KR20130109851A - Kit composed of ti dental implant and growth factors - Google Patents

Abstract

PURPOSE: An implant kit comprised of titanium implant and growth factors can drastically improve the synostotic properties of titanium implant. CONSTITUTION: A kit for implant does not coat growth factors on Ti implant (32), comprises ample which has growth factors as a main source other than Ti implant, and growth factors are liquidized. Growth factors are selected from BMPs comprising BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP-12 or are one or more selected from a group comprising TGF- β super group which is protein such as the fibr oblast growth factor and GDF, a platelet-derived growth factor, and an insulin-like growth factor, an epidermal growth factor and a transforming growth factor, and a keratinocyte growth factor 2 (KGF2).

Description

[0001] The present invention relates to an implant kit comprising a titanium implant and a growth factor,

The present invention is directed to an implant kit comprising a titanium implant and a growth factor. According to the present invention, osseointegration of a titanium implant can be remarkably improved.

In J. Vlacic-Zischke et al. (Biomaterials 32 2011 / 665-671), the surface of the implant is roughened by sand blasting and corroded with acid to form microprojections, which are then washed with sodium hydroxide and placed in the bone tissue. Type 2 secretion is accelerated and the duration of osseointegration is shortened, and the effect on osseointegration of osteogenic proteins is very important.

Anodic oxidized surface-treated implants were coated with bone morphogenetic protein type 2 and placed in a dense mandible of dogs. As a result, vertical bone augmentation effect and implant And that the osteogenic protein concentration was better at 1.5 mg / ml than at 0.75 mg / ml.

In an anodized surface-treated implant, the bone-forming protein type 2 was coated on the anodized surface, and the bone marrow-abundant bone was removed from the alveolar bone, resulting in 0.75 mg / ml and 1.5 mg / ml osteogenic protein concentration were effective for vertical bone regeneration.

In the above two articles, the effective concentration of osteogenic protein is 0.75 ~ 1.5mg / ml.

In addition, US Pat. No. 7,797,092 B2, invented by the present inventor, describes that the surface of the implant is roughened and the osteogenic protein type 2 is applied and lyophilized.

In these experiments, bone marrow tissue regeneration was observed in the medullary bone and vertical bone tissue growth was observed. By using these properties, osteogenic proteins can be applied to the bone in the region where the bone graft is composed.

Growth factors such as BMP-2 differentiate mesenchymal stem cells required for healing into various tissues by chemically moving them to the defect site. In patent WO 1993/000050, BMP-2 claimed to grow mesenchymal stem cells into bone tissue. In this patent, BMP-2 growth factor was not coated on titanium implants and lyophilized BMP- And implanted into titanium implants to promote osseointegration.

US Pat. No. 7,779,092 B2, invented by the present inventors, has been used by roughening the surface of an implant and applying osteogenic protein type 2 and lyophilization.

In these implants, bone marrow tissues were regenerated in the bone grains and vertical bone growth was observed. By using these properties, osteogenic proteins can be applied to the bone in the region where the bone graft is composed. However, this method has a disadvantage that the manufacture of the implant is very complicated and the manufacturing cost is high.

According to the manufacturing method,

i) a pretreatment step (implant surface machining step) for machining the surface of the implant;

ii) adding 4 mg of recombinant osteogenic protein to 1 ml of the acidic buffer solution separately to prepare a solution of a recombinant osteogenesis promoting protein (preparation step of BMP urine solution);

iii) 60 .mu.l of the BMP solution prepared in step ii) is put into a polypropylene tube of 0.1 ml capacity, and then the micropores are formed on the surface in step ii) (immersion step);

iv) a 0.5 ml polypropylene tube immersed with the implant is placed in a 1.5 ml polypropylene, sealed, and then frozen in a freezing chamber of minus 75 ± 0.5 for 3 to 4 hours (primary refrigeration step);

v) The lid of the frozen 1.5ml polypropylene tube was opened in a freezer, and the lid was opened in a freeze dryer pre-cooled to minus 75 ± 5 ° C and freeze-dried for 8 hours (secondary freeze-drying step) Applying a protein to the surface of the implant; And

vi) Dental implants were prepared by freeze-drying, packaging in an aseptic environment, and storage (storage) at room temperature or in a freezer under dehumidification, to which a recombinant osteogenesis promoting protein was applied.

