CN1237952C - Biologically active artificial teeth root and its preparation method - Google Patents

Abstract

The bioactive artificial tooth root and its preparation method relate to an artificial tooth root material with a porous calcium-phosphorus bioactive ceramic coating and bone morphogenetic protein (BMP) prepared by a bionic method on the surface and a preparation method thereof. The material is composed of a metal tooth root There is a layer of porous calcium-phosphorus bioactive ceramic coating with a double-layer structure on the surface of the substrate, and bone morphogenetic protein is also compounded on the surface of the porous calcium-phosphorus bioactive ceramic coating. The preparation method is: select pure titanium or titanium alloy to process Good artificial tooth root; the artificial tooth root is subjected to surface activation treatment, and then through two-step biomimetic deposition treatment, a porous calcium-phosphorous biological substance consisting of a dense calcium phosphate amorphous bottom layer and a porous bone-like apatite crystal phase surface layer is obtained on the surface of the artificial tooth root. Active ceramic coating: The artificial tooth root with porous calcium-phosphorus bioactive ceramic coating on the surface is immersed in a mixed solution composed of bone morphogenetic protein and phosphate buffered saline solution.

Description

Bioactive artificial tooth root and its preparation method

Technical field

The invention relates to a bioactive artificial tooth root and a preparation method thereof, in particular to an artificial tooth root material with porous calcium-phosphorus bioactive ceramic coating and bone morphogenetic protein (BMP) prepared by a bionic method on the surface and a preparation method thereof. It belongs to the technical field of biomedical materials.

Background technique

Artificial dental implants can restore the function of missing natural permanent teeth, which allows patients with tooth loss that cannot be repaired by traditional methods to receive fundamental treatment and improve their quality of life. The commonly used artificial tooth roots are metal materials, because they are biologically inert materials, and cannot form a firm physiological combination with the gum tissue. After implantation, they often loosen, resulting in the failure of artificial tooth root replacement. Using surface modification technology to prepare a biological coating (film) on the surface of the artificial tooth root metal matrix can reduce the dissolution of harmful metal ions in the human environment, improve its biocompatibility and biological activity, and make the artificial tooth root and gum tissue form Strong physical bond. The main inorganic substance of dental tissue is calcium phosphorus phase, so the bioactive layer composed of calcium phosphate, hydroxyapatite, bone-like apatite mixed with CO ₃ ^2- ions or calcium phosphorus ceramic phase such as octacalcium phosphate is the best way to improve artificial Ideal for root surfactants. In addition, compounding bone morphogenetic protein (BMP) on the surface of the artificial tooth root can significantly improve the ability of the surface of the artificial tooth root to induce osteogenesis at the initial stage of implantation.

A common method for preparing calcium-phosphorus bioceramic coatings on the surface of artificial tooth roots is plasma spraying technology or a composite method based on plasma spraying technology. Chinese patent ZL03113841.1 "Osteogenic Bioactive Artificial Tooth Root Implant Material and Its Manufacturing Method" discloses a composite method based on plasma spraying technology, that is, first plasma sprays a bioglass-ceramic gradient coating on the surface of the artificial tooth root, and then The surface of the coating is further compounded with BMP, basic fibroblast growth factor or transforming growth factor beta, and the prepared artificial tooth root has a good effect of inducing osteogenesis. However, the bioglass-ceramic gradient coating on the surface of the artificial tooth root is formed at high temperature under conditions that are very different from the human environment, and its composition and structure are very different from those of biological bone apatite, resulting in unstable long-term performance of the artificial tooth root.

Contents of Invention

Technical problem: The purpose of the present invention is to address the above-mentioned shortcomings of artificial tooth root materials, and propose a bioactive artificial tooth root whose surface BMP release period is prolonged, which is conducive to the full play of BMP-induced osteogenesis and its preparation method.

Technical solution: The bioactive artificial tooth root of the present invention is composed of a layer of porous calcium-phosphorus bioactive ceramic coating with a double-layer structure on the surface of the metal tooth root matrix, and bone is also compounded on the surface of the porous calcium-phosphorus bioactive ceramic coating. Morphogenic protein, the porous calcium phosphorus bioactive ceramic coating is composed of a calcium phosphate amorphous bottom layer and a bone-like apatite crystal phase surface layer in contact with the metal substrate, wherein the thickness of the calcium phosphate amorphous bottom layer is 1- 10 μm; the thickness of the bone-like apatite crystal phase surface layer is 10-100 μm.

