Preparation method of porous composite material based on hydroxyapatite, magnesium oxide and tannic acid

Abstract

The invention discloses a preparation method of a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, which comprises the following steps: by taking polyethylene glycol diacrylate as a photo-crosslinking monomer and diphenyl (2, 4, 6-trimethylbenzoyl) phosphine oxide as a photoinitiator, carrying out a hydrothermal reaction to prepare the porous composite material based on hydroxyapatite, magnesium oxide and tannic acid. Nano hydroxyapatite, nano magnesium oxide and tannic acid are uniformly dispersed in a monomer solution to form photocuring slurry, and the photocuring slurry is formed under ultraviolet light through a photocuring 3D printing technology. Wherein the nano hydroxyapatite provides osteoconductivity, the nano magnesium oxide releases magnesium ions to promote osteoblast differentiation, and the tannic acid endows the material with antibacterial and anti-inflammatory properties; according to the composite material bone scaffold, a Gyandroid structure in a three-period extremely small curved surface is adopted as a scaffold structure, and the structure is combined with the functional synergistic effect of all components, so that the prepared composite material bone scaffold has high porosity, excellent compressive strength, remarkable biological activity and active antibacterial and anti-inflammatory capacity at the same time, and repair and regeneration of bone tissues can be effectively promoted.

Description

TECHNICAL FIELD

[0001] The application relates to a preparation method of a composite material, in particular a preparation method of a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, and belongs to the technical field of bone defect treatment. BACKGROUND

[0002] Due to bone injury increase caused by trauma, bone loss and even congenital deformity, especially bone defects larger than critical bone defects, bone repair and regeneration have become an urgent need. Scaffolds, as an important part of scaffold tissue engineering, can provide temporary structural support for cell attachment, growth and proliferation. Hydroxyapatite is similar in chemical properties to the inorganic components of natural hard tissues such as bone and teeth. It has excellent biocompatibility, bioactivity and bone conductivity, and is therefore widely used in clinical bone repair. Magnesium oxide can promote the proliferation and differentiation of osteoblasts. It helps to accelerate the growth and repair of the skeleton. Tannic acid has good antibacterial and anti-inflammatory effects, and can inhibit the growth of bacteria and fungi and reduce inflammatory reactions after implanting the bone scaffold.

[0003] In the prior art, a 3D-printed bone repair material and a preparation method and application thereof are disclosed in CN119656378A. The bone repair material comprises: 70-90 parts of polylactic acid, 0.1-5 parts of infrared stimulus-responsive material, 5-18 parts of hydroxyapatite, 0.1-5 parts of bone active drug, 0.1-0.5 parts of antioxidant and 0.1-0.5 parts of lubricant. The 3D-printed bone repair material prepared by using PLA as a base material and combining infrared stimulus-responsive material, hydroxyapatite, bone active drug and other raw materials can efficiently promote bone repair and also has excellent mechanical properties and 3D-printing formability. The printed scaffold model has good flexibility and high mechanical strength. Under the action of infrared light, the release of hydroxyapatite and bone active drug in the PLA matrix can be accelerated, the bone repair speed is greatly improved, and the repair effect is good and fast. However, this kind of material still has some limitations: first, the degradation products of PLA may cause an acidic microenvironment, which is not conducive to bone integration; second, this kind of material usually lacks active antibacterial and anti-inflammatory ability, and there is a risk of infection after implantation, and infection is one of the main reasons for the failure of implantation surgery; third, simple physical mixing and traditional extrusion type 3D printing technology face challenges in precision and structural freedom when manufacturing scaffolds with complex and precise porous structures. SUMMARY

[0004] The application aims to provide a preparation method of a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, which solves at least one of the above technical problems, and the preparation method uses polyethylene glycol diacrylate as a photocrosslinking monomer, uses diphenyl (2, 4, 6-trimethylbenzoyl) phosphine oxide as a photoinitiator, uniformly disperses nano-hydroxyapatite, nano-magnesium oxide and tannic acid in a monomer solution to form a photocuring slurry, and forms a shape through a photocuring 3D printing technology under ultraviolet light.

