Bone repair scaffold as well as preparation method and application thereof

Abstract

The invention discloses a bone repair scaffold as well as a preparation method and application thereof. The bone repair scaffold is formed by curing a magnesium phosphate scaffold in a potassium salt solution, the magnesium phosphate scaffold is prepared from the following raw materials: trimagnesium phosphate and a printing ink carrier, the trimagnesium phosphate is magnesium hydrogen phosphate trihydrate and magnesium hydroxide, and the printing ink carrier is prepared from a gelatin solution, glycerol and a glutaraldehyde solution. The preparation method of the bone repair scaffold comprises the following steps: preparing trimagnesium phosphate powder from magnesium hydrogen phosphate trihydrate and magnesium hydroxide; uniformly mixing a gelatin aqueous solution, glycerol and a glutaraldehyde solution to obtain a printing ink carrier; mixing the trimagnesium phosphate powder with a printing ink carrier, and performing vertical deposition 3D printing to obtain a magnesium phosphate stent; and placing the magnesium phosphate scaffold in a dipotassium phosphate solution for maintenance to obtain the magnesium phosphate bone repair scaffold. The bone repair scaffold provided by the invention can achieve the effects of high mechanical strength and high porosity.

Description

Technical Field

[0001] The present invention relates to a medical material and a preparation method thereof, in particular to a bone repair scaffold and a preparation method and application thereof. Background Art

[0002] Bone tissue loss caused by various reasons such as fractures, tumors, and bone degeneration, resulting in large-area bone defects, is a huge challenge faced by orthopedic clinical treatment. In the face of the repair of such bone defects, methods such as autologous bone transplantation or allogeneic bone transplantation are usually used clinically. However, the source of autologous bone is limited, and allogeneic bone may cause diseases due to rejection reactions, restricting the development of clinical treatment.

[0003] Bone tissue engineering provides a new idea for clinically solving large-area bone defects. Artificial bone repair materials are expected to replace natural bone as new repair and filling materials. Among them, calcium phosphate-based bone repair materials have received extensive research and attention. The chemical composition of hydroxyapatite or calcium-deficient hydroxyapatite is similar to the inorganic components of natural bone. By releasing Ca and P elements through the biodegradation of the material itself, it can promote the biomineralization of bone cells and has good biocompatibility and osteoconductivity. However, the currently applied calcium phosphate materials have low mechanical strength and cannot meet the needs of repairing large-area load-bearing bone defects. Magnesium phosphate bone cement has the characteristics of fast setting and high mechanical strength. Research shows that a certain concentration of magnesium ions outside cells has the effect of promoting the activity of osteoblasts and inhibiting the activity of osteoclasts. Magnesium phosphate bone cement has good biological activity and osteogenic ability and has application prospects in load-bearing bone repair. However, the internal microstructure of magnesium phosphate bone cement is dense after curing and has a low porosity, which is not conducive to the growth of cells inside the implant. Summary of the Invention

[0004] Object of the Invention: The object of the present invention is to provide a bone repair scaffold with high mechanical strength and high porosity.

[0005] Another object of the present invention is to provide a preparation method of a bone repair scaffold with high mechanical strength and high porosity.

[0006] Another object of the present invention is to provide a use of a bone repair scaffold with high mechanical strength and high porosity.

[0007] Technical Solution: The bone repair scaffold described in the present invention is formed by curing a magnesium phosphate scaffold in a potassium salt solution. The raw materials of the magnesium phosphate scaffold include trimagnesium phosphate and a printing ink carrier. The trimagnesium phosphate is magnesium hydrogen phosphate trihydrate and magnesium hydroxide with a molar ratio of 3-1:1. The printing ink carrier is prepared from a gelatin solution, glycerol, and a glutaraldehyde solution.

[0008] Preferably, the potassium salt solution is a dipotassium hydrogen phosphate solution.

[0009] Preferably, the concentration of the dipotassium hydrogen phosphate solution is 1-5 mol / L.

[0010] The method for preparing the bone repair scaffold of the present invention includes the following steps:

[0011] S1. Mix magnesium hydrogen phosphate trihydrate and magnesium hydroxide, and dry them; calcine, cool, ball-mill the sintered cake in an ethanol medium, and dry it to obtain magnesium phosphate powder;

[0012] S2. Mix the gelatin aqueous solution, glycerol, and glutaraldehyde solution evenly to obtain a printing ink carrier;

[0013] S3. Mix the magnesium phosphate powder with the printing ink carrier to obtain 3D printing ink, and perform vertical deposition 3D printing with this ink to obtain a magnesium phosphate scaffold; place the magnesium phosphate scaffold in a dipotassium hydrogen phosphate solution for curing to obtain a magnesium phosphate bone repair scaffold.

[0014] Preferably, in S1, the mixing method of magnesium hydrogen phosphate trihydrate and magnesium hydroxide is ball-milling; the molar ratio of magnesium hydrogen phosphate trihydrate to magnesium hydroxide is 3-1:1; the calcination temperature is 1000-1250 °C; the calcination time is 2-5 h.

