A high-precision interconnected porous structure hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing forming method

Abstract

The application belongs to the field of material science engineering, and discloses a high-precision interconnected porous structure hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing forming method.The method uses potassium-doped hydroxyapatite and chitosan as raw materials, and the steps are as follows: preparing potassium-doped hydroxyapatite slurry; mixing the potassium-doped hydroxyapatite slurry and chitosan solution; extruding 3D printing forming at room temperature to obtain one-step formed 3D printing interconnected porous structure composite material.In the application, the hydroxyapatite powder is modified by potassium doping, and does not need to be printed in a solidification solution or treated by spraying a solidification liquid and the like for cross-linking, thereby avoiding high-temperature treatment and sintering processes and the like.The interconnected porous structure composite material 3D printing interconnected porous structure prepared by the method has high-precision structure and excellent mechanical properties, and realizes room temperature one-step extrusion 3D printing forming.The 3D printing formed porous material prepared by the method has potential application value in the fields of water treatment, biomedical scaffolds and the like.

Description

Technical Field

[0001] This invention belongs to the field of materials science and engineering, and relates to a high-precision interconnected porous hydroxyapatite / chitosan composite material and a room-temperature one-step 3D printing method, which has certain application value in water treatment, biomedical scaffolds and other fields. Background Technology

[0002] Hydroxyapatite is widely recognized as an excellent scaffold material; however, traditional preparation methods, such as foaming, sintering microspheres, and sol-gel methods, typically require high-temperature calcination, making the process complex and unsuitable for loading bioactive drugs. Unlike traditional methods, modern 3D printing technology uses selective laser sintering to mix hydroxyapatite with low-melting-point materials. However, the resulting scaffolds often suffer from poor shape and require additional processing, such as isostatic pressing to increase density. The entire preparation process is expensive and complex, and it remains difficult to load bioactive substances.

[0003] Other 3D printing methods (photopolymerization, inkjet, direct-write extrusion) typically involve mixing hydroxyapatite powder with polymer materials before extrusion printing. While direct-write extrusion 3D printing offers significant advantages in the biomedical field, including good biocompatibility and the ability to customize printing with multiple materials, current 3D printing direct-write extrusion deposition technologies usually require steps such as spraying during printing, soaking after printing, or UV curing. Liu Shuifeng from South China Agricultural University published a paper on the construction of a hydroxyapatite / polymer nanocomposite porous bio-scaffold using sodium alginate (SA), hydroxyapatite (HAP), and glucono-delta-lactone (GDL) as the main raw materials. Sodium alginate was in-situ gelled to form a hydrogel as a bio-ink, which was then obtained through extrusion 3D printing. The scaffold was then further soaked in a calcium chloride solution for cross-linking to improve its performance. These processes often result in poor structural control and low precision during printing, and due to the materials themselves, the scaffold's mechanical properties are also poor, thus limiting the application and development of 3D printing materials in related fields.

[0004] Therefore, it is hoped that a room-temperature extrusion 3D printing material and a one-step molding process can be developed. This material is non-biotoxic, requires no post-crosslinking treatment, and has a high-precision three-dimensional structure, with the aim of having certain applications in the fields of water treatment and biomedicine. Summary of the Invention

[0005] This invention addresses the technical challenges of high equipment and material costs, cumbersome post-processing, and potential biotoxicity risks associated with current hydroxyapatite scaffolds in 3D printing. It proposes a one-step, room-temperature 3D printing method for high-precision, interconnected, porous potassium-doped hydroxyapatite / chitosan composite scaffolds. By fully utilizing the slow-release effect of potassium ions and controlling the composition and process parameters, this invention prepares a highly injectable slurry with a suitable curing time for 3D printing. This process allows for room-temperature extrusion molding without sintering or cross-linking post-processing, ultimately yielding a high-precision, interconnected, porous 3D-printable scaffold material.

[0006] The technical solution of the present invention:

[0007] A high-precision interconnected porous hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing method is proposed. The method involves preparing a hydroxyapatite-chitosan mixed slurry by mixing potassium-doped hydroxyapatite powder and chitosan, and then extruding the hydroxyapatite-chitosan mixed slurry at room temperature for 3D printing to form a self-consolidated scaffold material.

[0008] The molar ratio of calcium + potassium to phosphorus in the potassium-doped hydroxyapatite powder is 5:3; the mass percentage of potassium in the potassium-doped hydroxyapatite powder, calculated as potassium oxide, is 10-25 wt%.

[0009] The potassium salt is potassium carbonate, potassium sulfate, or potassium hydroxide.

