Composite 3D printing biomaterial ink, preparation method and application thereof

Abstract

The application belongs to the technical field of biomaterial ink, and particularly relates to a composite 3D printing biomaterial ink, a preparation method and application thereof. The composite 3D printing biomaterial ink comprises, by weight percentage, 12-18% of polyethylene glycol 400, 28-22% of pluronic F127 solution, and the balance of self-curing artificial bone particles; wherein the self-curing artificial bone particles are one or more of dicalcium silicate, tricalcium silicate and calcium dihydrogen phosphate. The composite biomaterial ink prepared by the application has good printability, physical and chemical properties, in-vitro degradation behavior and in-vitro biocompatibility, and has a good application prospect in the field of bone tissue engineering.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biomaterial ink, and particularly relates to a composite 3D printing biomaterial ink and a preparation method and application thereof. BACKGROUND

[0002] Due to impaired bone regeneration, it is still challenging to repair critical-sized bone defects resulting from fractures, trauma, and surgical resection. Critical-sized bone defects are bone defects that do not heal spontaneously throughout a patient's life.

[0003] In tissue engineering, due to the adjustable microstructure and mechanical properties of 3D printed scaffolds, bone scaffolds manufactured by 3D printing technology have been proven to be an effective method for treating critical-sized bone defects. An ideal bone tissue engineering scaffold can obtain a structure and shape consistent with the design of the scaffold after being prepared into a shape. Therefore, researching a printable biomaterial ink is a prerequisite for the successful preparation of the scaffold. The biomaterial ink is currently defined as a printable biomaterial containing bioactive ingredients or molecules. A qualified biomaterial ink needs to have three requirements, which involve the three aspects of printability, mechanical properties and degradation behavior, and biocompatibility. Printability refers to the performance of the material that can be stably extruded in time and precisely controlled in space, which is directly related to whether the 3D printed product can achieve the expected structure and size accuracy. The mechanical properties require that the biomaterial ink after printing can have strong mechanical properties to support the morphology of the printed scaffold, the infusion of nutrients and degradation after implantation. The biocompatibility requires that the biomaterial ink has no toxic side effects and is suitable for cell adhesion, growth and proliferation.

[0004] Currently, polyethylene glycol 400 and pluronic F127 need to be crosslinked twice when used alone as a biomaterial ink, and the strength cannot meet the requirements of hard bone tissue; for example, pluronic F127 can only be used for soft tissue when used alone as a biomaterial ink, and the strength cannot meet the requirements of hard bone tissue; to further improve the effect, pluronic F127 is used in combination with other materials, and in order to meet the material requirements, pluronic F127 is usually used as a sacrificial material and removed after printing. Polyethylene glycol 400 is used in combination with other materials, and in order to meet the material requirements, polyethylene glycol 400 is usually used to improve the ductility of the material.

[0005] And the traditional artificial bone usually needs to be sintered at high temperature to obtain strength and porosity after being used alone in the preparation of a 3D printed scaffold, or needs to be pre-dissolved in an organic solvent to successfully print, which will affect the effectiveness of the bioactive molecules or drugs added during the printing process. SUMMARY

[0006] The present application aims at overcoming the deficiencies of the prior art, and provides a composite 3D printing biomaterial ink, a preparation method and application thereof.

[0007] To achieve the above-mentioned object, the technical scheme adopted by the present application is as follows:

[0008] A composite 3D printing biomaterial ink, the composite 3D printing biomaterial ink comprises, by weight percentage, 12-18% polyethylene glycol 400, 28-22% pluronic F127 solution, and the balance is self-curing artificial bone particles; wherein the self-curing artificial bone particles are one or more of dicalcium silicate, tricalcium silicate and calcium dihydrogen phosphate.

[0009] The molecular weight of the polyethylene glycol 400 is 400; the molecular weight of the pluronic F127 is 12.6kDa.

[0010] The pluronic F127 solution is an aqueous solution of pluronic F127 with a mass fraction of 17-20%.

[0011] The self-curing artificial bone particles are refined by a ball mill and sieved through a 400-mesh screen.

[0012] Further, according to the above-mentioned proportion, the polyethylene glycol 400 and the pluronic F127 solution are sequentially added to the self-curing artificial bone particles in proportion, and a paste suitable for 3D printing biomaterial is obtained after sufficient mixing.

