WO2022110522A1

WO2022110522A1 - Method for preparing degradable metal-organic matter composite bone repair material

Info

Publication number: WO2022110522A1
Application number: PCT/CN2021/072582
Authority: WO
Inventors: 陈英奇; 康斌; 曾晖
Original assignee: 北京大学深圳医院
Priority date: 2020-11-24
Filing date: 2021-01-18
Publication date: 2022-06-02
Also published as: CN112451742A; CN112451742B

Abstract

A method for preparing a degradable metal-organic matter composite bone repair material. The preparation method comprises performing a surface modification treatment on a degradable metal, and then polymerizing the modified metal with a hydrogel pre-polymerization liquid to prepare a porous or reticular metal-organic composite bone repair material having a significantly reduced degradation rate and a significantly improved compressive strength and compressive modulus.

Description

A kind of preparation method of degradable metal-organic composite bone repair material

technical field

The invention relates to the technical field of biomedical engineering, in particular to a preparation method of a degradable metal-organic composite bone repair material.

Background technique

Traffic accidents, trauma, tumor resection, congenital skeletal diseases, osteoarthritis and other large-segment bone defects can easily lead to high disability and teratogenic rates. According to statistics, the incidence of bone defects is 5-7%. More than 300 million people in the world suffer from bone defects caused by various causes. Large segmental bone defects have poor regeneration ability, and how to effectively repair such bone defects has always been one of the unsolved problems in the medical and material fields.

External intervention therapy is a necessary and effective method. The main clinical methods for bone defect treatment are autologous bone transplantation and allograft bone transplantation. Autologous bone has good osteogenic ability and minimal immune rejection, and is the "gold standard" for bone defect repair. cause complications, etc. Allogeneic bone transplantation has obvious deficiencies such as immune rejection, potential host tissue infection and tissue necrosis. With the development of regenerative medicine and biomaterials, bionic design of a new functional material that can replace and repair bone defects provides a feasible solution for the treatment of bone defects. An ideal bone repair material should have the following properties: 1. It has good biocompatibility and safety; 2. It should have a certain mechanical strength to provide mechanical support for bone defects with a certain load-bearing part; 3. It has good 4. It is degradable and the degradation rate can be adjusted; 5. It has a certain bionic micro-nano porous structure to provide space for new bone and blood vessels to grow in.

Currently, a large number of bone repair materials have been widely reported, with a wide variety, aiming to provide osteogenic activity, mechanical strength, or synergistic enhancement of both. Such as ceramic bone repair materials, ceramic/polymer bone repair materials, ceramic/hydrogel composite bone repair materials, etc.; polymer bone repair materials, such as polymer/bioactive glass composite materials, magnesium-containing polymer bone repair materials etc.; hydrogel materials, micro-nanofiber scaffolds, 3D printed scaffolds, porous metal scaffolds, etc., these materials all show good bone repair effect to a certain extent, and show good application prospects. Among them, the hydrogel prepared with natural polysaccharide as the base material has the characteristics of good biosafety, biocompatibility, degradability, and extracellular matrix-like structure, which makes this kind of material have obvious advantages in bone defect repair. It is widely used in the research of bone repair materials and has become a research hotspot in recent years. However, the mechanical strength of single natural polysaccharide hydrogel is insufficient, and it is difficult to be used for the repair of bone defects in parts with a certain bearing capacity.

Degradable metals, such as magnesium-based alloys and zinc-based alloys, are potential bone repair materials and have been a research hotspot in recent years. Magnesium and zinc are essential elements for the human body and participate in a variety of important metabolic processes in the human body. Magnesium alloys and zinc alloys have elastic moduli matching those of human cortical bone, which can provide mechanical support for bone defects and avoid the stress shielding effect of other non-degradable metals due to excessive stress. Magnesium alloys and zinc alloys are degradable in the human body, and the magnesium ions or zinc ions generated during the degradation process have good osteogenic and angiogenic activities at appropriate concentrations. Despite the above advantages, it is difficult to directly use bulk degradable metal for bone defect repair, because bulk metal occupies a large amount of space, which affects the ingrowth of new bone and blood vessels, and the degradation of a large amount of bulk metal will cause local accumulation of a large number of corrosion products. Bone defect repair. Therefore, degradable metals with porous structures or meshes will have more advantages than bulk metals in bone defect repair. However, although the porous structure is conducive to the ingrowth of tissues and blood vessels, the porous degradable metal has a large specific surface area, which will further accelerate its degradation during the degradation process, especially porous magnesium alloys. How to effectively slow down the degradation rate of porous degradable metals is a key issue that should be solved in the practical application of such porous degradable metals.

