CN113683789A - 3D printing hydrogel and preparation method thereof - Google Patents

Abstract

The invention discloses 3D printing hydrogel and a preparation method thereof, and belongs to the field of material science. The 3D printing hydrogel comprises the following components: GelMA, xanthan gum, CMC, a photoinitiator and water, wherein the mass ratio of GelMA to xanthan gum to CMC to the photoinitiator is 5-20: 1.5-2.5: 7-10: 0.5-1: 100. the invention takes GelMA as a main photocrosslinking component, fully utilizes the advantages of better biocompatibility and high photocrosslinking efficiency, simultaneously improves the shortages of brittleness and frangibility of GelMA hydrogel by virtue of the advantages of other components, and endows GelMA hydrogel with ideal printing precision.

Description

3D printing hydrogel and preparation method thereof

Technical Field

The invention relates to 3D printing hydrogel and a preparation method thereof, and belongs to the field of material science.

Background

Direct-writing 3D printing is an additive manufacturing technology which extrudes materials through an injector by air pressure or mechanical pressure and combines a computer program to prepare a specific structure, and has wide application prospects in the fields of mold manufacturing, bioengineering and the like. The ideal direct-writing 3D printing material should have good printing accuracy and stability, and its shape can be stably maintained for a long time after 3D printing through thermosetting or other physical and chemical changes.

Most direct-writing 3D printing at the present stage adopts a thermosetting mode to obtain a stable structure, and few photo-crosslinking technologies are used for realizing the conversion of 3D printing ink from solution to gel.

Disclosure of Invention

[ problem ] to

The 3D printing structure obtained by ubiquitous existing in the existing 3D printing direct-writing photo-crosslinking ink is brittle, lacks elasticity, is easy to break under the action of external force, often has certain cytotoxicity, and cannot meet the application requirements in the fields of bioengineering and medical health. And the problems of poor mechanical property and low printing precision of the biological material obtained by the existing direct-writing 3D printing generally exist.

[ solution ]

In order to solve at least one problem, GelMA is used as a photo-crosslinking component, and xanthan gum and sodium carboxymethyl cellulose (CMC) are added as printing performance adjusting components to obtain 3D printing ink; the 3D printing ink obtained by the invention meets ideal printing performance, simultaneously does not obviously reduce the photo-crosslinking efficiency of GelMA, fully utilizes the advantages of good biocompatibility and high photo-crosslinking efficiency of GelMA, simultaneously improves the defects of brittleness and frangibility of GelMA hydrogel by virtue of the advantages of other components, and endows the GelMA hydrogel with ideal printing precision.

A first object of the present invention is to provide a 3D printing ink, the composition of which comprises: GelMA, xanthan gum, CMC, a photoinitiator and water, wherein the mass ratio of GelMA to xanthan gum to CMC to the photoinitiator is 5-20: 1.5-2.5: 7-10: 0.5-1: 100.

in one embodiment of the present invention, the mass ratio of GelMA, xanthan gum, CMC, photoinitiator and water is 15: 2: 8: 0.5: 100.

in one embodiment of the present invention, the preparation method of GelMA comprises:

dissolving gelatin in water, and swelling; and then dripping methacrylic anhydride into the solution for reaction, adding water after the reaction is finished to terminate the reaction, dialyzing and drying to obtain the methacrylic acidylated gelatin GelMA.

In an embodiment of the present invention, the preparation method of GelMA specifically comprises:

dissolving 10g of gelatin in 100mL of water, swelling for 1 hour, then dropwise adding 6mL of methacrylic anhydride into the solution at 50 ℃, diluting the solution with 400mL of water after reacting for 3 hours to terminate the reaction, dialyzing for 3 days at 50 ℃ by using a dialysis bag with the cut-off molecular weight of 8000-15000, replacing water every 6 hours, and finally freeze-drying the solution for 2 days to obtain the methacrylic acidylated gelatin GelMA.

In one embodiment of the present invention, the photoinitiator comprises 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone (Irgacure 2959), and lithium phenyl-2, 4, 6-trimethylbenzoylphosphonate photoinitiator.

A second object of the present invention is to provide a method for preparing the 3D printing ink of the present invention, comprising the steps of:

and uniformly mixing GelMA, xanthan gum, CMC, a photoinitiator and water according to a mass ratio to obtain the 3D printing ink.

In one embodiment of the invention, the temperature of said mixing is not lower than 20 ℃.

The third purpose of the invention is to provide a method for preparing 3D printing hydrogel, which is to irradiate the 3D printing ink of the invention under the conditions of 365nm, 10W of ultraviolet light and a distance of 8-12cm for more than 15 min.

The fourth object of the invention is the 3D printing hydrogel prepared by the method of the invention.