[0013] The materials are mixed thoroughly before adding another material each time.

[0014] The application of the composite 3D printing biomaterial ink, the composite 3D printing biomaterial ink is used in the preparation of a printing biomaterial in 3D printing.

[0015] The diameter of the printing needle used in the 3D printing of the composite 3D printing biomaterial ink is 0.41-0.6mm.

[0016] Compared with the prior art, the present application has the following beneficial effects:

[0017] (1) In the present application, polyethylene glycol 400 is added to the biomaterial ink, which has a synergistic effect with pluronic F127 in the present application, and the effect is different from the original use effect, which acts as a dispersant and a retarder in the present application, disperses the self-curing artificial bone particles, reduces the viscosity of the self-curing artificial bone, prevents the occurrence of the plug phenomenon in the printing process, facilitates the smooth extrusion of the biomaterial ink in the 3D printing process, and ensures the good printability of the biomaterial ink.

[0018] (2) The pluronic F127 is added to the biomaterial ink in the present application, which has a synergistic effect with polyethylene glycol 400 in the present application, and the original use effect is different, and the effect in the present application is as a binder, which can bond the unreacted self-solidified artificial bone particles in the 3D printing process, so that the extruded biomaterial ink has sufficient initial strength to maintain the integrity of the shape, and ensures the good mechanical properties and degradation behavior of the printing support.

[0019] (3) The self-solidified artificial bone is added to the biomaterial ink in the present application, which avoids the failure of bioactive molecules in the high-temperature sintering process, and has good biocompatibility. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 The printing effect diagram of the comparative example 3;

[0021] Figure 2 The printing effect diagram of the example 1, the example 2, the example 3 and the example 4;

[0022] Figure 3 The printing effect diagram of the example 2 and the example 5;

[0023] Figure 4 The printing effect diagram of the printing head with different pore diameters of the example 5;

[0024] Figure 5 The solidification time of the composite 3D printing biomaterial ink manufactured by relying on the present application in the example 2 and the example 5 and the comparative example 1;

[0025] Figure 6 The compressive strength of the composite 3D printing biomaterial ink manufactured by relying on the present application in the example 2 and the comparative example 1;

[0026] Figure 7 The porosity of the composite 3D printing biomaterial ink manufactured by relying on the present application in the example 2 and the comparative example 1;

[0027] Figure 8 The crystallinity of the composite 3D printing biomaterial ink manufactured by relying on the present application in the example 2 and the comparative example 1;

[0028] Figure 9 The SEM diagram of the composite 3D printing biomaterial ink manufactured by relying on the present example 2;

[0029] Figure 10 The in-vitro degradation change of the composite 3D printing biomaterial ink manufactured by relying on the present example 2;

[0030] Figure 11 The in-vitro cell compatibility of the composite 3D printing biomaterial ink manufactured by relying on the present example 2. DETAILED DESCRIPTION

[0031] It should be noted that the following detailed description is illustrative only, and is intended to provide further description in order to provide a fuller enabling disclosure. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The materials used are all commercially available unless otherwise indicated.

[0032] The substances in the biomaterial ink of the present application have a synergistic effect when combined together. Polyethylene glycol 400 acts as a dispersant and a retarder in the present application, delaying the hydration process of the self-setting artificial bone and dispersing large particles generated during the hydration process to prevent the occurrence of the plug phenomenon during printing. Pluronic F127 acts as an adhesive to bond the particles together, preventing the occurrence of the collapse phenomenon during printing and providing the initial strength of the printed thread, so that the biomaterial ink of the present application can maintain a three-dimensional structure consistent with the program design at the beginning of 3D printing.

[0033] Example 1

[0034] This example is used to illustrate the composite 3D printing biomaterial ink and its preparation method

[0035] Add 17 g of Pluronic F127 powder to 83 g of deionized water and mix thoroughly, then place it at 4°C overnight to obtain a uniform Pluronic F127 aqueous solution. Mix 1.5 g of dicalcium silicate and 1.5 g of tricalcium silicate thoroughly, ball mill to refine, and sieve through a 400 mesh screen. To prepare the composite 3D printing biomaterial ink, first mix the dicalcium silicate and tricalcium silicate thoroughly, then add polyethylene glycol 400 and mix thoroughly, then add the Pluronic F127 aqueous solution and mix again.