The method of preparation is:

1) First, choose pure titanium or titanium alloy to process the artificial tooth root;

2) The artificial tooth root is subjected to surface activation treatment, and then through two-step biomimetic deposition treatment, a porous calcium-phosphorus bioactive ceramic composed of a dense calcium phosphate amorphous bottom layer and a porous bone-like apatite crystal phase surface layer is obtained on the surface of the artificial tooth root coating;

3) Soak the artificial tooth root with porous calcium-phosphorus bioactive ceramic coating on the surface in a mixed solution composed of bone morphogenetic protein and phosphate buffered saline solution, the concentration of bone morphogenetic protein is 0.1-50mg/L, at 20-40°C Soak for 5-15 hours, slowly stir once every 1-2 hours in the middle, take it out, and you can get the bioactive artificial tooth root material of the present invention.

The surface activation treatment uses boiling _{H2O2 aqueous} solution with a concentration of 10-60%, and the treatment time is 10-90 minutes. After taking it out and washing it, soak it in an aqueous NaOH solution with a temperature of 30-80°C and a concentration of 1-10M. 6-48 hours.

The two-step biomimetic deposition process includes the following steps:

1) Preparation of biomimetic calcification solution A: Active ingredient content of biomimetic calcification solution A in terms of ion concentration:

Sodium ion 500-850mM, magnesium ion 4.5-6.0mM, calcium ion 10.0-13.5mM, chloride ion 500-800mM, hydrogen phosphate ion 4.0-6.0mM, bicarbonate ion 15.0-30.0mM;

2) Preparation of biomimetic calcification solution B: active ingredient content of biomimetic calcification solution B in terms of ion concentration:

Sodium ion 100.0-180.0mM, potassium ion 4.0-5.5mM, magnesium ion 3.0-4.5mM, calcium ion 2.0-3.5mM, chloride ion 80.0-150.0mM, hydrogen phosphate ion 0.5-1.5mM, bicarbonate ion 6.5- 12.0mM, sulfate ion 0.5-1.0mM;

3) Biomimetic deposition treatment of calcium phosphate amorphous bottom layer: immerse the surface-activated artificial tooth root in the biomimetic calcification solution A at a temperature of 10-30 ° C, and take it out after biomimetic deposition treatment for 12-36 hours under stirring conditions, wash and dry , an amorphous calcium phosphate layer with a thickness of 1-10 μm is obtained on the surface of the artificial tooth root material;

4) Biomimetic deposition treatment of bone-like apatite crystalline phase surface layer: immerse the artificial tooth root with calcium phosphate amorphous layer on the surface in biomimetic calcification solution B at a temperature of 30-50°C, perform biomimetic deposition treatment for 12-144 hours, take it out, wash, After drying, a porous bone-like apatite crystal phase layer with a thickness of 10-100 μm is further deposited on the calcium phosphate amorphous layer on the surface of the artificial tooth root.

Beneficial effect:

(1) The bioactive artificial tooth root of the present invention has a layer of porous calcium-phosphorus bioactive ceramic coating prepared under a bionic method in a similar physiological environment on the surface of the metal substrate, and its surface is further compounded with bone morphogenetic protein (BMP). Dental root materials have good biological activity and osteogenic effect, and can form a firm physiological combination with gum tissue in a short period of time.

(2) The porous calcium-phosphorus ceramic coating on the surface of the artificial tooth root has a high bonding strength with the metal matrix, and has an ideal double-layer structure: the calcium phosphate amorphous bottom layer in contact with the metal surface is dense, which can inhibit the precipitation of toxic metal ions in the metal matrix, It can also be used as a "nucleus basal surface" to promote the deposition and growth of the bone-like apatite crystal phase surface layer; the bone-like apatite crystal phase surface layer is porous, with a thickness of 10-100 μm, has good biological activity, and is also a BMP The ideal carrier is conducive to the full play of BMP-induced osteogenesis.