Porous or mesh-like degradable metals can be prepared in the prior art, but after being prepared into porous or mesh-like shapes, the increase in specific surface area (increase in contact area with corrosive medium) will further accelerate their degradation, so how to effectively control the degradation of porous or mesh-like metals? The degradation rate is the key to its practical clinical application, however, there are very few reports on effectively regulating the degradation of porous or reticular metals and providing a good microenvironment for osteocytes and blood vessel ingrowth (such as compounding with ECM-like hydrogels). .

SUMMARY OF THE INVENTION

Aiming at the above-mentioned problems existing in the existing porous or reticular degradable metals, the present invention provides a method for preparing the A method for obtaining a degradable metal-organic composite bone repair material.

In order to achieve the above objects, the present invention adopts the following technical solutions.

A preparation method of a degradable metal-organic composite bone repair material, comprising the following steps:

S1. Soak the degradable metal in the surface treatment solution for 24 hours, then take it out, rinse with water and dry to obtain the modified degradable metal;

The surface treatment solution is a solution prepared by using 1.0-1.5 mg/mL Tris aqueous solution to prepare a solution with a polyphenolic compound content of 0.5-5.0 mg/mL, and then adding an amine compound to the solution to form a solution. The content of the compound was 1.0-2.0 mg/mL.

Preferably, the polyphenolic compound is selected from one of catecholamines, catechols, tannins, gallic acids, anthocyanins, and procyanidins. More preferably, the polyphenolic compound is dopamine.

Preferably, the amine compound is 2-aminoethyl methacrylate or ethylenediamine.

More preferably, the surface treatment solution is a solution formed by adding 2-aminoethyl methacrylate to the solution after preparing a solution with a dopamine content of 2.0 mg/mL with a 1.2 mg/mL Tris aqueous solution, so that The content of the 2-aminoethyl methacrylate was 2.0 mg/mL.

More preferably, the surface treatment solution is a solution with a dopamine content of 5.0 mg/mL prepared with a 1.2 mg/mL Tris aqueous solution, and then a solution formed by adding ethylenediamine to the solution. is 1.0 mg/mL.

Preferably, the degradable metal is magnesium, magnesium alloy, zinc, zinc alloy, iron or iron alloy.

More preferably, the degradable metal is a porous or reticulated degradable metal.

Preferably, before soaking the degradable metal in the surface treatment solution, the degradable metal is cleaned first; the cleaning treatment is as follows: firstly placing the degradable metal in acetone for ultrasonic cleaning, and then placing the degradable metal in a non-corrosive Ultrasonic cleaning was performed in water ethanol, and then the degradable metal was dried.

Preferably, the drying treatment is to dry the degradable metal with a dry nitrogen stream, and then place the degradable metal in a vacuum drying oven for use.

S2. Pour the hydrogel prepolymer solution into a container containing the modified degradable metal, and place the container in a vacuum box to vacuum for more than 0.5h;

The hydrogel prepolymerization solution is a solution containing 1mg/mL of ultraviolet photoinitiator in an aqueous solution of acrylic acid double bond and phosphoric acid modified natural polysaccharide of 5-40mg/mL; or the hydrogel prepolymerization solution is 18-22mg A solution containing 1 mg/mL of UV photoinitiator in an aqueous solution of methacrylic acid-modified natural polysaccharide/mL.

Preferably, the natural polysaccharide is chitosan, hyaluronic acid, gelatin or sodium alginate.

Preferably, the ultraviolet photoinitiator is 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone.

S3, irradiating the hydrogel prepolymer solution and the modified degradable metal treated in step 2 with ultraviolet light to obtain a degradable metal-organic composite bone repair material.