[0036] The percentage of each substance in the above system is 12% polyethylene glycol 400, 28% Pluronic F127 aqueous solution, and the rest is dicalcium silicate and tricalcium silicate, wherein the mass ratio of dicalcium silicate to tricalcium silicate is 1:1.

[0037] Example 2

[0038] This example is used to illustrate the composite 3D printing biomaterial ink and its preparation method

[0039] Add 17 g of Pluronic F127 powder to 83 g of deionized water and mix thoroughly, then place it at 4°C overnight to obtain a uniform Pluronic F127 aqueous solution.

[0040] The self-setting artificial bone particles are obtained by mixing 1.5 g of dicalcium silicate and 1.5 g of tricalcium silicate thoroughly, ball milling to refine, and sieving through a 400 mesh screen.

[0041] The preparation of the composite 3D printing biomaterial ink is as follows: firstly, the dicalcium silicate and tricalcium silicate are fully mixed and uniformly added with polyethylene glycol 400, fully mixed and uniformly added with the Pluronic F127 aqueous solution, and then mixed again.

[0042] The percentage of each substance in the above system is as follows: 14% polyethylene glycol 400, 26% Pluronic F127 aqueous solution, and the rest is dicalcium silicate and tricalcium silicate, wherein the mass ratio of dicalcium silicate to tricalcium silicate is 1:1.

[0043] Example 3

[0044] This example is used to illustrate the composite 3D printing biomaterial ink and the preparation method thereof

[0045] The Pluronic F127 powder of 17 g is fully mixed in 83 g of deionized water, placed at 4°C overnight, and a uniform Pluronic F127 aqueous solution is obtained. The dicalcium silicate of 1.5 g and the tricalcium silicate of 1.5 g are fully mixed, ball-milled, and sieved through a 400 mesh screen. The preparation of the composite 3D printing biomaterial ink is as follows: firstly, the dicalcium silicate and tricalcium silicate are fully mixed and uniformly added with polyethylene glycol 400, fully mixed and uniformly added with the Pluronic F127 aqueous solution, and then mixed again.

[0046] The percentage of each substance in the above system is as follows: 16% polyethylene glycol 400, 24% Pluronic F127 aqueous solution, and the rest is dicalcium silicate and tricalcium silicate, wherein the mass ratio of dicalcium silicate to tricalcium silicate is 1:1.

[0047] Example 4

[0048] This example is used to illustrate the composite 3D printing biomaterial ink and the preparation method thereof

[0049] The Pluronic F127 powder of 17 g is fully mixed in 83 g of deionized water, placed at 4°C overnight, and a uniform Pluronic F127 aqueous solution is obtained. The dicalcium silicate of 1.5 g and the tricalcium silicate of 1.5 g are fully mixed, ball-milled, and sieved through a 400 mesh screen. The preparation of the composite 3D printing biomaterial ink is as follows: firstly, the dicalcium silicate and tricalcium silicate are fully mixed and uniformly added with polyethylene glycol 400, fully mixed and uniformly added with the Pluronic F127 aqueous solution, and then mixed again.

[0050] The percentage of each substance in the above system is as follows: 16% polyethylene glycol 400, 24% Pluronic F127 aqueous solution, and the rest is dicalcium silicate and tricalcium silicate, wherein the mass ratio of dicalcium silicate to tricalcium silicate is 1:1.

[0051] Example 5

[0052] This embodiment is used to illustrate the composite 3D printing biomaterial ink and its preparation method

[0053] 20 g of Pluronic F127 powder was added to 80 g of deionized water and mixed thoroughly, placed at 4°C overnight to obtain a uniform Pluronic F127 aqueous solution.

[0054] The self-curing artificial bone particles were prepared by thoroughly mixing 1.3 g of dicalcium silicate, 1.3 g of tricalcium silicate and 0.4 g of calcium dihydrogen phosphate, ball-milling and sieving through a 400 mesh screen. The composite 3D printing biomaterial ink was prepared by first thoroughly mixing the dicalcium silicate, tricalcium silicate and calcium dihydrogen phosphate, adding polyethylene glycol 400, thoroughly mixing, then adding the Pluronic F127 aqueous solution, and mixing again. The mixture was denoted as Cps / PF / PEG.