Therefore, the manufacturing method is very complicated, and not only the manufacturing cost is high, but also care has to be taken for the storage thereof.

The present inventor has long been engaged in researches and clinical studies, and has found that, without using a coated implant in which a growth factor such as an osteogenic protein is previously applied to an implant and lyophilized, the growth factor is lyophilized and stored, The present inventors completed the present invention based on the conclusion that they have vascular regeneration and osteoblast proliferation effects necessary for healing of bone tissue even when they are applied to the surface of an implant. The titanium implant according to the present invention and the kit comprising the growth factor can be applied together with the implants that have been surface treated by various designs and various methods. In addition, when there is a defect in the bone tissue at the implantation site, titanium implant materials, The kit may further comprise a kit consisting of a growth factor and a shielding film and / or a scaffold.

Ti implants can be used successfully for osseointegration, as well as for normal osseous bone as well as for osseointegrated bone, using a kit in which an ample freeze-dried growth factor is added to a Ti implant ampoule for osseointegration of a Ti implant, If the bone defect is present, the Ti implant can be supported by the new volume bone with the normal volume using a kit comprising a bone graft material or a shielding film. Therefore, there is an effect of drastically improving side effects such as delay and failure of osseointegration in Ti implant placement.

1a. Ti implants (12) coated with pre-coated bone morphogenetic protein 2 and test group 2 coated with Ti implants (11) immediately prior to implantation and Ti implants without osteogenic protein 2 (13) To the tibia of a rabbit.
1b. Electron micrographs of the bone morphogenetic protein 2 coated on the Ti implant surface of the flame anodizing method,
1C. Tissue microscopic photographs of Ti implants without bone morphogenetic protein 2,
1d. Tissue microscopic photographs of the test group coated with Ti implants immediately before implantation of bone morphogenetic protein 2,
1E. Tissue micrographs of Ti implants with freeze-dried coating of bone morphogenic protein 2 on Ti implants,
2a. After quantification and purification of rhBMP-2, SDS-PAGE analysis revealed that U is non-reducing rhBMP-2, R is reduced rhBMP-2, Dimer is dimer fraction, Monomer is monomer fraction,
2b. A graph showing that pure rhBMP-2 was purified in the HPLC profile,
2c. As a result of an experiment in which the rhBMP-2 dimer was introduced into C2B12 cells, which is a myoblast cell, the alkaline phosphatase was secreted in a concentration-dependent manner for 3 days,
2d. Cells showing changes in osteoblastic morphology after administration of rhBMP-2 to muscle cells, C2C12 cells,
Figure 3. Kit consisting of Ti implant ampoule and growth factor ampoule,
Figure 4 Kit consisting of Ti implant and growth factor ampoule and bone graft ampoule,
Figure 5. Kit consisting of ampule and Ti implants filled with bone graft protein 2,
FIG. 6. Kit consisting of bone graft material ampoule and Ti implant coated with osteogenic protein 2 type,
Figure 7. Gel-type bone graft material and osteogenic protein stored in main machine. Kit consisting of ampoules and Ti implants of type 2,
Figure 8. Kit consisting of Polytetrafluoroethylen shielding membrane and growth factor ampoule and Ti implant ampoule,
Figure 9. Kit consisting of tea leaf and bone graft ampoule, growth factor ampoule and Ti implant ampoule.

In the present invention, a growth factor is applied to a Ti implant coated with any surface microstructure or a bone-active material, and the growth factor is separately supplied to an ampule while being freeze-dried without being coated on the Ti implant, I want to configure it as a configured kit. Ti implants coated with a solution of osteogenic protein 2 on a surface treated Ti implants with flame anodic oxidation and lyophilized were coated with a kit consisting of Ti implants and osteogenic protein 2 type ampoules, 2 type was solubilized and applied to the surface of the Ti implant. Through this test, it was found that bone fusion can be promoted by increasing the activity of osteoblast of bone tissue without coating Ti implant beforehand. When the Ti implant and the growth factor are respectively packaged in an ampule, the growth factor alone can be stored in the ampoule, thereby preventing the problem of coating the Ti implant. In other words, contamination or bacterial infection during the coating of growth factors on Ti implants can be completely blocked. It can also be combined with any surface and design Ti implants to facilitate accessibility.

