A method for manufacturing a macro-micro multi-level porous structure bioceramic green body

Abstract

The application discloses a kind of macro-micro multi-level pore structure bioceramic blank manufacturing method, comprising: preparation of bioceramic slurry with freeze-drying characteristics, establish the peripheral contour of the three-dimensional model of part corresponding to each layer two-dimensional graph, macro-pore milling path data, the whole system in low temperature environment, through scraper on the printing platform to lay a layer of ceramic slurry, adopt freeze plate from top to bottom to contact material layer and make it freeze solidification, establish ice crystal micro-pore pore-forming template;According to the milling path data, the selective milling of the solidified slurry is carried out by using milling equipment, and the frozen slurry at the contour and pore is removed to form a groove;Using extrusion molding equipment, extrude hydrogel along the milling path, and establish frozen hydrogel macro-pore pore-forming template.The formed circular macro-pore has good mechanical properties, and the micro-pore structure can be controlled by various parameters, the new method has strong designability of pore structure, wide application range of material, and does not need mold and support design in process.

Description

Technical Field

[0001] This invention relates to the field of 3D printing technology, specifically to a method for manufacturing a bioceramic preform with a macro-micro multi-level porous structure. Background Technology

[0002] In the treatment of bone defects, artificial scaffold implantation not only effectively solves the problems of bone source and rejection, but also promotes the regeneration of biological tissues, making it the most promising treatment method currently available. To adapt to the unique environment within the human body, artificial scaffolds should meet three basic requirements: ① Good biocompatibility and osteoinductive properties. Common scaffold materials currently include metals, polymers, and bioceramics. Among these, bioceramics possess excellent biocompatibility, osteoconductivity, and osteoinductive properties, promoting cell functionalization and expression, making them an ideal biological scaffold material; ② Internal macro- and micro-level porous structure. The main channels for nutrient metabolism required for bone regeneration cells to recruit, infiltrate, and vascularize from surrounding bone tissue should be at the hundred-micrometer level. The currently accepted optimal pore size range for bone regeneration is 100–500 μm. To promote the adhesion and migration of regenerating cells and the ingrowth of other tissues, even smaller micron-sized secondary pores are required. Cell kinetics suggests that cells exhibit good adhesion and diffusion behavior in pores of 0.2–1 μm, while in pores of 3–8 μm, cells exhibit a spherical phenotype similar to osteoblasts. The optimal pore sizes for ingrowth of blood vessels, fibroblasts, and osteoid are 5 μm, 5–15 μm, and 40–μm, respectively. ③ Personalized three-dimensional shape. Bone defects in clinical cases exhibit significant variability and irregularity, with the vast majority requiring customized scaffolds for treatment. Therefore, research on the personalized manufacturing of multi-level porous bioceramic scaffolds has significant medical application value in promoting my country's transformation from experience-based medicine to precision medicine.

[0003] Personalized manufacturing technology, particularly 3D printing, can fully meet patients' customized needs for complex scaffold structures and has garnered widespread attention in the field of regenerative medicine. Common ceramic 3D printing methods, such as direct ink writing (DIW), photopolymerization (SL), selective laser sintering / melting (SLS / SLM), and stereolithography (3DP), all employ selective forming techniques within the macroscopic forming manufacturing framework. For example, invention patent CN201711264821.6 discloses a method for preparing ceramic bone scaffolds based on photopolymerization 3D printing. This method uses photopolymerization (SLA) 3D printing technology to prepare personalized ZTA porous bone scaffolds, but it can only meet the processing requirements of the macroscopic main pores of ceramic scaffolds. The above methods are affected by factors such as filler density, material flowability, and post-processing of additives, often leaving a large number of microscale pores inside the parts. These micropores are considered defects because their shape, size, and distribution are extremely difficult to control, and they cannot meet the functional requirements of secondary pores in ceramic scaffolds. Therefore, if the integrated forming of macro- and micro-level porous structures can be achieved in the ceramic 3D printing process, it will shorten the scaffold manufacturing process and achieve structural optimization, material saving, and energy saving.

