COMPOSITE SCAFFOLD MATERIAL, PREPARATION METHOD THEREFOR AND USE THEREOF

Abstract

The present disclosure relates to the technical field of medicines, and in particular, to a composite scaffold material, a preparation method therefor and use thereof. The present disclosure provides a composite scaffold material, including a charged fiber framework material. The fiber framework material is coated with positively charged biocompatible materials and negatively charged biocompatible materials alternately, by means of electrostatic attraction. The composite scaffold material of the present disclosure overcomes the defects of traditional scaffold materials, such as poor hydrophilicity, biocompatibility, histiocyte adhesion ability, and biological induction activity. The composite scaffold material has better applicability when used for tissue adhesion, closure, leaking stoppage, hemostasis, isolation, repair, and adhesion prevention, and can also be used for preparing a drug carrier (e.g., sustained release carrier) and a tissue engineering scaffold material. Therefore the composite scaffold material has a wide range of industrial uses.

Claims

1. A composite scaffold material, comprising a charged fiber framework material, wherein the fiber framework material is coated with a positively charged biocompatible material and a negatively charged biocompatible material alternately by means of electrostatic attraction.

2. The composite scaffold material according to claim 1, further comprising one or more of the following: A1) the forms of the composite scaffold material and/or the fiber framework material are layers and/or spheres and/or tubes; A2) the fiber framework material is composed of a fiber; A3) a diameter of the fiber is 3 nm-60000 nm; A4) a volume percentage of the fiber in the fiber framework material is 20%-90%.

3. The composite scaffold material according to claim 2, further comprising one or more of the following: B1) the fiber is prepared by electrospinning and/or 3D printing; B2) the fiber constituting the fiber framework material is charged; B3) the fiber constituting the fiber framework material is a fiber obtained through charge modification treatment; B4) the fiber constituting the fiber framework material carries a positively charged group and/or a negatively charged group, wherein the positively charged group is selected from a group consisting of amino group, quaternary ammonium group, and a combination thereof; the negatively charged group is selected from a group consisting of mercapto group, carboxyl group, sulfonic group, phosphate group, and combinations thereof; B5) the fiber is a biocompatible material, and the fiber is a polymer material; B6) the fiber is a polymer biocompatible material, and the polymer biocompatible material is an organic synthesized polymer material and/or a natural biopolymer material; B7) the fiber is doped with a charged doping material, and the doping material is selected from a natural biopolymer material.

4. The composite scaffold material according to claim 3, wherein the natural biopolymer material is selected from a group consisting of polylysine, polyglutamic acid, collagen, silk fibroin, soy protein, elastin, hyaluronic acid, chitosan, carboxymethyl chitosan, carboxymethyl dextran, carboxymethyl glucose, heparin, alginic acid, chondroitin sulfate, carboxymethyl starch and carboxymethyl cellulose; the organic synthesized polymer material is selected from a group consisting of polylactic acid, polyglycolic acid, polycaprolactone, polylactic acid glycolic acid copolymer, polylactic acid caprolactone copolymer, polydioxanone, trimethylene carbonate, polyethylene, polypropylene, polytetrafluoroethylene, polyurethane, polyethylene glycol, polyvinylpyrrolidone, and combinations thereof.

5. The composite scaffold material according to claim 1, further comprising one or more of the following: C1) the fiber framework material is supplemented with a functional factor and/or a functional polypeptide, an amount of the added functional factor in the fiber framework material is not more than 50 wt %, and an amount of the added functional polypeptide in the fiber framework material is not more than 50 wt %; C2) the fiber framework material is coated with a positively charged biocompatible material and a negatively charged biocompatible material alternately by means of electrostatic self-assembly. C3) the positively charged biocompatible material is selected from a group consisting of polylysine, collagen, silk fibroin, fibronectin, laminin, fibrinogen, chitosan, and combinations thereof the negatively charged biocompatible material is selected from a group consisting of polyglutamic acid, collagen, silk fibroin, fibronectin, laminin, fibrinogen, hyaluronic acid, carboxymethyl chitosan, carboxymethyl dextran, carboxymethyl glucose, heparin, alginic acid, chondroitin sulfate, carboxymethyl starch, carboxymethyl cellulose, and combinations thereof; C4) the positively charged biocompatible material and/or the negatively charged biocompatible material are supplemented with a functional factor and/or a functional polypeptide, an amount of the added functional factor in the positively charged biocompatible material and/or the negatively charged biocompatible material is not more than 50 wt %, and an amount of the added functional polypeptide in the positively charged biocompatible material and/or the negatively charged biocompatible material is not more than 50 wt %.