Compared with the prior art, the beneficial effects of the present invention are:

In the present invention, a coating layer containing anti-corrosion and acrylic acid functional groups is first constructed on the degradable metal, and the modified degradable metal composite hydrogel prepolymerization solution initiates the polymerization of acrylic double bonds under ultraviolet light to form a degradable metal- Organic composite bone repair material. The degradable metal in the bone repair material of the present invention can provide mechanical support for the bone repair material, so that it can meet the requirements of bone defect repair; the surface coating of the modified degradable metal can provide corrosion protection function and provide corrosion protection for subsequent The hydrogel prepolymer solution provides polymerization sites; the hydrogel can provide a good microenvironment for the ingrowth of osteocytes and vascular cells, which is conducive to bone ingrowth and angiogenesis; at the same time, the hydrogel filled in the metal can be degraded. The glue can play a certain physical barrier, slowing down the contact between the corrosive medium and the degradable metal, thereby further slowing down the corrosion rate of the degradable metal; in addition, the metal ions released by the degradable metal during the degradation process can interact with the hydrogel in the hydrogel. Functional groups (such as phosphoric acid groups) are chelated, which can slow release metal ions and have a slow release effect.

By optimizing the composition and component content of the surface treatment liquid, the invention makes the coating formed on the surface of the degradable metal firm and has good anti-corrosion performance; The concentration of the hydrogel prepolymer not only makes the hydrogel prepolymer easily enter the pores of the reticulated/porous degradable metal to fully fill the pores, but also avoids the formation of loose hydrogels after the cross-linking reaction.

After testing, the bone repair material of the present invention has a certain mechanical strength, which can provide mechanical support for bone defects, and the hydrogel filled in the mesh or porous degradable metal has a three-dimensional bionic structure, which can provide bone cells and vascular cells growth. In a good microenvironment, the coating on the surface of degradable metal and the filled hydrogel can control the degradation rate of degradable metal and the release rate of osteogenic metal ions to meet the matching of material degradation and bone ingrowth rate and the balance of metal ion osteogenic activity. Purpose.

Description of drawings

Fig. 1 is the macroscopic topography of the degradable metal-organic composite bone repair material prepared in Example 4;

FIG. 2 is a comparison diagram of the compressive strength and compressive modulus of the degradable metal-organic composite bone repair material prepared in Example 4 and the hydrogel bone repair material without magnesium mesh.

Detailed ways

In order to more fully understand the technical content of the present invention, the technical solutions of the present invention will be further introduced and described below with reference to specific embodiments.

The preparation method of phosphoric acid-modified methacrylated natural polysaccharide is as follows:

(1) after dissolving the natural polysaccharide in the solvent, add methacrylic anhydride, and react at room temperature to obtain mixture A;

(2) dissolving phosphoric acid or phosphonic acid modified raw material in deionized water, adding MES, EDC and NHS successively, fully dissolving and stirring at room temperature to obtain mixture B;

(3) adding mixture A to mixture B, reacting at room temperature, adding deionized water for dilution, placing the diluent in a dialysis bag, dialysis in deionized water at room temperature, and freeze-drying after dialysis to obtain phosphoric acid-modified methacrylated Natural polysaccharides.

Preferably, the natural polysaccharide is one of chitosan, hyaluronic acid and sodium alginate.

Preferably, the ratio of natural polysaccharide, solvent for dissolving natural polysaccharide and methacrylic anhydride is 1-5g:100mL:0-1mL.

More preferably, the ratio of natural polysaccharide, solvent for dissolving natural polysaccharide and methacrylic anhydride is 1 g: 100 mL: 367 μL.

Preferably, when the natural polysaccharide is chitosan, in step (1), the solvent for dissolving chitosan is an aqueous acetic acid solution, and the volume fraction of the aqueous acetic acid solution is 0.5-10%

Preferably, when the natural polysaccharide is hyaluronic acid or sodium alginate, the solvent for dissolving hyaluronic acid or sodium alginate is deionized water, and after dissolving, sodium hydroxide solution is added to adjust the pH value to 7.3-8.5.

