Biological glass composite bone cement and electric field treatment method
阅读说明：本技术 生物玻璃复合骨水泥及电场处理方法 (Biological glass composite bone cement and electric field treatment method ) 是由 林健 姚爱华 朱子旻 张敏慧 张轩宇 于 2020-12-29 设计创作，主要内容包括：本发明涉及一种生物玻璃复合骨水泥及电场处理方法,电场处理方法包括对硼硅酸盐生物玻璃粉施加直流电场诱导表面预处理；还可以包括对硼硅酸盐生物玻璃复合骨水泥在固化后加载安全直流电场。与现有技术相比,本发明中,硼硅酸盐生物玻璃粉通过直流电场诱导表面预处理生成含扩散孔道的富硅玻璃相缓释膜层以提升由其制成的生物玻璃复合骨水泥使用初期生物安全性；硼硅酸盐生物玻璃复合骨水泥在固化后通过加载安全直流电场调控生物玻璃复合骨水泥的生物活性,实现骨组织的可控、可持续修复；生物玻璃复合骨水泥中引入纳米导电功能相,可以改善生物玻璃骨水泥的电导性能,提升直流电场诱导矿化效率；该技术可应用于骨组织工程中骨修复、再生等领域。(The invention relates to a bioglass composite bone cement and an electric field treatment method, wherein the electric field treatment method comprises the steps of applying direct current electric field induced surface pretreatment to borosilicate bioglass powder; and the method can also comprise loading a safe direct current electric field on the borosilicate bioglass composite bone cement after curing. Compared with the prior art, the borosilicate bioglass powder is subjected to surface pretreatment induced by a direct current electric field to generate a silicon-rich glass phase slow-release film layer containing diffusion pore channels so as to improve the biological safety of bioglass composite bone cement prepared from the borosilicate bioglass powder at the initial use stage; after being cured, the borosilicate bioglass composite bone cement regulates and controls the bioactivity of the bioglass composite bone cement by loading a safe direct current electric field, thereby realizing the controllable and sustainable repair of bone tissues; the nano conductive functional phase is introduced into the biological glass composite bone cement, so that the conductivity of the biological glass bone cement can be improved, and the induced mineralization efficiency of a direct current field is improved; the technology can be applied to the fields of bone repair, regeneration and the like in bone tissue engineering.)
1. An electric field processing method of bioglass composite bone cement is characterized by comprising the following steps of S1: and applying a direct current electric field to the borosilicate bioglass powder to induce surface pretreatment.
2. The electric field treatment method for bioglass composite bone cement as claimed in claim 1, characterized in that the borosilicate bioglass powder is subjected to direct current electric field induced surface pretreatment for generating a silicon-rich glass phase slow release film layer containing diffusion pores.
3. The electric field treatment method for bioglass composite bone cement as claimed in claim 1 or 2, wherein in step S1, borosilicate bioglass powder is placed in human body simulated body fluid and applied with a direct current electric field, the current is 100 to 300mA, and the time is 2 to 10h, so as to form a silicon-rich glass phase slow release film layer containing diffusion pores.
4. The electric field processing method for bioglass composite bone cement as claimed in claim 1, further comprising the step of S2: and loading a safe direct current electric field on the cured bioglass composite bone cement prepared from borosilicate bioglass powder.
5. The electric field treatment method for bioglass composite bone cement as claimed in claim 4, wherein a safe direct current electric field is applied to the bioglass composite bone cement after curing for regulating the release rate and mineralization rate of active ions in the borosilicate bioglass composite bone cement.
6. The electric field treatment method for bioglass composite bone cement as claimed in claim 5, wherein in step S2, after bioglass composite bone cement is solidified, a safe direct current electric field is applied to regulate the release rate of active ions in bioglass composite bone cement, the current of the direct current electric field is 0.1-90 mA, and the direct current electric field is applied for 1-24h every day.
7. The bioglass composite bone cement is characterized by comprising, by mass, 5-70 parts of solid-phase borosilicate bioglass powder, 30-95 parts of liquid-phase binder and 0-30 parts of nano conductive functional phase.
