CN112980169A - Fluorescence-labeled degradable 3D printing resin, preparation method and application - Google Patents
Fluorescence-labeled degradable 3D printing resin, preparation method and application Download PDFInfo
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Abstract
The invention discloses a fluorescence-labeled degradable 3D printing resin, a preparation method and application, and relates to the technical field of 3D printing materials. The fluorescence labeling degradable 3D printing resin is formed by compounding PLGA and quantum dots, wherein the quantum dots are selected from at least one quasi-zero-dimensional semiconductor nanocrystal which is composed of II-VI or III-V group elements and has a stable diameter within 20 nm. The quantum dots are adopted to replace conventional doped fluorescent powder and are compounded with PLGA to prepare the luminescent printing composite material, the quantum dots have good safety, stable luminescent intensity and good PLGA solubility, the luminescent performance of the composite material is improved by compounding the quantum dots and the PLGA, and the composite material can be widely applied to the field of medical implant materials.
Description
Technical Field
The invention relates to the technical field of 3D printing materials, in particular to a fluorescence-labeled degradable 3D printing resin, a preparation method and application.
Background
3D printing, also known as additive manufacturing, with Fused Deposition Modeling (FDM) being the most widely used 3D printing technique. The method is a technology for constructing an object by using materials such as high molecular polymers and the like in a layer-by-layer printing mode on the basis of a digital model file. At present, polylactic acid (PLA) is the most common material applied to FDM, and the material as a biodegradable high polymer has good processing performance and mechanical property, but has larger brittleness and longer degradation period, and the application is also limited. Polyglycolic acid (PGA) as another biodegradable high molecular polymer has a high synthesis cost and a low yield by ring-opening polymerization. Polylactic-co-glycolic acid (PLGA) combines the advantages of both PLA and PGA, and PLGA exhibits broader solubility than either pure polylactic or polyglycolic acid, enabling dissolution in more common solvents such as: chlorinated solvents, tetrahydrofuran, acetone or ethyl acetate, and the like.
At present, luminescent 3D printing composite materials are prepared by doping fluorescent powder on the market, the luminescent performance of the printed composite materials is often weakened, and the radioactive fluorescent powder is harmful to human bodies.
The quantum dot is a three-dimensional nanocrystal and has a plurality of excellent optical properties, such as wide excitation wavelength range, narrow and symmetrical emission wavelength range, high quantum yield, long fluorescence lifetime, stable optical properties and the like. The quantum dots can be used as fluorescent probes to mark different components of biological systems, such as tissues, cells, biological macromolecules and living body imaging of animals. However, quantum dots are affected by the preparation method, have poor water solubility, are easy to agglomerate, and have poor stability.
Therefore, it is urgently needed to develop a 3D printing material having stable, safe, and highly efficient luminescence properties.
Disclosure of Invention
The technical problem to be solved by the invention is that the existing 3D luminescent printing material has weak luminescent property and low safety and is difficult to be used for medical implant materials.
In order to solve the above problems, the present invention proposes the following technical solutions:
the invention provides a fluorescence labeling degradable 3D printing resin which is a composite material compounded by PLGA and quantum dots, wherein the quantum dots are selected from at least one quasi-zero-dimensional semiconductor nanocrystal consisting of II-VI or III-V group elements and having a stable diameter within 20 nm.
PLGA refers to polylactic acid-glycolic acid copolymer, and has wider solubility than pure polylactic acid or polyglycolic acid, and can be dissolved in more common solvents.
The further technical scheme is that the quantum dots are selected from at least one of CdTe, CdS, CdSe, ZnSe, ZnO, CdSe/ZnS, CdSe/CdS and CdS/ZnS.
The CdTe, CdS, CdSe, ZnSe, and ZnO are single-layer quantum dots.