[0005] The application achieves the above-mentioned purpose through the following technical solution: a preparation method of a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, comprising a porous composite material, characterized in that: the raw materials of the porous composite material comprise: 200-molecular-weight polyethylene glycol diacrylate, 600-molecular-weight polyethylene glycol diacrylate, nano-hydroxyapatite, nano-magnesium oxide, tannic acid, diphenyl (2, 4, 6-trimethylbenzoyl) phosphine oxide, 2, 5-bis (5-tert-butyl-2-benzoxazolyl) thiophene and ethanol. The preparation method of the porous composite material comprises the following steps: S1: Put nano-hydroxyapatite powder and nano-magnesium oxide powder into a drying oven for drying; S2: Measure equal weights of 200-molecular-weight and 600-molecular-weight polyethylene glycol diacrylate respectively, put them into a beaker, put a magnetic rotor into the beaker, and put the beaker into a magnetic stirring oil bath, to obtain a composite polyethylene glycol diacrylate solution through stirring; S3: Measure 1% diphenyl (2, 4, 6-trimethylbenzoyl) phosphine oxide powder and 0.2% 2, 5-bis (5-tert-butyl-2-benzoxazolyl) thiophene powder based on the weight of the composite polyethylene glycol diacrylate in step S2, and add them respectively into the composite polyethylene glycol diacrylate solution in step S2, to obtain a pure polyethylene glycol diacrylate photocuring solution through stirring; S4: Measure one-sixth of the weight of the composite polyethylene glycol diacrylate in step S2 of tannic acid powder and 5% nano-magnesium oxide powder, and add them respectively into the pure polyethylene glycol diacrylate photocuring solution in step S3, to obtain a magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution through stirring; S5: The nano-hydroxyapatite powder in step S1 and the magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution in step S4 are weighed and mixed in proportion, and stirring is performed to obtain a photocuring slurry for photocuring printing; S6: The Gyroid structure STL models in the three-period minimal surface of four different wall thicknesses are generated by MATLAB software, and the STL models of the four different wall thicknesses are imported into a slicing software for slicing processing to obtain four printing slice files; S7: The slurry obtained in step S5 is poured into the trough of a photocuring 3D printer, the printing slice file in step S6 is input into the photocuring 3D printer, and printing is started, and the stent is obtained after printing. S8: The support on the surface of the stent obtained in step S7 is removed, and the unhardened slurry remaining on the surface of the bone stent is washed with ethanol, and the final artificial bone stent is obtained after drying.

[0006] As a further scheme of the present application: the purity of nano-hydroxyapatite is ≥99%, the particle size is 50-100nm; the purity of nano-magnesium oxide is ≥99%, the particle size is 50-100nm; the purity of polyethylene glycol diacrylate with a molecular weight of 200 is ≥99%; the purity of polyethylene glycol diacrylate with a molecular weight of 600 is ≥99%; the purity of ethanol is ≥95%; the purity of diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide is ≥97%; the purity of 2,5-bis (5-tert-butyl-2-benzoxazolyl) thiophene is ≥99%.

[0007] As a further scheme of the present application: in S1, the drying temperature of nano-hydroxyapatite powder and nano-magnesium oxide powder in the drying oven is 75-85℃; the drying time is 5-7h.

[0008] As a further scheme of the present application: in S2, when preparing the composite polyethylene glycol diacrylate solution, the temperature of the magnetic stirring oil bath is set to 45-55℃, the rotor speed is set to 950-1050rpm, and the continuous stirring time of the magnetic rotor is 25-35min.

[0009] As a further scheme of the present application: in S3, when preparing the pure polyethylene glycol diacrylate photocuring solution, the rotor speed is set to 900-1100rpm, and the continuous stirring time of the magnetic rotor is 1-1.5h.

[0010] As a further scheme of the present application: in S4, when preparing the magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution, the rotor speed is set to 900-1000rpm, and the continuous stirring time of the magnetic rotor is 50-70min.

[0011] As a further scheme of the present application: in S5, the nano-hydroxyapatite powder and the magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution are weighed in a mass ratio of 5%-20%:95%-80%, and when the photocuring slurry is prepared, the rotor speed is set to 1400-1500 rpm, and the continuous stirring time of the magnetic rotor is 3-4 h.

[0012] As a further scheme of the present application: in S6, the size of the STL model generated by the MATLAB software is 5mmx5mmx7mm, and the four wall thicknesses are 0.5mm, 0.6mm, 0.7mm and 0.8mm.

