WO2016202100A1

WO2016202100A1 - Polyether ether ketone/nano hydroxyapatite dental implant and manufacturing method thereof

Info

Publication number: WO2016202100A1
Application number: PCT/CN2016/080480
Authority: WO
Inventors: 张利; 涂英; 李玉宝
Original assignee: 四川大学
Priority date: 2015-06-19
Filing date: 2016-04-28
Publication date: 2016-12-22
Also published as: CN104906635A; CN104906635B

Abstract

Disclosed is a polyether ether ketone/nano-hydroxyapatite dental implant consisting of a neck (1) and a root (2), the neck (1) of which is grafted with a fibronectin or a basic fibroblast growth factor, and the surface of the root (2) of which is a micron porous-nano bulge multistage microstructure. The method for manufacturing the dental implant comprises: preparing a workblank; grafting the fibronectin or basic fibroblast growth factor onto the surface of the neck (1) of the workblank; the root (2) of the workblank is immersed in a decafluoronaphthalene solution for etching, and then put into nano-hydroxyapatite powder to adhere a layer of nano-hydroxyapatite particles; and the workblank is immersed in the nano-hydroxyapatite slurry doped with Ag⁺ or Zn²⁺. The elastic modulus of the dental implant matches a human bone tissue, and the dental implant has a high biological activity and continuous antibacterial capacity, thereby improving the long-term success rate thereof.

Description

Polyetheretherketone/nano-hydroxyapatite dental implant and preparation method thereof

Technical field

The invention belongs to the field of dental implants, and relates to a composite dental implant and a preparation method thereof.

Background technique

At present, the dental implant systems commonly used at home and abroad use pure titanium or titanium alloy as the base material of dental implants. The root surface of the implant is also treated with micropores or coated with apatite coating, and its clinical short-term repair effect is remarkable. The five-year success rate can reach 90%, but the long-term success rate is still low, and the failure rate of clinical implantation for 10 years is as high as 35%. An important factor contributing to the unsatisfactory long-term effect is that the elastic modulus of the titanium implant material (>110GPa) is much higher than the elastic modulus of the human jaw, causing long-term stress shielding and stress stimulation, resulting in bone tissue around the implant. Absorption and implant loosening. It is also common to report on implant/tissue interface matching by low modulus treatment of the implant surface. Such as surface biological and chemical molecular modification, surface etching, spraying nano-hydroxyapatite coating, etc., or forming low-modulus porous TiO ₂ layer on the surface of titanium implant by anodic oxidation method, electron beam layer-by-layer melting method, etc. However, the above method only promotes the bonding strength between the implant and the surrounding bone tissue from the surface, and the clinical planting failure caused by the interface mechanical mismatch problem caused by the elastic modulus problem remains unchanged, and the problem cannot be fundamentally solved. . Therefore, the exploration of dental implant materials with low elastic modulus and high bioactivity is an urgent problem to be solved. It has been reported that the elastic modulus of CF-PEEK composites can be adjusted to about 15GPa, which is close to the elastic modulus of cortical bone, and it is easier to conduct load, but it lacks biological activity and black color, which affects planting and aesthetic effects. ZrO ₂ -PEEK composites have good elastic modulus, wear resistance and impact strength, and the color is closer to natural teeth, but also lacks biological activity. The successful use of polymer-based composites for the manufacture of dental implants and the achievement of good long-term implant effects have not been reported.

On the other hand, infection around the implant is another important factor leading to plant failure. In addition to the high elastic modulus, the existing dental implants provide a pathway for bacterial invasion. The improper design of the surface structure of the neck and the gingival tissue is not reliable. It also provides a pathway for bacterial invasion. Will eventually cause the implant to fail.

Summary of the invention

The object of the present invention is to provide a polyetheretherketone/nano-hydroxyapatite dental implant and a manufacturing method thereof according to the deficiencies of the prior art, so as to match the elastic modulus of the dental implant with the human bone tissue, and have High bioactivity and sustained antibacterial ability to increase the long-term success rate of planting.