Growth factors include BMPs selected from BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP- TGF-beta superfamily, a protein such as fibroblast growth factor or GDF, a platelet-derived growth factor, an insulin-like growth factor, an insulin-like growth factor, An epithelial growth factor and a translational growth factor, a keratinocyte growth factor 2 (KGF2), and a MP52 protein and a gene recombinant protein of the growth factors. do. In Example 1, the bone morphogenetic protein type 2 was prepared by a recombinant method and identified and confirmed by a cell test. The concentration of osteogenic protein type 2 is 0.1-1.5 mg / ml and the dosage is in the range of 0.01 cc to 3 cc.

In addition to Ti implants and growth factors, PCL, PLA, PLGA, PGA synthetic absorbent polymers; Natural absorbent polymers of alginic acid, chitosan, collagen, hyaluronic acid, cellulose and mixtures thereof; poly (ethylene terephthalate), poly (butylene terephthalate), poly (methyl methacrylate), poly (hydroxyethyl methacrylate), poly (N- poly (lactic acid), poly (ethylene oxide), poly (lactide-co-glycolides), poly (s-caprolactone), polyanhydrides, polyphenols, polyphosphazenes, synthetic polymers of ortho-esters and polyimides, and synthetic bone, allografts, heterogeneous bone, and synthetic bone composed of autogenous teeth, allogeneic teeth, It is a prerequisite for the fusion of the Ti implants that the space lacking in the bone tissue at the site of implantation is filled with bone graft material and the new bone tissue is inserted into the Ti implant In Example 2, a kit composed of a Ti implant, a synthetic bone ampoule composed of calcium triphosphate salt and calcium hydroxyapatite, and a bone morphogenetic protein type 2 ampoule was constructed. In Example 3, Is implanted in bone graft material and one ampoule to construct a Ti implant and kit, or a Ti implant and kit with a growth factor coated on the bone graft material.

Bone graft materials include PCL, PLA, PLGA, PGA synthetic absorbable polymeric materials; The gel-like bone graft material prepared by mixing the solution of the natural absorbable polymer material of alginic acid, chitosan, collagen, hyaluronic acid, cellulose and the mixture of the natural absorbable polymer material with the powder of the bone graft material can be constructed as a syringe container instead of an ampoule. A syringe container containing a gel - like bone graft composed of a cellulose solution and calcium phosphate phosphate powder was prepared.

In addition to Ti implants and growth factors, PCL, PLA, PLGA, PGA synthetic absorbent polymers; Natural absorbent polymeric material of alginic acid, chitosan, collagen, hyaluronic acid, cellulose, or a mixture thereof; poly (ethylene terephthalate), poly (butylene terephthalate), poly (methyl methacrylate), poly (hydroxyethyl methacrylate), poly (N- poly (lactic acid), poly (ethylene oxide), poly (lactide-co-glycolides), poly (s-caprolactone), polyanhydrides, shielding membranes selected from the group consisting of polyphosphazenes, poly (synthetic polymers of ortho-esters or polyimides, and metal thin films of titanium and stainless steel) can be further comprised of kits comprising growth factor ampoules and implant ampoules, And growth factors can constitute Ti implants and kits.This is because the implantation of bacteria and the cells other than the bone tissue do not grow on the interface between the Ti implants and the bone tissue during the fusion process of the Ti implants In addition, in Example 7, a calcium phosphate synthetic bone and an osteogenic protein type 2 growth factor were co-cultured in the same manner as in Example 7. In addition, A kit consisting of stored ampoules, Ti implant ampoules and polytetrafluoroethylen sheets was constructed.

Test Example 1

Observation of the osseointegration effect of the Ti implant of the present invention and the kit composed of the BMP-2 lyophilized ampoule through the rabbit tibial transplantation experiment:

1. Animal test method:

In a male rabbit, a test group (11) implanted with a bone morphogenetic protein type 2 (concentration 0.025 mg / ml rhBMP-2) solution was applied to a Ti implant immediately before implantation of a Ti implant, (12) and control group (13) with only Ti implants without osteogenic proteins were histologically compared with those of the control group (13). Fig. 1B is an electron micrograph of the surface of a lyophilized implant coated with a Ti-type implant 2, and Fig. 14 is a lyophilized osteogenic protein 2 type.

