Dental implant with osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure and preparation method thereof
阅读说明：本技术 具有成骨-抗炎-血糖三维响应结构的牙种植体及其制备方法 (Dental implant with osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure and preparation method thereof ) 是由 王琪 王倩 张鹏 周欣奕 赵鹏飞 聂鲁凌霄 梁星 丁一 于 2019-12-11 设计创作，主要内容包括：本发明提供了具有成骨-抗炎-血糖三维响应结构的牙种植体,由牙种植体和具有成骨-抗炎-血糖三维响应结构的药物控释体系组成,所述药物控释体系由成骨层、抗炎层和血糖感应层组成,成骨层由壳聚糖水凝胶和分散在其中的纳米羟基磷灰石组成,抗炎层由交联季铵化壳聚糖水凝胶和分散在其中的抗炎物质和葡萄糖氧化酶组成,血糖感应层是由葡萄糖氧化酶组成的涂层；牙种植体表面具有纳米孔结构,药物控释体系的成骨层填充在牙种植体的纳米孔结构中并将牙种植体包覆,抗炎层包覆成骨层,血糖感应层包覆抗炎层。该牙种植体能在高血糖状态下促进骨整合,为伴糖尿病牙种植患者提供新的抗炎处理技术,可满足伴糖尿病患者牙种植修复的临床需求。(The invention provides a dental implant with an osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, which consists of a dental implant and a drug controlled release system with an osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, wherein the drug controlled release system consists of an osteogenesis layer, an anti-inflammatory layer and a blood sugar sensing layer, the osteogenesis layer consists of chitosan hydrogel and nano hydroxyapatite dispersed in the chitosan hydrogel, the anti-inflammatory layer consists of cross-linked quaternized chitosan hydrogel and anti-inflammatory substances and glucose oxidase dispersed in the chitosan hydrogel, and the blood sugar sensing layer is a coating consisting of glucose oxidase; the surface of the dental implant is provided with a nano-pore structure, an osteogenesis layer of a drug controlled release system is filled in the nano-pore structure of the dental implant and coats the dental implant, an anti-inflammatory layer coats the osteogenesis layer, and a blood sugar sensing layer coats the anti-inflammatory layer. The dental implant can promote osseointegration under the hyperglycemia state, provides a new anti-inflammatory treatment technology for the dental implant patients with diabetes, and can meet the clinical requirements of dental implant repair of the dental implants patients with diabetes.)
1. A dental implant with an osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure is characterized by consisting of a dental implant and a drug controlled release system which coats the dental implant and has the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure,
the controlled drug release system consists of an osteogenic layer, an anti-inflammatory layer and a blood sugar sensing layer, wherein the osteogenic layer consists of chitosan hydrogel and nano hydroxyapatite dispersed in the chitosan hydrogel, the content of the nano hydroxyapatite in the osteogenic layer is 50-70 wt%, the water content of the osteogenic layer is not more than 20 wt%, the anti-inflammatory layer consists of cross-linked quaternized chitosan hydrogel and an anti-inflammatory substance and glucose oxidase dispersed in the cross-linked quaternized chitosan hydrogel, the contents of the anti-inflammatory substance and the glucose oxidase in the anti-inflammatory layer are respectively 40-50 wt% and 20-30 wt%, the water content of the anti-inflammatory layer is not more than 60 wt%, and the blood sugar sensing layer is a coating consisting of the glucose oxidase; the surface of the dental implant is provided with a nano-pore structure, an osteogenesis layer of a drug controlled release system is filled in the nano-pore structure on the surface of the dental implant and coats the dental implant, an anti-inflammatory layer coats the osteogenesis layer, and a blood sugar sensing layer coats the anti-inflammatory layer.
2. The dental implant with an osteogenic-anti-inflammatory-blood glucose three-dimensional response structure according to claim 1, wherein the osteogenic layer further comprises a protein for regulating bone repair, the nano-hydroxyapatite and the protein for regulating bone repair are dispersed in the chitosan hydrogel, and the content of the protein for regulating bone repair is 10 wt.% to 25 wt.%.
3. The dental implant having a three-dimensional osteogenic-anti-inflammatory-glycemic response structure according to claim 2, wherein the protein regulating bone repair is at least one of insulin growth factor i, bone morphogenetic protein, transforming growth factor, and basic fibroblast growth factor.