8. The bioglass composite bone cement as in claim 7, wherein the liquid phase binder is a polymethyl methacrylate or sodium alginate mixed solution;
the polymethyl methacrylate mixed solution is prepared by mixing 100 parts of polymethyl methacrylate powder, 50 parts of methyl methacrylate, 0.5 part of dibenzoyl peroxide and 0.3 part of N, N-dimethyl-p-toluidine by mass;
the sodium alginate mixed solution is prepared by mixing 2 parts of sodium alginate, 3 parts of disodium hydrogen phosphate, 1 part of gluconolactone and 100 parts of water according to parts by mass;
after the mixed solution of the liquid phase binder is prepared, the solid phase borosilicate bioglass powder and the nanometer conductive functional phase are added and uniformly mixed, and the bioglass composite bone cement is formed after solidification.
9. The bioglass composite bone cement as claimed in claim 7, wherein the weight part of the nano conductive functional phase is 0-30 parts, but not 0.
10. The bioglass composite bone cement as claimed in claim 7, wherein the nano conductive functional phase comprises one or more of titanium nitride particles of 10-500 nm and gold nanoparticles of 10-100 nm.
Technical Field
The invention belongs to the technical field of biological materials, and particularly relates to a biological glass composite bone cement and an electric field treatment method.
Background
In recent years, bone diseases have become an important problem today due to accidents such as traffic accidents, diseases, and natural disasters and the aging of the population. According to statistics, 300 million bone trauma patients, osteoporosis patients and osteoarthritis patients in China are nearly 2 hundred million people every year, and bone tissue defect and damage become important diseases affecting the health and life of people. The bioactive glass bone cement taking borosilicate bioglass powder as a solid phase is a novel biomedical bone repair material and has excellent biocompatibility, bioactivity and biodegradability. The material as biomedical material has the advantages of metal, polymer and biological inert material, can be directly and chemically combined with human bone, and can be mineralized on the surface to form hydroxyapatite required by human bone growth in vivo biochemical environment, induce bone cell proliferation and promote bone reconstruction.
However, the applicant has found that borate bioglass releases active ions at a faster rate during the initial 1-2 day period of use. In addition, in the middle and later period after 1-2 weeks of use, the release of active ions in the bioglass is obviously reduced.
Disclosure of Invention
The applicant of the present invention has found that, in view of the release of active ions such as boron and calcium from borosilicate bioglass in human body or human body Simulant (SBF) and the mineralization mechanism for forming hydroxyapatite, etc., the release rate of active ions from borosilicate bioglass is fast at the initial stage of use, and therefore, it is necessary to limit the boron content in bioglass and the amount of bioglass used in composite bone cement. In the middle and later period, the release of active ions in the bioglass is obviously reduced, so that the bioactivity is too low, and the bone repair process is delayed.
The invention aims to provide a bioglass composite bone cement and an electric field treatment method. Through direct current electric field induction borosilicate bioglass powder preliminary treatment, pull out boron, the calcium ion part on borosilicate bioglass powder surface layer in order to form rich silicon glass looks rete, and generate the diffusion pore of easy middle and later stage ion diffusion, slow down bioglass composite bone cement in the active ion release of using the initial stage in order to promote biological safety, but do not influence the active ion release of middle and later stage. In addition, after the bioglass composite bone cement is implanted, a human body safe direct current electric field is applied outside an implanted part (or human body simulated body fluid in which the bone cement is placed) to regulate and control the ion release and mineralization speed of bioglass in the composite bone cement so as to keep excellent bioactivity, realize the overall process control of biosafety and bioactivity and obviously improve the bone repair efficiency of the bioglass bone cement. The introduction of noble metal nanocrystalline or nano titanium nitride with excellent chemical stability, high conductivity and low toxic and side effects is beneficial to improving the electric field sensitivity of the bioglass composite bone cement, thereby accelerating the release of active ions in bioglass and the generation of hydroxyapatite and accelerating the sustainable repair of bone tissues.
The purpose of the invention can be realized by the following technical scheme:
the invention provides a method for processing an electric field of bioglass composite bone cement, which comprises the following steps of S1: and applying a direct current electric field to the borosilicate bioglass powder to induce surface pretreatment.
Preferably, the borosilicate bioglass powder is subjected to direct-current electric field induced surface pretreatment for generating a silicon-rich glass phase slow-release film layer containing diffusion pores.
