Preparation method of 3D printing white calcium stone composite scaffold capable of simultaneously enhancing mechanical properties and biological properties based on liquid phase sintering and ion substitution

Abstract

The invention discloses a preparation method of a 3D printing white phosphorite composite scaffold capable of simultaneously enhancing mechanical properties and biological properties based on liquid-phase sintering and ion substitution. According to the method, a desktop-level DLP (Digital Light Processing) printing technology is adopted as a forming process, white phosphorus calcium stone is taken as a base material, and the microstructure and phase composition of the scaffold can be synchronously regulated and controlled through the synergistic effect of a liquid phase sintering mechanism introduced by doping Li3PO4 and an ion substitution reaction, so that the comprehensive improvement of mechanical properties, degradation characteristics and biological activity is finally realized. The invention provides a promising solution for solving the problem of insufficient mechanical properties of calcium phosphate ceramics in the bone defect repair process.

Description

Technical Field

[0001] The present invention relates to a preparation method of a 3D printed whitlowite composite scaffold based on liquid phase sintering and ion substitution, which can simultaneously enhance mechanical properties and biological properties. Background Art

[0002] Severe bone defects that exceed the body's ability to repair itself can be caused by a variety of factors, including trauma, infection, and disease. However, autologous and allogeneic bone transplants are limited by limited donor resources and immune rejection. Bone scaffolds that mimic the structure, material, and function of natural bone offer new hope for patients. As the extracellular matrix that supports osteoblast attachment and promotes bone tissue growth, bone scaffolds provide a suitable microenvironment and microstructure for biochemical reactions at the bone defect site. While promoting bone regeneration, bone scaffolds also serve as temporary support structures. They must meet the following basic performance requirements: an interconnected porous structure to facilitate osteoblast migration and material transport; mechanical properties compatible with native bone tissue to provide temporary structural support; a degradation rate coordinated with new bone formation while providing a suitable fluid microenvironment for osteocytes; and excellent bioactivity to stimulate osteoblast proliferation and differentiation. White phosphate is a naturally occurring magnesium-containing calcium phosphate mineral. The magnesium ions in it play a key role as essential trace elements in tissue metabolism. However, similar to most calcium phosphate ceramic materials, white phosphate generally has inherent defects such as low mechanical strength, degradation rate that does not match the bone regeneration process, and bioresponsiveness that needs to be improved.

[0003] Common strategies for enhancing the mechanical properties of calcium phosphate scaffolds include nanoparticle reinforcement, inorganic fiber modification, and microstructural optimization through the addition of sintering aids. While both nanoparticle reinforcement and inorganic fiber modification can improve mechanical properties, the former can easily lead to particle agglomeration due to its high surface energy, while the latter can often cause dimensional distortion due to the large fiber aspect ratio. In contrast, microstructural modification using sintering aids improves mechanical properties while making it easier to maintain dimensional stability.

[0004] Li3PO4, a sintering aid, has a melting point of 800-900°C and can induce liquid phase formation below the sintering temperature of white calcium apatite, thereby promoting microstructural optimization and enhancing mechanical properties. Furthermore, the ionic radius of Li ions in the matrix is ​​smaller than that of Ca ions, and this difference may induce ion substitution. By generating an intergranular phase with an accelerated degradation rate, this system can simultaneously regulate degradation characteristics while optimizing ion release behavior and enhancing bioactivity. By introducing the synergistic effect of the liquid-phase sintering mechanism and ion substitution reaction through Li3PO4 doping, the microstructure and phase composition of the scaffold can be simultaneously controlled, ultimately achieving a comprehensive improvement in mechanical properties, degradation characteristics, and bioactivity.

[0005] The present invention proposes a method for preparing a whitlockite composite scaffold with excellent mechanical properties and biological activity by using desktop-level DLP printing technology as a molding process, using whitlockite as a matrix material and Li3PO4 as a sintering aid. Summary of the Invention

[0006] The purpose of the present invention is to provide a preparation method of a 3D printed whitlowite composite scaffold based on liquid phase sintering and ion substitution to simultaneously enhance mechanical and biological properties.

[0007] In order to achieve the above technical objectives, the present invention adopts the following technical solutions:

[0008] Step 1: Prepare the photosensitive resin component corresponding to the photosensitive ceramic slurry in a dark place.

[0009] Step 2: Place the white phosphate particles and Li3PO4 powder in the same beaker according to the proportion.