The polyetheretherketone/nanohydroxyapatite dental implant of the present invention comprises a neck and a root, and the base material of the dental implant is a polyetheretherketone/nanohydroxyapatite composite material, the neck thereof Grafted with fibronectin or basic fibroblast growth factor, the subsurface of the root is a microporous-nano-convex multi-level microstructure, and the surface layer of the root is a nano-hydroxyapatite layer containing Ag ⁺ or Zn ²⁺ .

The method for preparing the polyetheretherketone/nanohydroxyapatite dental implant of the present invention has the following steps:

(1) The polyetheretherketone powder and the nano-hydroxyapatite powder are compounded and mixed according to the mass ratio (1-7):10 to obtain a polyetheretherketone/nano-hydroxyapatite composite material, and then the polyether ether. The ketone/nano-hydroxyapatite composite material is processed into a dental implant-like blank;

(2) The body obtained in the step (1) is ultrasonically washed and dried in ethanol, and the neck of the body after washing and drying is at a concentration of 5 to 60 μg/mL of a fibronectin solution or a concentration of 5 to 100 μg/L. The immersion in the basic fibroblast growth factor solution is carried out for 0.5 to 1 hour, and then the body after the neck immersion treatment is irradiated with ultraviolet light having an energy density of 250-350 mJ/cm ² for 0.5 to 1 h, and after the irradiation is finished, The surface of the green body is washed by deionized water and naturally dried to obtain a green body to which the surface of the neck is adhered with fibronectin or basic fibroblast growth factor;

(3) The root of the body to which the surface of the neck obtained by the step (2) is adhered with fibronectin or basic fibroblast growth factor is immersed in a solution of decafluoronaphthalene at a concentration of 10 to 15 g/L for 0.5 to 1 hour. Forming a micron-sized porous structure on the root surface of the green body, and then placing the etched green body root into the nano hydroxyapatite powder to adhere a layer of nano hydroxyapatite particles to form a microporous surface on the root surface - nano-protrusion multi-level microstructure;

Roots obtained blank (4) The step (3) doped at a concentration of 0.01 ~ 0.04mol / L of the slurry of nano-hydroxyapatite or Ag ⁺ Zn ²⁺ soaked 1 ~ 3h taken out and dried, i.e., A polyetheretherketone/nano-hydroxyapatite dental implant was obtained.

In the above method, the concentration of the nano hydroxyapatite slurry in the step (4) is 10 to 30 g/L.

In the above method, the polyetheretherketone powder and the nano hydroxyapatite powder are uniformly mixed in the step (1), and the polyetheretherketone/nano hydroxyapatite composite material is processed into a dental implant by mechanical blending. The blank is formed by a compression molding process.

Compared with the prior art, the present invention has the following beneficial effects:

1. The base of the dental implant of the present invention is a polyetheretherketone/nano-hydroxyapatite composite material, and the elastic modulus of the polyetheretherketone/nano-hydroxyapatite composite material is 9-14 GPa, and the human body The elastic modulus of the bone is close and non-cytotoxic, so the composite has excellent mechanical compatibility and biocompatibility. The implant of this material can avoid planting caused by long-term stress shielding and stress stimulation. The absorption of bone tissue around the body and the loosening of the implant, the stability is obviously improved, and it has high biological activity. It is an excellent new dental implant, which is beneficial. In order to improve the long-term success rate of planting.

2. The root sub-surface layer of the polyetheretherketone/nano-hydroxyapatite dental implant of the present invention is a microporous-nano-convex multi-stage microstructure, and the root surface layer is a nano-hydroxyphosphate containing Ag ⁺ or Zn2 ⁺ . The stone layer, which is similar to the micro- and nano-scale pores, fibers and ridge structures existing in the extracellular matrix structure of the body, is beneficial to the adsorption of osteoblasts and fibroblasts to form bone-binding with bone, preventing bacterial adhesion and Reproduction. On the other hand, the dental implant neck is grafted with fibronectin or basic fibroblast growth factor, which can accelerate the adhesion, proliferation and differentiation of fibroblasts, promote the rapid attachment and growth of gingival tissues in the neck of the implant, and make the teeth The neck of the implant is tightly combined with the gingival tissue to form a firm interface, thereby preventing bacteria in the mouth from entering the joint between the implant and the bone, and avoiding infection around the implant. Therefore, the polyetheretherketone/nano-hydroxyapatite dental implant of the invention has the sustained antibacterial ability, is beneficial to the long-term retention of the implant, and improves the long-term success rate of the planting.