4. The dental implant having an osteogenic-anti-inflammatory-glycemic three-dimensional response structure according to any one of claims 1 to 3, wherein the anti-inflammatory agent is at least one of metronidazole, TNF- α antibody, and interleukin 10.
5. The dental implant having an osteogenic-anti-inflammatory-blood glucose three-dimensional response structure according to any one of claims 1 to 3, wherein the pore diameter of the nano-pore structure on the surface of the dental implant is 20nm to 1 μm, and the pore depth is 50 nm to 500 nm.
6. The dental implant with an osteogenesis-anti-inflammatory-blood glucose three-dimensional response structure according to claim 5, wherein the dental implant is a dental implant made of metal or alloy material.
7. The dental implant having an osteogenic-anti-inflammatory-blood glucose three-dimensional response structure according to any one of claims 1 to 3, wherein the thickness of the osteogenic layer is 100nm to 20 μm, the thickness of the anti-inflammatory layer is 100nm to 50 μm, and the thickness of the blood glucose sensing layer is 100nm to 30 μm.
8. The method for preparing a dental implant having an osteogenic-anti-inflammatory-glycemic three-dimensional response structure according to any one of claims 1 to 7, comprising the steps of:
(1) preparing osteogenic layer
① soaking the dental implant with the surface having the nano-pore structure in 0.5-2.0 mg/mL dopamine solution for 12-24 h, taking out and drying;
②, dispersing 1-5 parts by mass of nano hydroxyapatite in water to form a hydroxyapatite suspension, fully mixing the hydroxyapatite suspension with 0-15 parts by mass of protein for regulating and controlling bone repair and 5-20 parts by mass of chitosan gel, dropwise adding the obtained mixed solution to the surface of the dental implant treated in the step ①, performing negative pressure treatment to enable the mixed solution to enter a nano-pore structure on the surface of the dental implant and coat the dental implant to form a bone formation layer, drying until the water content of the bone formation layer is not more than 20 wt%, and enabling the bone formation layer to be in a gel state after drying;
the chitosan gel is chitosan hydrogel with the chitosan concentration of 0.01-0.1 g/mL;
(2) preparation of an anti-inflammatory layer
Dispersing 10-25 parts by mass of quaternized chitosan in water to form quaternized chitosan gel, adding 5-20 parts by mass of anti-inflammatory substances and 1-10 parts by mass of glucose oxidase into the quaternized chitosan gel, fully mixing, then adding 2-8 parts by mass of sodium tripolyphosphate, fully mixing to form reaction liquid, immersing the substrate treated in the step (1) in the reaction liquid to enable the quaternized chitosan and the sodium tripolyphosphate to have a crosslinking reaction, simultaneously enabling the sodium tripolyphosphate and part of chitosan in an osteogenic layer to have a crosslinking reaction, forming an anti-inflammatory layer on the surface of the osteogenic layer, and drying until the water content of the anti-inflammatory layer is not more than 60 wt%, wherein the anti-inflammatory layer is in a gel state after drying;
in the step, the time of crosslinking reaction is controlled to be 20 min-48 h, and the concentration of quaternized chitosan in the quaternized chitosan gel is 5 multiplied by 10-4～1×10-1g/mL；
(3) Preparing a blood glucose sensing layer
Coating 1-10 parts by mass of a glucose oxidase solution with the concentration of 0.1-2.0 g/mL on the surface of the dental implant treated in the step (2), and drying to form a blood sugar sensing layer on the surface of the anti-inflammatory layer to obtain the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structureImplant of meridian Co60Sealing after irradiation and disinfection, and storing at 0-4 ℃;
the drying described in the steps (1) ②, (2) and (3) means drying at a temperature of not more than 37 ℃.
9. The method for preparing a dental implant having an osteogenic-anti-inflammatory-glycaemic three-dimensional response structure according to claim 8, wherein the dental implant having a nanoporous structure on the surface thereof is prepared by:
taking the dental implant as an anode, graphite as a cathode and H2SO4Solution, HF solution, H3PO4-HF mixed acid or H2SO4Using HF mixed acid as electrolyte, corroding the dental implant by adopting an electrochemical oxidation method to form a nano-pore structure on the surface of the dental implant, then washing with water, and drying to obtain the dental implant with the nano-pore structure on the surface;
said H2SO4The concentration of the solution is 0.02-1.5 mol/L, the concentration of HF is 0.05-2.0 mol/L, H2SO4H in HF mixed acid2SO4The concentration of (A) is 0.5-6.0 mol/L, HF, the concentration of (B) is 0.05-0.50 mol/L, H3PO4H in HF mixed acid3PO4The concentration of (b) is 0.5 to 3.0mol/L, HF, and the concentration of (c) is 0.05 to 0.50 mol/L.
