Dry storage method for strontium-doped pure titanium implant

Abstract

The invention discloses a dry storage method for a strontium-doped pure titanium implant. The method is particularly suitable for the strontium-doped pure titanium implant stored for a long time, so that the super-hydrophilicity of the implant is maintained, and hydrocarbon pollutant pollution in air is prevented. The method comprises the following steps: soaking a freshly prepared strontium-doped pure titanium implant in a mixed solution of 0.1 mol / L potassium chloride and 0.1 mol / L strontium chloride for 12 hours, and then air-drying the implant in a super clean bench for 2 hours to form a salt layer protection layer, so that surface active sites are prevented from being exposed in air to gradually lose hydrophilicity, and meanwhile, the problem that strontium ions are released too early due to wet storage is avoided. The protective layer may have the potential of hydrophilic protection for 3-5 years, the implant is flushed and removed by normal saline before an implantation operation so as to ensure the biological safety of the material, and the stored super-hydrophilic surface can accelerate the osseointegration performance of the material, optimize the implantation effect of the material and shorten the waiting time of a patient from the implantation operation to final tooth wearing.

Description

Technical Field

[0001] The present invention relates to a dry storage method for superhydrophilicity of a strontium-doped pure titanium implant surface. Background Art

[0002] Currently, the strontium-doped pure titanium implant prepared according to the invention patent (ZL201410269386.6) has good superhydrophilicity and strontium ion slow-release ability. The former helps to accelerate the adhesion of proteins and cells on the material surface after implantation, and the latter helps to promote osteogenic differentiation and inhibit osteoclastic differentiation. Both can ultimately accelerate the bone integration performance of the material, shorten the waiting time of the patient from implant surgery to final tooth wearing, improve the clinical efficacy of the implant, and is especially suitable for implant surgeries for diabetic, osteoporosis, and elderly patients. However, there is a long storage period from the processing and preparation of the implant to the final surgery. Although it can be vacuum packaged during storage, there will still be a certain amount of air leakage during long-term storage, which causes the implant surface to be contaminated by hydrocarbon pollutants in the air. By occupying the active sites on the implant surface, the high surface energy drops to low surface energy, resulting in a decrease in surface hydrophilicity and further affecting the bone bonding ability. Taking the implant of the clinically commonly used Straumann ® system as an example, its large-grit sandblasted and acid-etched (SLA) surface is stored by vacuum packaging. However, when the hydrophilicity test is performed on the stored surface, the surface contact angle is still as high as 127°, showing obvious hydrophobicity. Although the existing wet storage method can reduce surface contamination by soaking in physiological saline to further isolate air, such as the SLActive brand implant of the Straumann ® system, the wet storage itself is not suitable for the surface of the strontium-doped pure titanium implant because the strontium ions on the material surface will continuously be released into the storage solution during wet storage, resulting in loss during clinical application and unable to perform the designed function of promoting osteogenesis by strontium element. Therefore, a storage method that can maintain the superhydrophilicity of the implant during long-term storage and avoid premature loss of strontium ions is needed. Summary of the Invention

[0003] In order to overcome the compatibility problem that the existing wet storage technology cannot maintain the hydrophilicity and strontium ion slow-release ability on the surface of the strontium-doped pure titanium implant at the same time, the present invention provides a dry storage method for the strontium-doped pure titanium implant. This method forms a stable salt protection layer on the material surface through short-time soaking in a specific salt solution and natural air drying, thereby maintaining the superhydrophilicity and strontium ion slow-release ability of the implant at the same time.

[0004] The technical solution adopted by the present invention to solve its technical problems is: A dry storage method for a strontium-doped pure titanium implant, 1) Freshly prepare a strontium-doped pure titanium implant; 2) Immerse the implant processed according to step 1) in a mixed solution of 0.1 mol / L potassium chloride and 0.1 mol / L strontium chloride for 12 hours; 3) After taking it out, air-dry it in a laminar flow cabinet for 2 hours to form a uniform salt layer protection on the surface of the implant, and then place it in vacuum packaging for long-term storage.

[0005] For step 1), prepare a strontium-doped pure titanium implant: Use 250 - 500 μm green silicon carbide (SiC) particles to sandblast the surface of pure titanium under the parameters of 0.2 MPa, 10 mm distance, and 20 s duration. Then, use hydrofluoric acid, nitric acid, hydrochloric acid, and sulfuric acid for acid etching to obtain a large particle sandblasted and acid-etched surface. Ultrasonically clean it in acetone, 75% ethanol, and double-distilled water for 15 min respectively and dry it with nitrogen. On this basis, conduct a hydrothermal reaction by soaking it in 0.02 mol / L strontium hydroxide octahydrate at 220 °C for 12 h to prepare a fresh strontium-doped pure titanium implant.