[0055] The percentage of each substance in the above system was 14% polyethylene glycol 400, 26% Pluronic F127 aqueous solution, and the balance being dicalcium silicate, tricalcium silicate and calcium dihydrogen phosphate. The amount of dicalcium silicate, tricalcium silicate and calcium dihydrogen phosphate was configured according to the description of the preparation process of the self-curing artificial bone particles above.

[0056] Comparative Example 1

[0057] 17 g of Pluronic F127 powder was added to 83 g of deionized water and mixed thoroughly, placed at 4°C overnight to obtain a uniform Pluronic F127 aqueous solution. 1.5 g of dicalcium silicate and 1.5 g of tricalcium silicate were thoroughly mixed, ball-milled and sieved through a 400 mesh screen. 1.3 g of Pluronic F127 aqueous solution was thoroughly mixed with the above-described dicalcium silicate and tricalcium silicate, and the mixture was denoted as Cas / PF.

[0058] Comparative Example 2

[0059] 1.5 g of dicalcium silicate and 1.5 g of tricalcium silicate were thoroughly mixed, ball-milled and sieved through a 400 mesh screen. 0.7 g of PEG400 was added and thoroughly mixed with the above-described dicalcium silicate and tricalcium silicate, and the mixture was denoted as Cas / PEG.

[0060] Comparative Example 3

[0061] Add 17 g of Pluronic F127 powder into 83 g of deionized water, mix well, and place at 4℃ overnight to obtain a uniform Pluronic F127 aqueous solution. Mix 1.5 g of dicalcium silicate and 1.5 g of tricalcium silicate well, ball mill to refine, and sieve through a 400 mesh screen. To prepare the composite 3D printing biomaterial ink, first mix the dicalcium silicate and tricalcium silicate well, then add polyethylene glycol 600, mix well, and then add the Pluronic F127 aqueous solution, and mix well again.

[0062] The percentages of the above substances in the system are 18% polyethylene glycol 600, 22% Pluronic F127 aqueous solution, and the balance dicalcium silicate and tricalcium silicate, wherein the mass ratio of dicalcium silicate to tricalcium silicate is 1:1.

[0063] The materials prepared in the above examples and comparative examples were tested for effects.

[0064] Effect Example 1

[0065] The printable performance of the composite biomaterial of Comparative Example 1 was tested.

[0066] The composite biomaterial prepared in Comparative Example 1 was loaded into a printing cartridge, a printing support was printed, and the inner diameter of the printing needle was 0.41 mm or 0.60 mm. It was found that the slurry did not have fluidity and could not be extruded from the printing needle. This shows that the composite biomaterial in which Pluronic F127 is compounded with self-curing artificial bone alone in Comparative Example 1 does not have printable performance.

[0067] Effect Example 2

[0068] The printable performance of the composite biomaterial of Comparative Example 2 was tested.

[0069] The composite biomaterial prepared in Comparative Example 2 was loaded into a printing cartridge, a printing support was printed, and the inner diameter of the printing needle was 0.41 mm or 0.60 mm. It was found that the slurry did not have fluidity and could not be extruded from the printing needle, and the slurry could not be cured in 20 days, and other performances could not be tested. This shows that the composite biomaterial in which polyethylene glycol 400 is compounded with self-curing artificial bone alone in Comparative Example 2 does not have printable performance.

[0070] Effect Example 3

[0071] The printable performance of the composite biomaterial of Comparative Example 3 was tested.

[0072] The composite biomaterial prepared in Comparative Example 3 was loaded into a printing cartridge, a printing support was printed, and the inner diameter of the printing needle was 0.41 mm. The results were as follows: Figure 1It can be seen that the material filament is not uniform, the pores are not obvious, and the complete scaffold cannot be printed, and the structure does not meet the design requirements. It is explained that the composite biomaterial used in Comparative Example 3 does not have a printable performance.

[0073] The printable performance of the composite 3D printing biomaterial ink of Examples 1, 2, 3 and 4 was tested.

[0074] The composite 3D printing biomaterial ink prepared in Examples 1, 2, 3 and 4 was loaded into a printing cartridge, and a 6mmx10mmx10mm cube was printed, and the inner diameter of the printing needle was 0.41mm, and the results were as shown in Figure 2 It can be seen that the surface pores are clear, which indicates that the composite 3D printing biomaterial ink of Examples 1, 2, 3 and 4 of the present application has a printable performance.