[0015] Preferably, in S1, the ball-milling speed of the sintered cake in an ethanol medium is 300-400 rpm; the ball-milling time of the sintered cake in an ethanol medium is 4-18 h.

[0016] Preferably, in S2, the concentration of the glutaraldehyde solution is 1 wt%; the concentration of the gelatin solution is 5-10% (w / v).

[0017] Preferably, in S2, the volume feeding ratio of the gelatin solution, glycerol, and 1 wt% glutaraldehyde solution is 80-110:8-12:1, and more preferably 100:10:1.

[0018] Preferably, in S3, the solid-liquid ratio of the mixing of the magnesium phosphate powder and the printing ink carrier is 0.6-1 g / mL; the concentration of the dipotassium hydrogen phosphate solution is 1-5 mol / L.

[0019] The use of a bone repair scaffold in the repair of load-bearing bones.

[0020] Principle of the invention: The 3D printing technology is applied clinically. Through CT data reconstruction, a repair model conforming to the shape of the patient's trauma is constructed, which has been proven to have good application prospects in clinical personalized treatment. In the field of bone tissue engineering, the 3D printing technology can not only be used to construct a material model matching the defect, but also be used to regulate the pore size and porosity of the repair material to make it more suitable for cell and blood vessel growth, and improve the healing and repair ability of the trauma. In the present invention, glutaraldehyde is added to the gelatin and glycerol solution loaded with magnesium phosphate tribasic to further crosslink the gelatin, forming a gel suitable for 3D printing stacking. After 3D printing and forming, it is soaked in potassium hydrogen phosphate solution. Magnesium phosphate tribasic and potassium salt hydrate to form potassium magnesium phosphate, and then form a hydrogel network, covering the unreacted magnesium phosphate tribasic to form a solidified body, so that the prepared bone repair scaffold has good mechanical strength and bone growth promoting ability; Utilizing the self-curing ability of magnesium phosphate and potassium ions, the prepared bone repair scaffold has good mechanical properties and certain load-bearing capacity. At the same time, the 3D printing technology overcomes the shortcoming of low porosity of traditional magnesium phosphate bone cement, making it more suitable for cell and blood vessel growth and improving the healing and repair ability of bone defects.

[0021] Advantages: Compared with the prior art, the present invention has the following remarkable advantages: (1) The 3D printing "ink" with gelatin, glycerol and glutaraldehyde as carriers in the present invention is loaded with magnesium phosphate tribasic and printed at room temperature by a low-temperature nozzle. After 3D printing and forming, it is soaked in potassium hydrogen phosphate solution, so that the prepared bone repair scaffold has good mechanical strength (the highest compressive strength can reach 15 MPa), porosity and bone growth promoting ability at the same time; (2) By using the 3D printing method to prepare the magnesium phosphate bone repair scaffold, it can be personalized to match the bone defect site of the patient and match the bone trauma. The preparation method of the present invention is simple and has broad application prospects in the field of orthopedic clinical personalized treatment; (3) Utilizing the self-curing ability of magnesium phosphate and potassium ions, the prepared bone repair scaffold has good mechanical properties and strong load-bearing capacity. At the same time, the 3D printing technology overcomes the shortcoming of low porosity of traditional magnesium phosphate bone cement, making it more suitable for cell and blood vessel growth and improving the healing and repair ability of bone defects. Description of the drawings

[0022] Figure 1 It is a schematic diagram of the overall appearance of the bone repair scaffold prepared by the present invention. Detailed implementation manners

[0023] The technical solutions of the present invention will be further described below in conjunction with the embodiments.

[0024] Example 1

[0025] The bone repair scaffold described in the present invention is formed by curing a magnesium phosphate scaffold in a potassium salt solution. The raw materials of the magnesium phosphate scaffold include trimagnesium phosphate and a printing ink carrier. The trimagnesium phosphate is a mixture of magnesium hydrogen phosphate trihydrate and magnesium hydroxide with a molar ratio of 2.9:1. The printing ink carrier includes a gelatin solution, glycerol, and a glutaraldehyde solution.

[0026] The preparation method of the bone repair scaffold shown in the present invention includes the following steps:

[0027] S1. Mix 120 g of magnesium hydrogen phosphate trihydrate powder and 20 g of magnesium hydroxide powder in an ethanol medium by ball milling at 300 rpm for 2 h, and dry at 60 °C. The dried mixed powder is calcined in a muffle furnace at 1150 °C for 5 h, and the product is ball milled in an ethanol medium at 400 rpm for 18 h and dried at 60 °C to obtain trimagnesium phosphate powder.

[0028] S2. Weigh 5 g of gelatin and add it to 50 mL of ultrapure water, and dissolve it by magnetic stirring in a water bath at 50 °C to prepare a 10% (w / v) gelatin solution. Take 5 mL of the above gelatin solution, add 0.5 mL of glycerol and 0.05 mL of 1 wt% glutaraldehyde solution, and stir evenly in a water bath at 37 °C to obtain a printing ink carrier.