[0010] The potassium-doped hydroxyapatite powder has a nanoscale microstructure, with a length of 20–100 nm and a width of 5–10 nm.

[0011] A hydroxyapatite-chitosan mixed slurry was prepared by combining potassium-doped hydroxyapatite powder and chitosan. Specifically, the potassium-doped hydroxyapatite powder was first added to deionized water and ultrasonically dispersed to form a potassium-doped hydroxyapatite slurry. Then, chitosan was dissolved in acetic acid solution to obtain a chitosan solution. The potassium-doped hydroxyapatite slurry was added dropwise to the chitosan solution and stirred in a magnetic stirrer at a temperature of 30-75℃ and a speed of 600-1000 rpm to obtain the hydroxyapatite-chitosan mixed slurry.

[0012] In the hydroxyapatite-chitosan mixed slurry, the mass ratio of chitosan to potassium-doped hydroxyapatite is 1:1 to 1:2.

[0013] The degree of deacetylation of the chitosan is 80-95%; the chitosan mass concentration in the chitosan solution is 1-8%, and the acetic acid mass concentration is 2-6%.

[0014] The stirring time is 2.5 to 4.5 hours.

[0015] The diameter of the extrusion head for 3D printing is 0.2–1.2 mm, the layer height is 0.1–0.6 mm, the printing speed is 0.1 mm / s–50 mm / s, and the printing air pressure is 30–800 kPa.

[0016] The potassium-doped hydroxyapatite is uniformly distributed inside and on the surface of the interconnected porous structure.

[0017] Printing in a curing solution is unnecessary, as is cross-linking treatments such as spraying curing liquid, and high-temperature treatments such as sintering are also eliminated. The printing environment is kept at room temperature, and the substrate needs to be left to stand for 5–15 minutes after printing.

[0018] The beneficial effects of the present invention are as follows: The present invention provides a high-precision continuous porous potassium-doped hydroxyapatite / chitosan composite material room temperature one-step 3D printing method. Starting from the modification of hydroxyapatite, the injectability and setting time of the hydroxyapatite / chitosan composite slurry are obtained, so that the slurry can be used for direct writing 3D printing, thereby obtaining well-formed and high-precision engineering scaffolds.

[0019] Specifically, it includes the following aspects:

[0020] (1) Introducing potassium-doped hydroxyapatite into the composite system significantly improves the injectability (over 90%) and uniformity of the slurry. By controlling the potassium ion release concentration in the potassium-doped hydroxyapatite and adjusting the chitosan composition and process, a processing window suitable for 3D printing is provided. The preparation method of this invention adopts room-temperature one-step extrusion printing with self-curing, requiring no high-energy beam assisted sintering (such as laser or electron beam), no ultraviolet light assisted curing, and no other complex post-processing steps such as subsequent glue removal and high-temperature sintering, providing a new and convenient approach for the 3D printing of hydroxyapatite in bone tissue engineering scaffolds and water treatment.

[0021] (2) The hydroxyapatite and chitosan used in this invention have high safety and good biocompatibility. The printed bone scaffold has a suitable porosity and pore size structure, which is conducive to bone tissue growth, thus giving the scaffold excellent biocompatibility and osteoconductivity. The interconnected porous structure is conducive to the transport of nutrients, the growth of blood vessels, and can promote cell attachment, proliferation, and differentiation.

[0022] (3) The potassium-doped hydroxyapatite / chitosan composite scaffold material prepared by this invention is 3D printed at around room temperature. This low-temperature 3D printing technology helps with the maintenance of the scaffold and the compatibility of its components, avoiding contamination. Compared with products that require high-temperature sintering or high-temperature printing after printing, it has a higher activity advantage.

[0023] (4) The room temperature one-step forming process used in this invention is conducive to the addition of drugs and highly active factors, and even active cells, so that the scaffold can have higher biological activity. Attached Figure Description

[0024] Figure 1 This is the sample obtained in Example 1. It is basically impossible to mold, collapses and fuses very easily, is basically impossible to print, and quickly fuses and collapses after printing, making it impossible to obtain a practical support material.

[0025] Figure 2 shows the sample obtained in Example 2; where (a) shows the sample with high precision, and (b) shows that after (a) is left for a period of time, the layers are still distinct and maintain high precision.

[0026] Figure 3 This is the sample obtained in Example 3.

[0027] Figure 4 The sample obtained in Example 6 is shown in (a) where some nodes of the printed sample will fuse to a certain extent, and the overall molding quality is acceptable; and (b) where the sample collapses and fuses quickly after molding, and the precision is poor. Detailed Implementation

[0028] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings and technical solutions.

