~ 1.0 vol% acid, 0.5 ~ 5wt% nano titania (TiO ₂ ) powder mixed with Calcium Acetate and β-Glycerol Phosphate electrolyte And a second step of forming a nano-titania coating on the surface of the implanted implant by using the implanted implant deposited in the electrolyte as an anode and applying a power source to the surface of the implantable implant by anodic oxidation. It provides a method of coating.

The implantable implant coated with nano titania by the anodic oxidation method provided by the present invention and its coating method can form fine nano titania particles contained in an electrolyte on a matrix, thereby improving osteoadhesion of the implant. have.

In addition, the implantable implant coated with nano titania by the anodic oxidation method provided by the present invention and the coating method has the advantage that the particles attached to the surface of the base to improve the adhesion of the bone nano titania is not toxic to the human body.

1 and 2 are surface shape photographs of the control group 1 observed using a scanning electron microscope,
3 and 4 are photographs of the surface shape of an implantable implant specimen coated with nano titania by an anodization method according to an embodiment of the present invention observed using a scanning electron microscope,
Figure 5 shows the results of the EDS component analysis of the matrix tissue and the particle portion of the specimen of the implanted implant implanted with nano titania by an anodizing method according to an embodiment of the present invention,
Figure 6 shows the analysis (area mapping) of the major element distribution for the nano-titania-coated specimens according to an embodiment of the present invention,
7 is a graph showing the results of XRD analysis of the Example and the control,
8 is a diagram showing a spectrum according to XPS analysis to determine the chemical bonding state of the known surface component and the coating powder,
9 to 12 are graphs showing the results of finding the chemical species and the composition of the main elements by profile processing the detection results for each element obtained in the narrow scan mode for the major elements Ti, O, Ca, P,
FIG. 13 illustrates the surface shape of the specimens of nano-titania-coated implants and control specimens, which were immersed in SBF solution for 1 week and 2 weeks, respectively, and were observed by scanning electron microscopy, according to an embodiment of the present invention. Representation,
FIG. 14 is an SEM image of MG-63 osteoblast attachment after 3 days of attachment of a specimen and a control according to an embodiment of the present invention. FIG.
FIG. 15 is an SEM image of MG-63 osteoblast attachment after 7 days of attachment of a specimen and a control according to an embodiment of the present invention. FIG.
16 is a graph showing the results of observing the cell proliferation rate after attaching the specimen according to an embodiment of the present invention,
Figure 17 shows a slide photograph showing the histological results after the transplantation test of the control and the Example

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the drawings.

The implantable implant coated with nano titania by the anodic oxidation method according to the present invention coats nano titania on the surface of the Ti matrix by using the anodization method.

As electrolyte, 0.1 ~ 1.0 vol% of acid was added based on Calcium Acetate and β-Glycerol Phosphate, which is one of the biological materials and can produce Ca-P, which is a basic component of bone tissue. . In addition, 0.5 ~ 5wt% of nano titania (TiO ₂ ) powder was mixed. Thereafter, the implantable implant to be coated is connected to an electrically conductive holder, and then the implantable implant is placed in the electrolyte, and the power is supplied by using the platinum electrode as a cathode.

1 and 2 are surface shape photographs of a control group observed using a scanning electron microscope, and FIGS. 3 and 4 are nano titania coated coatings by an anodizing method according to an embodiment of the present invention observed using a scanning electron microscope. Surface shape photograph of a type implant specimen.

Control group

Control 1 shown in FIGS. 1 and 2 is a scanning electron micrograph of a titanium specimen sample subjected to anodization by a general anodization method. The electrolytes were anodized with Calcium Acetate and β-Glycerol Phosphate without the addition of acid or nano titania.

Example

The specimen of the implantable implant coated with nano titania by the anodic oxidation method shown in FIGS. 3 and 4 is based on Calcium Acetate and β-Glycerol Phosphate (0.4M Calcium Acetate + Alcium Acetate and β-Glycerol Phosphate were added to distilled water at a molar concentration of 0.04M beat-GP.), 0.5 vol% of acid, and 1.0 wt% of nano titania (TiO ₂ ) were added to the electrolyte. The platinum electrode was used as the cathode to anodize while 250 V power was applied thereto.

1 to 4, the control 1 shown in FIGS. 1 and 2, in which nano titania is not added to the electrolyte, shows a surface shape of a specimen in which an anodization treatment is generally known. In addition, in the case of the control 2 using distilled water as the electrolyte it can be seen that the coating of nano titania is not made well. On the other hand, looking at the specimen in which the anodic oxidation method according to the embodiment of the present invention shown in Figures 3 and 4, the material is estimated to be nano titania on the porous composite structure expected to be Ca-P, Ti oxide on the surface of cp-Ti Evenly distributed.