[0013] As a further scheme of the present application: in S6, the slicing parameters of the slicing software are: the layer thickness is set to 0.05mm, the exposure time of the bottom 5 layers is 30S, and the normal exposure time is 10s.

[0014] As a further scheme of the present application: in S8, the drying temperature of the artificial bone scaffold is set to 30-40℃, and the drying time is 3-3.5h.

[0015] The beneficial effects of the present application are: 1) The polyethylene glycol diacrylate selected in the present application has good biocompatibility, low cost and water solubility, can undergo crosslinking reaction with a photoinitiator (diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide) under 408nm ultraviolet light, and can be converted from a small molecular low viscosity monomer (liquid state) to a stable polymer (solid state), and form a high-precision solid structure; 2) The tannic acid selected in the present application has good antibacterial and anti-inflammatory effects, can inhibit the growth of bacteria and fungi and reduce the inflammatory reaction after being implanted into the bone scaffold; the nano-magnesium oxide added in the scaffold will slowly release magnesium ions after being implanted, the magnesium ions can stimulate the differentiation of bone cells and accelerate the generation of new bone tissue, can promote the proliferation and differentiation of osteoblasts, and can help to accelerate the growth and repair of the skeleton; the inorganic components of hydroxyapatite and natural hard tissues such as bones and teeth are similar in chemical properties, it has excellent biocompatibility, bioactivity and bone conduction, and by adding nano-hydroxyapatite, nano-magnesium oxide and tannic acid in the photocured polymer, the mechanical properties, biocompatibility and antibacterial properties of the photocured polymer can be increased, and the proliferation and differentiation of osteoblasts can be promoted, so that the photocured polymer becomes a bone scaffold material; 3) The Gyroid structure in the tri-periodic minimal surface selected in the present application has higher compressive strength and deformation work absorption capacity, and the Gyroid structure in the tri-periodic minimal surface can provide good compressive performance and high porosity as the bone scaffold structure. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1Figure 1 shows the four different wall thickness Gyroid structure scaffolds described in the present invention; Figure 2 Figure 2 shows the four different wall thickness Gyroid structure porosity histograms described in the present invention; Figure 3 Figure 3 shows the scaffold compression curve graphs for Examples 2-5 described in the present invention; Figure 4 Figure 4 shows the scaffold compression strength histograms for Examples 2-5 described in the present invention; Figure 5 Figure 5 shows the scaffold expansion rate histograms for Examples 2-5 described in the present invention; Figure 6 Figure 6 shows the scaffold electron microscope graphs at 150x and 1000x for Examples 2-5 described in the present invention; Figure 7 Figure 7 shows the slurry rheology test graphs for Examples 2-5 described in the present invention. DETAILED DESCRIPTION

[0017] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the scope of protection of the present application.

[0018] Example 1, as shown in the present embodiment provides a preparation method of a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, including a porous composite material, and raw materials of the porous composite material include: 200 molecular weight polyethylene glycol diacrylate, 600 molecular weight polyethylene glycol diacrylate, nano-hydroxyapatite, nano-magnesium oxide, tannic acid, diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide, 2,5-bis (5-tert-butyl-2-benzoxazolyl) thiophene, and ethanol. Figures 1 to 7 The purity of the nano-hydroxyapatite is ≥99%, and the particle size is 50-100 nm; the purity of the nano-magnesium oxide is ≥99%, and the particle size is 50-100 nm; the purity of the 200 molecular weight polyethylene glycol diacrylate and the 600 molecular weight polyethylene glycol diacrylate is both ≥99%; the purity of the ethanol is ≥95%; the purity of the diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide is ≥97%; and the purity of the 2,5-bis (5-tert-butyl-2-benzoxazolyl) thiophene is ≥99%.

[0019] The equipment used in the preparation of the porous composite material includes but is not limited to a drying box, a magnetic stirring oil bath, an ANYCUBIC light-cured 3D printer