[0075] Example 4

[0076] The printable performance of the composite 3D printing biomaterial ink of Example 2 and Example 5 was tested.

[0077] The composite 3D printing biomaterial ink prepared in Example 2 and Example 5 was loaded into a printing cartridge, and a 6mmx10mmx10mm cube and an 8mmx8mm cylinder were printed, respectively, and the inner diameter of the printing needle was 0.41mm, and the results were as shown in Figure 3 It can be seen that the surface pores are clear. It is explained that the composite 3D printing biomaterial ink of Examples 2 and 5 of the present application has a printable performance.

[0078] Example 5

[0079] The printing effect diagram of the printing head with different pore diameters of Example 5 was tested.

[0080] The composite 3D printing biomaterial ink prepared in Example 5 was loaded into a printing cartridge, and a 6mmx10mmx10mm cube was printed, and the inner diameter of the printing needle was 0.41-0.60mm, and the results were as shown in Figure 4 It can be seen that the surface pores are clear. It is explained that the composite 3D printing biomaterial ink of the present application can be applied to the construction of a biomimetic macroporous composite scaffold.

[0081] Example 6

[0082] The curing time of the composite 3D printing biomaterial ink prepared in the present application was tested.

[0083] The Vicat device was used to evaluate the curing time of Example 2, Example 5 and Comparative Example 1 according to the ASTM C187-98 standard, and the results were as shown in Figure 5The composite 3D printing biomaterial ink obtained in Example 2 and Comparative Example 1 were respectively placed in a mold with a diameter of 17 mm and a height of 2 mm, and placed in a constant temperature and humidity incubator with a temperature of 37°C and a humidity of 100%. After 7 days, the composite 3D printing biomaterial ink was taken out and dried at 37°C for 4 hours for measurement. From Figure 4 It can be seen from Table 1 that the composite 3D printing biomaterial ink prepared in Example 2 and Example 5 exhibits a longer solidification time, indicating that the composite 3D printing biomaterial ink prepared in Example 2 and Example 5 has a longer printable time.

[0084] Example 7

[0085] The compressive strength and porosity of the composite 3D printing biomaterial ink prepared in the application were tested.

[0086] The compressive strength of Example 2 and Comparative Example 1 was evaluated using a universal testing machine at a loading rate of 1 mm / min, and the results are shown in Table 2. Figure 6 The composite 3D printing biomaterial ink obtained in Example 2 and Comparative Example 1 were respectively placed in a mold with a diameter of 6 mm and a height of 12 mm, and placed in a constant temperature and humidity incubator with a temperature of 37°C and a humidity of 100% for 7 days. After taking out, the composite 3D printing biomaterial ink was dried at 37°C for 4 hours for measurement. From Figure 6 and Figure 7 It can be seen from Table 3 that the composite 3D printing biomaterial ink prepared in Example 2 exhibits higher compressive strength and lower porosity compared to Comparative Example 1, indicating that the composite 3D printing biomaterial ink prepared in Example 2 has good support performance and can maintain good structure and shape after printing.

[0087] Example 8

[0088] The crystallinity of the composite 3D printing biomaterial ink prepared in the application was tested.

[0089] The crystallinity of the hydrated product of the composite 3D printing biomaterial ink prepared in the application was tested, and the results are shown in Table 4. Figure 8 The composite 3D printing biomaterial ink obtained in Example 2 and Comparative Example 1 were respectively placed in a mold with a diameter of 6 mm and a height of 12 mm, and placed in a constant temperature and humidity incubator with a temperature of 37°C and a humidity of 100% for 7 days. After taking out, the composite 3D printing biomaterial ink was dried at 37°C for 4 hours, and then ground, refined and dispersed for measurement. From Figure 8 It can be seen from Table 5 that the composite 3D printing biomaterial ink prepared in Example 2 exhibits un-hydrated tricalcium silicate and more calcium hydroxide in the XRD pattern compared to Comparative Example 1, further indicating that the composite 3D printing biomaterial ink prepared in Example 4 has a longer printable time.

[0090] Example 9

[0091] The effect example studies the SEM image of the printed scaffold prepared from the composite 3D printing biomaterial ink prepared in Example 2.