2. Experimental Results:

In histological comparison, the 8-week healing result of the 8-week healing result of the control group of the Ti-coated osteogenic protein 2-type implants and the 8-week healing result of the test group implanted with the bone implantation protein- In the histological photographs (Fig. 1e), a new bone was formed above the implant and in the bone marrow for the test group (Fig. 1c) without using the bone morphogenetic protein type 2. The contact between the two groups of Ti implants and bone tissue There was no significant difference in area value.

Therefore, there is no difference in efficiency even when using a kit consisting of a lyophilized ampoule of osteogenic protein type 2 and a Ti implant storage ampoule separately to be coated immediately prior to implanting the Ti implant without pre-coating the osteogenic protein 2 type on the Ti implants.

Example 1

This example illustrates a method for producing BMP-2 (rhBMP-2) by a recombinant DNA technique, which is a known method. Other growth factors used in the present invention are all known, and these known growth factors are used in the present invention.

1. Production of rhBMP-2:

1) Cloning of Human BMP-2 gene:

To obtain human BMP-2 gene, total cellular RNA was extracted from U2OS cells using Trizol (Gibco BRL, NY, USA) solution and reverse transcription reaction was performed. Polymerase chain reaction (PCR) was performed using 5'-AATTTACAGCTTCTAGCGACACCCACAACCCT-3 '. PCR products were isolated and inserted into pGEM-T vector (Promega, USA) and cloned using E. coli (DH5a) cells.

2) High-density cell culture:

The fermentation tank (KoBioTec, Incheon, Korea) was used for the cultivation at a high density using the method of Fatemeh et al. Liposomes were prepared by adding sterilized nutrient media (Glucose 33.3 g / L, peptone 10 g / L, yeastextract 5 g / L, MgSO4 1 g / L, CaCl2 0.048 g / L, ZnSO40.0176 g / L, CuSO4 0.008 g / Lt; / RTI > for 24 hours.

3) Protein purification:

The suspension was stored at -80 ° C deep freezer (Nihon Freezer, Japan). The frozen suspension was thawed at the refrigeration temperature, and the cells were disrupted by pressurization, followed by centrifugation at 5,500 xg at 4 ° C for 45 minutes. When the mature rhBMP-2 that has undergone the re-denaturation has the original tertiary structure, the N-terminus has a heparin-binding site.

2. Biochemical properties of purified rhBMP-2:

1) Purity and identification test of rhBMP-2 stock solution: SDS-PAGE:

As a result of the test, the rhBMP-2 stock solution showed the same migration distance as the standard solution and showed a purity of 95% or more (FIG.

2) HPLC (High performance Liquid Chromatography) analysis:

Purified rhBMP-2 dimer was dissolved in 0.1% TFA (Trifluoroacetic acid) at a concentration of 1 ug / μl and the protein in each fraction was detected on a C4 reversed-phase HPLC column (4.6 mm × 50 mm, 300 Å 5 umparticle size; Gracevydac, Respectively. Test results of the rhBMP-2 stock solution showed the same holding time as the standard solution, and the rhBMP-2 stock solution should exhibit the same holding time as the standard solution, and the test result was appropriate (FIG. 2B).

3. Production and purification of rhBMP-2 protein:

And then subjected to affinity chromatography on a heparin column. As a result, as shown in FIG. 1A, most monomers and a small amount of dimer were eluted from the 0.3M NaCl fraction and the dimers eluted from the 0.5M NaCl fraction. Purified rhBMP-2 monomers and monomers were identified by DS-PAGE analysis. The molecular weight of the monomer was about 14 kDa, and the dimer had the same size band as the monomer in the non - reducing condition because the two monomers were connected by the disulfide bond. The size of the dimer was about 28 kDa.

4. In vitro test of purified rhBMP-2:

As a result of observing rhBMP-2 in myoblasts, after 3 days of culture, alkaline phosphatase, which is a typical protein of osteoblast, was secreted (Fig. 2c), and the morphology of the cells was transformed into osteoblasts in microscopic findings (Fig. 2d). Therefore, rhBMP-2 confirmed its function as an osteogenic protein.

Example 2

A kit consisting of an implant and an osteogenic protein type 2 ampoule.

The osteogenic protein 2 is injected into the ampule at a concentration of 1 cc at a concentration of 1.5 mg / ml prepared in Example 1, and is lyophilized and sealed in a freeze dryer under the conditions shown in Table 1 below. This osteogenic protein type 2 ampule 31 is composed of a kit with a Ti implant 32 (Fig. 3).