Preferably, in step (1) and step (2), the mass ratio of natural polysaccharide and phosphoric acid or phosphonic acid modified raw material is 10:1-1:5.

More preferably, the mass ratio of natural polysaccharide and phosphoric acid or phosphonic acid modified raw material in step (1) and step (2) is 2:1.

Preferably, in step (2), the modified raw material of phosphoric acid or phosphonic acid is one of 3-phosphonopropionic acid, creatine phosphate, alenphosphoric acid or phosphoethanolamine; the modified raw material of phosphoric acid or phosphonic acid, MES, The mass ratio of EDC and NHS is 0.1-10:50-80:3-9:1-3.

More preferably, the mass ratio of phosphoric acid or phosphonic acid modified raw material, MES, EDC and NHS is 5:53.3:9:3.

Preferably, in step (3), a dialysis bag with a molecular weight of 12-14 kDa is used for dialysis.

Taking phosphoric acid modified methacrylated chitosan as an example, the preparation of phosphoric acid modified methacrylated chitosan includes the following steps:

(1) Dissolve 1 g of chitosan in 100 mL of acetic acid aqueous solution with a volume fraction of 1%, add 367 μL of methacrylic anhydride (MA) dropwise after dissolving, and react at room temperature for 24 h to obtain methacrylated chitosan (CSMA). ).

(2) Dissolve 0.5g 3-phosphonopropionic acid in 50mL deionized water, add 5.33g 2-(N-morpholine)ethanesulfonic acid monohydrate (MES monohydrate), add 0.9g EDC (1-Ethyl -3-(3'-dimethylaminopropyl)carbodiimide) and 0.3 g of NHS (N-hydroxysuccinimide) were fully dissolved and stirred at room temperature for 30 min.

(3) adding the liquid after the reaction of chitosan and methacrylic acid in step (1) dropwise to the 3-phosphonopropionic acid solution in step (2), stirring while adding dropwise, after all the dropwise additions After reacting at room temperature for 24 hours, add 100 mL of deionized water for dilution, place the dilution in a 12-14kDa dialysis bag, and dialyze the deionized water at room temperature for 5 days. Change the deionized water every morning and evening, and keep stirring. Freeze-dried to obtain white loose phosphoric acid-modified methacrylated chitosan (CSMAP).

Above-mentioned MES is 2-(N-morpholine) ethanesulfonic acid monohydrate, EDC is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and NHS is N-hydroxyl Succinimide.

Example 1

This embodiment provides a preparation method of a degradable metal-organic composite bone repair material. The degradable metal used in this example is a reticulated AZ31 magnesium alloy, the hollow grid is square, the side length of the square is 1.5 mm, the width of the grid metal bars is 0.25 mm, and the thickness of the magnesium mesh is 0.25 mm.

Specific steps are as follows:

(1) Ultrasonic cleaning of the degradable metal in acetone for 3 times, 5 minutes each time, followed by ultrasonic cleaning in absolute ethanol for 3 times, 5 minutes each time, after taking out, blow dry under a dry nitrogen stream, and place it in a vacuum drying oven Save it for later use.

(2) Prepare a 2 mg/mL dopamine solution in an open beaker with a 1.2 mg/mL Tris aqueous solution, then add 2 mg/mL 2-aminoethyl methacrylate to the solution, and stir openly at room temperature After half an hour, a mixed solution containing dopamine and 2-aminoethyl methacrylate, that is, a surface treatment solution was obtained.

(3) Immerse the degradable metal cleaned in step (1) in the surface treatment solution prepared in step (2), soak the beaker at room temperature for 24 hours, take out the degradable metal, and rinse it with deionized water, Then, it is blown dry under a stream of dry nitrogen to obtain the modified degradable metal. The modified degradable metal was stored in a vacuum drying oven until use.

(4) Dissolve phosphoric acid-modified methacrylated chitosan in deionized water at a concentration of 20 mg/mL, and add 1 mg/mL of UV photoinitiator 2-hydroxy-4'-(2- hydroxyethoxy)-2-methylpropiophenone to obtain a hydrogel prepolymer solution.