[0020] Example 2, as shown in the present embodiment provides a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, including a porous composite material, and raw materials of the porous composite material include: 200 molecular weight polyethylene glycol diacrylate, 600 molecular weight polyethylene glycol diacrylate, nano-hydroxyapatite, nano-magnesium oxide, tannic acid, diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide, 2,5-bis (5-tert-butyl-2-benzoxazolyl) thiophene, and ethanol. Figures 1 to 7 ​As shown, a method for preparing a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, comprising the following preparation steps: S1: Put nano-hydroxyapatite powder and nano-magnesium oxide powder into a drying oven and dry at 80 degrees Celsius for 6 hours to remove water from the powder; S2: Weigh 7.5g and 7.5g of polyethylene glycol diacrylate with molecular weights of 200 and 600 respectively into a beaker, put a magnetic rotor into the beaker, and put the beaker into a magnetic stirring oil bath pot, set the temperature of the magnetic stirring oil bath pot to 50 degrees Celsius, set the rotor speed to 1000 rpm, and continue stirring for 0.5 hours to obtain a composite polyethylene glycol diacrylate solution; S3: Weigh 1% of diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide powder and 0.2% of 2,5-bis (5-tert-butyl-2-benzoxazolyl) thienyl powder based on the weight of the composite polyethylene glycol diacrylate of step S2, and add them to the composite polyethylene glycol diacrylate solution of step S2, and stir for 1 hour under continuous stirring of the magnetic rotor, with the rotor speed set to 1000 rpm, to obtain a pure polyethylene glycol diacrylate photocuring solution; S4: Weigh 0.25g of tannic acid powder and 0.75g of nano-magnesium oxide powder of step S1 respectively, and add them to the pure polyethylene glycol diacrylate photocuring solution of step S3, and stir for 1 hour under continuous stirring of the magnetic rotor, with the rotor speed set to 1000 rpm, to obtain a magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution; S5: Mix the nano-hydroxyapatite powder in step S1 with the magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution of step S4 in a ratio of 5%:95% by mass, and stir for 3 hours under continuous stirring of the magnetic rotor, with the rotor speed set to 1500 rpm, to obtain a 5% hydroxyapatite-containing photocuring slurry; S6: Generate Gyroid structure STL models with wall thicknesses of 0.5mm, 0.6mm, 0.7mm and 0.8mm in the three-period minimal surface by MATLAB software, with the model size being 5mm×5mm×7mm, and import the STL models of the four different wall thicknesses into the slicing software, with the slicing parameters being: layer thickness set to 0.05mm, bottom 5 layers exposure time set to 30S, and normal exposure time set to 10s, to obtain four printing slice files.

[0021] S7: Pour the 5% hydroxyapatite photocuring slurry obtained in step S5 into the trough of the photocuring 3D printer, input the four printing slice files of different wall thicknesses into the photocuring 3D printer, and start printing, to obtain a scaffold after the printing is completed. S8: Remove the support of the scaffold surface obtained in step S6, and rinse the bone scaffold surface with ethanol to remove the un-solidified slurry, and place the scaffold in a drying oven with a temperature setting of 40 degrees Celsius, and dry for 3 hours to obtain a 5% hydroxyapatite artificial bone scaffold.

[0022] Example three, a method for preparing a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, comprising the following preparation steps: S1: Put the nano-hydroxyapatite powder and nano-magnesium oxide powder into a drying oven and dry at 80 degrees Celsius for 6 hours to remove the water in the powder; S2: Weigh 7.5g and 7.5g of polyethylene glycol diacrylate with molecular weights of 200 and 600 respectively into a beaker, put a magnetic rotor in the beaker, and put the beaker into a magnetic stirring oil bath pot, set the temperature of the magnetic stirring oil bath pot to 50 degrees Celsius, set the rotor speed to 1000 rpm, and continue stirring for 0.5 hours to obtain a composite polyethylene glycol diacrylate solution; S3: Weigh 1% of diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide powder and 0.2% of 2,5-bis (5-tert-butyl-2-benzoxazolyl) thienyl powder based on the weight of the composite polyethylene glycol diacrylate of step S2, and add them to the composite polyethylene glycol diacrylate solution of step S2, and stir for 1 hour under the continuous stirring of the magnetic rotor, with the rotor speed set to 1000 rpm, to obtain a pure polyethylene glycol diacrylate photocuring solution; S4: Weigh 0.25g of tannic acid powder and 0.75g of nano-magnesium oxide powder of step S1 respectively, and add them to the pure polyethylene glycol diacrylate photocuring solution of step S3, and stir for 1 hour under the continuous stirring of the magnetic rotor, with the rotor speed set to 1000 rpm, to obtain a magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution; S5: Mix the nano-hydroxyapatite powder in step S1 with the magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution of step S4 in a ratio of 10:90 by mass, and stir for 3 hours under the continuous stirring of the magnetic rotor, with the rotor speed set to 1500 rpm, to obtain a 10% hydroxyapatite-containing photocuring slurry; S6: Generate Gyroid structure STL models with wall thicknesses of 0.5mm, 0.6mm, 0.7mm, and 0.8mm in the three-period minimal surface by MATLAB software, with the model size being 5mm×5mm×7mm, and import the STL models of the four different wall thicknesses into the slicing software, with the slicing parameters being: layer thickness set to 0.05mm, bottom 5 layers exposure time set to 30S, and normal exposure time set to 10s, to obtain four printing slice files.