[0029] Example 1

[0030] 2g of chitosan was dissolved in a 3wt% (acetic acid concentration) aqueous solution of acetic acid and stirred at 60℃ and 800rpm using a magnetic stirrer to prepare a 5wt% chitosan-acetic acid solution. 3.0g of undoped potassium hydroxyapatite was mixed with deionized water and sonicated for 10-20 minutes using an ultrasonic cell disruptor to ensure uniform dispersion. The potassium-doped hydroxyapatite suspension was added dropwise to the chitosan-acetic acid solution at a mass ratio of 2:3, and stirring was continued for 3 hours to obtain a uniformly mixed potassium-doped hydroxyapatite-chitosan suspension. The composite gel ink was printed using a DIW printer under the following conditions: 3D printer extruder diameter of 0.3mm, layer height of 0.3mm, printing speed of 30mm / s, and printing pressure of 400kPa. The resulting sample was almost impossible to mold, easily collapsed and fused, and was practically unprintable (e.g., Figure 1 As shown in the image, the material quickly fused and collapsed after printing, making it impossible to obtain a practical support material.

[0031] Example 2

[0032] 2g of chitosan was dissolved in a 3wt% (acetic acid concentration) aqueous solution of acetic acid and stirred vigorously until clear and transparent to prepare a 5wt% chitosan gel ink. 3g of potassium hydroxyapatite was mixed with deionized water and sonicated for 10-20 minutes using an ultrasonic cell disruptor to ensure uniform dispersion. The potassium hydroxyapatite suspension was added dropwise to the chitosan ink at a mass ratio of 2:3, and stirring continued for 3 hours to obtain a potassium hydroxyapatite-chitosan composite ink. The composite gel ink was printed using a DIW printer under the following conditions: 3D printing extruder diameter of 0.3mm, layer height of 0.3mm, printing speed of 30mm / s, and printing pressure of 400kPa. The obtained sample showed high precision (Figure 2(a)). After a period of time, the layers remained distinct and maintained high precision (Figure 2(b)). Freeze-drying was then performed to obtain the potassium hydroxyapatite / chitosan composite scaffold.

[0033] Example 3

[0034] 2g of chitosan was dissolved in a 3wt% (acetic acid concentration) aqueous solution of acetic acid, and stirred at 60℃ and 800rpm using a magnetic stirrer to prepare a 5wt% chitosan-acetic acid solution. 6g of potassium-doped hydroxyapatite was mixed with deionized water and sonicated for 10-20 minutes using an ultrasonic cell disruptor to ensure uniform dispersion. The potassium-doped hydroxyapatite suspension was added dropwise to the chitosan-acetic acid solution at a chitosan to potassium-doped hydroxyapatite mass ratio of 1:3, and stirring was continued for 3 hours to obtain a uniformly mixed potassium-doped hydroxyapatite-chitosan suspension. The composite gel ink was then printed using a DIW printer under the following conditions: 3D printer extruder diameter of 0.3mm, layer height of 0.3mm, printing speed of 30mm / s, and printing pressure of 400kPa. Figure 3 As shown, printing cannot be achieved.

[0035] Example 4

[0036] 2.0 g of chitosan was dissolved in a 2 wt% (acetic acid concentration) aqueous solution of acetic acid and stirred at 60°C and 800 rpm using a magnetic stirrer to prepare a 5 wt% chitosan-acetic acid solution. 4.0 g of potassium-doped hydroxyapatite was mixed with deionized water and sonicated for 10-20 minutes using an ultrasonic cell disruptor to ensure uniform dispersion. The potassium-doped hydroxyapatite suspension was added dropwise to the chitosan-acetic acid solution at a chitosan to potassium-doped hydroxyapatite mass ratio of 1:2, and stirring was continued for 3 hours to obtain a uniformly mixed potassium-doped hydroxyapatite-chitosan suspension. The composite gel ink was printed using a DIW printer under the following conditions: 3D printer extruder diameter of 0.3 mm, layer height of 0.3 mm, printing speed of 30 mm / s, and printing pressure of 350 kPa. The resulting sample was intact. After freeze-drying, the potassium-doped hydroxyapatite / chitosan composite scaffold was obtained.