Preferably, in step S1, the borosilicate bioglass powder is placed in a human body Simulated Body Fluid (SBF) and a direct current electric field is applied, wherein the current is 100 to 300mA and the time is 2 to 10 hours, so as to form a silicon-rich glass phase slow release film layer containing diffusion pores.
Preferably, the method further comprises the step S2: and loading a safe direct current electric field on the cured bioglass composite bone cement prepared from borosilicate bioglass powder.
Preferably, the safe direct current electric field is loaded on the bioglass composite bone cement after solidification, and is used for regulating and controlling the release speed and the mineralization speed of active ions in the bioglass composite bone cement.
Preferably, in step S2, after the bioglass composite bone cement is cured, a safe direct current field is applied to regulate the release rate of active ions in the bioglass composite bone cement, the current of the direct current field is 0.1 to 90mA, and the direct current field is applied for 1 to 24 hours per day.
Preferably, in step S2, the DC electric field current is 0.1-10 mA when applied to human body.
The second aspect of the invention provides bioglass composite bone cement which comprises, by mass, 5-70 parts of solid borosilicate bioglass powder, 30-95 parts of liquid phase binder and 0-30 parts of nano conductive functional phase.
Preferably, the liquid phase binder is polymethyl methacrylate or sodium alginate mixed solution;
the polymethyl methacrylate mixed solution is prepared by mixing 100 parts of polymethyl methacrylate powder, 50 parts of methyl methacrylate, 0.5 part of dibenzoyl peroxide and 0.3 part of N, N-dimethyl-p-toluidine by mass;
the sodium alginate mixed solution is prepared by mixing 2 parts of sodium alginate, 3 parts of disodium hydrogen phosphate, 1 part of gluconolactone and 100 parts of water according to parts by mass;
after the mixed solution of the liquid phase binder is prepared, the solid phase borosilicate bioglass powder and the nanometer conductive functional phase are added and uniformly mixed, and the bioglass composite bone cement is formed after solidification.
Preferably, in the bioglass composite bone cement, the mass part of the nano conductive functional phase is 0-30 parts, but 0 is not included.
Preferably, the nano conductive functional phase comprises one or more of titanium nitride particles with the particle size of 10-500 nm and gold nanoparticles with the particle size of 10-100 nm.
Compared with the prior art, the invention has at least one of the following beneficial effects:
1. the borosilicate bioglass powder is subjected to surface pretreatment by using a direct current electric field, so that boron, calcium and other ions on the surface layer of the powder can be partially pulled out quickly to form a silicon-rich glass phase film layer and form a diffusion pore channel suitable for the ion diffusion in the middle and later stages; therefore, in the initial stage of implantation of the bioglass composite bone cement prepared from the bioglass composite bone cement, the surface layer of the glass powder contains less boron and calcium, so that the release of active ions is less, and the biological safety of the composite bone cement in the initial stage of implantation (implantation for 1-2 days) is guaranteed; and the existence of the diffusion channel can ensure that active ions such as boron, calcium and the like in the glass can be rapidly separated out in the middle and later periods, and the better biological activity of the glass is effectively maintained.
2. A human body safe direct current electric field is applied in vitro in the middle and later stages (after being implanted for 1-2 weeks) of the borosilicate bioglass composite bone cement implantation, the release speed of active ions in bioglass can be regulated and controlled, the slower and slower mineralization process can be accelerated again, the degradation and mineralization of bioglass and the growth of self bones are accelerated in vitro, and the healing of fracture parts is promoted.
3. On the basis of bioactive glass, a nano conductive functional phase such as titanium nitride, nano gold particles and the like is introduced, so that the conductivity of the bioglass bone cement can be improved, and the direct-current electric field induced mineralization efficiency is improved.
4. The middle and later period bone repair performance of the bioactive glass can be regulated and controlled by changing the introduction amount of the nano conductive functional phase and the parameters of an external electric field, so that the requirements of postoperative rehabilitation of different parts of bone repair are met.
Drawings
FIG. 1 is a schematic view of an electric field processing apparatus for immersing borosilicate bioglass powder or composite bone cement in a human body simulated body fluid.
Fig. 2 shows the surface morphology (1) and the calcium-phosphorus ratio (2) of borosilicate bioglass particles after being soaked in human simulated body fluid and treated by an electric field for 1h and 3d every day, wherein a1 and a2 are control groups without an electric field, b1 and b2 are samples loaded with 30mA, c1 and c2 are samples loaded with 60mA, and d1 and d2 are samples loaded with 90 mA.