A fifth object of the present invention is a method of preparing a 3D printed model, comprising the steps of:

3D printing is carried out on the 3D printing ink to obtain a 3D printing model.

In an embodiment of the present invention, the parameters of 3D printing are:

the diameter of the needle head is 0.5mm, the pressure is 180-200 kilopascals, the printing speed is 2mm/s, the lifting height of each layer is 0.5mm, the printing size is 20.0 multiplied by 20.0mm, and the distance is 1.5 mm.

In one embodiment of the invention, after the 3D model is printed, the model is irradiated for more than 15min under the conditions of 365nm and 10W of ultraviolet light and the distance of 8-12cm, so that the solid shape effect is obtained.

A sixth object of the invention is a 3D printed model obtained by the method according to the invention.

[ advantageous effects ]

(1) According to the invention, GelMA is used as a photo-crosslinking component, and xanthan gum and CMC are added as printing performance adjusting components, so that the ideal printing performance is met, and the photo-crosslinking efficiency of GelMA is not reduced obviously.

(2) The invention takes GelMA as a main photocrosslinking component, fully utilizes the advantages of better biocompatibility and high photocrosslinking efficiency, simultaneously improves the shortages of brittleness and frangibility of GelMA hydrogel by virtue of the advantages of other components, and endows GelMA hydrogel with ideal printing precision.

Drawings

Fig. 1 is a graph of the effect of xanthan gum concentration on 3D printing performance.

FIG. 2 shows the printing effects of the 3D printing inks obtained in example 1 and comparative examples 3 to 5.

FIG. 3 is a solid post-print model prepared with the ink of example 1, wherein (a) is a perspective view; (b) is a top view.

FIG. 4 is a test of the elasticity of a solid post-print model prepared with the ink of example 1.

FIG. 5 is a cross-section of a mesh of a solid post-print model prepared with the ink of example 1.

Fig. 6 is a graph showing the effect of xanthan gum dosage on the void area of the cross section of a 3D printing mesh after setting.

Fig. 7 is a graph of the effect of xanthan gum concentration on photocrosslinking efficiency in 3D printing inks.

Fig. 8 is a graph of the effect of CMC usage on cross-sectional void area of 3D printed mesh after consolidation.

Fig. 9 is a graph of the effect of CMC concentration on photocrosslinking efficiency in 3D printing inks.

FIG. 10 shows the results of the test in comparative example 7.

Detailed Description

The following description of the preferred embodiments of the present invention is provided for the purpose of better illustrating the invention and is not intended to limit the invention thereto.

The parameters of 3D printing in the examples are:

the diameter of the needle head is 0.7mm, the pressure is 180-200 kilopascals, the printing speed is 2mm/s, the lifting height of each layer is 0.5mm, the printing size is 20.0 multiplied by 20.0mm, and the distance is 1.0 mm.

Example 1

A method of preparing a 3D printing ink comprising the steps of:

GelMA, xanthan gum, CMC, a photoinitiator Irgacure 2959 and water in a mass ratio of 15: 2: 8: 0.5: 100, and mixing uniformly to obtain the 3D printing ink.

Control example 1 optimization of amount of xanthan gum

In example 1, the mass ratio of GelMA, xanthan gum, CMC, photoinitiator Irgacure 2959 and water is adjusted to 15: 1: 8: 0.5: 100, respectively; the rest was kept the same as in example 1, and 3D printing ink was obtained.

Control example 2 optimization of amount of xanthan gum

In example 1, the mass ratio of GelMA, xanthan gum, CMC, photoinitiator Irgacure 2959 and water is adjusted to 15: 3: 8: 0.5: 100, respectively; the rest was kept the same as in example 1, and 3D printing ink was obtained.

3D printing is carried out on the 3D printing ink obtained in the embodiment 1 and the comparison examples 1 and 2 to obtain a 3D printing model; the test results for the 3D printing model are as follows:

fig. 1 is a graph of the effect of xanthan gum concentration on 3D printing performance. As can be seen from fig. 1: during the 3D printing performance adjustment using xanthan gum it was found that: the 3D printing ink prepared from low-concentration (1% mass concentration of xanthan gum relative to water) xanthan gum has poor definition, and a 3D printing structure with high structure precision cannot be formed. While high concentration of xanthan gum (3% mass concentration of xanthan gum relative to water) can result in excessive solution viscosity, which affects print continuity. The xanthan gum with proper concentration (the mass concentration of the xanthan gum relative to the water is 2%) has relatively good 3D printing definition, and the printing process is stable and continuous.

Comparative example 3

The xanthan gum in example 1 was omitted and the rest was the same as in example 1 to obtain a 3D printing ink.

Comparative example 4

The CMC in example 1 was omitted, and 3D printing ink was obtained in accordance with example 1.