The bioactive artificial tooth root has a layer of porous calcium-phosphorus bioactive ceramic coating with a double-layer structure prepared by a biomimetic method on the surface of the metal matrix under a similar physiological environment, and the surface is further compounded with bone morphogenetic protein (BMP). The porous calcium-phosphorus ceramic coating has high bonding strength with the metal substrate. It is composed of a calcium phosphate amorphous bottom layer in contact with the metal surface and a bone-like apatite crystal phase surface layer. The calcium phosphate amorphous bottom layer is dense and has a thickness of 1-10 μm. Inhibit the precipitation of toxic metal ions in the metal matrix; the bone-like apatite crystal phase surface layer is porous, with a thickness of 10-100 μm, has good biological activity, and is also an ideal carrier for BMP. The composite of artificial tooth root and BMP usually adopts solution impregnation method, and BMP can penetrate deeply into the porous bone-like apatite crystal phase layer through capillary action, so that the carrying capacity of BMP on the surface of artificial tooth root is greatly increased. After the artificial tooth root is implanted in the human body, the release period of BMP on its surface is prolonged, which is conducive to the full play of BMP-induced osteogenesis.

Specific instance method

Example 1

(1) First choose pure titanium to process the artificial tooth root;

(2) Surface activation treatment of artificial tooth roots: After ultrasonically cleaning the artificial tooth roots with acetone, 70% alcohol, and distilled water in sequence, treat them with 20% boiling H ₂ O ₂ aqueous solution for 45 minutes, take them out and rinse them. , and soaked in a 4M NaOH aqueous solution at a temperature of 30-50°C for 24-36 hours, then rinsed with distilled water, and dried at 70°C.

(3) Biomimetic deposition treatment of calcium phosphate amorphous bottom layer: immerse the artificial tooth root treated with surface activation in the biomimetic calcification solution A at a temperature of 20°C. Ion 4.5mM, Calcium ion 12.5mM, Chloride ion 610.0mM, Hydrogen phosphate ion 5.0mM, Bicarbonate ion 18.0mM. The biomimetic calcification solution A was stirred with a magnetic stirrer, taken out after 12-24 hours of biomimetic deposition treatment, ultrasonically cleaned with distilled water, and dried at room temperature. A dense amorphous calcium phosphate layer with a thickness of 1.5-2.0 μm was obtained on the surface of the artificial tooth root.

(4) Biomimetic deposition treatment of bone-like apatite crystal phase surface layer: immerse the artificial tooth root with calcium phosphate amorphous layer on the surface in biomimetic calcification solution B at a temperature of 30°C, the active ingredient content of biomimetic calcification solution B is calculated by ion concentration : Sodium ion 120.0mM, Potassium ion 5.0mM, Magnesium ion 3.5mM, Calcium ion 2.5mM, Chloride ion 120.0mM, Hydrogen phosphate ion 1.0mM, Bicarbonate ion 11.0mM, Sulfate ion 0.5mM. After 12-36 hours of biomimetic deposition treatment, it was taken out, ultrasonically cleaned with distilled water, and dried at room temperature. A porous bone-like apatite crystalline phase surface layer with a thickness of 15-20 μm was further deposited on the amorphous bottom layer of calcium phosphate on the surface of the artificial tooth root.

(5) Soak the artificial tooth root with porous calcium-phosphorus bioactive ceramic coating on the surface in a mixed solution composed of bone morphogenetic protein and phosphate buffered saline solution with a concentration of 0.1mol/L, and the concentration of bone morphogenetic protein is 0.1-50mg /L, soak at 20-40°C for 5-15 hours, stir slowly every 1-2 hours in the middle, and take it out;

(6) After the above-mentioned taken out artificial tooth root is rinsed with alcohol, vacuum-dried, sterilized, stored aseptically, and set aside, the bioactive artificial tooth root of the present invention can be obtained.

Example 2

(1) First choose Ti6Al4V alloy to process the artificial tooth root;

(2) Surface activation treatment _of the artificial tooth root: After the artificial tooth root is ultrasonically cleaned with acetone, 70% alcohol, and distilled water, it is treated with a boiling _H2O2 aqueous solution with a concentration of 30% for 90 minutes. , and then soaked in an aqueous NaOH solution with a temperature of 60-70°C and a concentration of 8M for 24-36 hours, took out distilled water to rinse, and dried at 70°C.

(3) Biomimetic deposition treatment of calcium phosphate amorphous bottom layer: immerse the artificial tooth root treated with surface activation in the biomimetic calcification solution A at a temperature of 30°C. Ion 4.5mM, Calcium ion 12.5mM, Chloride ion 610.0mM, Hydrogen phosphate ion 5.0mM, Bicarbonate ion 18.0mM. The biomimetic calcification solution A was stirred with a magnetic stirrer, taken out after 24-36 hours of biomimetic deposition treatment, ultrasonically cleaned with distilled water, and dried at room temperature. A dense amorphous calcium phosphate layer with a thickness of 7.5-9.0 μm was obtained on the surface of the artificial tooth root.