CdSe/ZnS, CdSe/CdS and CdS/ZnS are quantum dots with a core-shell structure, a narrow-bandgap semiconductor nano particle is used as a core, another semiconductor nano material with a similar crystal structure and a larger bandgap is used for coating to form a composite nano particle with the core-shell structure, and a shell layer is covered on the surface of the core quantum dot through surface modification to purify the surface of the quantum dot, so that the luminous efficiency is remarkably improved, and the light stability is improved.
The further technical scheme is that the surface of the quantum dot is modified by the following organic matters:
at least one of polyethyleneimine, dimethylaminoethyl polymethacrylate and 4-vinylpyridine.
Understandably, the polyethyleneimine is an amphiphilic dendritic polymer, so that the water solubility and the oxidation resistance of the quantum dot can be improved; the polymethyl methacrylate dimethyl aminoethyl methacrylate is a polybase ligand, so that the stability of the quantum dots in a polar solvent can be improved, and the agglomeration is reduced; the 4-vinylpyridine has the effects of increasing the solubility of the quantum dot in a polar solvent and increasing the stability of the quantum dot.
The further technical scheme is that the mass fraction of the quantum dots of the composite material is 0.5-4%.
The further technical scheme is that the particle size of the quantum dots is 2-20 nm.
It should be noted that, according to the luminescent characteristics of the quantum dots, as the size of the quantum dots is reduced, the fluorescence of the quantum dots undergoes blue shift, so that the invention selects the range of the particle size of the quantum dots between 2 nm and 20nm according to the characteristics of the medical implant material to obtain a good emission spectrum.
The further technical proposal is that the PLGA is at least one selected from alternating copolymer and block copolymer obtained by ring-opening polymerization of lactide and glycolide.
The composite material is further prepared by dissolving PLGA and quantum dots in an organic solvent and then blending.
The further technical scheme is that the organic solvent is at least one selected from dichloromethane, chloroform, tetrahydrofuran, acetone and ethyl acetate.
The invention provides a preparation method of a fluorescence labeling degradable 3D printing resin, which comprises the following steps:
(1) fully dissolving PLGA in an organic solvent to prepare a PLGA solution with the weight percent of 4-6 at room temperature; adding a quantum dot solution into the PLGA solution, and fully and uniformly mixing; distilling and drying the mixed solution to constant weight to obtain a PLGA/quantum dot composite material;
(2) carrying out blending extrusion granulation on the PLGA/quantum dot composite material by using a double-screw extruder, and fully drying to obtain composite material granules;
(3) extruding and drawing the composite material granules by using a double-screw extruder again to obtain a standard wire material for 3D printing with the diameter of 1.75 mm;
the organic solvent is at least one of dichloromethane, trichloromethane, tetrahydrofuran, acetone and ethyl acetate.
The invention also provides application of the fluorescence labeling degradable 3D printing resin in the field of medical implant materials.
Compared with the prior art, the invention can achieve the following technical effects:
the fluorescence-labeled degradable 3D printing resin disclosed by the invention adopts quantum dots to replace conventional doped fluorescent powder, and is compounded with PLGA to prepare the luminescent printing composite material, the quantum dots have good safety and stable luminescent intensity, the PLGA has good solubility, the luminescent performance of the composite material is greatly improved by compounding the quantum dots and the PLGA, and the composite material can be widely applied to the field of medical implant materials.
The fluorescence labeling degradable 3D printing resin has higher tensile strength and compression strength and good comprehensive printing performance, can be used for printing luminous bodies with different shapes according to different designs, is applied to medical degradable materials, has a simple preparation method, and is suitable for industrial production.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
FIG. 1 is an emission spectrum of an artificial bone scaffolding material according to an example of the present invention and a comparative example.
Detailed Description
The technical solutions in the embodiments will be described clearly and completely with reference to the accompanying drawings in the embodiments of the present invention, wherein like reference numerals represent like elements in the drawings. It is apparent that the embodiments to be described below are only a part of the embodiments of the present invention, and not all of them. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It will be understood that the terms "comprises" and/or "comprising," when used in this specification and the appended claims, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.
It is also to be understood that the terminology used in the description of the embodiments of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the embodiments of the invention. As used in the description of embodiments of the present invention and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.