3. The method of the invention is simple and easy to operate, and is easy to produce on a large scale.

DRAWINGS

Figure 1 is a schematic illustration of a polyetheretherketone/nano-hydroxyapatite dental implant of the present invention.

In the figure, 1-neck, 2-root.

detailed description

The polyetheretherketone/nano-hydroxyapatite dental implant of the present invention and its preparation method will be further described below by way of specific embodiments.

In the following examples, the fibronectin solution and the basic fibroblast growth factor solution were purchased from Sigma Aldrich (Shanghai) Trading Co., Ltd., and the polyetheretherketone resin was purchased from Shanghai Chaoju New Material Technology Co., Ltd. The ultraviolet irradiation is performed by a CHG-200 type ultraviolet light collecting device.

In the following examples, the preparation method of the nano hydroxyapatite powder is as follows:

Using trisodium phosphate and calcium nitrate as raw materials, the following equations are prepared in an aqueous medium:

l0Ca(NO ₃ ) ₂ +6Na ₃ PO ₄ +2NaOH-Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ +20NaNO ₃

Weigh a certain amount of trisodium phosphate and calcium nitrate, and prepare a 1mol/L solution with deionized water, and slowly add the calcium nitrate solution to the trisodium phosphate solution while stirring at a constant temperature of 50-60 °C. The sodium hydroxide solution was adjusted to pH >9. After the completion of the dropwise addition, stirring was continued for 1 hour, and after standing for 3 days, it was washed with deionized water for 5 times to prepare a nano-hydroxyapatite slurry, and the slurry was adjusted to pH=7 with a weak acid to dry the obtained nano-hydroxyapatite powder. .

The preparation method of the nano hydroxyapatite slurry doped with Ag ⁺ or Zn ²⁺ is as follows:

According to the concentration of the nano-hydroxyapatite slurry required, a certain amount of nano-hydroxyapatite powder prepared according to the above method is weighed into deionized water, and ultrasonically shaken and dispersed for several minutes to obtain a nano-hydroxyapatite slurry. the slurry was added to a certain concentration (the concentration of Ag ⁺ required to be formulated in accordance with nano-hydroxyapatite slurry) solution of AgNO _3, stirred after exchange adsorption, ion sufficient centrifugation, washed with deionized water to the filtrate Without Ag+, a nano-hydroxyapatite slurry doped with Ag ⁺ was obtained.

A nano-hydroxyapatite slurry doped with Zn ²⁺ was prepared by the same method.

In the following examples, the elastic modulus of the dental implant was measured by a Shimadzu AG-IC vertical electronic universal testing machine.

In the following examples, the test methods for the antimicrobial properties of dental implants are as follows:

The strains used in this test were Staphylococcus aureus (S. aureus, ATCC 6538) and Escherichia coli (E. coli, 8399). The above two strains were each made into a bacterial suspension having a concentration of 106 CFU/mL in a PBS solution. Take 4 sterile test tubes, two of which are added with 200 μL of S. aureus suspension, and the other two are added to E. coli suspension. The dental implant neck material prepared in the example is ground and formulated into a mass fraction of 10%. To the dental implant neck sample, add the dental implant neck sample solution to a suspension of Staphylococcus aureus and an E. coli suspension, each 5 mL, and the remaining yellow Staphylococcus suspension and Another E. coli suspension was used as a blank control group. After 48 hours, 50 μL of the bacterial solution was removed from each tube and diluted with 5 mL of physiological saline. 500 μL of the diluted bacterial solution was placed on 4 broth medium solid plates and placed in a 37 ° C incubator. After 48 hours, the viable colony count was taken out and the experiment was repeated three times.

The inhibition rate Y was calculated according to the equation: Y = (Nc - Ns) / Nc × 100%, Nc represents the number of bacterial colonies in the blank control group, and Ns represents the number of bacterial colonies in the experimental group.