(5) taking the modified degradable metal obtained in step (3) and placing it in a beaker, pouring the hydrogel prepolymer solution obtained in step (4) into the beaker to completely cover the degradable metal, and then placing the beaker in Vacuum for half an hour in a vacuum box.

(6) placing the beaker in step (5) under ultraviolet light (wavelength is 400nm-10nm), and irradiating for 20 minutes to obtain a mesh-like degradable metal-organic composite bone repair material.

The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 26.8 μA/cm ² , and the self-corrosion current density of the unmodified AZ31 is 269.1 μA/cm ² . The degradable metal-organic composite bone repair material prepared in this example has a compressive strength of 49 MPa and a compressive modulus of 80 MPa.

In other embodiments, pure magnesium, as well as biomedical magnesium alloys such as AZ91 and WE43, can also be used; and the pore connectivity rate is more than 80% and the pore size is conducive to the inflow of the hydrogel prepolymer solution and the hydrogel. Porous degradable metal in which the prepolymer solution is connected in the porous structure.

Example 2

This embodiment provides a preparation method of a degradable metal-organic composite bone repair material. The degradable metal used in this example is the same as that in Example 1, which is a meshed AZ31 magnesium alloy, the hollow mesh is square, the side length of the square is 1.5mm, the width of the mesh metal bars is 0.25mm, and the magnesium mesh The thickness is 0.25mm.

Specific steps are as follows:

(1) Ultrasonic cleaning of the degradable metal in acetone for 3 times, 5 min each time, followed by ultrasonic cleaning in absolute ethanol for 3 times, 5 min each time, take out and blow dry under a stream of dry nitrogen, and place in a vacuum drying box for use.

(2) Prepare a 5 mg/mL dopamine solution with a 1.2 mg/mL Tris aqueous solution in an open beaker, then add 1 mg/mL 2-aminoethyl methacrylate to the solution, and stir openly at room temperature After half an hour, a mixed solution containing dopamine and 2-aminoethyl methacrylate, that is, a surface treatment solution was obtained.

(3) Immerse the degradable metal cleaned in step (1) in the mixed solution of step (2). After soaking the beaker at room temperature for 24 hours, take out the degradable metal and rinse it gently with deionized water. Blow dry under a stream of dry nitrogen to obtain the modified degradable metal. The modified degradable metal was stored in a vacuum drying oven until use.

(5) taking the modified degradable metal obtained in step (3) and placing it in a beaker, pouring the hydrogel prepolymer solution obtained in step (4) into the beaker to completely cover the modified degradable metal, and then adding The beaker was placed in a vacuum box and evacuated for half an hour.

The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 28.2 μA/cm ² . The compressive strength of the degradable metal-organic composite bone repair material prepared in this example is 50 MPa, and the compressive modulus is 48 MPa.

Example 3

Specific steps are as follows:

(2) prepare a 5 mg/mL dopamine solution with a 1.2 mg/mL Tris aqueous solution in an open beaker, then add 1 mg/mL ethylenediamine to the solution, and stir openly at room temperature for half an hour to obtain a dopamine-containing solution Mixed solution with ethylenediamine, namely surface treatment solution.

The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 29.1 μA/cm ² . The compressive strength of the degradable metal-organic composite bone repair material prepared in this example is 47 MPa, and the compressive modulus is 79 MPa.

Example 4

Specific steps are as follows:

(4) Dissolve methacrylated chitosan in deionized water at a concentration of 20 mg/mL, and add 1 mg/mL of UV photoinitiator 2-hydroxy-4'-(2-hydroxyethyl) to the solution after dissolving oxy)-2-methylpropiophenone to obtain a hydrogel prepolymer solution.

The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 27.0 μA/cm ² . The macroscopic morphology of the degradable metal-organic composite bone repair material prepared in this example is shown in Figure 1. The compressive strength of the degradable metal-organic composite bone repair material prepared in this example is 49MPa, and the compressive modulus is 78MPa, as shown in Figure 2. In FIG. 2 , the material without magnesium mesh is a hydrogel bone repair material formed by irradiating the hydrogel prepolymer solution described in this embodiment with ultraviolet light.