[0037] Example 5

[0038] 2.0 g of chitosan was dissolved in a 2 wt% (acetic acid concentration) aqueous solution of acetic acid and stirred at 60°C and 800 rpm using a magnetic stirrer to prepare a 5 wt% chitosan-acetic acid solution. 2.0 g of potassium-doped hydroxyapatite was mixed with deionized water and sonicated for 10-20 minutes using an ultrasonic cell disruptor to ensure uniform dispersion. The potassium-doped hydroxyapatite suspension was added dropwise to the chitosan-acetic acid solution at a mass ratio of 1:1, and stirring was continued for 5 hours to obtain a uniformly mixed potassium-doped hydroxyapatite-chitosan suspension. The composite gel ink was printed using a DIW printer under the following conditions: extruder diameter of 0.3 mm, layer height of 0.3 mm, printing speed of 30 mm / s, and printing pressure of 800 kPa. The resulting sample was well-formed, although the printing process had some limitations in terms of flow; the printed sample had high precision. Then, freeze-drying is performed to obtain the potassium-doped hydroxyapatite / chitosan composite scaffold.

[0039] Example 6

[0040] 2g of chitosan was dissolved in a 3wt% (acetic acid concentration) aqueous solution of acetic acid and stirred at 60℃ and 800rpm using a magnetic stirrer to prepare a 5wt% chitosan-acetic acid solution. 2.0g of undoped potassium hydroxyapatite was mixed with deionized water and sonicated for 10-20 minutes using an ultrasonic cell disruptor to ensure uniform dispersion. The potassium-doped hydroxyapatite suspension was added dropwise to the chitosan-acetic acid solution at a mass ratio of 1:1, and stirring was continued for 3 hours to obtain a uniformly mixed potassium-doped hydroxyapatite-chitosan suspension. The composite gel ink was printed using a DIW printer under the following conditions: 3D printer extruder diameter of 0.3mm, layer height of 0.3mm, printing speed of 30mm / s, and printing pressure of 400kPa. Some nodes of the printed sample showed some fusion, but the overall molding quality was acceptable. Figure 4 (a) The molded sample quickly collapsed and fused, resulting in poor precision. (See figure) Figure 4 (b)

Claims

1. A high-precision interconnected porous structure hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing forming method, characterized in that, The steps are as follows: A hydroxyapatite-chitosan mixed slurry is prepared by mixing potassium-doped hydroxyapatite powder with chitosan. The hydroxyapatite-chitosan mixed slurry is then extruded at room temperature and 3D printed to form a self-consolidated shape, thus obtaining a hydroxyapatite / chitosan scaffold material. In the hydroxyapatite-chitosan mixed slurry, the mass ratio of chitosan to potassium-doped hydroxyapatite is 1:1 to 1:2; The molar ratio of calcium + potassium to phosphorus in the potassium-doped hydroxyapatite powder is 5:3; the mass percentage of potassium in the potassium-doped hydroxyapatite powder, calculated as potassium oxide, is 10~25 wt%.

2. The high precision interconnected porous structure hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing forming method according to claim 1, characterized in that, A hydroxyapatite-chitosan mixed slurry was prepared by combining potassium-doped hydroxyapatite powder and chitosan. Specifically, the potassium-doped hydroxyapatite powder was first added to deionized water and ultrasonically dispersed to form a potassium-doped hydroxyapatite slurry. Then, chitosan was dissolved in acetic acid solution to obtain a chitosan solution. The potassium-doped hydroxyapatite slurry was added dropwise to the chitosan solution and stirred in a magnetic stirrer at a temperature of 30~75℃ and a speed of 600~1000rpm to obtain the hydroxyapatite-chitosan mixed slurry.

3. The high-precision interconnected porous hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing method according to claim 2, characterized in that, The degree of deacetylation of the chitosan is 80-95%; the chitosan mass concentration in the chitosan solution is 1-8%, and the acetic acid mass concentration is 2-6%.

4. The high-precision interconnected porous hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing method according to claim 2, characterized in that, The stirring time is 2.5~4.5 h.

5. The high-precision interconnected porous hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing method according to any one of claims 1-4, characterized in that, The 3D printing extruder has a diameter of 0.2~1.2mm, a layer height of 0.1~0.6mm, a printing speed of 0.1mm / s~50mm / s, and a printing air pressure of 30~800kPa.

6. The high-precision interconnected porous hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing method according to any one of claims 1-4, characterized in that, The microstructure of the potassium-doped hydroxyapatite powder is nanoscale, with a length of 20~100nm and a width of 5~10nm.

7. The high-precision interconnected porous hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing method according to any one of claims 1-4, characterized in that, The printing environment is at room temperature, and the substrate needs to be placed on the printing plate for 5-15 minutes after printing.

8. The high-precision interconnected porous hydroxyapatite / chitosan composite scaffold room temperature one-step 3D printing method according to claim 1, characterized in that, The potassium is potassium carbonate, potassium sulfate, or potassium hydroxide.

Images