Figure 5 shows the results of the EDS component analysis of the matrix and the portion of the matrix portion of the specimen of the implanted implant implanted with nano titania by an anodization method according to an embodiment of the present invention. The matrix part was composed entirely of Ti, Ca, P, and O, and the particle part was composed of Ti, O.

FIG. 6 shows anare mapping of major element distributions for nano titania-coated specimens according to an embodiment of the present invention. As a result of mapping to Ti, Ca, P, and O elements, it can be confirmed that Ca, P, Ti, and O are uniformly distributed. From the results of the component analysis, the matrix structure (A) was formed with a complex of Ti oxide and Calcium phosphate compound, and the particle part (B) was identified as Ti oxide and titania. According to the component ratio observed in the matrix tissue, the ratio of Ca-P was about 1.83.

Phase identification of the experimental and control groups was performed using D-max Rint XRD (Rint 2400, Japan). As a result, both the control group and the experimental group observed both Ti (metallic) and Anatase (TiO ₂ ) peaks. 7 shows the results of XRD analysis. No phase associated with Calcium phosphate was observed.

XPS analysis was performed to determine the chemical bonding state of the known surface component and the coating powder. The analytical instrument used a Perkin-Elmer ESCA system (Φ 5800 ESCA system, USA). 8 shows the survey spectrum observed in the wide scan mode. Table 1 shows the concentration of each element detected on the survey spectrum. Both the control and the examples were present in the form of Ti oxide and Calcium Phosphate on the surface, and Ti oxide appeared as the main constituent material. In addition, the concentration of Ti oxide was higher in Examples than in the control.

C 1s O1s P 2p Ca 2p Ti 2p Control 18.79 50.18 9.25 7.66 14.12 Embodiment 18.55 54.95 3.12 6.39 16.99

9 to 12 are graphs showing the chemical species of the major elements and their configurations by profile processing the detection results for each element obtained in the narrow scan mode for the major elements Ti, O, Ca, and P.

In the case of O, it was composed of O ^{2 −} and OH ⁻ states, and a relatively large amount of O ^{2 −} was present. This means that the surface tissue is likely to be present as an oxide. There was no significant difference between the control and experimental groups.

In the case of Ti, the Ti ^{3 +} , Ti ^{4 +} state was mainly present. Compared with the previous analysis results for O, it appears that it is most likely to exist as Ti oxide state or CaTiO ₃ . In the experimental group, 4+ state Ti showed a relatively higher ratio than the control group.

In case of Ca, Ca, CaO was present. In the experimental group using P25, the ratio of CaO was higher than that of Ca. In the case of P, P 2p peak was observed and it was possible to exist in the form of Ca and compound.

After depositing the specimens of the Example and the control in the analogous fluid (SBF; Simulated Body Fluid), after a certain period of time, the specimens were taken and qualitatively compared the bioactivity through surface observation. As an example, a specimen coated with P25 as a nano titania powder was used. Table 2 shows the main components of the SBF solution used in the bioactivity experiment was used directly prepared.

SBF Solution Composition Medium Addition amount (g) (1ℓ) NaCl 7.996 NaHCO ₃ 0.35 KCl 0.224 K ₂ HPO ₄ · 3H ₂ O 0.174 MgCl ₂ · 6H ₂ O 0.305 1M-HCl 40 ml CaCl ₂  0.278 Na ₂ SO ₄ 0.071 NH ₂ C (CH ₂ OH) 3 6.057

FIG. 13 illustrates the surface shape of the specimens of nano-titania-coated implants and control specimens, which were immersed in SBF solution for 1 week and 2 weeks, respectively, and were observed by scanning electron microscopy, according to an embodiment of the present invention. It is shown. It can be seen that the Calcium Phosphate-based material is evenly distributed in the experimental group compared to the control group. Based on this, it was determined that nano titania is coated through anodic oxidation to induce relatively good bioactivity.

14 is an SEM image of MG-63 osteoblast attachment after 3 days of attachment of the specimen and the control according to an embodiment of the present invention, FIG. 15 is 7 days after attachment of the specimen and the control according to an embodiment of the present invention. SEM image of -63 osteoblast adhesion.

Bone  cell( Osteoblast cell Evaluation of adhesion of

Specimens and control specimens according to an embodiment of the present invention were each sterilized by EO gas and put into two wells of 24 in each group. 5 passages of MG-63 (KCLB No.21427) pseudo-osteoblasts were diluted in 1 × 10 ⁴ / ml concentrations in Dimethyl sulfoxide (DMEM, Welgene) containing 10% Fetal bovin serum (FBS, Gibco). 1 ml of the wells were dispensed and incubated for 3 days and 7 days in 37 ℃, 5% CO ₂ incubator (VS-9160C, Vison scientific).