10. The method for preparing a dental implant having a three-dimensional osteogenesis-anti-inflammatory-glycemia response structure as set forth in claim 9, wherein the dental implant is corroded by electrochemical oxidation under a controlled voltage of 5 to 35V and a controlled current density of 0.2 to 15mA/cm2The electrochemical oxidation time is 30 s-60 min.
Technical Field
The invention belongs to the field of dental implants, and relates to a dental implant with a three-dimensional osteogenesis-anti-inflammatory-blood sugar response structure and a preparation method thereof.
Background
Implant restoration has become a conventional means of restoration of dentition loss or defects. However, for complex cases, such as patients with systemic diseases such as diabetes and osteoporosis, the current titanium implant surface modification mode and preparation process cannot meet complex clinical requirements, and the implantation repair is still relatively contraindicated, so that the clinical application range of the titanium implant is limited. Therefore, the development of dental implants suitable for patients with systemic diseases has become a new challenge in the field of implant repair.
Diabetes is liable to cause imbalance of bone metabolism, aggravation of local inflammatory reaction and serious destruction of periodontal tissues of patients. Hyperglycemia promotes the increase of the level of inflammatory mediators in vivo, and is an important factor influencing the prognosis of the implant surgery. Poor postoperative blood glucose control of a patient can lead to increased inflammatory mediators around the implant, reduce osseointegration, and cause complications such as peri-implant inflammation and implant loosening. Therefore, in order to implant and repair a diabetic patient, it is necessary to provide a structure suitable for bone tissue ingrowth and promote osseointegration in addition to having a local anti-inflammatory effect in a hyperglycemic state, which is advantageous in reducing the burden of systemic administration on the diabetic patient during implant and repair.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a dental implant with an osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure and a preparation method thereof, so as to reduce the burden of systemic medication through local drug release, promote osseointegration in a hyperglycemic state, provide a new anti-inflammatory treatment technology for a patient with dental implantation of diabetes and better meet the clinical requirements of dental implantation repair of the patient with the dental implantation of diabetes.
The invention provides a dental implant with a osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, which consists of a dental implant and a drug controlled release system which coats the dental implant and has the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure,
the controlled drug release system consists of an osteogenic layer, an anti-inflammatory layer and a blood sugar sensing layer, wherein the osteogenic layer consists of chitosan hydrogel and nano hydroxyapatite dispersed in the chitosan hydrogel, the content of the nano hydroxyapatite in the osteogenic layer is 50-70 wt%, the water content of the osteogenic layer is not more than 20 wt%, the anti-inflammatory layer consists of cross-linked quaternized chitosan hydrogel and an anti-inflammatory substance and glucose oxidase dispersed in the cross-linked quaternized chitosan hydrogel, the contents of the anti-inflammatory substance and the glucose oxidase in the anti-inflammatory layer are respectively 40-50 wt% and 20-30 wt%, the water content of the anti-inflammatory layer is not more than 60 wt%, and the blood sugar sensing layer is a coating consisting of the glucose oxidase; the surface of the dental implant is provided with a nano-pore structure, an osteogenesis layer of a drug controlled release system is filled in the nano-pore structure on the surface of the dental implant and coats the dental implant, an anti-inflammatory layer coats the osteogenesis layer, and a blood sugar sensing layer coats the anti-inflammatory layer.
In the technical scheme of the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, the osteogenesis layer further comprises a protein for regulating and controlling bone repair, the nano-hydroxyapatite and the protein for regulating and controlling bone repair are dispersed in the chitosan hydrogel, and the content of the protein for regulating and controlling bone repair is 10-25 wt.%. Preferably, the protein regulating bone repair is at least one of insulin growth factor i, bone morphogenetic protein, transforming growth factor and basic fibroblast growth factor.
In the above-mentioned dental implant having an osteogenesis-anti-inflammatory-blood glucose three-dimensional response structure, the anti-inflammatory substance is preferably at least one of metronidazole, TNF- α antibody and
In the technical scheme of the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, the pore diameter of the nano-pore structure on the surface of the dental implant is preferably 20 nm-1 mu m, and the pore depth is preferably 50-500 nm. The dental implant serving as the modification base is preferably a dental implant made of metal or alloy, and further, the implant is a medical pure titanium or titanium alloy implant.