Unless otherwise specified,% of component content in examples and comparative examples refers to mass%.
Example 1
Weighing a certain mass of PLGA, dissolving the PLGA in dichloromethane, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to prepare a PLGA solution with the weight percent of 5; adding the CdTe quantum dot solution modified with 1-thioglycerol on the surface into the PLGA solution, and ultrasonically stirring until the CdTe quantum dot solution and the PLGA solution are fully and uniformly mixed. And distilling the mixed solution at 40 ℃ and drying to constant weight to obtain the PLGA/quantum dot composite material with the quantum dot content of 0.5%.
And (3) carrying out blending extrusion granulation on the PLGA/CdTe composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Example 2
Weighing a certain mass of PLGA, dissolving the PLGA in chloroform, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to prepare a PLGA solution with the weight percent of 5; adding a solution with the surface modified with tri-n-octylphosphine oxide CdSe quantum dots into the PLGA solution, and performing ultrasonic stirring treatment again to fully and uniformly mix the two solutions. And distilling the mixed solution at 65 ℃ and drying to constant weight to obtain the PLGA/quantum dot composite material with the quantum dot content of 1.0%.
And (3) blending, extruding and granulating the PLGA/CdSe composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Example 3
Weighing a certain mass of PLGA, dissolving the PLGA in chloroform, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to prepare a PLGA solution with the weight percent of 5; adding a solution of the quantum dots with the surface modified with the tri-n-octylphosphine oxide CdSe-ZnS into the PLGA solution, and carrying out ultrasonic stirring treatment again to fully and uniformly mix the two solutions. And distilling the mixed solution at 65 ℃ and drying to constant weight to obtain the PLGA/CdSe-ZnS composite material with the quantum dot content of 2.0%.
And (3) carrying out blending extrusion granulation on the PLGA/quantum dot composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Example 4
Weighing a certain mass of PLGA, dissolving the PLGA in chloroform, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to prepare a PLGA solution with the weight percent of 5; adding a solution of the quantum dots with the surface modified with the tri-n-octylphosphine oxide CdSe-ZnS into the PLGA solution, and carrying out ultrasonic stirring treatment again to fully and uniformly mix the two solutions. And distilling the mixed solution at 65 ℃ and drying to constant weight to obtain the PLGA/CdSe-ZnS composite material with the quantum dot content of 4.0%.
And (3) carrying out blending extrusion granulation on the PLGA/quantum dot composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Example 5
Weighing a certain mass of PLGA, dissolving the PLGA in ethyl acetate, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to obtain a PLGA solution with the weight percent of 5.5; adding the CdS/ZnS quantum dot solution subjected to surface modification by using 4-vinylpyridine into the PLGA solution, and performing ultrasonic stirring treatment again to fully and uniformly mix the two solutions. And distilling the mixed solution at 65 ℃ and drying to constant weight to obtain the PLGA/CdS/ZnS composite material with the quantum dot content of 3.0%.
And (3) carrying out blending extrusion granulation on the PLGA/quantum dot composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Example 6
Weighing a certain mass of PLGA, dissolving the PLGA in acetone, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to prepare a PLGA solution with the weight percent of 4; adding the CdSe/CdS quantum dot solution with the surface modified by the poly-dimethylamino ethyl methacrylate into the PLGA solution, and performing ultrasonic stirring treatment again to fully and uniformly mix the two solutions. And distilling the mixed solution at 65 ℃ and drying to constant weight to obtain the PLGA/CdSe/CdS composite material with the quantum dot content of 3.5%.
And (3) carrying out blending extrusion granulation on the PLGA/quantum dot composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Example 7
Weighing a certain mass of PLGA, dissolving the PLGA in tetrahydrofuran, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to obtain a 5 wt% PLGA solution; adding a ZnO quantum dot solution subjected to surface modification by using polyethyleneimine into the PLGA solution, and performing ultrasonic stirring treatment again to fully and uniformly mix the two solutions. And distilling the mixed solution at 65 ℃ and drying to constant weight to obtain the PLGA/ZnO composite material with the quantum dot content of 2.5%.