[0006] In the method described above, the superhydrophilicity of the implant can still be maintained during the 12-month storage, with a contact angle < 5°. At the same time, before the surgical implantation of the implant, the surface salt layer is fully dissolved and removed by flushing with normal saline to ensure the biological safety after implantation.

[0007] The beneficial effects of the present invention are as follows It can maintain the hydrophilicity of the surface of the strontium-doped pure titanium implant during the storage period, while minimizing the reduction of the strontium ion concentration on the material surface. At the same time, before clinical application, the surface salt layer is fully removed by simply flushing and dissolving with normal saline to ensure biological safety, which is simple and easy to operate. Description of the Drawings

[0008] Figure 1 It is a schematic diagram of the molecular mechanism of the present invention (including the left, middle, and right parts).

[0009] Figure 2 It is a schematic diagram of the process flow of the present invention (including steps A to G).

[0010] Figure 3 It is a scanning electron microscope result diagram of the surface before and after dry storage and saline cleaning and the surface of the freshly prepared strontium-doped pure titanium implant (including parts A, B, and C).

[0011] Figure 4 It is an X-ray photoelectron spectroscopy diagram of the surface before and after dry storage and saline cleaning (including parts A and B).

[0012] Figure 5It is a graph showing the strontium ion release concentration results of dry storage, wet storage for 3 months, and freshly prepared strontium-doped pure titanium implants. Ion concentration tests were performed at 1, 3, 7, 14, and 21 days after soaking respectively.

[0013] Figure 6 It is a graph showing the hydrophilicity test results of dry storage, sealed storage only, and freshly prepared strontium-doped pure titanium implants.

[0014] In the figure: 1. Oxygen atom, 2. Titanium atom, 3. Strontium atom, 4. Salt layer formed by the mixture of strontium chloride and potassium chloride. Detailed implementation manners

[0015] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0016] In Figure 1 the left part is strontium titanate crystals on the surface of the strontium-doped implant with the crystal structure shown. The titanium atoms and oxygen atoms on the material surface have unsaturated bonds, thus having high surface energy and being prone to adsorbing external substances; Figure 1 In the middle part, potassium ions, strontium ions, and chloride ions in the soaking solution are easily attracted by this high surface energy. Their appropriate concentrations of 0.1 mol / L each enable them to form a thin salt layer on the surface under natural air drying for 2 h ( Figure 1 right part), and uniformly cover the surface through microscopic mechanical interlocking with this surface having micro-roughness.

[0017] In Figure 2Among them, first, according to the national invention patent (ZL201410269386.6), a hydrothermal reaction of soaking in 0.02 mol / L strontium hydroxide octahydrate at 220 °C for 12 h was carried out on the basis of the surface of large-particle sandblasting and acid etching (A) to prepare a strontium-doped pure titanium implant (B). On this basis, it was soaked in a mixed solution of 0.1 mol / L potassium chloride and 0.1 mol / L strontium chloride for 12 h and naturally air-dried for 2 h to form a uniform salt layer (C-D). Among them, strontium ions inhibit the release of strontium ions on the material surface into the solution during the 12-h soaking according to the common ion effect; potassium ions are more likely to be adsorbed on the material surface in the solution and form a salt layer during the air-drying period due to their weak hydration; chloride ions make the salt layer easier to be removed by physiological saline after the storage period due to the high solubility of strontium chloride; the concentration of the mixed solution of 0.1 mol / L potassium chloride and 0.1 mol / L strontium chloride is the appropriate concentration explored, aiming to form a sufficient, uniform and not thick salt protection layer on the surface. The above specific parameters were obtained from preliminary pre-experiments. Preliminary experiment 1 showed that a 12-h soaking was appropriate. Soaking times of 18 h and 24 h would both cause an increase in strontium ion loss, while soaking times of 2 h and 6 h did not form a uniform salt layer; Preliminary experiment 2 showed that when the respective concentrations in the mixed solution were 0.01 mol / L, a sufficient salt layer could not be formed, so the surface could not be evenly covered; when the concentrations were 0.5 mol / L and 1 mol / L, the formed salt layer was too thick and could not be washed clean during subsequent rinsing, thus unable to ensure the biological safety after implantation; Preliminary experiment 3 showed that natural air-drying in a laminar flow hood for 2 h could basically dry the surface liquid and preliminarily precipitate the salt layer. E represents vacuum packaging it, so as to store the surface hydrophilicity to the greatest extent through the double insurance of the surface salt layer and vacuum packaging. F represents that after unpacking before surgery, the surface is rinsed with physiological saline sprayed by surgical instruments for 5 minutes, and the surface salt layer can be fully removed, exposing the super-hydrophilic active sites and immediately implanting them into the body (G) to give full play to the excellent bone integration performance of the material.