6. The composite scaffold material according to claim 5, wherein the functional factor is selected from a group consisting of fibronectin, laminin, vascular endothelial growth factor, fibrinogen, nerve growth factor, epidermal growth factor, fibroblast growth factor, transforming growth factor, bone morphogenetic protein, insulin-like growth factor, platelet-derived growth factor, hydroxyapatite, strontium chloride, thrombin, and combinations thereof; the functional polypeptide is selected from a group consisting of RGD polypeptide, polypeptide containing -arginine-glycine-aspartic acid, polypeptide containing -valine-glycine-valine-alanine-proline-glycine, polypeptide containing -isoleucine-lysine-valine-alanine-valine, and combinations thereof.

7. The composite scaffold material according to claim 1, wherein the fiber framework material accounts for 5-95% of a total mass of the composite scaffold material, and the positively charged biocompatible material and the negatively charged biocompatible material account for 5-95% of a total mass of the composite scaffold material.

8. A preparation method for the composite scaffold material according to claim 1, comprising: forming a polymer biocompatible material into a fiber framework material by electrospinning and/or 3D printing, and alternately coating the fiber framework material with a positively charged biocompatible material and a negatively charged biocompatible material by electrostatic self-assembly.

9. The preparation method according to claim 8, further comprising one or more of the following: D1) an injection speed in electrospinning is 0.001-90 mm/min, a positive voltage of a high voltage generator is 0.1-40 kv, a negative voltage of the high voltage generator is 0.1-10 kv, and a distance between a spinning injector and a receiving device is 3-30 cm, a speed of 3D printing is 0.001 mm-100 mm/min, a printing temperature is −20° C.-400° C., and the electrostatic self-assembly adopts spraying and/or soaking method; D2) drying and sterilizing are operated after the self-assembly; D3) electrospinning and/or 3D printing are carried out in the presence of a solvent, and the solvent is selected from a group consisting of formic acid, acetic acid, ethanol, acetone, dimethylformamide, dimethylacetamide, tetrahydrofuran, dimethyl sulfoxide, hexafluoroisopropanol, trifluoroethanol, dichloromethane, trichloromethane, methanol, chloroform, dioxane, trifluoroethane, trifluoroacetic acid, water, normal saline, buffer solution, and combinations thereof.

10. Use of the composite scaffold material according to claim 1 in the preparation of biocompatible materials, preferably in the preparation of tissue adhesive films, tissue repair and regeneration patches, drug carrier materials and/or tissue engineering scaffold materials.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0023] FIG. 1 is a schematic diagram of the scanning electron microscope test results of Embodiment 10 of the present disclosure.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] The embodiments of the present disclosure will be described below through exemplary embodiments. Those skilled in the art can easily understand other advantages and effects of the present disclosure according to contents disclosed by the specification. The present disclosure can also be implemented or applied through other different exemplary embodiments. Various modifications or changes can also be made to all details in the specification based on different points of view and applications without departing from the spirit of the present disclosure.

[0025] It should be noted that processing equipment or devices not specifically noted in the following embodiments are all conventional equipment or devices in the field.

[0026] In addition, it should be understood that one or more method steps mentioned in the present disclosure are not exclusive of other method steps that may exist before or after the combined steps or that other method steps may be inserted between these explicitly mentioned steps, unless otherwise stated; it should also be understood that the combined connection relationship between one or more equipment/devices mentioned in the present disclosure does not exclude that there may be other equipment/devices before or after the combined equipment/devices or that other equipment/devices may be inserted between these explicitly mentioned equipment/devices, unless otherwise stated. Moreover, unless otherwise stated, the numbering of each method step is only a convenient tool for identifying each method step, and is not intended to limit the order of each method step or to limit the scope of the present disclosure. The change or adjustment of the relative relationship shall also be regarded as the scope in which the present disclosure may be implemented without substantially changing the technical content.