And (3) carrying out blending extrusion granulation on the PLGA/quantum dot composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Example 8
Weighing a certain mass of PLGA, dissolving the PLGA in acetone, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to obtain a PLGA solution with the weight percent of 6; and adding the CdS quantum dot solution subjected to surface modification by using polyethyleneimine into the PLGA solution, and performing ultrasonic stirring treatment again to fully and uniformly mix the two solutions. And distilling the mixed solution at 65 ℃ and drying to constant weight to obtain the PLGA/CdS composite material with the quantum dot content of 1.5%.
And (3) carrying out blending extrusion granulation on the PLGA/quantum dot composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Example 9
Weighing a certain mass of PLGA, dissolving the PLGA in chloroform, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to prepare a PLGA solution with the weight percent of 5; adding a ZnSe quantum dot solution with the surface modified by 4-vinylpyridine into the PLGA solution, and carrying out ultrasonic stirring treatment again to fully and uniformly mix the two solutions. And distilling the mixed solution at 65 ℃ and drying to constant weight to obtain the PLGA/ZnSe composite material with the quantum dot content of 3.3%.
And (3) carrying out blending extrusion granulation on the PLGA/quantum dot composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Comparative example 1
Weighing a certain mass of PLGA, dissolving the PLGA in chloroform, and performing ultrasonic stirring treatment at room temperature until the PLGA is fully dissolved to prepare a PLGA solution with the weight percent of 5; adding fluorescent powder Y into PLGA solution2O3∶Eu3+And carrying out ultrasonic stirring treatment again, and fully and uniformly mixing. Distilling the mixed solution at 65 ℃ and drying to constant weight to obtain PLGA/Y with the content of doped fluorescent powder being 4.0%2O3∶Eu3+A composite material.
Mixing PLGA/Y2O3∶Eu3+And (3) carrying out blending extrusion granulation on the composite material by using a double-screw extruder, and fully drying to obtain the composite material granules. And extruding and drawing the dried composite material granules by using a double-screw extruder again to obtain the standard wire with the diameter of 1.75mm for 3D printing.
Comparative example 2
Comparative example 2 is a standard wire for 3D printing made from pure GLPA resin.
Performance test experiment
3D printing is carried out on the 3D printing standard wire prepared in the examples 1-4 and the comparative examples 1-2 to prepare the honeycomb grid-shaped artificial bone scaffold material. The specific method comprises the following steps:
a support material with the model size of 10 multiplied by 5mm is designed by Solidworks, a printing head with the thickness of 0.4mm is selected, the printing interval in the direction of X, Y is 0.4mm, and the printing layer is thick.
And respectively testing the tensile strength, the compressive strength, the porosity, the hardness and the fluorescence intensity of the bracket material.
The test results are shown in table 1 and fig. 1.
Table 1 shows the results of physical property test data of the artificial bone scaffold materials of the examples and comparative examples of the present invention
| Tensile Strength (MPa) | Compressive Strength (MPa) | Porosity% | Hardness (shoreD) | |
| Example 1 | 10 | 14 | 65 | 50 |
| Example 2 | 11 | 15 | 65 | 51 |
| Example 3 | 12 | 16 | 69 | 49 |
| Example 4 | 11 | 14 | 68 | 50 |
| Example 5 | 10 | 15 | 67 | 51 |
| Example 6 | 12 | 16 | 69 | 51 |
| Example 7 | 11 | 14 | 68 | 50 |
| Example 8 | 11 | 15 | 68 | 49 |
| Example 9 | 10 | 14 | 66 | 50 |
| Comparative example 1 | 9 | 13 | 68 | 51 |
| Comparative example 2 | 11 | 14 | 66 | 50 |
The emission spectra of the artificial bone scaffold materials of the examples and comparative examples are shown in fig. 1.