[0023] S7: Pour the 10% hydroxyapatite photocuring slurry obtained in step S5 into the hopper of the photocuring 3D printer, input four different wall thickness printing slice files into the photocuring 3D printer, and start printing. The printed scaffold is obtained; S8: Remove the support from the surface of the scaffold obtained in step S6, rinse the surface of the bone scaffold with ethanol to remove the unhardened slurry, and place the scaffold in a drying oven set at 40°C for 3 hours to obtain a 10% hydroxyapatite artificial bone scaffold.

[0024] Example Four, a preparation method of a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, comprising the following preparation steps: S1: Dry the nano-hydroxyapatite powder and nano-magnesium oxide powder in a drying oven at 80°C for 6 hours to remove the water in the powder; S2: Weigh 7.5g and 7.5g of polyethylene glycol diacrylate with molecular weights of 200 and 600 respectively into a beaker, place a magnetic rotor in the beaker, and place the beaker in a magnetic stirring oil bath pot. The temperature of the magnetic stirring oil bath pot is set to 50°C, the rotor speed is set to 1000 rpm, and the stirring is continued for 0.5 hours to obtain a composite polyethylene glycol diacrylate solution; S3: Weigh 1% of diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide powder and 0.2% of 2,5-bis (5-tert-butyl-2-benzoxazolyl) thiophene powder based on the weight of the composite polyethylene glycol diacrylate in step S2, and add them to the composite polyethylene glycol diacrylate solution in step S2, and stir for 1 hour under the continuous stirring of the magnetic rotor, with the rotor speed set to 1000 rpm, to obtain a pure polyethylene glycol diacrylate photocuring solution; S4: Weigh 0.25g of tannic acid powder and 0.75g of nano-magnesium oxide powder in step S1 respectively, and add them to the pure polyethylene glycol diacrylate photocuring solution in step S3, and stir for 1 hour under the continuous stirring of the magnetic rotor, with the rotor speed set to 1000 rpm, to obtain a magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution; S5: Mix the nano-hydroxyapatite powder in step S1 with the magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution in step S4 in a ratio of 15%:85% by mass, and stir for 3 hours under the continuous stirring of the magnetic rotor, with the rotor speed set to 1500 rpm, to obtain a 15% hydroxyapatite-containing photocuring slurry; S6: Generate the STL model of the Gyroid structure in the three-period minimal surface with wall thickness of 0.5mm, 0.6mm, 0.7mm, and 0.8mm respectively by MATLAB software, the model size is 5mmx5mmx7mm, and import the STL models of four different wall thicknesses into the slicing software, the slicing parameters are: layer thickness is set to 0.05mm, bottom 5 layers exposure time is 30S, normal exposure time is 10s, four kinds of printing slice files are obtained; S7: Pour the 15% hydroxyapatite photocuring slurry obtained in step S5 into the trough of the photocuring 3D printer, input the printing slice files of four different wall thicknesses into the photocuring 3D printer, and start printing, the scaffold is obtained after printing is completed; S8: Remove the support on the surface of the scaffold obtained in step S6, and flush the unhardened slurry remaining on the surface of the bone scaffold with ethanol, and put the scaffold into a drying oven with a temperature setting of 40 degrees Celsius, and dry for 3 hours to obtain a 15% hydroxyapatite artificial bone scaffold.