Example 1

In this embodiment, the preparation method of the polyetheretherketone/nano-hydroxyapatite dental implant is as follows:

(1) The polyetheretherketone powder and the nano-hydroxyapatite powder are compounded and thoroughly mixed according to the mass ratio of 1:10 by mechanical blending method to obtain a polyetheretherketone/nano-hydroxyapatite composite material, and a molding machine is used. Processing the polyetheretherketone/nano-hydroxyapatite composite into a dental implant-like blank;

(2) The body obtained in the step (1) was ultrasonically cleaned in ethanol for 5 minutes, and then vacuum dried. The neck of the washed and dried body was immersed in a 5 μg/mL solution of fibronectin for 0.5 hour, and then the neck was removed. The immersed green body was irradiated with ultraviolet light having an energy density of 250 mJ/cm ² for 0.5 h. After the irradiation, the surface of the green body was washed with deionized water and naturally dried to obtain a green body with adhesion protein adhered to the neck surface. ;

(3) The root of the body obtained in the step (2) is immersed in a solution of decafluoronaphthalene having a concentration of 10 g/L for 0.5 hour to form a micron-sized porous structure on the root surface of the green body, and then the etched The root of the body is placed in the nano-hydroxyapatite powder to adhere a layer of nano-hydroxyapatite particles, so that the surface of the root forms micro-porous-nano-convex multi-level micro structure;

(4) The root of the body obtained in the step (3) is immersed in the nano-hydroxyapatite slurry doped with Ag ⁺ concentration of 0.01 mol/L for 1 hour, and then taken out in a vacuum to obtain polyetheretherketone/nano. A hydroxyapatite dental implant having a concentration of 10 g/L of the nano hydroxyapatite slurry.

The elastic modulus of the polyetheretherketone/nano-hydroxyapatite dental implant obtained in this example was 9 GPa, and the inhibition rates of S. aureus and E. coli were 93% and 92%, respectively, after 48 h.

Example 2

(1) The polyetheretherketone powder and the nano-hydroxyapatite powder were mixed and mixed according to the mass ratio of 4:10 by mechanical blending method to obtain a polyetheretherketone/nano-hydroxyapatite composite material, and a molding machine was used. Processing the polyetheretherketone/nano-hydroxyapatite composite into a dental implant-like blank;

(3) The root of the body obtained in the step (2) is immersed in a decafluoronaphthalene solution having a concentration of 13 g/L for 0.7 hour to form a micron-sized porous structure on the root surface of the green body, and then the etched The root of the body is placed in the nano-hydroxyapatite powder to adhere a layer of nano-hydroxyapatite particles to form a microporous-nano-convex multi-level microstructure on the surface of the root;

(4) The root of the body obtained in the step (3) is immersed in the nano-hydroxyapatite slurry doped with Ag ⁺ at a concentration of 0.03 mol/L for 1 hour, and then taken out in a vacuum to obtain polyetheretherketone/nano. A hydroxyapatite dental implant having a concentration of 200 g/L of the nano hydroxyapatite slurry.

The elastic modulus of the polyetheretherketone/nano-hydroxyapatite dental implant obtained in this example was 12 GPa, and the inhibition rates of S. aureus and E. coli were 96% and 94%, respectively, after 48 h.

Example 3

(1) The polyetheretherketone powder and the nano-hydroxyapatite powder were mixed and mixed according to the mass ratio of 7:10 by mechanical blending method to obtain a polyetheretherketone/nano-hydroxyapatite composite material, and a molding machine was used. Processing the polyetheretherketone/nano-hydroxyapatite composite into a dental implant-like blank;

(2) The body obtained in the step (1) is ultrasonically cleaned in ethanol for 10 minutes, and then vacuum-dried. The neck of the washed and dried body is soaked in a concentration of 60 μg/mL of the fibronectin solution for 1 hour, and then the neck is soaked. The treated green body is irradiated with ultraviolet light having an energy density of 350 mJ/cm ² for 1 hour, and after the irradiation is finished, the surface of the green body is washed with deionized water and naturally dried to obtain a green body to which the surface of the neck is adhered with adhesion protein;