[0010] Step 3: Mix the white jatropha particles and Li3PO4 powder with the photosensitive resin, maintaining the mass fraction of the white jatropha plus the Li3PO4 powder at 75 wt%.

[0011] Step 4: ball-milling the prepared photosensitive ceramic slurry in a ball mill. After the ball milling, the slurry is heated in an ultrasonic cleaning machine to obtain a composite ceramic slurry that can be used for photocuring molding.

[0012] Step 5: Slice the STL format model of the orthogonal periodic structure and import it into the light-curing printer.

[0013] Step 6: Photocuring prints an orthogonal periodic structure to obtain a white phosphate / Li3PO4 composite ceramic bone scaffold green body.

[0014] Step 7: Degreasing and sintering the white jasperite / Li3PO4 composite ceramic bone scaffold green body to remove the resin component in the green body and sintering to obtain the white jasperite / Li3PO4 composite ceramic bone scaffold.

[0015] Preferably, in step 1, the mass ratio of 1,6-hexanediol diacrylate monomer (HDDA) in the resin to the resin system is 60-64 wt%; the mass ratio of tripropylene glycol diacrylate monomer (TPGDA) to the resin system is 15-16.2 wt%; the mass ratio of BYK-111 dispersant to the resin system is 18-22 wt%; the mass ratio of phenyl bis(2,4,6-trimethylbenzoyl) phosphine oxide (BAPO) to the resin system is 1.8-2.2 wt%; and the mass ratio of 4-methoxyphenol (MEHQ) light inhibitor to the resin system is 0.3-0.5 wt%.

[0016] Preferably, the step 2 is: preparing a white jasperite / Li3PO4 mixed powder in a ratio of 0.05-0.5 wt% of Li3PO4 to the powder mass.

[0017] Preferably, step 3 is: mixing the white phosphate particles and Li3PO4 powder with the photosensitive resin, maintaining the mass fraction of the white phosphate plus the Li3PO4 powder at 75 wt%, and ultrasonically stirring the photosensitive ceramic slurry in the glass beaker with a 70°C aqueous solution for 5 minutes.

[0018] Preferably, step 4 is: ball milling the prepared photosensitive ceramic slurry in a ball mill, the grinding ball material is zirconia or natural agate, the speed of the ball mill is controlled at 700-900 rpm, and the ball milling time is 3-5 hours; after the ball milling is completed, the slurry is heated at 70°C in an ultrasonic cleaning machine for 5 minutes to obtain a composite ceramic slurry that can be used for photocuring molding.

[0019] Preferably, step 5 is: slicing the model to be formed and importing it into a DLP, LCD or SLA light-curing printer for layer-by-layer printing, with the printing parameters set to a layer thickness of 40-200 μm, an exposure time of 3-10 seconds, a bottom layer exposure time of 10-60 seconds, and 5-20 bottom layers.

[0020] Preferably, the step 6 is: performing photocuring printing on the orthogonal periodic structure, and maintaining the temperature inside the photocuring printing device at 40-50°C.

[0021] Preferably, step 7 is as follows: first, dry the printed blank in a 50°C constant temperature drying oven for 4-8 hours, then debind and sinter the bone scaffold blank in a muffle furnace or tubular furnace. The temperature in the debinding stage is set as follows: heating the muffle furnace from room temperature to 100°C at a heating rate of 2°C / minute and then holding for 30 minutes; then, heating the furnace from 100°C to 200°C at a heating rate of 2°C / minute; then, heating the furnace from 200°C to 400°C at a heating rate of 1°C / minute and then holding for 120 minutes; then, heating the furnace from 400°C to 600°C at a heating rate of 1°C / minute and holding for 120 minutes. The temperature in the sintering stage is set as follows: heating the furnace from 600°C to 800-1100°C at a heating rate of 4-8°C / minute and holding for 1-4 hours.

[0022] The present invention has the following beneficial effects:

[0023] Doping with Li3PO4 promotes the formation of a liquid phase inside the scaffold, thereby improving the density of the scaffold and reducing the unit cell volume through ion substitution. At the same time, liquid phase sintering enhances material diffusion and promotes the increase of grain size. Under these effects, the mechanical properties of the scaffold are improved. At the same time, doping with Li3PO4 promotes the release of more Ca and PO4 into the solution. 3- , Li plasma, and enhanced the biomineralization and cell response capabilities of the scaffold. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The morphologies of the bone scaffolds corresponding to Examples 1-4 and Comparative Example 1 are shown.