Temperature() -30 -20 -10 Time (hours) 3 One One

Example 3

Ti bone calcium phosphate synthetic bone composed of Ti implant and calcium phosphate synthetic bone ampoule and osteogenic protein type 2 ampoule was manufactured as follows. A tricalcium phosphate-based slurry was prepared by adding a tricalcium phosphate-based powder and a gelatin solution to a mixer having a blade and stirred, and the tricalcium phosphate-based powder was added to the tricalcium phosphate-based slurry while rotating the mixer having the above- And the size of the tricalcium phosphate-based granules is controlled by adding or adding the tricalcium phosphate-based powder. The tricalcium phosphate-based granules and the tricalcium phosphate-based powders which did not form granules were separated by using a sieve, and the separated tricalcium phosphate-based granules were dried. The dried tricalcium phosphate-based granules were dried at a temperature of 600 to 1000 ° C To remove the gelatin and to form pores in the tricalcium phosphate-based granules. Place this in a 1 cc volume ampoule and seal it through the instrument. The osteogenic protein 2 is injected into the ampule at a concentration of 1 cc at a concentration of 1.5 mg / ml prepared in Example 1, and the mixture is lyophilized and sealed in the freeze dryer under the conditions shown in Table 1. A kit composed of a bone graft material ampoule 41, a bone morphogenetic protein type 2 ampule 42 and a Ti implant 43 is constructed.

Example 4

Kit consisting of ampoule and Ti implants with growth factor encapsulated with bone graft material:

The bone graft material of tricalcium phosphate granules is prepared as described in Example 2 and the osteogenic protein type 2 is prepared as described in Example 1. [ 1.5 mg / ml Concentration 1 cc After lyophilization of osteogenic protein form 2 in an ampoule as shown in Table 1, 1 cc tricalcium phosphate-based granules are sealed in an ampoule. The osteogenic protein type 2 53 is composed of an ampoule 500 stored together with the bone graft material 52 and a kit composed of a 4 mm wide 10 mm Ti implant 51.

Example 5.

A kit consisting of ampoules and Ti implants stored with growth factors coated on bone grafts:

The bone graft material of tricalcium phosphate granules is prepared as described in Example 2 and the osteogenic protein type 2 is prepared as described in Example 1. [ The osteogenic protein type 2 1.5 mg / ml stock solution is injected into 1 cc ampoule, and the tricalcium phosphate-based granules are placed in the ampoule, lyophilized under the conditions of Table 1, and sealed. The bone morphogenetic protein 2 is composed of an ampoule 62 coated with the bone graft material and a kit composed of a 4 mm wide and 10 mm long Ti implant 61.

Example 6.

Gel-like bone graft material consisting of cellulose solution and calcium phosphate synthetic powder bone Syringe container and osteogenesis kit consisting of protein type 2 Ampol and Ti implant:

The syringe container 73, in which a 1 to 20% solution of cellulose was impregnated with a 0.5 cc calcium phosphate synthetic powder bone, was lyophilized as shown in Table 1, and a 0.5 cc osteogenic protein type 2 ampule 72 and a Ti implant 71 .

Example 7.

Kit consisting of shielding membrane of Polytetrafluoroethlylen sheet and Ti implant ampoule and osteogenic protein type 2 ampoule:

A shielding film 83 having a thickness of 0.1 mm to 0.3 mm and a thickness of 10 mm x 20 mm is composed of a kit consisting of a 0.25 mg osteogenic protein type 2 ampoule 81 and a 4 mm wide 10 mm Ti implant 82 in a thickness of 0.1 mm to 0.3 mm Polytetrafluoroethlylen sheet.

Example 8.

Kits composed of ampoules and Ti implants and polytetrafluoroethylen sheets stored with osteogenic protein type 2 growth factor calcium phosphate synthetic bone:

A 0.25 mg osteogenic protein 2 type lyophilized ampoule 92, 0.5 cc calcium phosphate synthetic bone ampoule 91, a 4 mm diameter 10 mm Ti implanted ampoule 93 and a 0.1 to 0.3 mm thick Polytetrafluoroethlylen sheet And a shielding film 94 cut to a size of 10 mm x 20 mm.