[0018] In Figure 3 In the shown embodiment, the salt layer on the dry storage surface in part A can be seen to be evenly distributed on the material surface and fully cover the micro-nano porous morphology on the surface to protect the surface active sites from being occupied by hydrocarbon pollutants. In part B, the surface after cleaning with physiological saline can reach a structure similar to that of the freshly prepared strontium-doped pure titanium implant surface in part C, and its surface is characterized by a micro-nano porous morphology structure, effectively maintaining its good super-hydrophilicity.

[0019] In Figure 4In the illustrated embodiment, the detected atoms on the visible dry storage surface of part A include titanium, strontium, oxygen, potassium, chlorine and a small amount of carbon atoms. After the surface of part B is washed with normal saline, potassium and chlorine atoms can no longer be detected, indicating that the intraoperative normal saline irrigation helps to fully remove the salt layer on the material surface, thus ensuring the biosafety after implantation.

[0020] In Figure 5 In the illustrated embodiment, for the dry storage method with a storage period of 3 months, the strontium ion concentration on its surface is similar to that of the freshly prepared strontium-doped pure titanium implant surface, indicating that the dry storage method effectively inhibits the loss of surface strontium ions during storage. The strontium ion concentration on the surface of the wet storage is so low that it is almost undetectable, indicating that the traditional method of maintaining hydrophilicity by wet storage is not applicable to strontium-doped pure titanium implants.

[0021] In Figure 6 In the illustrated embodiment, for the dry storage method after a storage period of 6 months, the contact angles of its surface and the freshly prepared strontium-doped pure titanium implant surface are both less than 5°, indicating that it effectively maintains the superhydrophilicity of the material during the storage period. For the group only with sealed storage, the contact angle test within 6 months has reached more than 60°, indicating a significant decrease in its hydrophilicity.

[0022] The embodiments described above can be further combined or replaced. The embodiments are only descriptions of the preferred embodiments of the present invention, and do not limit the concept and scope of the present invention. Without departing from the design idea of the present invention, various changes and improvements made by those of ordinary skill in the art to the technical solutions of the present invention all fall within the protection scope of the present invention. The protection scope of the present invention is given by the appended claims and any equivalents thereof.

Claims

1. A dry storage method for strontium-doped pure titanium implants, characterized in that: 1) Freshly prepare strontium-doped pure titanium implants; 2) Immerse the implants processed according to step 1) in a mixed solution of 0.1 mol / L potassium chloride and 0.1 mol / L strontium chloride for 12 hours; 3) After taking out, air dry in a laminar flow hood for 2 hours to form a uniform salt layer protective layer on the surface of the implant, and then place it in vacuum packaging for long-term storage.

2. The method according to claim 1, characterized in that: For step 1), prepare strontium-doped pure titanium implants: Use green silicon carbide (SiC) particles with a size of 250 - 500 μm to sandblast the surface of pure titanium under the parameters of 0.2 MPa, 10 mm distance, and 20 s duration. Then use hydrofluoric acid, nitric acid, hydrochloric acid, and sulfuric acid for acid etching to obtain a large particle sandblasted and acid etched surface. Ultrasonic it in acetone, 75% ethanol, and double-distilled water for 15 min respectively and dry it with nitrogen. On this basis, carry out a hydrothermal reaction by soaking in 0.02 mol / L strontium hydroxide octahydrate at 220 °C for 12 h to prepare fresh strontium-doped pure titanium implants.

3. The method according to claim 1, characterized in that: During the detection after 12 months of storage, the superhydrophilicity of the implant can still be maintained, with a contact angle < 5°. At the same time, before the surgical implantation of the implant, the surface salt layer is fully dissolved and removed by flushing with normal saline to ensure the biological safety after implantation.

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