In the above technical solution of the dental implant having the three-dimensional osteogenesis-anti-inflammatory-blood glucose response structure, the thickness of the osteogenesis layer, the anti-inflammatory layer and the blood glucose sensing layer is determined and adjusted according to the actual condition of the patient, preferably, the thickness of the osteogenesis layer is 100nm to 20 μm, the thickness of the anti-inflammatory layer is 100nm to 50 μm, and the thickness of the blood glucose sensing layer is 100nm to 30 μm.
In the technical scheme of the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, in the cross-linked quaternized chitosan hydrogel forming the anti-inflammatory layer, cross-linked quaternized chitosan is formed by cross-linking reaction of quaternized chitosan and sodium tripolyphosphate.
The invention also provides a preparation method of the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, which comprises the following steps:
(1) preparing osteogenic layer
① soaking the dental implant with the surface having the nano-pore structure in 0.5-2.0 mg/mL dopamine solution for 12-24 h, taking out and drying;
②, dispersing 1-5 parts by mass of nano hydroxyapatite in water to form a hydroxyapatite suspension, fully mixing the hydroxyapatite suspension with 0-15 parts by mass of protein for regulating and controlling bone repair and 10-20 parts by mass of chitosan gel, dropwise adding the obtained mixed solution to the surface of the dental implant treated in the
the chitosan gel is chitosan hydrogel with the chitosan concentration of 0.01-0.1 g/mL;
(2) preparation of an anti-inflammatory layer
Dispersing 10-25 parts by mass of quaternized chitosan in water to form quaternized chitosan gel, adding 5-20 parts by mass of anti-inflammatory substances and 1-10 parts by mass of glucose oxidase into the quaternized chitosan gel, fully mixing, then adding 2-8 parts by mass of sodium tripolyphosphate, fully mixing to form reaction liquid, immersing the substrate treated in the step (1) in the reaction liquid to enable the quaternized chitosan and the sodium tripolyphosphate to have a crosslinking reaction, simultaneously enabling the sodium tripolyphosphate and part of chitosan in an osteogenic layer to have a crosslinking reaction, forming an anti-inflammatory layer on the surface of the osteogenic layer, and drying until the water content of the anti-inflammatory layer is not more than 60 wt%, wherein the anti-inflammatory layer is in a gel state after drying;
in the step, the time of crosslinking reaction is controlled to be 20 min-48 h, and the concentration of quaternized chitosan in the quaternized chitosan gel is 5 multiplied by 10-4～1×10-1g/mL；
(3) Preparing a blood glucose sensing layer
Coating 1-10 parts by mass of a glucose oxidase solution with the concentration of 0.1-2.0 g/mL on the surface of the dental implant treated in the step (2), drying to form a blood sugar sensing layer on the surface of the anti-inflammatory layer to obtain the dental implant with an osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, and treating the dental implant with Co60Sealing after irradiation and disinfection, and storing at 0-4 ℃;
the drying described in the steps (1) ②, (2) and (3) means drying at a temperature of not more than 37 ℃.
Preferably, in the method for preparing a dental implant having a three-dimensional osteogenesis-anti-inflammatory-glycemia response structure, the method for preparing a dental implant having a nanoporous structure on the surface comprises the following steps:
taking the dental implant as an anode, graphite as a cathode and H2SO4Solution, HF solution, H3PO4-HF mixed acid or H2SO4Using HF mixed acid as electrolyte, corroding the dental implant by adopting an electrochemical oxidation method to form a nano-pore structure on the surface of the dental implant, then washing with water, and drying to obtain the dental implant with the nano-pore structure on the surface;
said H2SO4The concentration of the solution is 0.02-1.5 mol/L, the concentration of HF is 0.05-2.0 mol/L, H2SO4H in HF mixed acid2SO4The concentration of (A) is 0.5-6.0 mol/L, HF, the concentration of (B) is 0.05-0.50 mol/L, H3PO4H in HF mixed acid3PO4The concentration of (b) is 0.5 to 3.0mol/L, HF, and the concentration of (c) is 0.05 to 0.50 mol/L.
Erosion of dental implants by electrochemical oxidationThe voltage is usually controlled to be 5-35V and the current density is controlled to be 0.2-15 mA/cm2The electrochemical oxidation time is 30 s-60 min; when the electrochemical oxidation method is adopted to corrode the dental implant, the temperature of the electrolyte is preferably controlled to be room temperature by adopting a water bath.