[0025] Figure 2 These are the compression and bending mechanical property test results corresponding to Examples 1-4 and Comparative Example 1.

[0026] Figure 3 The degradation and ion release of the composite bone scaffolds corresponding to Examples 1-4 and Comparative Example 1 within 4 weeks.

[0027] Figure 4 The staining results of the composite bone scaffolds corresponding to Examples 1-4 and Comparative Example 1 within 7 days after inoculation of osteoblasts are shown. DETAILED DESCRIPTION

[0028] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below, but the content of the present invention is not limited thereto. Where specific conditions are not specified in the embodiments, the conditions are carried out according to conventional conditions or the conditions recommended by the manufacturer. Where the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially.

[0029] Example 1

[0030] The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution as described in Example 1 comprises the following steps:

[0031] (1) The mass ratio of 1,6-hexanediol diacrylate monomer (HDDA) in the resin system is 62 wt%; the mass ratio of tripropylene glycol diacrylate monomer (TPGDA) in the resin system is 15.6 wt%; the mass ratio of BYK-111 dispersant in the resin system is 20 wt%; the mass ratio of phenyl bis(2,4,6-trimethylbenzoyl)phosphine oxide (BAPO) in the resin system is 2 wt%; and the mass ratio of 4-methoxyphenol (MEHQ) photoinhibitor in the resin system is 0.4 wt%.

[0032] (2) Prepare a mixed powder of white phosphate / Li3PO4 in a ratio of 0.05 wt% of Li3PO4 to powder mass.

[0033] (3) Mix the white phosphate particles and Li3PO4 powder with the photosensitive resin, keeping the mass fraction of the white phosphate plus Li3PO4 powder at 75 wt%. At the same time, use a 70°C aqueous solution to ultrasonically stir the photosensitive ceramic slurry in a glass beaker for 5 minutes.

[0034] (4) The prepared photosensitive ceramic slurry is ball-milled in a ball mill. The grinding balls are made of zirconium oxide or natural agate. The speed of the ball mill is controlled at 800 rpm and the ball-milling time is 4.5 hours. After the ball milling, the slurry is heated at 70°C in an ultrasonic cleaning machine for 5 minutes to obtain a composite ceramic slurry that can be used for photocuring molding.

[0035] (5) The model to be formed is sliced ​​and imported into a DLP light-curing printer for layer-by-layer printing. The printing parameters are set to a layer thickness of 50 μm, an exposure time of 5 seconds, a bottom layer exposure time of 60 seconds, and a bottom layer number of 5 layers.

[0036] (6) Photocuring printing orthogonal periodic structure, maintaining the temperature inside the photocuring printing equipment at 50℃.

[0037] Example 2

[0038] The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution as described in Example 2 comprises the following steps:

[0039] (1) The mass ratio of 1,6-hexanediol diacrylate monomer (HDDA) in the resin system is 62 wt%; the mass ratio of tripropylene glycol diacrylate monomer (TPGDA) in the resin system is 15.6 wt%; the mass ratio of BYK-111 dispersant in the resin system is 20 wt%; the mass ratio of phenyl bis(2,4,6-trimethylbenzoyl)phosphine oxide (BAPO) in the resin system is 2 wt%; and the mass ratio of 4-methoxyphenol (MEHQ) photoinhibitor in the resin system is 0.4 wt%.

[0040] (2) Prepare a mixed powder of white phosphate / Li3PO4 in a ratio of 0.1 wt% of Li3PO4 to powder mass.

[0041] (3) Mix the white phosphate particles and Li3PO4 powder with the photosensitive resin, keeping the mass fraction of the white phosphate plus Li3PO4 powder at 75 wt%. At the same time, use a 70°C aqueous solution to ultrasonically stir the photosensitive ceramic slurry in a glass beaker for 5 minutes.

[0042] (4) The prepared photosensitive ceramic slurry is ball-milled in a ball mill. The grinding balls are made of zirconium oxide or natural agate. The speed of the ball mill is controlled at 800 rpm and the ball-milling time is 4.5 hours. After the ball milling, the slurry is heated at 70°C in an ultrasonic cleaning machine for 5 minutes to obtain a composite ceramic slurry that can be used for photocuring molding.