Example 5

This embodiment provides a preparation method of a degradable metal-organic composite bone repair material. The degradable metal used in this example is the same as that of Example 1, and the preparation method of this example is basically the same as that of Example 1, except that the component concentrations of the surface treatment liquid used are different, that is, the steps (2) The method for preparing the surface treatment liquid is as follows:

A 6 mg/mL dopamine solution was prepared in an open beaker with 1.2 mg/mL Tris aqueous solution, then 2 mg/mL 2-aminoethyl methacrylate was added to the solution, and the solution was stirred openly for half an hour at room temperature. A mixed solution containing dopamine and 2-aminoethyl methacrylate, that is, a surface treatment solution is obtained.

The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 45.5 μA/cm ² ; the compressive strength of the degradable metal-organic composite bone repair material prepared in this example is 42 MPa, and the compressive strength The modulus is 65MPa.

Example 6

A 0.3 mg/mL dopamine solution was prepared in an open beaker with 1.2 mg/mL Tris aqueous solution, then 2 mg/mL 2-aminoethyl methacrylate was added to the solution, and the solution was stirred openly for half an hour at room temperature , to obtain a mixed solution containing dopamine and 2-aminoethyl methacrylate, that is, a surface treatment solution.

The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 102.2 μA/cm ² ; the compressive strength of the degradable metal-organic composite bone repair material prepared in this example is 42 MPa, and the compressive strength The modulus was 49MPa.

Example 7

This embodiment provides a preparation method of a degradable metal-organic composite bone repair material. The degradable metal used in this example is the same as that of Example 4, and the preparation method of this example is basically the same as that of Example 4, except that the component concentrations of the used surface treatment liquid are different, that is, the steps (2) The method for preparing the surface treatment liquid is as follows:

A 6 mg/mL dopamine solution was prepared in an open beaker with a 1.2 mg/mL Tris aqueous solution, then 1 mg/mL ethylenediamine was added to the solution, and the solution was stirred openly for half an hour at room temperature to obtain a solution containing dopamine and ethylenediamine. A mixed solution of amines, that is, a surface treatment solution.

The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 80.5 μA/cm ² ; the compressive strength of the degradable metal-organic composite bone repair material prepared in this example is 48 MPa, and the compressive strength The modulus was 76MPa.

Example 8

A 0.3 mg/mL dopamine solution was prepared in an open beaker with a 1.2 mg/mL Tris aqueous solution, then 1 mg/mL ethylenediamine was added to the solution, and the solution was stirred openly for half an hour at room temperature to obtain a solution containing dopamine and ethylenediamine. The mixed solution of diamine is the surface treatment solution.

The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 75.5 μA/cm ² ; the compressive strength of the degradable metal-organic composite bone repair material prepared in this example is 45 MPa, and the compressive strength The modulus was 74MPa.

Example 9

This embodiment provides a preparation method of a degradable metal-organic composite bone repair material. The degradable metal used in this example is the same as that of Example 1, and the preparation method of this example is basically the same as that of Example 1, except that the component concentrations of the hydrogel prepolymer solution used are different , that is, the method for preparing the hydrogel prepolymer solution in step (4) is as follows:

Using the same phosphoric acid modified methacrylated chitosan as in Example 1, the phosphoric acid modified methacrylated chitosan was dissolved in deionized water at a concentration of 3 mg/mL, and 1 mg/mL was added to the solution after dissolving. 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone as an ultraviolet photoinitiator to obtain a hydrogel prepolymerization solution.

For the degradable metal-organic composite bone repair material prepared in this example, the hydrogel cannot be formed because the concentration of the hydrogel prepolymer solution is too small and its viscosity is too small.

Example 10

Using the same phosphoric acid-modified methacrylated chitosan as in Example 1, the phosphoric acid-modified methacrylated chitosan was dissolved in deionized water at a concentration of 5 mg/mL, and 1 mg/mL was added to the solution after dissolving. 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone as an ultraviolet photoinitiator to obtain a hydrogel prepolymerization solution.

In the degradable metal-organic composite bone repair material prepared in this example, the hydrogel can fully enter the pores of the modified degradable metal, and the filling effect is good, and no loose pores appear in the hydrogel.