[0025] Example five, a preparation method of a porous composite material based on hydroxyapatite, magnesium oxide and tannic acid, comprising the following preparation steps: S1: Put the nano-hydroxyapatite powder and nano-magnesium oxide powder into a drying oven and dry at 80 degrees Celsius for 6 hours to remove the water in the powder; S2: Weigh 7.5g and 7.5g of polyethylene glycol diacrylate with molecular weights of 200 and 600 respectively into a beaker, put a magnetic rotor in the beaker, and put the beaker into a magnetic stirring oil bath pot, set the temperature of the magnetic stirring oil bath pot to 50 degrees Celsius, set the rotor speed to 1000rpm, and continue stirring for 0.5 hours to obtain a composite polyethylene glycol diacrylate solution; S3: Weigh 1% of diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide powder and 0.2% of 2,5-bis (5-tert-butyl-2-benzoxazolyl) thiofene powder based on the weight of the composite polyethylene glycol diacrylate in step S2, and add them to the composite polyethylene glycol diacrylate solution in step S2, and stir for 1 hour under the continuous stirring of the magnetic rotor, set the rotor speed to 1000rpm, to obtain a pure polyethylene glycol diacrylate photocuring solution; S4: Weigh 0.25g of tannic acid powder and 0.75g of nano-magnesium oxide powder in step S1 respectively, and add them to the pure polyethylene glycol diacrylate photocuring solution in step S3, and stir for 1 hour under the continuous stirring of the magnetic rotor, set the rotor speed to 1000rpm, to obtain a magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution; S5: Weigh the nano hydroxyapatite powder from step S1 and mix it with the magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution from step S4 at a mass ratio of 20%:80%. Stir for 3 hours under continuous stirring of a magnetic rotor with the rotor speed set to 1500 rpm to obtain a photocuring slurry with a hydroxyapatite content of 20%. S6: Using MATLAB software, Gyroid structure STL models with wall thicknesses of 0.5mm, 0.6mm, 0.7mm, and 0.8mm were generated in three-period minimal surfaces. The model size was 5mm×5mm×7mm. The four STL models with different wall thicknesses were then imported into the slicing software. The slicing parameters were: layer thickness set to 0.05mm, exposure time for the bottom 5 layers to be 30s, and normal exposure time to be 10s. Four types of printable slice files were obtained. S7: Pour the 20% hydroxyapatite photocurable slurry obtained in step S5 into the material tank of the photocurable 3D printer, input the printing slice files of four different wall thicknesses into the photocurable 3D printer, and start printing. After printing, the bracket is obtained. S8: Remove the support from the surface of the scaffold obtained in step S7, rinse the surface of the bone scaffold with ethanol to remove any remaining uncured slurry, and place the scaffold in a drying oven set at 40 degrees Celsius for 3 hours to obtain an artificial bone scaffold with 20% hydroxyapatite.

[0026] Test case The porosity of four artificial bone scaffolds with different wall thicknesses was tested using the Archimedes' displacement method. The test results are as follows: Figure 2 As shown, the porosity of the scaffold decreases with increasing wall thickness. Higher porosity is beneficial for the transport and delivery of substances within bone tissue, but excessive porosity can affect the compressive strength of the scaffold. Therefore, it is necessary to balance the values ​​between porosity and compressive strength.

[0027] Compressive strength tests were conducted on artificial bone scaffolds with a wall thickness of 0.7 mm and different percentages of hydroxyapatite content. The tests were performed on a mechanical testing machine according to GB / T4740-1999 standard. To ensure statistical significance, multiple tests were conducted, and the average value was taken. The test results are shown below. Figure 3 and Figure 4 As shown in Example 2 to Example 5, the hydroxyapatite content increased, and the compressive strength showed a trend of first increasing and then decreasing. The highest compressive strength was 5.74 MPa in Example 2, which is consistent with the compressive strength range of human cancellous bone (2-6 MPa).

[0028] Expansion tests were conducted on artificial bone scaffolds with a wall thickness of 0.7 mm and different percentages of hydroxyapatite content. First, the dry weight of each scaffold was measured. ), and then transferred to a 24-well plate. 5 ml of PBS solution was dropped into each well plate to make it fully immersed. Then incubate for 24 hours at 37℃ environment. After the incubation, the scaffold was taken out, wiped dry with a paper towel, and then the wet weight was measured ), the swelling ratio was calculated using the following formula. The swelling ratio of artificial bone scaffolds with different hydroxyapatite contents is shown in Table 2 Figure 5 As shown in Table 2, polyethylene glycol diacrylate is a hydrogel, which has a micro three-dimensional network structure inside after curing, and has water absorption characteristics. The swelling ratio of the scaffolds of Examples 2 to 5 gradually decreases, which is due to the increase of the content of hydroxyapatite filling the micro three-dimensional structure inside the polyethylene glycol diacrylate, reducing the water absorption.