Embodiment 1

[0027] Preparing a drying culture dish (ϕ=12 cm, washed, sterilized and dehydrogenated), using as an electrospinning receiver; weighing 1 g PLGA and 0.2 g collagen, adding 10 ml hexafluoroisopropanol to prepare an electrospinning A solution of degradable polymer material PLGA and cationic group material; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 0.1-0.3 mm/min, adjusting the positive voltage to 15V and negative voltage to 2V, adjusting the receiving distance of the receiving device to 15 cm; the fibers are received as a film-like structure to prepare an electrospun membrane A.

[0028] Weighing 0.5 g carboxymethyl dextran, dissolving in water and adjusting pH=6 to prepare B solution with anionic groups; pouring the above solution into the culture dish that has prepared electrospun membrane A, soaking, drying and forming membrane, and assembling a layer of carboxymethyl dextran membrane B on electrospun membrane A.

[0029] Continuing to prepare an electrospun membrane A on the carboxymethyl dextran membrane, assembling a layer of carboxymethyl dextran membrane B on the electrospun membrane A, and coating 20 times alternately, rinsing with water-for-injection, freeze-drying, peeling off the membrane, and sterilizing the product by irradiation.

Embodiment 2

[0030] Preparing a drying culture dish (,washed, sterilized and dehydrogenated) using as an electrospinning receiver; weighing 1 g PLA and 0.2 g chitosan and adding 10 ml hexafluoroisopropanol to prepare an A solution of degradable polymer material PLA and cationic group material; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 0.5 mm/min, adjusting the positive voltage to 15V and negative voltage to 2V, adjusting the receiving distance of the receiving device to 10 cm, and electrospinning 20 layers of electrospun membrane A.

[0031] Weighing 0.5 g carboxymethyl dextran, dissolving in water and adjusting pH=6 to prepare B solution with anionic group material. Pouring the above solution into the polypropylene culture dish that has prepared electrospun membrane A, soaking, drying and forming membrane. Sterilizing the product with ethylene oxide.

Embodiment 3

[0032] Preparing a drying culture dish (4)=12 cm, washed, sterilized and dehydrogenated),; weighing 0.5 g hyaluronic acid, dissolving in water and adjusting pH=6 to prepare A solution with anionic group material. Spraying the above A solution on the culture dish and drying and forming membrane A; weighing 0.5 g chitosan, dissolving in water and adjusting pH=4 to prepare B solution of cationic group material; spraying B solution on the membrane A to make the B solution to assemble under the action of electrostatic force; coating 20 times alternately by electrostatic assembly to obtain the electrostatic assembly membrane. Weighing 1 g PCL and 0.2 g polylysine and adding 10 ml hexafluoroisopropanol to prepare an electrospinning C solution of degradable polymer material PCL and cationic group material; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 1.0 mm/min, adjusting the positive voltage to 15V and negative voltage to 3V, adjusting the receiving distance of the receiving device to 20 cm, and wrapping the electrospinning fibers on the prepared electrostatic assembly membrane, and freeze-drying. Sterilizing the product by irradiation.

Embodiment 4

[0033] Preparing a drying polypropylene culture dish (ϕ=12 cm, washed, sterilized and depyrogenated), and using as an electrospinning receiver; weighing 1 g PLGA and 0.2 g hyaluronic acid and adding 10 ml hexafluoroisopropanol to prepare an electrospinning A solution of degradable polymer material PLGA and anionic group material; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 0.3 mm/min, adjusting the positive voltage to 15V and negative voltage to 2V, adjusting the receiving distance of the receiving device to 15 cm; the fibers are received as a film-like structure to prepare an electrospun membrane A.

[0034] Weighing 0.5 g collagen, dissolving in water and adjusting pH=6 to prepare B solution with cationic groups; pouring the above solution into the culture dish that has prepared electrospun membrane A, soaking, drying and forming membrane, and assembling a layer of collagen membrane B on the electrospun membrane A.

[0035] Continuing to prepare an electrospun membrane A on the collagen membrane, assembling a layer of collagen membrane B on the electrospun membrane A, and repeating the superimposition 50 times, rinsing with water-for-injection, freeze-drying, peeling off the membrane, and sterilizing the product by irradiation.