FIG. 3 is XRD spectra of borosilicate bioglass particles immersed in simulated body fluid of human body at current intensities of 0mA, 30mA, 60mA, and 90mA, respectively, after being treated with electric field for 1h and 14d each day.
Detailed Description
An electric field processing method of bioglass composite bone cement comprises the following steps of S1: and applying a direct current electric field to the borosilicate bioglass powder to induce surface pretreatment.
In step S1, preferably, a dc electric field induced surface pretreatment is applied to borosilicate bioglass powder for generating a silicon-rich glass phase slow-release film layer containing diffusion channels. Preferably, the borosilicate bioglass powder is placed in human body simulation body fluid and a direct current electric field is applied, the current is 100-300 mA, and the time is 2-10 h, so that the silicon-rich glass phase slow release film layer containing the diffusion pore channel is formed.
Preferably, the processing method further includes step S2: and loading a safe direct current electric field on the cured bioglass composite bone cement prepared from borosilicate bioglass powder.
In step S2, a safe dc electric field is preferably applied to the cured bioglass composite bone cement for regulating the release rate and mineralization rate of active ions in the borosilicate bioglass composite bone cement. Further preferably, after the bioglass composite bone cement is solidified, a safe direct current field is applied to regulate and control the release speed of active ions in the bioglass composite bone cement, the current of the direct current field is 0.1-90 mA, and the direct current field is applied for 1-24 hours every day.
The bioglass composite bone cement disclosed by the invention can be composed of 5-70 parts by mass of solid borosilicate bioglass powder, 30-95 parts by mass of liquid-phase binder and 0-30 parts by mass of nano conductive functional phase.
The liquid phase binder is preferably polymethyl methacrylate or sodium alginate mixed solution; the polymethyl methacrylate mixed solution can be prepared by mixing 100 parts of polymethyl methacrylate powder, 50 parts of methyl methacrylate, 0.5 part of dibenzoyl peroxide and 0.3 part of N, N-dimethyl-p-toluidine by mass; the sodium alginate mixed solution can be prepared by mixing 2 parts of sodium alginate, 3 parts of disodium hydrogen phosphate, 1 part of gluconolactone and 100 parts of water according to parts by mass; after the mixed solution of the liquid phase binder is prepared, the solid phase borosilicate bioglass powder and the nanometer conductive functional phase are added and uniformly mixed, and the bioglass composite bone cement is formed after solidification. Preferably, in the bioglass composite bone cement, the weight part of the nano conductive functional phase is 0-30 parts, but 0 is not included. Further preferably, the nano conductive functional phase comprises one or more of titanium nitride particles with the particle size of 10-500 nm and gold nanoparticles with the particle size of 10-100 nm.
The invention is further illustrated below with reference to examples and figures. The embodiments of the present invention are not limited to the following specific embodiments. The present invention can be modified as appropriate without changing the scope of the right.
Example 1
The basic chemical composition is 54SiO2-6Na2O-8K2O-8MgO-22CaO-2P2O5(mol%) borosilicate bioglass powder is placed in human body Simulated Body Fluid (SBF) at 37 ℃ and is applied with a direct current electric field for pretreatment, the application time is 5h, the current is 200mA, and a silicon-rich glass phase slow release film layer containing diffusion pore channels is generated on the surfaces of bioglass powder particles. And then taking 50 parts by mass of the pretreated borosilicate bioglass powder, 40 parts by mass of sodium alginate mixed solution and 10 parts by mass of titanium nitride nano conductive functional phase with the average particle size of 400nm to prepare the borosilicate bioglass composite bone cement, curing and molding the borosilicate bioglass composite bone cement, and soaking the borosilicate bioglass composite bone cement in human body Simulation Body Fluid (SBF) to keep a constant temperature environment of 37 ℃. The change of the concentration of active ions in the soaking solution is tested by using an inductive coupling plasma emission instrument, the release amount of boron ions and calcium ions of the bioglass composite bone cement soaked in the soaking solution on day 1 is respectively reduced by 9 percent and 7 percent, and the release amount of boron ions and calcium ions is respectively increased by 3 percent and 2 percent on the third day compared with a control group which is not pretreated by an electric field.