[0043] (5) The model to be formed is sliced ​​and imported into a DLP light-curing printer for layer-by-layer printing. The printing parameters are set to a layer thickness of 50 μm, an exposure time of 5 seconds, a bottom layer exposure time of 60 seconds, and a bottom layer number of 5 layers.

[0044] (6) Photocuring printing orthogonal periodic structure, maintaining the temperature inside the photocuring printing equipment at 50℃.

[0045] Example 3

[0046] The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution as described in Example 3 comprises the following steps:

[0047] (1) The mass ratio of 1,6-hexanediol diacrylate monomer (HDDA) in the resin system is 62 wt%; the mass ratio of tripropylene glycol diacrylate monomer (TPGDA) in the resin system is 15.6 wt%; the mass ratio of BYK-111 dispersant in the resin system is 20 wt%; the mass ratio of phenyl bis(2,4,6-trimethylbenzoyl)phosphine oxide (BAPO) in the resin system is 2 wt%; and the mass ratio of 4-methoxyphenol (MEHQ) photoinhibitor in the resin system is 0.4 wt%.

[0048] (2) Prepare a mixed powder of white phosphate / Li3PO4 in a ratio of 0.25 wt% of Li3PO4 to powder mass.

[0049] (3) Mix the white phosphate particles and Li3PO4 powder with the photosensitive resin, keeping the mass fraction of the white phosphate plus Li3PO4 powder at 75 wt%. At the same time, use a 70°C aqueous solution to ultrasonically stir the photosensitive ceramic slurry in a glass beaker for 5 minutes.

[0050] (4) The prepared photosensitive ceramic slurry is ball-milled in a ball mill. The grinding balls are made of zirconium oxide or natural agate. The speed of the ball mill is controlled at 800 rpm and the ball-milling time is 4.5 hours. After the ball milling, the slurry is heated at 70°C in an ultrasonic cleaning machine for 5 minutes to obtain a composite ceramic slurry that can be used for photocuring molding.

[0051] (5) The model to be formed is sliced ​​and imported into a DLP light-curing printer for layer-by-layer printing. The printing parameters are set to a layer thickness of 50 μm, an exposure time of 5 seconds, a bottom layer exposure time of 60 seconds, and a bottom layer number of 5 layers.

[0052] (6) Photocuring printing orthogonal periodic structure, maintaining the temperature inside the photocuring printing equipment at 50℃.

[0053] Example 4

[0054] The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution as described in Example 4 comprises the following steps:

[0055] (1) The mass ratio of 1,6-hexanediol diacrylate monomer (HDDA) in the resin system is 62 wt%; the mass ratio of tripropylene glycol diacrylate monomer (TPGDA) in the resin system is 15.6 wt%; the mass ratio of BYK-111 dispersant in the resin system is 20 wt%; the mass ratio of phenyl bis(2,4,6-trimethylbenzoyl)phosphine oxide (BAPO) in the resin system is 2 wt%; and the mass ratio of 4-methoxyphenol (MEHQ) photoinhibitor in the resin system is 0.4 wt%.

[0056] (2) Prepare a mixed powder of white phosphate / Li3PO4 in a ratio of 0.5 wt% of Li3PO4 to powder mass.

[0057] (3) Mix the white phosphate particles and Li3PO4 powder with the photosensitive resin, keeping the mass fraction of the white phosphate plus Li3PO4 powder at 75 wt%. At the same time, use a 70°C aqueous solution to ultrasonically stir the photosensitive ceramic slurry in a glass beaker for 5 minutes.

[0058] (4) The prepared photosensitive ceramic slurry is ball-milled in a ball mill. The grinding balls are made of zirconium oxide or natural agate. The speed of the ball mill is controlled at 800 rpm and the ball-milling time is 4.5 hours. After the ball milling, the slurry is heated at 70°C in an ultrasonic cleaning machine for 5 minutes to obtain a composite ceramic slurry that can be used for photocuring molding.

[0059] (5) The model to be formed is sliced ​​and imported into a DLP light-curing printer for layer-by-layer printing. The printing parameters are set to a layer thickness of 50 μm, an exposure time of 5 seconds, a bottom layer exposure time of 60 seconds, and a bottom layer number of 5 layers.

[0060] (6) Photocuring printing orthogonal periodic structure, maintaining the temperature inside the photocuring printing equipment at 50℃.