Example 11

Using the same phosphoric acid-modified methacrylated chitosan as in Example 1, the phosphoric acid-modified methacrylated chitosan was dissolved in deionized water at a concentration of 40 mg/mL, and 1 mg/mL was added to the solution after dissolving. 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone as an ultraviolet photoinitiator to obtain a hydrogel prepolymerization solution.

Example 12

Using the same phosphoric acid-modified methacrylated chitosan as in Example 1, the phosphoric acid-modified methacrylated chitosan was dissolved in deionized water at a concentration of 45 mg/mL, and 1 mg/mL was added to the solution after dissolving. 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone as an ultraviolet photoinitiator to obtain a hydrogel prepolymerization solution.

For the degradable metal-organic composite bone repair material prepared in this example, because the concentration of the hydrogel prepolymer solution is too high and its viscosity is too high, it is difficult for the hydrogel prepolymer solution to enter the pores of the modified degradable metal. Fully filled, the uniformity of the composite is poor.

Example 13

This embodiment provides a preparation method of a degradable metal-organic composite bone repair material. The degradable metal used in this example is the same as that of Example 4, and the preparation method of this example is basically the same as that of Example 1, except that the component concentrations of the hydrogel prepolymer solution used are different , that is, the method for preparing the hydrogel prepolymer solution in step (4) is as follows:

The methacrylated chitosan was dissolved in deionized water at a concentration of 3 mg/mL, and 2 mg/mL of dopamine Tris aqueous solution and 1 mg/mL of UV photoinitiator 2-hydroxy-4'- (2-hydroxyethoxy)-2-methylpropiophenone to obtain a hydrogel prepolymerized solution. (The dopamine Tris aqueous solution is the same as that of Example 4.)

Example 14

The methacrylated chitosan was dissolved in deionized water at a concentration of 45 mg/mL, and 2 mg/mL dopamine Tris aqueous solution and 1 mg/mL UV photoinitiator 2-hydroxy-4'- (2-hydroxyethoxy)-2-methylpropiophenone to obtain a hydrogel prepolymerized solution. (The dopamine Tris aqueous solution is the same as that of Example 4.)

Example 15

This embodiment provides a preparation method of a degradable metal-organic composite bone repair material. The degradable metal used in this example is reticulated zinc metal, the hollow mesh is square, the side length of the square is 1.5 mm, the width of the mesh metal bars is 0.25 mm, and the thickness of the zinc mesh is 0.25 mm.

The preparation method of this example is the same as that of Example 4 except that the degradable metal used is different from that of Example 4. The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 12.4 μA/cm ² ; the compressive strength of the degradable metal-organic composite bone repair material prepared in this example is 53 MPa, and the compressive strength The modulus was 83MPa.

Example 16

This embodiment provides a preparation method of a degradable metal-organic composite bone repair material. The degradable metal used in this embodiment is a meshed iron alloy, the hollow mesh is square, the side length of the square is 1.5 mm, the width of the mesh metal bars is 0.25 mm, and the thickness of the iron mesh is 0.25 mm.

The preparation method of this example is the same as that of Example 4 except that the degradable metal used is different from that of Example 4. The self-corrosion current density of the modified degradable metal prepared in step (3) of this example is 5.3 μA/cm ² ; the compressive strength of the degradable metal-organic composite bone repair material prepared in this example is 56 MPa, and the compressive strength The modulus was 87MPa.

In other embodiments, the dopamine in the used surface treatment liquid can also be replaced by catechol, tannin, gallic acid, anthocyanin, procyanidin, etc.; Chitosan or methacrylated chitosan, in which chitosan can also be replaced by hyaluronic acid, gelatin or sodium alginate, such as phosphoric acid modified methacrylated chitosan, methacrylated gelatin can be modified with phosphoric acid , phosphoric acid-modified methacrylated hyaluronic acid, phosphoric acid-modified methacrylated sodium alginate, etc.

The above is only to further illustrate the technical content of the present invention with examples, so as to facilitate the readers to understand more easily, but it does not mean that the embodiments of the present invention are limited to this. Any technical extension or re-creation according to the present invention is subject to protection of the present invention.