11 ............ Ti implant implanted with bone formation protein type 2 immediately before implantation,
12 ............ Ti implant implanted with lyophilized osteogenic protein 2 on the implant surface,
13 ............ Ti implants without bone formation protein type 2,
14 .............. Freeze-dried bone-forming protein 2 coated on the Ti implant surface,
31 ............ Osteogenic protein type 2 ampoule,
32 ............ Ti implants,
41 ............. bone graft material ampoule,
42 ............. osteogenic protein type 2 ampoule,
43 ............ Ti implant,
500 ............. The bone formation protein type 2 is an ampoule enclosed with bone graft material,
51 ............ Ti implant,
52 ............. bone graft material,
53 ............. osteogenic protein type 2 ampoule,
61 ............ Ti implants,
62 ............. bone graft protein 2 type coated bone graft material ampoule,
71 ............ Ti implants,
72 ............. osteogenic protein type 2 ampoule,
73 .............. Gelled bone graft material stored in the main machine,
81 ............. osteogenic protein type 2 ampoule,
82 ............ Ti implants,
83 ............ Polytetrafluoroethylen shielding film,
91 ............. bone graft material ampoule,
92 ............. osteogenic protein type 2 ampoule,
93 ............ Ti implants,
94 ............. Polytetrafluoroethylen shielding film.

Claims (6)

A Ti implant kit comprising a growth factor in addition to the Ti implant and coating the growth factor on the Ti implant to apply the solution to the growth factor immediately before the Ti implant is placed.
The growth factor according to claim 1, wherein the growth factors are BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP-12 and BMP- BMPs selected from 13, co-duplexes of amino acids constituting them (conjugates made by twisting amino acids of B2 and amino acids of B4), fibroblast growth factor or protein such as GDF, TGF-β super group, platelet-derived growth factor, One or more implant kits selected from the group consisting of insulin-like growth factor, epidermal growth factor and transformative growth factor, keratinocyte growth factor 2 (KGF2) and MP52 protein and recombinant protein of said growth factor .
The method of claim 1, 2, PCL, PLA, PLGA, PGA synthetic absorbent polymer in addition to the Ti implant; Natural absorbent polymers of alginic acid, chitosan, collagen, hyaluronic acid and cellulose and mixtures thereof; poly (vinylidene fluoride), poly (tetrafluoroethylene), poly (vinyl alcohol), poly (hydroxyalkanoate), poly (ethylene terephthalate), poly (butylene terephthalate), poly (methyl methacrylate), poly (hydroxyethyl methacrylate), poly (N- isopropylacrylamide), poly (dimethyl siloxane), polydioxanone, and polypyrrole, poly (glycolic acid), poly (lactic acids), poly (ethylene oxides), poly (lactide-co-glycolides), poly (s-caprolactone), polyanhydrides, A kit for Ti implant further comprising polyphosphazenes, poly (ortho-esters and polyimides) synthetic polymers; and synthetic bones, allogeneic bone, xenograft, demineralized bone and calcium phosphate.
[4] The kit for a Ti implant according to claim 3, wherein the combination of the growth factor and the bone graft material is composed of a lyophilized vial and a bone graft vial, or a combination of growth factors and bone graft material.
The kit for a Ti implant according to claim 4, wherein the bone graft material is contained in a gel-like scaffold, filled in a syringe or vial, freeze-dried, and stored in a vial or a syringe.
The method according to claim 5, PCL, PLA, PLGA, PGA synthetic absorbent polymer in addition to the implant and growth factor; Natural absorbent polymers of alginic acid, chitosan, collagen, hyaluronic acid, cellulose, or mixtures thereof; poly (vinylidene fluoride), poly (tetrafluoroethylene), poly (vinyl alcohol), poly (hydroxyalkanoate), poly (ethylene terephthalate), poly (butylene terephthalate), poly (methyl methacrylate), poly (hydroxyethyl methacrylate), poly (N- isopropylacrylamide), poly (dimethyl siloxane), polydioxanone, and polypyrrole, poly (glycolic acid), poly (lactic acids), poly (ethylene oxides), poly (lactide-co-glycolides), poly (s-caprolactone), polyanhydrides, A kit for Ti implants further comprising a shielding film selected from the group consisting of polyphosphazenes, poly (ortho-esters or polyimides), and metal thin films of titanium and stainless steel, or further configured with bone graft material.

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