At the end of each incubation, remove the specimen and wash it with Phosphate-buffered saline (PBS, Gibco), fix the cells soaked in Karnovy fixative (2% Glutaraldehyde, 2% paraformaldehyde, 0.5% CaCl ₂ ) for 12 hours. The excess primary fixative was washed with PBS. In order to protect the lipids and stabilize the sample, it was fixed with 1% OsO ₄ (osmium tetroxide) for 1 hour, and when OsO ₄ and alcohol were directly contacted, washed with PBS again for 10 minutes to prevent black staining from inside and outside of the sample. . After washing with water, the cells were dehydrated in order of low alcohol to anhydrous alcohol. After drying the critical point in CPD (Critical point dryer, HCP-2 Hitachi), the coating was made to 300 thickness using Ion coater (Eiko IB-3) to increase the conductivity of the sample and to emit a lot of secondary electrons. . After the coating, the cells attached to the specimens were observed by scanning electron microscopy (FE-SEM, S-800, Hitachi).

As a result of observing cell adhesion after 3 days and 7 days, no inhibition of cell adhesion or cell destruction was observed in the control and experimental groups, and osteoblasts were attached. After 7 days, the cell proliferation was active and showed the form of several layers. 14 and 15 show cell photographs of the degree of cell adhesion after 3 and 7 days of culture.

Bone  cell( Osteoblast cell ) Cells Growth rate

Specimen from each group were EO gas sterilized and placed in 8 wells in each group in 24 wells. 5 passages of MG-63 (KCLB No.21427) pseudo-osteoblasts were diluted in DMEM containing 10% FBS to a concentration of 1 × 10 ⁴ / ml, and 1 ml aliquots were added to the wells containing the specimens. Incubated for 3 days, 7 days in a% CO ₂ incubator.

At the end of each incubation, MTT (Methylthiazol tetrazolium bromide, Sigma-Aldrich) was dissolved in PBS solution at 5 mg / ml, and the solution was dispensed on the specimen on which cells were loaded by 0.2 ml. After incubation in a CO ₂ incubator for 4 hours, the specimens were transferred to a new 24-well, and 1 ml of Dimethyl sulfoxide (DMSO, Amresco) was added to each well. After 30 minutes in a CO ₂ incubator was taken out and shaken for 5 minutes with a stirrer so that no crystals remain. The reacted 1 ml solution was transferred to 96-well by dividing 0.2 ml 4 times per specimen. Cell proliferation was evaluated by measuring the absorbance (OD) at 570 nm wavelength using an ELISA reader (Benchmark plus, BiO-RAD).

 The expression related to the cell proliferation rate used in this experiment is as follows.

16 is a graph showing the cell proliferation rate of the control and the Example.

As a result of observing cell proliferation after 3 days and 7 days, no toxicity was observed in both the control and the examples, and no significant difference was observed between the control and the examples.

Transplant test

Implant tests according to ISO 10993-6 were conducted at the Dental Materials Testing and Development Center, Kyung Hee University. Experimental configuration was carried out divided into a control (MAO treatment) and Example (Nano Titania P25 treatment). The test animals used four albino rabbits, and each of the transplant test sites used rabbit tibia. In order to determine whether the initial bone fusion was observed for 4 weeks after transplantation, the histological results were examined.

 Figure 17 shows a slide photograph showing the histological results after the progress of the transplantation test of the control and the Example. The transplantation test showed no inflammation or foreign body reaction in histopathological evaluation of the biological response, and the tissue and initial bone fusion for the test sample were suitable. In particular, the experimental group was found to have faster initial bone adhesion than the control group.

Claims (4)

A base formed of Ca-P and Ti oxides; And
An implantable implant coated with nano titania by anodizing, comprising: nano titania coated particles coated on the entire surface of the substrate by anodizing. An implantable implant in which nanotitania is coated by anodizing by depositing 0.5 to 5 wt% of nano titania (TiO ₂ ) powder in an electrolyte solution. 3. The method of claim 2,
Electrolyte is an implant type implant coated with nano titania by anodic oxidation method characterized in that 0.1 to 1.0 vol% acid mixed with Calcium Acetate and β-Glycerol Phosphate electrolyte. Immersing the implantable implant in an electrolyte solution in which 0.1 to 1.0 vol% of acid and 0.5 to 5 wt% of nano titania (TiO ₂ ) powder are mixed with Calcium Acetate and β-Glycerol Phosphate electrolyte; And
A second step of forming a nano-titania coating on the surface of the implanted implant by applying the power to the implanted implant deposited in the electrolyte as an anode and applying nano-titania to the surface of the implantable implant; How to coat.

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