(3) The root of the body obtained in the step (2) is immersed in a decafluoronaphthalene solution having a concentration of 15 g/L and etched for 1 hour. The root surface of the green body is formed into a micron-sized porous structure, and then the etched green body root is placed in the nano hydroxyapatite powder to adhere a layer of nano hydroxyapatite particles to form a microporous surface on the root surface. Nano-convex multi-level microstructure;

(4) The root of the body obtained in the step (3) is immersed in a nano-hydroxyapatite slurry doped with Ag ⁺ at a concentration of 0.04 mol/L for 1.5 hours, and then taken out in a vacuum to obtain polyetheretherketone/ A nano-hydroxyapatite dental implant having a concentration of 30 g/L of the nano-hydroxyapatite slurry.

The elastic modulus of the polyetheretherketone/nano-hydroxyapatite dental implant obtained in this example was 14 GPa, and the inhibition rates of S. aureus and E. coli were 97% and 96%, respectively, after 48 h.

Example 4

(2) The body obtained in the step (1) was ultrasonically cleaned in ethanol for 5 minutes, and then vacuum dried. The neck of the washed and dried body was immersed in a basic fibroblast growth factor solution at a concentration of 5 μg/L for 0.5 hour. After taking out, the body after the neck soaking treatment is irradiated with ultraviolet light having an energy density of 250 mJ/cm ² for 0.5 h. After the irradiation, the surface of the blank is washed with deionized water and naturally dried to obtain a surface adhered to the neck. a blank of basic fibroblast growth factor;

(3) The root of the body obtained in the step (2) is immersed in a solution of decafluoronaphthalene having a concentration of 10 g/L for 0.5 hour to form a micron-sized porous structure on the root surface of the green body, and then the etched The root of the body is placed in the nano-hydroxyapatite powder to adhere a layer of nano-hydroxyapatite particles to form a microporous-nano-convex multi-level microstructure on the surface of the root;

(4) The green body obtained in the step (3) is immersed in a nano-hydroxyapatite slurry doped with a concentration of 0.01 mol/L of Zn ²⁺ for 0.5 h, and then taken out in a vacuum to obtain polyetheretherketone/ A nano-hydroxyapatite dental implant having a concentration of 10 g/L of the nano-hydroxyapatite slurry.

The elastic modulus of the polyetheretherketone/nano-hydroxyapatite dental implant obtained in this example was 9 GPa, and the inhibition rates of S. aureus and E. coli were 92% and 90%, respectively, after 48 h.

Example 5

(1) The polyetheretherketone powder and the nano-hydroxyapatite powder were mixed and mixed according to the mass ratio of 4:10 by mechanical blending method to obtain a polyetheretherketone/nano-hydroxyapatite composite material, and a molding machine was used. Polyetheretherketone/nano The hydroxyapatite composite material is processed into a dental implant-like blank;

(2) The body obtained in the step (1) was ultrasonically cleaned in ethanol for 5 minutes, and then vacuum dried. The neck of the washed and dried body was immersed in a basic fibroblast growth factor solution at a concentration of 50 μg/L for 0.7 hour. After taking out, the body after the neck soaking treatment is irradiated with ultraviolet light having an energy density of 300 mJ/cm ² for 0.7 h. After the irradiation, the surface of the blank is washed with deionized water and naturally dried to obtain a surface adhered to the neck. a blank of basic fibroblast growth factor;

(4) The root of the body obtained in the step (3) is immersed in a nano-hydroxyapatite slurry doped with Zn ²⁺ having a concentration of 0.03 mol/L for 0.7 hour, and then taken out, and dried under vacuum to obtain polyetheretherketone. / Nano hydroxyapatite dental implant having a concentration of 20 g/L of the nano hydroxyapatite slurry.