Embodiment 5

[0036] Preparing a culture dish (washed, sterilized and dehydrogenated) with a diameter of 12 cm, drying, and using as an electrospinning receiver; weighing 1 g PLA and 0.2 g carboxymethyl dextran and adding 10 ml hexafluoroisopropanol to prepare an A solution of degradable polymer material PLA and anionic group material; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 0.1-0.3 mm/min, adjusting the positive voltage to 15V and negative voltage to 2V, adjusting the receiving distance of the receiving device to 15 cm, and electrospinning 50 layers of electrospun membrane A.

[0037] Weighing 0.5 g chitosan, dissolving in water and adjusting pH=4 to prepare B solution with cationic group material. Pouring the above solution into the culture dish that has prepared electrospun membrane A, soaking and drying into a membrane. Sterilizing the product with ethylene oxide.

Embodiment 6

[0038] Preparing a culture dish (washed, sterilized and dehydrogenated) with a diameter of 12 cm, drying, and using as an electrospinning receiver; weighing 1 g PLA and 0.2 g hyaluronic acid and adding 10 ml hexafluoroisopropanol to prepare an A solution of degradable polymer material PLA and anionic group material; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 2.5 mm/min, adjusting the positive voltage to 20V and negative voltage to 4V, adjusting the receiving distance of the receiving device to 25 cm, and electrospinning 20 layers of electrospun membrane A.

[0039] Weighing 0.5 g collagen, dissolving in acetic acid solution and adjusting pH=6 to prepare B solution with cationic group material; adding 10% thrombin (concentration: 2000 IU/ml) to B solution. Pouring the above solution into the culture dish that has prepared electrospun membrane A, soaking and drying into a membrane. Sterilizing the product by irradiation.

Embodiment 7

[0040] Preparing a culture dish (washed, sterilized and dehydrogenated) with a diameter of 12 cm, drying, and using as an electrospinning receiver; weighing 1 g PLGA and 0.2 g collagen and adding 10 ml hexafluoroisopropanol to prepare an electrospinning A solution of degradable polymer material PLGA and cationic group material, adding RGD polypeptide to A solution; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 0.8 mm/min, adjusting the positive voltage to 12V and negative voltage to 2V, adjusting the receiving distance of the receiving device to 10 cm; the fibers are received as a film-like structure to prepare an electrospun membrane A.

[0041] Weighing 0.5 g carboxymethyl dextran, dissolving in water and adjusting pH=6 to prepare B solution with anionic groups; pouring the above solution into the culture dish that has prepared electrospun membrane A, soaking and drying into a membrane, and assembling a layer of carboxymethyl dextran membrane B on electrospun membrane A.

[0042] Continuing to prepare an electrospun membrane A on the carboxymethyl dextran membrane, assembling a layer of carboxymethyl dextran membrane B on the electrospun membrane A, and repeating the superimposition 20 times. Rinsing with water-for-injection, freeze-drying, and sterilizing the product with ethylene oxide.

Embodiment 8

[0043] Using a rotatable hollow duct (washed, sterilized and dehydrogenated) as an electrospinning receiver; weighing 1 g PLGA and 0.2 g collagen and adding 10 ml hexafluoroisopropanol to prepare an electrospinning A solution of degradable polymer material PLGA and cationic group material; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 0.2 mm/min, adjusting the positive voltage to 10V and negative voltage to 1V, adjusting the receiving distance of the receiving device to 15 cm, and preparing a tubular electrospun membrane.

[0044] Weighing 0.5 g hyaluronic acid, dissolving in water and adjusting pH=6 to prepare B solution with anionic groups; soaking the above electrospinning duct into the B solution for electrostatic assembly, drying into a membrane, rinsing with water-for-injection, freeze-drying, and sterilizing the product by irradiation.

Embodiment 9

[0045] Using a roller as an electrospinning receiver, and wrapping a layer of aluminum foil (washed, sterilized and dehydrogenated) on the roller; weighing 1 g PLGA and 0.2 g collagen and adding 10 ml hexafluoroisopropanol to prepare an electrospinning A solution of degradable polymer material PLGA and cationic group material; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 0.4 mm/min, adjusting the positive voltage to 15V and negative voltage to 2V, adjusting the receiving distance of the receiving device to 15 cm; the fibers are received as a film-like structure, which is torn off from the aluminum foil to prepare an electrospun membrane A.