Example 2
Taking 10 parts by mass of a basic chemical composition of 54SiO2-6Na2O-8K2O-8MgO-22CaO-2P2O5Mixing borosilicate bioglass powder (mol%) with 90 parts of PMMA (polymethyl methacrylate) solution to prepare borosilicate bioglass composite bone cement, curing and molding, soaking in human body Simulation Body Fluid (SBF), keeping the temperature of 37 ℃ constant, applying a direct current electric field for 1h to the human body simulation body fluid containing the bone cement every day after 8 days, wherein the current is respectively 30mA, 60mA and 90mA, setting a control group without an electric field, soaking in the human body simulation body fluid for 1h and 3d in the electric field every day, and then treating the mixtureThe surface appearance and the calcium-phosphorus ratio of the borosilicate bioglass particles are shown in fig. 2, and it can be seen from the graph that hydroxyapatite particles precipitated on the surface of the borosilicate bioglass particles in the degradation process are increased continuously along with the increase of the loading current intensity, the hydroxyapatite particles are converted into a compact needle-shaped hydroxyapatite layer similar to the human skeleton structure from the particles, and the calcium-phosphorus ratio Ca/P of the borosilicate bioglass particles is also gradually close to 1.67 theoretical calcium-phosphorus ratio of the hydroxyapatite, which shows that the loading of a direct current electric field obviously promotes the mineralization efficiency of the borosilicate bioglass and the composite bone cement thereof. For the test group with the current of 60mA, the relative content of the hydroxyapatite in the bone cement is analyzed by utilizing an X-ray diffraction spectrum, and compared with a control group without an electric field, the hydroxyapatite generation rate is improved by 2.3 times after 21 days.
Example 3
The basic chemical composition is 54SiO2-6Na2O-8K2O-8MgO-22CaO-2P2O5(mol%) borosilicate bioglass powder is placed in human body Simulation Body Fluid (SBF) at 45 ℃ and is applied with a direct current electric field for pretreatment, the application time is 3h, the current is 300mA, and a silicon-rich glass phase slow release film layer containing diffusion pores is generated on the surfaces of bioglass powder particles. And further taking 70 parts by mass of the pretreated borosilicate bioglass powder and 30 parts by mass of sodium alginate mixed solution to prepare the borosilicate bioglass composite bone cement, curing and molding the borosilicate bioglass composite bone cement, and soaking the borosilicate bioglass composite bone cement in human body Simulated Body Fluid (SBF) to keep a constant temperature environment of 37 ℃. The change of the concentration of active ions in the soaking solution is tested by using an inductive coupling plasma emission instrument, the release amount of boron ions and calcium ions of the bioglass composite bone cement soaked in the soaking solution for the 1 st day is respectively reduced by 12 percent and 10 percent compared with that of a control group which is not pretreated by an electric field, and the release amount of boron ions and calcium ions is respectively increased by 4 percent and 3 percent for the third day. And applying a direct current electric field for 5 hours with 5mA of current to the human body simulated body fluid containing the bone cement every day after the biological glass composite bone cement is soaked for 10 days. The relative content of the hydroxyapatite in the bone cement is analyzed by utilizing an X-ray diffraction spectrum, and compared with a control group without an electric field, the hydroxyapatite generation rate is improved by 30 percent after 21 days.