Still further preferably, prior to eroding the dental implant by electrochemical oxidation, the dental implant is pre-treated by: performing sand blasting treatment on the dental implant to increase the roughness of the surface of the dental implant, then sequentially cleaning the dental implant with acetone, ethanol and water, drying the dental implant, and sequentially cleaning the dental implant with HF-H2SO4Washing with mixed acid and water; the HF-H2SO4The concentration of HF in the mixed acid is 0.2-1.5 mol/L, H2SO4The concentration of (b) is 2.0-7.0 mol/L.
In order to improve the nanoporous structure on the surface of the dental implant when preparing the dental implant having the nanoporous structure on the surface, the dental implant corroded by the electrochemical oxidation method may be subjected to a heat treatment. For example, the dental implant corroded by the electrochemical oxidation method is placed at 400-500 ℃ for heat treatment.
In the step (1) of the preparation method of the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, the negative pressure treatment is preferably kept still for 1-30 min under the condition of-0.4-0.02 MPa, and the temperature during the negative pressure treatment is preferably controlled to be 0-37 ℃.
In the preparation method step (1) of the dental implant with the osteogenesis-anti-inflammatory-blood glucose three-dimensional response structure, the concentration of the hydroxyapatite suspension is preferably 0.1-5.0 g/mL.
In the preparation method of the dental implant with the osteogenesis-anti-inflammatory-blood glucose three-dimensional response structure, in the step (1) ①, preferably, 1-5 parts by mass of the dental implant with the surface having the nanopore structure is soaked in a dopamine solution.
In the step (1) ② of the preparation method of the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, in order to promote the mixed solution to enter the nanopore structure on the surface of the dental implant during negative pressure treatment, the mixed solution obtained can be dropwise added to the surface of the implant treated in the
In the step (2) of the preparation method of the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, the time of the cross-linking reaction is preferably controlled to be 6-24 hours.
In the step (3) of the preparation method of the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, the drying refers to drying until the surface of the blood sugar sensing layer is free of moisture.
As shown in figures 1-2, the dental implant with the osteogenic-anti-inflammatory-blood sugar three-dimensional response structure provided by the invention is characterized in that a drug controlled release system with the osteogenic-anti-inflammatory-blood sugar three-dimensional response structure and coating the dental implant is designed on the basis of the dental implant, the drug controlled release system takes natural high molecular substance chitosan and derivative quaternized chitosan thereof as a main substrate, and consists of an osteogenic layer, an anti-inflammatory layer and a blood sugar sensing layer, nano hydroxyapatite is loaded in the osteogenic layer or protein for regulating and controlling bone repair is loaded on the basis of the natural high molecular substance chitosan, anti-inflammatory substance and glucose oxidase are loaded in the anti-inflammatory layer, and the blood sugar sensing layer is a coating consisting of glucose oxidase. The effect of staged release of different drugs is achieved by utilizing the adjustability of blood glucose response of a drug controlled release system and combining the spatial distribution difference of the drugs. The glucose oxidase on the outer layer of the drug controlled release system is used as the forefront of glucose response, the drugs can be rapidly released when the blood glucose concentration is abnormal (such as 11-15 mmol/L and above), the glucose oxidase is embedded in the middle layer and loaded with anti-inflammatory substances, the primary drugs are released after the blood glucose response, the glucose oxidase is also released along with the slow degradation of the matrix on the outer layer, the pH environment is maintained, meanwhile, the rest anti-inflammatory substances are released to prolong the drug release period, after the anti-inflammatory period, the nano-hydroxyapatite on the inner layer is slowly released, a nano-pore microstructure beneficial to the growth of bone tissues is gradually formed on the surface of the dental implant, and the protein for regulating and controlling bone repair is added, so that the bone integration can.