(4) Biomimetic deposition treatment of bone-like apatite crystal phase surface layer: immerse the artificial tooth root with the calcium phosphate amorphous layer on the surface in the biomimetic calcification solution B at a temperature of 50°C, and the active ingredient content of the biomimetic calcification solution B is calculated by ion concentration : Sodium ion 120.0mM, Potassium ion 5.0mM, Magnesium ion 3.5mM, Calcium ion 2.5mM, Chloride ion 120.0mM, Hydrogen phosphate ion 1.0mM, Bicarbonate ion 11.0mM, Sulfate ion 0.5mM. After 72-144 hours of biomimetic deposition treatment, it was taken out, ultrasonically cleaned with distilled water, and dried at room temperature. A porous bone-like apatite crystalline phase surface layer with a thickness of 60-80 μm was further deposited on the amorphous bottom layer of calcium phosphate on the surface of the artificial tooth root.

(5) Soak the artificial tooth root with porous calcium-phosphorus bioactive ceramic coating on the surface in a mixed solution composed of bone morphogenetic protein and phosphate buffered saline solution with a concentration of 0.1mol/L, and the concentration of bone morphogenetic protein is 0.1-50mg /L, soak at 20-40°C for 5-15 hours, stir slowly every 1-2 hours in the middle, and take it out;

(6) After the above-mentioned taken out artificial tooth root is rinsed with alcohol, vacuum-dried, sterilized, stored aseptically, and set aside, the bioactive artificial tooth root of the present invention can be obtained.

Example 3

(1) First choose Ti6Al4V alloy to process the artificial tooth root;

(2) Surface activation treatment _of the artificial tooth root: After the artificial tooth root is ultrasonically cleaned with acetone, 70% alcohol, and distilled water, it is treated with a boiling _H2O2 aqueous solution with a concentration of 30% for 90 minutes. , and then soaked in an aqueous NaOH solution with a temperature of 60-70°C and a concentration of 8M for 24-36 hours, took out distilled water to rinse, and dried at 70°C.

(3) Biomimetic deposition treatment of calcium phosphate amorphous bottom layer: immerse the artificial tooth root treated with surface activation in the biomimetic calcification solution A at a temperature of 30°C. Ion 4.5mM, Calcium ion 12.5mM, Chloride ion 610.0mM, Hydrogen phosphate ion 5.0mM, Bicarbonate ion 18.0mM. The biomimetic calcification solution A was stirred with a magnetic stirrer, taken out after 24-36 hours of biomimetic deposition treatment, ultrasonically cleaned with distilled water, and dried at room temperature. A dense amorphous calcium phosphate layer with a thickness of 7.5-9.0 μm was obtained on the surface of the artificial tooth root.

(4) Biomimetic deposition treatment of bone-like apatite crystal phase surface layer: immerse the artificial tooth root with the calcium phosphate amorphous layer on the surface in the biomimetic calcification solution B at a temperature of 50°C, and the active ingredient content of the biomimetic calcification solution B is calculated by ion concentration : Sodium ion 120.0mM, Potassium ion 5.0mM, Magnesium ion 3.5mM, Calcium ion 2.5mM, Chloride ion 120.0mM, Hydrogen phosphate ion 1.0mM, Bicarbonate ion 11.0mM, Sulfate ion 0.5mM. After 48-64 hours of biomimetic deposition treatment, it was taken out, ultrasonically cleaned with distilled water, and dried at room temperature. A porous bone-like apatite crystalline phase surface layer with a thickness of 40-50 μm was further deposited on the calcium phosphate amorphous bottom layer on the surface of the artificial tooth root.

(5) Soak the artificial tooth root with porous calcium-phosphorus bioactive ceramic coating on the surface in a mixed solution composed of bone morphogenetic protein and phosphate buffered saline solution with a concentration of 0.1mol/L, and the concentration of bone morphogenetic protein is 0.1-50mg /L, soak at 20-40°C for 5-15 hours, stir slowly every 1-2 hours in the middle, and take it out;

(6) After taking out the above-mentioned artificial tooth root and rinsing it with alcohol, vacuum-dry, sterilize and store it aseptically for later use, the bioactive artificial tooth root of the present invention can be obtained.