[0061] Comparative Example 1

[0062] The difference between this comparative example and Examples 1-4 is that Li3PO4 powder is not added to the photosensitive ceramic slurry. Other conditions are the same, and the final product is a white phosphate bone scaffold.

[0063] Observation of the morphology of the bone scaffold revealed that the white calcium phosphate scaffold was white in appearance, retaining a complete orthogonal periodic porous structure without obvious defects.

[0064] The results of the compression mechanical test showed that the compressive strength of the white phosphate scaffold was 24.1 MPa and the bending strength was 43.6 MPa, which were slightly weaker than the mechanical properties in Example 2.

[0065] The results of the degradation experiment and ion release test showed that the degradation rate of the white phosphate scaffold was slower than that of the embodiment, with a mass loss of 0.61% after 4 weeks. No Li ions were detected in the solution after degradation, and the Ca ion concentration in the solution was 7.28 ppm at the fourth week of degradation.

[0066] The fluorescence staining results after 7 days of culture of osteoblasts inoculated on the bone scaffold showed that the cells on the surface of the white calcium phosphate scaffold had a certain degree of proliferation, but the overall number was small.

Claims

1. A method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution, characterized in that A photosensitive resin component corresponding to a photosensitive ceramic slurry is prepared in the dark; white patite particles and Li3PO4 powder are placed in the same beaker in proportion; the white patite particles and Li3PO4 powder are mixed with a photosensitive resin, maintaining the mass fraction of the white patite plus the Li3PO4 powder at 75 wt%; the prepared photosensitive ceramic slurry is ball-milled in a ball mill, and the slurry is heated in an ultrasonic cleaner after ball milling to obtain a composite ceramic slurry that can be used for photocuring; an STL format model of an orthogonal periodic structure is sliced ​​and imported into a photocuring printer; the orthogonal periodic structure is photocured to obtain a white patite / Li3PO4 composite ceramic bone scaffold green body; the white patite / Li3PO4 composite ceramic bone scaffold green body is placed in a muffle furnace for degreasing and sintering heat treatment to remove the resin component in the green body, and then sintered to obtain a white patite / Li3PO4 composite ceramic bone scaffold.

2. The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution according to claim 1, characterized in that: The mass ratio of 1,6-hexanediol diacrylate monomer (HDDA) in the resin system is 60-64 wt%; the mass ratio of tripropylene glycol diacrylate monomer (TPGDA) in the resin system is 15-16.2 wt%; the mass ratio of BYK-111 dispersant in the resin system is 18-22 wt%; the mass ratio of phenyl bis(2,4,6-trimethylbenzoyl)phosphine oxide (BAPO) in the resin system is 1.8-2.2 wt%; and the mass ratio of 4-methoxyphenol (MEHQ) light inhibitor in the resin system is 0.3-0.5 wt%.

3. The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution according to claim 1, characterized in that: The white phosphate / Li3PO4 mixed powder is prepared in a ratio of Li3PO4 to powder mass ratio of 0.05-0.5 wt%.

4. The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution according to claim 1, characterized in that: The white apatite particles and Li3PO4 powder were mixed with the photosensitive resin, maintaining the mass fraction of the white apatite plus the Li3PO4 powder at 75 wt%, and the photosensitive ceramic slurry in the glass beaker was ultrasonically stirred for 5 minutes using a 70°C aqueous solution.

5. The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution according to claim 1, characterized in that: The prepared photosensitive ceramic slurry is ball-milled in a ball mill. The grinding ball material is zirconia or natural agate. The speed of the ball mill is controlled at 700-900 rpm and the ball-milling time is 3-5 hours. After the ball milling, the slurry is heated at 70°C in an ultrasonic cleaner for 5 minutes to obtain a composite ceramic slurry that can be used for photocuring molding.

6. The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution according to claim 1, characterized in that: After slicing the model to be formed, import it into a DLP, LCD, or SLA light-curing printer for layer-by-layer printing. The printing parameters are set to a layer thickness of 40-200 μm, an exposure time of 3-10 seconds, a bottom layer exposure time of 10-60 seconds, and 5-20 bottom layers.

7. The method for preparing a 3D printed whitlowite composite scaffold with enhanced mechanical and biological properties based on liquid phase sintering and ion substitution according to claim 1, characterized in that: The orthogonal periodic structure of the light-curing printing device maintains the temperature inside the light-curing printing device at 40-50°C.

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