Comparative example 5

The mass ratio of GelMA, xanthan gum, CMC, the photoinitiator Irgacure 2959 and water in example 1 was adjusted to 15: 2: 4: 0.5: 100, otherwise in accordance with example 1, 3D printing ink was obtained.

The 3D printing inks obtained in example 1 and comparative examples 3 to 5 were printed, with the following results:

FIG. 2 shows the printing effects of the 3D printing inks obtained in example 1 and comparative examples 3 to 5. As can be seen from fig. 2: the use of CMC (control 3) alone as a print performance modifier did not result in a continuous printed line, with the ink droplets being extruded from the needle as individual droplets. The 3D printing ink prepared by using xanthan gum alone (comparative example 4) can prepare continuous and stable lines, but has a significant collapse phenomenon, which causes the prepared 3D printing structure to collapse rapidly in practical application, and also affects the precision of 3D printing. The lines formed by 3D printing of the ink prepared by introducing the two into the 3D printing ink formula together do not show obvious collapse performance, and the mass ratio of GelMA, xanthan gum, CMC, photoinitiator Irgacure 2959 to water is 15: 2: 8: 0.5: 100, the better printing performance is obtained.

And (3) irradiating the 3D printing model prepared by the ink of the embodiment 1 for 15min under the conditions of 365nm and 10W of ultraviolet light and the distance of 10cm to obtain the 3D printing model after solid forming.

FIG. 3 is a solid post-print model prepared with the ink of example 1, as can be seen in FIG. 3: the number of printing layers of the printing model is 14, and no remarkable collapse phenomenon is observed; from the top view, it can be observed that the lattice structure of the sample is clear and that no voids are blocked.

FIG. 4 is a test of the elasticity of the solid-form print model prepared with the ink of example 1, as can be seen in FIG. 4: the 3D printed model of example 1 can be bent to a large extent and the 14-layer lattice structure can be bent to 41 ° and restored without significant structural damage. This shows that the 3D printed product prepared in example 1 has a certain elasticity and can be restored after deformation. The advantage improves the application potential of the material in the fields of biological engineering and the like.

FIG. 5 is a cross-section of a mesh of a solid post-print model prepared with the ink of example 1. The specific test method is to use a super-depth-of-field microscope to shoot and measure the cross-section void condition of the 3D printing grid structure, compare the cross-section void condition of the prepared grid structure with a theoretical void area value which should be obtained after parameter design, take 9 voids for each sample, and calculate an average value (as shown in figure 5). This parameter can effectively reflect the collapse performance of the ink and its 3D printing accuracy, with lower voids compared to theoretical values indicating that the ink is prone to collapse and no way to obtain a clear multilayer 3D printed structure and vice versa.

EXAMPLE 2 optimization of the amount of xanthan gum

A method of preparing a 3D printing ink comprising the steps of:

GelMA, xanthan gum, a photoinitiator Irgacure 2959 and water in a mass ratio of 10: 2: 0.5: 100. 10: 2: 1: 100. 10: 2: 2: 100. 10: 2: 3: 100. 10: 2: 4: 100. 10: 2: 5: 100, and mixing uniformly to obtain the 3D printing ink.

Printing the 3D printing ink obtained in the embodiment 2 to obtain a 3D printing model, then irradiating the 3D printing model for 15min under the conditions of 365nm and 10W ultraviolet light and a distance of 10cm to obtain a 3D printing model (3D printing hydrogel) after solid forming, and then performing performance test, wherein the results are as follows:

fig. 6 is a graph showing the effect of xanthan gum dosage on the void area of the cross section of a 3D printing mesh after setting. As can be seen from fig. 6: the 3D printing grid cross-section gaps after the solid shape obtained in embodiment 2 can have obvious gaps when the mass concentration of the xanthan gum relative to water is 1%, and reach 67% when the mass concentration of the xanthan gum is 2%, the subsequent increase of the xanthan gum concentration is continued, and the increase of the gap area is relatively small, which shows that the introduction of the xanthan gum can significantly improve the 3D printing definition of the ink, and the increase effect is more obvious when the concentration is higher.

Fig. 7 is a graph of the effect of xanthan gum concentration on the photocrosslinking efficiency of 3D printing inks. As can be seen from fig. 7: as the concentration of xanthan gum increases, the photocrosslinking time required to form the hydrogel increases. When the concentration of the xanthan gum is 2%, the hydrogel can complete photocrosslinking within 15min to form stable hydrogel. Xanthan gum itself has a yellowish color, and if the solution is colored during photocrosslinking, the light utilization rate is reduced, resulting in a longer time for photocrosslinking to form a gel.