[0029] S3. Mix 3 g of trimagnesium phosphate powder with 5 mL of the printing ink carrier, stir magnetically for 10 min to obtain 3D printing ink. Load the 3D printing ink into a low-temperature printing nozzle, select a discharge needle with a diameter of 0.3 - 0.5 mm, and perform vertical deposition 3D printing to obtain a magnesium phosphate scaffold. Place it in a 3 mol / L potassium hydrogen phosphate solution for curing for more than 24 h to obtain a magnesium phosphate bone repair scaffold.

[0030] Use a universal testing machine to test the compressive strength of the magnesium phosphate bone repair scaffold, and its compressive strength is 6 MPa.

[0031] Use the ethanol weighing method to test the porosity of the magnesium phosphate bone repair scaffold, and its porosity is 64.2%.

[0032] Example 2

[0033] The same parts as in Example 1 will not be described in detail. The difference is that the addition amount of trimagnesium phosphate powder in S3 is 4 g.

[0034] Use a universal testing machine to test the compressive strength of the magnesium phosphate bone repair scaffold, and its compressive strength is 9 MPa.

[0035] Use the ethanol weighing method to test the porosity of the magnesium phosphate bone repair scaffold, and its porosity is 64.2%.

[0036] Example 3

[0037] The same parts as those in Embodiment 1 will not be described in detail. The difference is that the addition amount of magnesium phosphate powder in S3 is 4 g.

[0038] The compressive strength of the magnesium phosphate bone repair scaffold was tested using a universal testing machine, and the obtained compressive strength was 15 MPa.

[0039] The porosity of the magnesium phosphate bone repair scaffold was tested using the ethanol weighing method, and the obtained porosity was 64.2%.

[0040] Comparative Example 1

[0041] The same parts as those in Embodiment 1 will not be described in detail. The difference is that the solution used for curing in S3 is deionized water.

[0042] The compressive strength of the magnesium phosphate bone repair scaffold was tested using a universal testing machine, and the obtained compressive strength was 3 MPa.

[0043] The porosity of the magnesium phosphate bone repair scaffold was tested using the ethanol weighing method, and the obtained porosity was 64.2%.

Claims

1. A bone repair scaffold, characterized in that: The bone repair scaffold is formed by curing a magnesium phosphate scaffold in a potassium salt solution. The raw materials of the magnesium phosphate scaffold include trimagnesium phosphate and a printing ink carrier. The trimagnesium phosphate is magnesium hydrogen phosphate trihydrate and magnesium hydroxide in a molar ratio of 3-1:

1. The printing ink carrier is prepared from a gelatin solution, glycerol and glutaraldehyde solution.

2. The bone repair scaffold according to claim 1, characterized in that: The potassium salt solution is dipotassium hydrogen phosphate solution.

3. The bone repair scaffold according to claim 2, characterized in that: The concentration of the dipotassium hydrogen phosphate solution is 1-5 mol / L.

4. A method for preparing the bone repair scaffold according to claim 1, characterized in that: The following steps are involved: S1, mixing magnesium hydrogen phosphate trihydrate and magnesium hydroxide, drying; calcining, cooling, ball milling the sintered cake in an ethanol medium, and drying to obtain trimagnesium phosphate powder; S2, mixing the gelatin aqueous solution, glycerol and glutaraldehyde solution evenly to obtain a printing ink carrier; S3. Mixing trimagnesium phosphate powder with a printing ink carrier to obtain 3D printing ink, and using the ink to perform vertical deposition 3D printing to obtain a magnesium phosphate scaffold; curing the magnesium phosphate scaffold in a dipotassium hydrogen phosphate solution to obtain a magnesium phosphate bone repair scaffold.

5. The preparation method according to claim 4, characterized in that: In S1, the magnesium hydrogen phosphate trihydrate and magnesium hydroxide are mixed by ball milling; the molar ratio of magnesium hydrogen phosphate trihydrate and magnesium hydroxide is 3-1:1; the calcination temperature is 1000-1250° C.; and the calcination time is 2-5 hours.

6. The preparation method according to claim 4, characterized in that: In S1, the ball milling speed of the sintered cake in the ethanol medium is 300-400 rpm; the ball milling time of the sintered cake in the ethanol medium is 4-18 hours.

7. The preparation method according to claim 4, characterized in that: In S2, the concentration of the glutaraldehyde solution is 1 wt%; the concentration of the gelatin solution is 5-10% (w / v).

8. The preparation method according to claim 7, characterized in that: In S2, the volume ratio of the gelatin solution, glycerol and 1wt% glutaraldehyde solution is 80-110:8-12:

1.

9. The preparation method according to claim 4, characterized in that: In S3, the solid-liquid ratio of the mixture of the trimagnesium phosphate powder and the printing ink carrier is 0.6-1 g / mL; the concentration of the dipotassium hydrogen phosphate solution is 1-5 mol / L.

10. Use of the bone repair scaffold according to claim 1 in load-bearing bone repair.

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