[0029] Swelling ratio = ; The surface morphology of the scaffold was analyzed by scanning electron microscopy (SEM), as shown in Table 3 Figure 6 The layer structure of each example scaffold can be seen at 150 and 1000 times, which conforms to the working principle of the DLP printer. The distribution of nano-magnesium oxide and nano-hydroxyapatite on the surface of the scaffold is relatively uniform, and there is aggregation in some areas. It is worth noting that as the weight percentage of nano-magnesium oxide and nano-hydroxyapatite increases, the surface roughness of the scaffold also increases.

[0030] The rheological behavior of the slurry prepared in the four examples was analyzed using an MCR302 rheometer (Anton Paar, Austria). The coaxial cylinder test type was used in the test, and the viscosity test was carried out in continuous shear mode, with a shear rate from 0.1 (1 / s) to 1000 (1 / s). Figure 7 The viscosity change of the slurry of the four examples under different shear rates is shown in Table 4. The rheological curves of Examples 3, 4, and 5 reach a constant value when the shear rate exceeds 200 (1 / s). The rheological curve of Example 5 reaches a constant value when the shear rate exceeds 800 (1 / s). The viscosity of the slurry increases with the increase of the shear rate, which is called shear thinning phenomenon.

[0031] A porous bone scaffold with excellent mechanical properties, bioactivity and antibacterial and anti-inflammatory functions is constructed by uniformly compounding bioactive nano-hydroxyapatite, nano-magnesium oxide and tannic acid in a polyethylene glycol diacrylate photocrosslinking polymer matrix through a photocuring three-dimensional printing technology. The core is the functional synergy of the components and the precise manufacturing of the structure. Under the irradiation of 408 nm ultraviolet light, the photoinitiator diphenyl (2, 4, 6-trimethylbenzoyl) phosphine oxide generates free radicals, which initiate the crosslinking polymerization reaction of polyethylene glycol diacrylate monomers, and the nanoparticles dispersed therein are firmly coated. Nano-hydroxyapatite, as a bone conduction component, simulates the inorganic environment of natural bone and provides an interface for osteoblasts to adhere and grow. Nano-magnesium oxide slowly releases magnesium ions in the body fluid environment, which can effectively stimulate and promote the proliferation and differentiation of osteoblasts, thereby accelerating the formation of new bone. Tannic acid endows the material with broad-spectrum antibacterial and anti-inflammatory properties, inhibits the growth of bacteria and fungi in the early stage of implantation, and reduces the inflammatory response of the body, creating a good local microenvironment for bone healing. The three-periodic minimal surface Gyroid structure is adopted, which, through its continuous non-self-intersecting curved surface characteristics, realizes high porosity to ensure nutrient substance transmission and cell migration, and endows the scaffold with excellent compressive strength and energy absorption capacity.

[0032] It is apparent for those skilled in the art that the present application is not limited to the details of the above-described exemplary embodiments, but can be implemented in other concrete forms without departing from the spirit or essential characteristics of the present application. Therefore, the embodiments should be considered in all aspects as illustrative and not restrictive, and the scope of the present application is defined by the appended claims rather than the above description, and it is intended to encompass all changes falling within the meaning and range of equivalents of the elements of the claims. Any reference signs in the claims should not be considered as limiting the claims involved.

[0033] In addition, it should be understood that although the present specification is described in terms of embodiments, not every embodiment contains only one independent technical solution, and the description of the specification is only for the sake of clarity, and those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can be appropriately combined to form other embodiments that those skilled in the art can understand.