According to the results of the table 1 and the figure 1, the fluorescence-labeled degradable 3D printing resin provided by the invention has higher tensile strength and compressive strength and good comprehensive printing performance; from the emission spectrum, the fluorescence intensity of the fluorescence-labeled degradable 3D printing resin provided by the invention is far higher than that of the comparative examples 1-2 due to the fact that quantum dots are used as the luminescent material, and the fluorescence intensity is shown to be far higher than that of the comparative examples 1-2, which shows that the luminescent printing composite material is prepared by adopting the quantum dots to replace conventional doped fluorescent powder and compounding the quantum dots with PLGA, the luminescent performance of the composite material is greatly improved, and the luminescent intensity is also improved along with the increase of the content of the quantum dots.
It should be noted that the content of the quantum dots in the invention is preferably in the range of 0.5-4%, and more preferably in the range of 1.5-4%. The content of the quantum dots exceeds 4%, the luminous intensity is not greatly improved, and the cost is higher; the content of the quantum dots is less than 0.5%, and the luminous intensity is weak, so that the fluorescence observation is not facilitated.
In the above embodiments, the descriptions of the respective embodiments have respective emphasis, and for parts that are not described in detail in a certain embodiment, reference may be made to related descriptions of other embodiments.
While the invention has been described with reference to specific embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. The fluorescence-labeled degradable 3D printing resin is characterized in that the fluorescence-labeled degradable 3D printing resin is a composite material formed by compounding PLGA and quantum dots, and the quantum dots are selected from at least one quasi-zero-dimensional semiconductor nanocrystal consisting of II-VI or III-V group elements and having a stable diameter within 20 nm.
2. The fluorescently labeled degradable 3D printing resin of claim 1, wherein said quantum dots are selected from at least one of CdTe, CdS, CdSe, ZnSe, ZnO, CdSe/ZnS, CdSe/CdS, CdS/ZnS.
3. The fluorescence-labeled degradable 3D printing resin according to claim 1, wherein the quantum dots are surface-modified with the following organic substances:
at least one of polyethyleneimine, dimethylaminoethyl polymethacrylate and 4-vinylpyridine.
4. The fluorescence-labeled degradable 3D printing resin according to claim 1, wherein the mass fraction of the quantum dots of the composite material is 0.5-4%.
5. The fluorescence-labeled degradable 3D printing resin according to claim 1, wherein the quantum dot particle size is 2-20 nm.
6. The fluorescently labeled degradable 3D printing resin of claim 1, wherein said PLGA is at least one selected from the group consisting of alternating copolymers and block copolymers obtained by ring opening polymerization of lactide and glycolide.
7. The fluorescence-labeled degradable 3D printing resin according to claim 1, wherein the composite material is prepared by dissolving PLGA and quantum dots in an organic solvent and then blending.
8. The fluorescently labeled degradable 3D printing resin of claim 7, wherein said organic solvent is selected from at least one of dichloromethane, chloroform, tetrahydrofuran, acetone, and ethyl acetate.
9. The method for preparing a fluorescence-labeled degradable 3D printing resin according to any one of claims 1 to 8, comprising the steps of:
(1) fully dissolving PLGA in an organic solvent to prepare a PLGA solution with the weight percent of 4-6 at room temperature; adding a quantum dot solution into the PLGA solution, and fully and uniformly mixing; distilling and drying the mixed solution to constant weight to obtain a PLGA/quantum dot composite material;
(2) blending, extruding and granulating the PLGA/quantum dot composite material, and fully drying to obtain composite material granules;
(3) drawing the composite material granules to obtain 1.75mm diameter standard wires for 3D printing;
the organic solvent is at least one of dichloromethane, trichloromethane, tetrahydrofuran, acetone and ethyl acetate.
10. Use of the fluorescently labeled degradable 3D printed resin according to any one of claims 1 to 8 or the fluorescently labeled degradable 3D printed resin prepared according to claim 9 in the field of medical implant materials.
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