Example 4
The basic chemical composition is 54SiO2-6Na2O-8K2O-8MgO-22CaO-2P2O5(mol%) borosilicate bioglass powder is placed in human body Simulated Body Fluid (SBF) at 37 ℃ and is applied with a direct current electric field for pretreatment, the application time is 2h, the current is 100mA, and a silicon-rich glass phase slow release film layer containing diffusion pore channels is generated on the surfaces of bioglass powder particles. And then taking 20 parts by mass of the pretreated borosilicate bioglass powder, 75 parts by mass of PMMA mixed solution and 5 parts by mass of nanogold conductive functional phase with the average particle size of 50nm to prepare the borosilicate bioglass composite bone cement, curing and molding the borosilicate bioglass composite bone cement, and soaking the borosilicate bioglass composite bone cement in human body Simulation Body Fluid (SBF) to keep a constant temperature environment of 37 ℃. The change of the concentration of active ions in the soaking solution is tested by using an inductive coupling plasma emission instrument, the release amount of boron ions and calcium ions of the bioglass composite bone cement soaked in the soaking solution for the 1 st day is reduced by 3 percent compared with that of a control group which is not pretreated by an electric field, and the biological glass composite bone cement soaked in the soaking solution for the third day is the same as that of the control group. After the biological glass composite bone cement is soaked for 15 days, a direct current electric field is applied to human body simulation body fluid containing the bone cement every day for 1h, the current intensities are respectively 30mA, 60mA and 90mA, a control group without the electric field is arranged, an XRD spectrum of borosilicate biological glass particles after being soaked in the human body simulation body fluid and being subjected to electric field treatment for 1h and 14d every day is shown in figure 3, and as can be seen from figure 3, along with the increase of the loading current intensity, the HA precipitation amount of hydroxyapatite in a sample is obviously increased, compared with the control group without the electric field (0mA), the hydroxyapatite generation rate is greatly increased, even calcium carbonate crystals beneficial to bone repair appear in the sample loaded with 90mA, and the effect of the direct current electric field loading on the mineralization promotion of the borosilicate biological glass and the composite bone cement thereof is shown.
For the test group with the current of 30mA, the relative content of the hydroxyapatite in the bone cement is analyzed by utilizing an X-ray diffraction spectrum, and compared with a control group without an electric field, the hydroxyapatite generation rate is improved by 40 percent after 21 days.
Example 5
The basic chemical composition is 54SiO2-6Na2O-8K2O-8MgO-22CaO-2P2O5(mol%) borosilicate bioglass powder is placed in human body Simulated Body Fluid (SBF) at 40 ℃ and is applied with a direct current electric field for pretreatment, the application time is 10h, the current is 150mA, and diffusion-containing pore channels are generated on the surfaces of bioglass powder particlesThe silicon-rich glass phase slow release film layer. And then taking 35 parts by mass of the pretreated borosilicate bioglass powder, 60 parts by mass of PMMA mixed solution and 5 parts by mass of titanium nitride nano conductive functional phase with the average particle size of 20nm to prepare the borosilicate bioglass composite bone cement, curing and molding the borosilicate bioglass composite bone cement, and soaking the borosilicate bioglass composite bone cement in human body Simulation Body Fluid (SBF) to keep a constant temperature environment of 37 ℃. The change of the concentration of active ions in the soaking solution is tested by using an inductive coupling plasma emission instrument, the release amount of boron ions and calcium ions of the bioglass composite bone cement soaked in the soaking solution for the 1 st day is respectively reduced by 11 percent and 8 percent, and the release amount of boron ions and calcium ions is respectively increased by 3 percent and 2 percent in the soaking solution for the third day compared with a control group which is not pretreated by an electric field. And applying a direct current electric field to the human body simulated body fluid containing the bone cement for 24 hours every day after the biological glass composite bone cement is soaked for 8 days, wherein the current is 0.5 mA. The relative content of the hydroxyapatite in the bone cement is analyzed by utilizing an X-ray diffraction spectrum, and compared with a control group without an electric field, the hydroxyapatite generation rate is improved by 15 percent after 21 days.
The above example was carried out in the apparatus shown in FIG. 1. The bioglass powder or bioglass bone cement is placed in a thermostatic bath with 37 ℃ for storing human body simulation body fluid, and a direct current electric field is loaded on a sample by utilizing a direct current power supply and a platinum electrode in a constant current mode.
In the above embodiment, the polymethyl methacrylate mixed solution is prepared by mixing, by mass, 100 parts of polymethyl methacrylate powder, 50 parts of methyl methacrylate, 0.5 part of dibenzoyl peroxide, and 0.3 part of N, N-dimethyl-p-toluidine; the sodium alginate mixed solution is prepared by mixing 2 parts of sodium alginate, 3 parts of disodium hydrogen phosphate, 1 part of gluconolactone and 100 parts of water according to parts by mass; after the mixed solution of the liquid phase binder is prepared, the solid phase borosilicate bioglass powder and the nanometer conductive functional phase are added and uniformly mixed, and the bioglass composite bone cement is formed after solidification.
The embodiments described above are intended to facilitate the understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.