Example 3 optimization of CMC dosage

A method of preparing a 3D printing ink comprising the steps of:

GelMA, xanthan gum, CMC, a photoinitiator Irgacure 2959 and water in a mass ratio of 10: 2: 1: 0.5: 100. 10: 2: 2: 0.5: 100. 10: 2: 3: 0.5: 100. 10: 2: 4: 0.5: 100. 10: 2: 5: 0.5: 100. 10: 2: 6: 0.5: 100. 10: 2: 7: 0.5: 100. 10: 2: 8: 0.5: 100. 10: 2: 9: 0.5: 100. 10: 2: 10: 0.5: 100, and mixing uniformly to obtain the 3D printing ink.

Printing the 3D printing ink obtained in the embodiment 2 to obtain a 3D printing model, then irradiating the 3D printing model for 15min under the conditions of 365nm and 10W ultraviolet light and a distance of 10cm to obtain a solid 3D printing model, and then performing performance test, wherein the result is as follows:

fig. 8 is a graph of the effect of CMC usage on cross-sectional void area of 3D printed mesh after consolidation. As can be seen from fig. 8: the cross-sectional voids of the 3D printing mesh after solid formation obtained in example 3 show a tendency of continuously increasing with the increase of the CMC concentration, and when the CMC concentration exceeds 8% by mass relative to water, the increase is relatively small, so that the concentration is selected as an optimal formulation.

Fig. 9 is a graph of the effect of CMC concentration on photocrosslinking efficiency in 3D printing inks. As can be seen from fig. 9: the increase of the concentration of the CMC can not obviously affect the photo-crosslinking efficiency of the solution, and the main reason is that the CMC solution is colorless and transparent, and can not affect the effective utilization of light in the photo-crosslinking process.

Comparative example 6

The xanthan gum in example 1 was adjusted to "carrageenan" and the rest was kept the same as in example 1, to obtain a 3D printing ink.

And (3) carrying out performance test on the obtained 3D printing ink, wherein the test result is as follows:

in the high temperature (60 ℃) environment, the carrageenan can generate reversible gelation phenomenon at the high temperature (60 ℃) and has poor viscosity regulation effect, so that good definition cannot be obtained.

Comparative example 7

The xanthan gum in example 1 was adjusted to "sodium alginate" and "chitosan", and the rest was kept the same as example 1, to obtain 3D printing ink.

And (3) carrying out performance test on the obtained 3D printing ink, wherein the test result is as follows:

as shown in fig. 10, after replacing xanthan gum with chitosan, the printed lines had some gel particles, which may be due to microgel formed by chitosan itself during the solution preparation process, which severely affected the accuracy of the printed lines and also had significant collapse. Sodium alginate is also remarkably collapsed, which shows that xanthan gum plays a crucial role in 3D printing definition, and common polysaccharide macromolecules such as sodium alginate cannot substitute the common polysaccharide macromolecules.

Claims (10)

1. A 3D printing ink, characterized in that its composition comprises: GelMA, xanthan gum, CMC, a photoinitiator and water, wherein the mass ratio of GelMA to xanthan gum to CMC to the photoinitiator is 5-20: 1.5-2.5: 7-10: 0.5-1: 100.

2. the 3D printing ink according to claim 1, wherein the mass ratio of GelMA, xanthan gum, CMC, photoinitiator and water is 15: 2: 8: 0.5: 100.

3. a 3D printing ink according to claim 1 or 2, characterised in that the photoinitiator comprises 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone, lithium phenyl-2, 4, 6-trimethylbenzoylphosphonate photoinitiator.

4. A method of preparing a 3D printing ink according to any of claims 1 to 3, comprising the steps of:

GelMA, xanthan gum, CMC, a photoinitiator and water are mixed according to a mass ratio of 5-20: 1.5-2.5: 7-10: 0.5-1: 100, and uniformly mixing to obtain the 3D printing ink.

5. The method according to claim 4, wherein the mass ratio of GelMA, xanthan gum, CMC, photoinitiator and water is 15: 2: 8: 0.5: 100.

6. a method for preparing 3D printing hydrogel, which is characterized in that the 3D printing ink of any one of claims 1 to 3 is irradiated for more than 15min under the conditions of 365nm and 10W of ultraviolet light and the distance of 8-12 cm.

7. The 3D printed hydrogel prepared by the method of claim 6.

8. A method for preparing a 3D printing model is characterized by comprising the following steps:

3D printing ink according to any one of claims 1 to 3 is subjected to 3D printing to obtain a 3D printing model.

9. The method according to claim 8, wherein the parameters of the 3D printing are:

the diameter of the needle head is 0.5mm, the pressure is 180-200 kilopascals, the printing speed is 2mm/s, the lifting height of each layer is 0.5mm, the printing size is 20.0 multiplied by 20.0mm, and the distance is 1.5 mm.

10. A 3D printed model obtained by the method of claim 8 or 9.

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