[0046] Weighing 0.5 g sodium carboxymethylcellulose, dissolving in water and adjusting pH=6 to prepare B solution with anionic groups, adding 0.5 g metformin hydrochloride to B solution to dissolve; soaking the above electrospun membrane into the B solution for electrostatic assembly, drying into a membrane, rinsing with water-for-injection, freeze-drying, and sterilizing the product by irradiation.

Embodiment 10

[0047] Preparing a culture dish (washed, sterilized and dehydrogenated) with a diameter of 12 cm, drying, and using as an electrospinning receiver; weighing 1 g PLGA, adding 10 ml acetone to dissolve, and preparing an electrospinning A solution of degradable polymer material PLGA; adding the above solution to the injector of the electrospinning device, adjusting the injection rate of the micro-injection pump to 0.1-0.3 mm/min, adjusting the positive voltage to 15V and negative voltage to 2V, adjusting the receiving distance of the receiving device to 15 cm; the fibers are received as a film-like structure to prepare an electrospun membrane A.

[0048] Weighing 0.5 g carboxymethyl dextran, dissolving in water and adjusting pH=6 to prepare B solution with anionic groups; pouring the above solution into the culture dish that has prepared electrospun membrane A, soaking and drying into a membrane, and assembling a layer of carboxymethyl dextran membrane B on electrospun membrane A.

[0049] Weighing 0.5 g collagen, dissolving in acetic acid solution to dissolve, and preparing C solution with cationic groups; pouring the above solution into the culture dish, soaking and drying into a membrane, and assembling a layer of collagen on the membrane B through electrostatic assembly. Alternately superimposing B solution and C solution for 20 times and then superimposing A by electrospinning; continuously and alternately repeating 5 times, rinsing with water-for-injection, freeze-drying, and sterilizing the product with ethylene oxide.

Embodiment 11

[0050] Weighing 1 g PLGA, adding 10 ml acetone to dissolve, preparing 3D printing A solution of degradable polymer material PLGA; adding the above solution to the 3D printing device, importing the meningeal tissue related data into the computer, 3D printing into A membrane, the printing rate is 0.1 mm/min, the printing temperature is 10° C.

[0051] Weighing 0.1 g hyaluronic acid, dissolving in water and adjusting pH=6 to prepare B solution with anionic groups; placing the above 3D printing membrane A into the solution for soaking, drying into a membrane, and assembling a layer of carboxymethyl dextran membrane B on the 3D printing membrane A.

[0052] Weighing 0.1 g collagen, dissolving in acetic acid solution to dissolve, and preparing C solution with cationic groups; placing the above 3D printing membrane into the solution C for soaking, drying into a membrane, and assembling a layer of collagen on the membrane B through electrostatic assembly. Alternately superimposing B solution and C solution for 20 times; rinsing with water-for-injection, freeze-drying, and sterilizing the product by irradiation.

Embodiment 12

[0053] The samples prepared by the Embodiments were tested for their hydrophilicity, mechanical properties, immersion shrinkage, and scanning electron microscope. For the preparation method of the PLGA electrospun membrane used in this Embodiment, please refer to the preparation method of the electrospun membrane A in Embodiment 10.

[0054] 1. Hydrophilicity. The hydrophilicity of the samples was evaluated by the contact angle, and the technical standard for measuring the contact angle refers to GB/T 30447-2013. The results are shown in Table 1:

TABLE-US-00001 TABLE 1 Samples Contact angle° PLGA electrospun membrane 140.3 composite scaffold material of Embodiment 1 66.3 composite scaffold material of Embodiment 2 70.1 composite scaffold material of Embodiment 3 85.2 composite scaffold material of Embodiment 4 77.9 composite scaffold material of Embodiment 5 65.9 composite scaffold material of Embodiment 6 59.4 composite scaffold material of Embodiment 7 71.2 composite scaffold material of Embodiment 8 62.4 composite scaffold material of Embodiment 9 64.6 composite scaffold material of Embodiment 10 66.6 composite scaffold material of Embodiment 11 73.3

[0055] The test results show that all the composite scaffold materials made by the Embodiments of this technique have a contact angle of less than 90°. The single PLGA electrospun membrane has a contact angle of 140°, indicating that the scaffold material has changed from highly hydrophobic to hydrophilic.