Claims

1. A method for preparing a porous composite material based on hydroxyapatite, magnesium oxide, and tannic acid, comprising the porous composite material, characterized in that: The raw materials of the porous composite material include: 200 molecular weight polyethylene glycol diacrylate, 600 molecular weight polyethylene glycol diacrylate, nano-hydroxyapatite, nano-magnesium oxide, tannic acid, diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide, 2,5-bis(5-tert-butyl-2-benzoxazolyl)thiophene, and ethanol; The method for preparing the porous composite material includes the following steps: S1: Place nano-hydroxyapatite powder and nano-magnesium oxide powder in a drying oven and dry them for later use; S2: Weigh equal weights of polyethylene glycol diacrylate with molecular weights of 200 and 600 and add them to a beaker. Place a magnetic rotor in the beaker and then place the beaker in a magnetic stirring oil bath. Stir to obtain a composite polyethylene glycol diacrylate solution. S3: Weigh 1% by weight of diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide powder and 0.2% by weight of 2,5-bis(5-tert-butyl-2-benzoxazolyl)thiophene powder based on the composite polyethylene glycol diacrylate from step S2, and add them to the composite polyethylene glycol diacrylate solution from step S2. After stirring, pure polyethylene glycol diacrylate is obtained by photocuring. S4: Weigh one-sixth of the weight of the composite polyethylene glycol diacrylate from step S2, along with 5% nano magnesium oxide powder, and add them to the pure polyethylene glycol diacrylate photocuring solution from step S3. After stirring, a magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution is obtained. S5: Weigh the nano hydroxyapatite powder from step S1 and the magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution from step S4 and mix them in proportion. After stirring, a photocuring paste for photocuring printing is obtained. S6: Generate Gyroid structure STL models with four different wall thicknesses in three-period minimal surfaces using MATLAB software, and import the four different wall thicknesses STL models into slicing software for slicing processing to obtain four printable slice files. S7: Pour the slurry obtained in step S5 into the material tank of the photopolymer 3D printer, input the printing slice file in step S6 into the photopolymer 3D printer, and start printing. After printing is completed, a bracket is obtained. S8: Remove the support from the surface of the scaffold obtained in step S7, rinse the surface of the bone scaffold with ethanol to remove any remaining uncured slurry, and then dry it to obtain the final artificial bone scaffold.

2. The preparation method according to claim 1, characterized in that: The purity of the nano-hydroxyapatite is ≥99%, and the particle size is 50-100 nm; the purity of the nano-magnesium oxide is ≥99%, and the particle size is 50-100 nm; the purity of 200 molecular weight polyethylene glycol diacrylate and 600 molecular weight polyethylene glycol diacrylate are both ≥99%; the purity of ethanol is ≥95%; the purity of diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide is ≥97%; and the purity of 2,5-bis(5-tert-butyl-2-benzoxazolyl)thiophene is ≥99%.

3. The preparation method according to claim 1, characterized in that: In step S1, the drying temperature of the nano-hydroxyapatite powder and the nano-magnesium oxide powder in the drying oven is 75-85℃; the drying time is 5-7h.

4. The preparation method according to claim 1, characterized in that: In step S2, when preparing the composite polyethylene glycol diacrylate solution, the temperature of the magnetic stirring oil bath is set to 45-55℃, the rotor speed is set to 950-1050rpm, and the continuous stirring time of the magnetic rotor is 25-35min.

5. The preparation method according to claim 1, characterized in that: In step S3, when preparing the pure polyethylene glycol diacrylate photocurable solution, the rotor speed is set to 900-1100 rpm, and the continuous stirring time of the magnetic rotor is 1-1.5 h.

6. The preparation method according to claim 1, characterized in that: In step S4, when preparing the magnesium oxide / tannic acid / polyethylene glycol diacrylate photocurable solution, the rotor speed is set to 900-1000 rpm, and the continuous stirring time of the magnetic rotor is 50-70 min.

7. The preparation method according to claim 1, characterized in that: In step S5, nano-hydroxyapatite powder and magnesium oxide / tannic acid / polyethylene glycol diacrylate photocuring solution are weighed at a mass ratio of 5%–20%: 95%–80%, and when preparing the photocuring slurry, the rotor speed is set to 1400–1500 rpm, and the continuous stirring time of the magnetic rotor is 3–4 hours.

8. The preparation method according to claim 1, characterized in that: In S6, the STL model generated by MATLAB software has a size of 5mm×5mm×7mm, and the four wall thicknesses are 0.5mm, 0.6mm, 0.7mm and 0.8mm respectively.

9. The preparation method according to claim 1, characterized in that: In S6, the slicing parameters of the slicing software are: layer thickness set to 0.05mm, exposure time for the bottom 5 layers is 30s, and normal exposure time is 10s.

10. The preparation method according to claim 1, characterized in that: In step S8, the drying temperature of the artificial bone scaffold is set to 30-40℃, and the drying time is 3-3.5h.

Images