Industrial Applicability:

The degradable metal in the bone repair material of the present invention can provide mechanical support for the bone repair material, so that it can meet the requirements of bone defect repair; the surface coating of the modified degradable metal can provide corrosion protection function and provide corrosion protection for subsequent The hydrogel prepolymer solution provides polymerization sites; the hydrogel can provide a good microenvironment for the ingrowth of osteocytes and vascular cells, which is conducive to bone ingrowth and angiogenesis; at the same time, the hydrogel filled in the metal can be degraded. The glue can play a certain physical barrier, slowing down the contact between the corrosive medium and the degradable metal, thereby further slowing down the corrosion rate of the degradable metal; in addition, the metal ions released by the degradable metal during the degradation process can interact with the hydrogel in the hydrogel. Functional groups (such as phosphoric acid groups) are chelated, which can slow release metal ions and have a slow release effect.

Claims

A preparation method of a degradable metal-organic composite bone repair material, characterized in that it comprises the following steps:

S1. Soak the degradable metal in the surface treatment solution for 24 hours, then take it out, rinse with water and dry to obtain the modified degradable metal;

The surface treatment solution is a solution prepared by using 1.0-1.5 mg/mL Tris aqueous solution to prepare a solution with a polyphenolic compound content of 0.5-5.0 mg/mL, and then adding an amine compound to the solution to form a solution. The content of the compound is 1.0-2.0 mg/mL;

S2. Pour the hydrogel prepolymer solution into a container containing the modified degradable metal, and place the container in a vacuum box to vacuum for more than 0.5h;

The hydrogel prepolymerization solution is a solution containing 1mg/mL ultraviolet photoinitiator in the aqueous solution of acrylic acid double bond and phosphoric acid modified natural polysaccharide of 5-40mg/mL, or the hydrogel prepolymerization solution is 18-22mg/mL. A solution containing 1 mg/mL of UV photoinitiator in an aqueous solution of methacrylic acid-modified natural polysaccharide;

S3, irradiating the hydrogel prepolymer solution and the modified degradable metal treated in step 2 with ultraviolet light to obtain a degradable metal-organic composite bone repair material.
The method for preparing a degradable metal-organic composite bone repair material according to claim 1, wherein the degradable metal is magnesium, magnesium alloy, zinc, zinc alloy, iron or iron alloy.
The method for preparing a degradable metal-organic composite bone repair material according to claim 2, wherein the degradable metal is a porous or reticulated degradable metal.
The preparation method of the degradable metal-organic composite bone repair material according to claim 1, characterized in that, before soaking the degradable metal in the surface treatment solution, the degradable metal is cleaned first; the cleaning treatment is: First, the degradable metal is placed in acetone for ultrasonic cleaning, then the degradable metal is placed in anhydrous ethanol for ultrasonic cleaning, and then the degradable metal is dried.
The method for preparing a degradable metal-organic composite bone repair material according to claim 4, wherein the drying treatment is to dry the degradable metal with a dry nitrogen stream, and then place the degradable metal in a vacuum drying oven in standby.
The method for preparing a degradable metal-organic composite bone repair material according to claim 1, wherein the polyphenolic compound is selected from the group consisting of catecholamines, catechols, tannins, gallic acids, anthocyanins, procyanidins one of the.
The method for preparing a degradable metal-organic composite bone repair material according to claim 1, wherein the polyphenolic compound is dopamine.
The method for preparing a degradable metal-organic composite bone repair material according to claim 1, wherein the amine compound is 2-aminoethyl methacrylate or ethylenediamine.
The method for preparing a degradable metal-organic composite bone repair material according to claim 1, wherein the surface treatment solution is prepared by using a 1.2 mg/mL Tris aqueous solution to prepare a solution with a dopamine content of 5.0 mg/mL, A solution formed by adding ethylenediamine to the solution was added, and the content of the ethylenediamine was 1.0 mg/mL.
The method for preparing a degradable metal-organic composite bone repair material according to claim 1, wherein the natural polysaccharide described in step S2 is chitosan, hyaluronic acid, gelatin or sodium alginate.