[0092] The 6mmx10mmx10mm cubic scaffold prepared from the composite 3D printing biomaterial ink obtained in Example 2 is placed in a constant temperature and humidity incubator at a temperature of 37℃ and a humidity of 100% for 7 days, and after being taken out, is dried at 37℃ for 4 hours, and is measured. The results are shown in Figure 9 The surface pores are clearly visible, and the pore size is 750μm-820μm. It is shown that the composite 3D printing biomaterial ink of the application can be applied to the construction of the biomimetic macroporous composite scaffold.

[0093] Effect example 10

[0094] The effect example studies the in vitro degradation change of the printed scaffold prepared from the composite 3D printing biomaterial ink prepared in Example 2.

[0095] The 6mmx10mmx10mm cubic scaffold prepared from the composite 3D printing biomaterial ink obtained in Example 2 is placed in a constant temperature and humidity incubator at a temperature of 37℃ and a humidity of 100% for 7 days, and after being taken out, is dried at 37℃ for 4 hours, and is placed in a Tris-HCl buffer solution with a pH of 7.4, and is placed for 1, 3, 5, 7, 10, 14, 21 and 28 days respectively, and the pH and mass loss change are recorded. The results are shown in Figure 10 The pH increases with time, and the mass decreases with time. It is shown that the macroporous composite scaffold constructed from the composite 3D printing biomaterial ink of the application has a good in vitro degradation rate and a stable degradation environment.

[0096] Effect example 11

[0097] The effect example studies the cell compatibility of the composite 3D printing biomaterial ink.

[0098] The 6mmx10mmx10mm cubic scaffold prepared from the composite 3D printing biomaterial ink obtained in Example 2 is placed in a constant temperature and humidity incubator at a temperature of 37℃ and a humidity of 100% for 7 days, and after being taken out, is dried at 37℃ for 4 hours, and is placed in DMEM, and is soaked for 3 days, and a volume fraction of 10% fetal bovine serum and 0.2% double antibody are added to prepare an extraction liquid medium. The osteoblasts are cultured with the extraction liquid medium for 1 day and 3 days respectively, and the cells cultured in the ordinary medium are used as a standard reference. The results are shown in Figure 11 The medium prepared from the composite 3D printing biomaterial ink is more conducive to the growth of cells. It is shown that the composite 3D printing biomaterial ink of the application has good in vitro cell compatibility.

[0099] Finally, it should be noted that the above examples are used to illustrate the technical solutions of the present application and are not intended to limit the scope of protection of the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or equivalently replaced without departing from the essence and scope of the technical solutions of the present application.

Claims

1. A composite 3D printing biomaterial ink, characterized in that, The composite 3D printing biomaterial ink comprises, by weight percentage, 12-18% polyethylene glycol 400, 28-22% pluronic F127 solution, and the balance being self-curing artificial bone particles; wherein the self-curing artificial bone particles are one or more of dicalcium silicate, tricalcium silicate, and calcium dihydrogen phosphate; The polyethylene glycol 400 has a molecular weight of 400; and the pluronic F127 has a molecular weight of 12.6 kDa.

2. The composite 3D printing biomaterial ink according to claim 1, wherein, The pluronic F127 solution is an aqueous solution of pluronic F127 having a mass fraction of 17-20%.

3. The composite 3D printing biomaterial ink according to claim 1, wherein, The self-curing artificial bone particles are refined by a ball mill and sieved through a 400-mesh screen.

4. The method for preparing the composite 3D printing biomaterial ink according to claim 1, characterized in that, The polyethylene glycol 400 and the pluronic F127 solution are added to the self-curing artificial bone particles in the above proportions, and a paste suitable for 3D printing biomaterials is obtained after thorough mixing. The materials are thoroughly mixed before adding another material each time.

5. The method for preparing the composite 3D printing biomaterial ink according to claim 4, characterized in that, The composite 3D printing biomaterial ink is used for preparing a printing biomaterial in 3D printing.

6. Use of the composite 3D printing biomaterial ink according to claim 1, characterized in that: The diameter of a printing needle used in 3D printing with the composite 3D printing biomaterial ink is 0.41-0.6 mm.

7. Use of a composite 3D printing biomaterial ink according to claim 6, characterized in that: ​

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