Example 6

(2) The body obtained in the step (1) was ultrasonically cleaned in ethanol for 10 minutes, and then vacuum dried. The neck of the washed and dried body was immersed in a basic fibroblast growth factor solution at a concentration of 100 μg/L for 1 hour. Then, the body after the neck soaking treatment is irradiated with ultraviolet light having an energy density of 350 mJ/cm ² for 1 hour. After the irradiation, the surface of the blank is washed with deionized water and naturally dried to obtain an alkali adhesion to the neck surface. a body of fibroblast growth factor;

(3) The root of the body obtained in the step (2) is immersed in a decafluoronaphthalene solution having a concentration of 15 g/L for 1 hour to form a micron-sized porous structure on the root surface of the green body, and then the etched The root of the body is placed in the nano-hydroxyapatite powder to adhere a layer of nano-hydroxyapatite particles to form a microporous-nano-convex multi-level microstructure on the surface of the root;

(4) The root of the body obtained in the step (3) is immersed in a nano-hydroxyapatite slurry doped with Zn ²⁺ having a concentration of 0.04 mol/L for 3 hours, and then taken out in a vacuum to obtain polyetheretherketone/ A nano-hydroxyapatite dental implant having a concentration of 30 g/L of the nano-hydroxyapatite slurry.

The elastic modulus of the polyetheretherketone/nano-hydroxyapatite dental implant obtained in this example was 14 GPa, and the inhibition rates of S. aureus and E. coli were 97% and 95%, respectively, after 48 hours.

Claims

A polyetheretherketone/nano-hydroxyapatite dental implant consisting of a neck (1) and a root (2), characterized in that the base material of the dental implant is polyetheretherketone/nanohydroxyphosphorus In stone composites, the neck is grafted with fibronectin or basic fibroblast growth factor, and the subsurface layer of the root is microporous-nano-convex multi-level microstructure, and the surface layer of the root is nano-hydroxyl containing Ag + or Zn 2+ . Apatite layer.
A method for preparing a polyetheretherketone/nano-hydroxyapatite dental implant, characterized in that the process steps are as follows:

(1) The polyetheretherketone powder and the nano-hydroxyapatite powder are compounded and mixed according to the mass ratio (1-7):10 to obtain a polyetheretherketone/nano-hydroxyapatite composite material, and then the polyether ether. The ketone/nano-hydroxyapatite composite material is processed into a dental implant-like blank;

(2) The body obtained in the step (1) is ultrasonically washed and dried in ethanol, and the neck of the body after washing and drying is at a concentration of 5 to 60 μg/mL of a fibronectin solution or a concentration of 5 to 100 μg/L. The immersion in the basic fibroblast growth factor solution is carried out for 0.5 to 1 hour, and then the body after the neck immersion treatment is irradiated with ultraviolet light having an energy density of 250-350 mJ/cm 2 for 0.5 to 1 h, and after the irradiation is finished, The surface of the green body is washed by deionized water and naturally dried to obtain a green body to which the surface of the neck is adhered with fibronectin or basic fibroblast growth factor;

(3) The root of the body to which the surface of the neck obtained by the step (2) is adhered with fibronectin or basic fibroblast growth factor is immersed in a solution of decafluoronaphthalene at a concentration of 10 to 15 g/L for 0.5 to 1 hour. Forming a micron-sized porous structure on the root surface of the green body, and then placing the etched green body root into the nano hydroxyapatite powder to adhere a layer of nano hydroxyapatite particles to form a microporous surface on the root surface - nano-protrusion multi-level microstructure;

(4) The root of the body obtained in the step (3) is immersed in a nano-hydroxyapatite slurry doped with Ag + or Zn 2+ having a concentration of 0.01 to 0.04 mol/L for 1 to 3 hours, and dried, that is, A polyetheretherketone/nano-hydroxyapatite dental implant was obtained.
The method for producing a polyetheretherketone/nanohydroxyapatite dental implant according to claim 2, wherein the concentration of the nano-hydroxyapatite slurry in the step (4) is 10 to 30 g/L.
The method for preparing a polyetheretherketone/nano-hydroxyapatite dental implant according to claim 2 or 3, wherein the polyetheretherketone powder and the nano-hydroxyapatite powder are uniformly mixed in the step (1). In the mechanical blending method, the polyetheretherketone/nano-hydroxyapatite composite material is processed into a dental implant-like blank body by a compression molding process.