Apparently, the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, rather than limiting the implementation of the present invention. For those of ordinary skill in the art, other different forms of changes or changes can also be made on the basis of the above description, and it is not necessary and impossible to exhaustively enumerate all the implementation modes here, and these are derived from the spirit of the present invention. Obvious changes or modifications are still within the protection scope of the present invention.

Claims (4)

1. A bioactive artificial tooth root, characterized in that, the composition of the bioactive artificial tooth root is to be provided with a layer of porous calcium-phosphorus bioactive ceramic coating with a double-layer structure on the surface of the metal tooth root matrix, and the porous calcium-phosphorus bioactive ceramic coating The surface of the coating is also compounded with bone morphogenetic protein. The porous calcium-phosphorus bioactive ceramic coating is composed of a calcium phosphate amorphous bottom layer in contact with the metal substrate and a bone-like apatite crystal phase surface layer, wherein the phosphoric acid The thickness of the calcium amorphous bottom layer is 1-10 μm; the thickness of the bone-like apatite crystal phase surface layer is 10-100 μm. 2. A preparation method of bioactive artificial tooth root as claimed in claim 1, characterized in that the preparation method is: 1) First, choose pure titanium or titanium alloy to process the artificial tooth root; 2) The artificial tooth root is subjected to surface activation treatment, and then through two-step biomimetic deposition treatment, a porous calcium-phosphorus bioactive ceramic composed of a dense calcium phosphate amorphous bottom layer and a porous bone-like apatite crystal phase surface layer is obtained on the surface of the artificial tooth root coating; 3) Soak the artificial tooth root with porous calcium-phosphorus bioactive ceramic coating on the surface in a mixed solution composed of bone morphogenetic protein and phosphate buffered saline solution, the concentration of bone morphogenetic protein is 0.1-50mg/L, at 20-40°C Soak for 5-15 hours, slowly stir once every 1-2 hours in the middle, take it out, and you can get the bioactive artificial tooth root. 3. The preparation method of bioactive artificial tooth root as claimed in claim 2, characterized in that the surface activation treatment adopts a concentration of 10-60% boiling H ₂ O ₂ aqueous solution, the treatment time is 10-90 minutes, after taking out and washing , and then soaked in an aqueous NaOH solution with a temperature of 30-80°C and a concentration of 1-10M for 6-48 hours. 4. The preparation method of bioactive artificial tooth root as claimed in claim 2, is characterized in that two-step biomimetic deposition process comprises the steps: 1) Preparation of biomimetic calcification solution A: Active ingredient content of biomimetic calcification solution A in terms of ion concentration: Sodium ion 500-850mM, magnesium ion 4.5-6.0mM, calcium ion 10.0-13.5mM, chloride ion 500-800mM, hydrogen phosphate ion 4.0-6.0mM, bicarbonate ion 15.0-30.0mM; 2) Preparation of biomimetic calcification solution B: active ingredient content of biomimetic calcification solution B in terms of ion concentration: Sodium ion 100.0-180.0mM, potassium ion 4.0-5.5mM, magnesium ion 3.0-4.5mM, calcium ion 2.0-3.5mM, chloride ion 80.0-150.0mM, hydrogen phosphate ion 0.5-1.5mM, bicarbonate ion 6.5- 12.0mM, sulfate ion 0.5-1.0mM; 3) Biomimetic deposition treatment of calcium phosphate amorphous bottom layer: immerse the surface-activated artificial tooth root in the biomimetic calcification solution A at a temperature of 10-30 ° C, and take it out after biomimetic deposition treatment for 12-36 hours under stirring conditions, wash and dry , an amorphous calcium phosphate layer with a thickness of 1-10 μm is obtained on the surface of the artificial tooth root material; 4) Biomimetic deposition treatment of bone-like apatite crystal phase surface layer: immerse the artificial tooth root material with calcium phosphate amorphous layer on the surface in biomimetic calcification solution B at a temperature of 30-50°C, perform biomimetic deposition treatment for 12-144 hours, take it out, and wash , dry, and further deposit a porous bone-like apatite crystal phase layer with a thickness of 10-100 μm on the calcium phosphate amorphous layer on the surface of the artificial tooth root material.