[0056] 2. Mechanical property. The technical standard for measuring mechanical properties refers to GB/T 1014.1-2006. The results are shown in Table 2:

TABLE-US-00002 TABLE 2 Young's Maximum Fracture Tensile Breaking modulus of force strength strength elongation elasticity Samples N KPa KPa % KPa PLGA electrospun 4.874 385.401 2235.736 12.207 167680.221 membrane composite scaffold 10.111 666.852 4932.027 18.092 182749.963 material of Embodiment 1 composite scaffold 13.12 844.328 6399.578 20.72 268842.696 material of Embodiment 2 composite scaffold 5.77 485.465 3258.239 16.55 105181.774 material of Embodiment 3 composite scaffold 7.375 689.407 3192.468 14.783 437042.252 material of Embodiment 4 composite scaffold 10.129 1090.393 8424.110 19.135 310431.341 material of Embodiment 5 composite scaffold 5.001 538.357 4841.700 15.086 209072.405 material of Embodiment 6 composite scaffold 5.462 656.906 4551.920 19.438 190560.441 material of Embodiment 7 composite scaffold 3.981 547.155 5926.771 12.687 111679.501 material of Embodiment 8 composite scaffold 4.873 536.340 5957.428 11.568 144981.253 material of Embodiment 9 composite scaffold 6.553 398.122 3956.092 16.095 170848.495 material of Embodiment 10 composite scaffold 2.873 430.025 3428.527 15.455 265741.466 material of Embodiment 11

[0057] 3. Immersion experiment. Placing the samples in physiological saline and then placing in a constant temperature incubator, measuring the surface area change rate at 10 min, 20 min, 30 min, 2 h and 24 h. The test results are shown in Table 3:

TABLE-US-00003 TABLE 3 Samples Immersing time 10 min 20 min 30 min 2 h 24 h PLGA electrospun Area change rate % 16.2 22.6 24.4 31.3 54.7 membrane composite scaffold material Area change rate % 5.3 7.7 8.2 12.2 18.5 of Embodiment 1 composite scaffold material Area change rate % 5.1 7.3 8.0 11.9 18.3 of Embodiment 2 composite scaffold material Area change rate % 6.6 8.1 8.8 12.7 19.2 of Embodiment 3 composite scaffold material Area change rate % 5.5 6.9 8.2 11.9 17.8 of Embodiment 4 composite scaffold material Area change rate % 7.2 9.3 11.5 16.7 20.9 of Embodiment 5 composite scaffold material Area change rate % 6.4 8.4 9.2 12.1 19.6 of Embodiment 6 composite scaffold material Area change rate % 4.1 6.6 7.6 9.5 14.2 of Embodiment 7 composite scaffold material Area change rate % 8.3 10.8 14.6 18.2 22.2 of Embodiment 8 composite scaffold material Area change rate % 4.4 7.0 7.6 10.3 11.7 of Embodiment 9 composite scaffold material Area change rate % 5.2 7.5 8.4 10.6 12.0 of Embodiment 10 composite scaffold material Area change rate % 4.3 7.6 9.0 11.1 12.3 of Embodiment 11

[0058] 4. Scanning electron microscope test. Technical standard: GB/T 16594-2008. The scanning electron microscope test results of the materials prepared in Embodiment 10 are shown in FIG. 1.

[0059] As mentioned above, the present disclosure effectively overcomes various shortcomings in the existing technology and has high industrial utilization value.

[0060] The above-mentioned embodiments are just used for exemplarily describing the principle and effects of the present disclosure instead of limiting the present disclosure. Modifications or variations of the above-described embodiments may be made by those skilled in the art without departing from the spirit and scope of the disclosure. Therefore, all equivalent modifications or changes made by those who have common knowledge in the art without departing from the spirit and technical concept disclosed by the present disclosure shall be still covered by the claims of the present disclosure.