Compared with the prior art, the technical scheme of the invention has the following beneficial technical effects:
1. the invention provides a dental implant with an osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, wherein a drug controlled-release system with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure and coating the dental implant is designed on the surface of the dental implant, and the drug controlled-release system takes natural high molecular substance chitosan and quaternized chitosan derivatives thereof as a main matrix and consists of an osteogenesis layer, an anti-inflammatory layer and a blood sugar induction layer. The drug controlled release system is provided with a double-layer glucose oxidase and an outermost glucose oxidase coating, and can quickly release drugs when the blood glucose concentration is abnormal as the forefront of glucose response, the glucose oxidase is embedded in the middle layer and loaded with anti-inflammatory substances, the primary drugs are released after the blood glucose response, the glucose oxidase is also released along with the slow degradation of the outer-layer matrix, the pH environment is maintained, the pore diameter of the matrix is adjusted, the residual anti-inflammatory substances are released, the drug release period is prolonged, a stable anti-inflammatory microenvironment is formed, after the anti-inflammatory period, the nano-hydroxyapatite in the inner layer is slowly released, a nano-pore microstructure beneficial to the growth of bone tissues is gradually formed on the surface of the dental implant, and the protein for regulating and controlling bone repair is added. The dental implant provided by the invention can reduce the burden of systemic medication through local drug release, promote osseointegration in a hyperglycemic state, and better meet the clinical requirements of complicated cases accompanied with diabetes dental implantation.
2. In the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, the surface of the dental implant serving as a modified base is provided with the porous microstructure, and the porous microstructure is not only favorable for peripheral cell adhesion, but also capable of loading hydroxyapatite and protein for regulating and controlling bone repair, promoting the adhesion and proliferation of osteoblasts and being favorable for shortening the osseointegration time.
3. In the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, the material of the drug controlled release system with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure for coating the dental implant is an absorbable and degradable material, is non-toxic and harmless, does not need secondary operation, does not influence the activity of protein by a cross-linking agent adopted by the drug controlled release system, and can quickly release anti-inflammatory substances loaded in the system when the blood sugar concentration is abnormally increased to resist the inflammatory state caused by hyperglycemia, thereby being beneficial to the anti-inflammatory and repair treatment of periodontal tissues under the high sugar state.
4. The invention also provides a preparation method of the dental implant with the osteogenesis-anti-inflammatory-blood sugar three-dimensional response structure, which has the characteristics of simple operation, good controllability, no need of using special reagents and equipment, contribution to reduction of production cost and easiness in production realization.
Drawings
FIG. 1 is a schematic view of a dental implant having an osteogenic-anti-inflammatory-glycemic three-dimensional response structure according to the present invention, wherein (B) is a partially enlarged view of (A) and (C) is a partially enlarged view of (B);
FIG. 2 is another schematic view of a dental implant having an osteogenic-anti-inflammatory-glycemic three-dimensional response structure according to the present invention, wherein (B) is a partially enlarged view of (A) and (C) is a partially enlarged view of (B);
in FIGS. 1-2, the first and second electrodes are shown,
fig. 3 is a scanning electron microscope image of the implant having a nanoporous structure on the surface prepared in step (1) of example 1.
Fig. 4 is a partially enlarged view of fig. 3.
Fig. 5 is a partially enlarged view of fig. 4.
FIG. 6 is a 24-hour cumulative release profile of an anti-inflammatory substance after a dental implant having a three-dimensional osteogenic-anti-inflammatory-glycemic response structure prepared in example 1 responded to blood glucose at various concentrations.
FIG. 7 is a one-week cumulative release profile of an anti-inflammatory agent in response to different concentrations of blood glucose from dental implants having a three-dimensional osteogenic-anti-inflammatory-blood glucose response structure prepared in example 1.
Fig. 8 is a toluidine blue staining result of 3 weeks after the implantation of the maxilla of the diabetic periodontitis-accompanied mouse of the dental implant having an osteogenesis-anti-inflammatory-blood glucose three-dimensional response structure prepared in example 1, at a magnification of 30 times.
Fig. 9 is toluidine blue staining results of 3 weeks after the implantation of the maxilla of the diabetic periodontitis-accompanied mouse of the dental implant having an osteogenesis-anti-inflammatory-blood glucose three-dimensional response structure prepared in example 1, at a magnification of 80 times.
Fig. 10 is a toluidine blue staining result of 3 weeks after the implantation of the maxilla of the diabetic periodontitis-accompanied mouse of the dental implant having an osteogenesis-anti-inflammatory-blood glucose three-dimensional response structure prepared in example 1, at a magnification of 200 times.
Detailed Description
The dental implant having a three-dimensional osteogenic-anti-inflammatory-glycemic response structure and the method for preparing the same according to the present invention are further illustrated by the following examples. It should be noted that the following examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention, and those skilled in the art can make certain insubstantial modifications and adaptations of the present invention based on the above disclosure and still fall within the scope of the present invention.
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