[0004] To create microporous structures during 3D printing, pore-forming techniques from materials science need to be introduced. Freeze casting, which uses slurry solvent crystals as templates for pore creation, boasts advantages such as wide material applicability, environmental friendliness, low cost, strong pore design flexibility, and pore structures closely resembling natural materials (e.g., bones, shells), giving it a natural advantage in biostructure forming. The idea of ​​using freeze-drying principles for microporous ceramic 3D printing has gained widespread acceptance among scholars both domestically and internationally. For example, invention patent CN202210719283.X discloses an artificial bone scaffold and method based on 3D printing technology. This method uses extrusion 3D printing to form a bioceramic scaffold at low temperatures, using the movement of the extruder head to form macropores and freeze-drying ice templates to form micropores. However, the strict requirements on material rheology and the non-directional freezing conditions of this low-temperature direct writing method make it difficult to fully utilize the advantages of freeze-drying in creating micropores. Furthermore, the low-temperature direct writing method relies on the material's own weight to form the structure, resulting in main pores that are generally concave rhomboid in shape. Severe stress concentration makes the support more prone to cracking at the filament joints. Additionally, due to the limited bonding tightness between the extruded filaments, its tensile strength is an order of magnitude lower than its compressive strength. Moreover, the lack of controllable freezing direction in the low-temperature environment results in a non-directional distribution of the micropore structure, further reducing the mechanical properties of the support. In addition, the direct writing method lacks effective support, making it difficult to form cantilever / tilted structures. Summary of the Invention

[0005] The purpose of this invention is to provide a method for manufacturing a bioceramic preform with a macro-micro multi-level porous structure, so as to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a method for manufacturing a bioceramic preform with a macro-micro multi-level porous structure, comprising the following steps: S1: Prepare a slurry with freeze-drying properties; establish a three-dimensional model of the printing target; perform layer processing on the three-dimensional model; extract the contour and main channel data of each layer as the milling path for the milling cutter. S2: In a low-temperature environment, a layer of slurry is laid on the printing platform by a scraper, and a freezing plate is used to contact the slurry layer from top to bottom to freeze it; then, a milling machine is used to mill the frozen slurry layer according to the milling path obtained in step S1 to remove the frozen slurry at the contour and main channel to form a groove network; continuing in a low-temperature environment, according to the milling path data in S1, a hydrogel is extruded along the groove network using an extrusion molding machine so that the grooves are filled with hydrogel; after the hydrogel freezes, the printer platform is adjusted to descend one layer; S3: Repeat step S2 continuously to obtain a solidified green body surrounded by the frozen solidification slurry layer by layer; S4: The ice in the solidified green body is sublimated and removed by freeze dryer to form a dried green body surrounded by dry slurry; the dried green body is placed in a degreasing furnace for degreasing to obtain a green body without organic matter; then the excess material on the outside of the dried green body is removed to obtain a porous ceramic green body.

[0007] Preferably, the slurry is a slurry with freeze-drying properties, and its components include 5 to 90 parts by weight of bioceramic powder, 1 to 30 parts by weight of binder, and the remainder being solvent.

[0008] Preferably, the solvent is water, and the ceramic powder is composed of one or more of alumina ceramics, zirconium oxide ceramics, hydroxyl lime ceramics, and tricalcium phosphate ceramics.

[0009] Preferably, the adhesive is a water-soluble organic adhesive, and is one or more of carboxymethyl cellulose, polyvinyl alcohol, acrylic acid, epoxy resin, and polyurethane.

[0010] Preferably, in step S2, the low-temperature environment refers to a temperature below the solidification point of the ceramic slurry.

[0011] Preferably, in step S2, the temperature of the freezing plate is -10 to -60°C.

[0012] Preferably, in step S2, the milling cutter is a ball end mill.

[0013] Preferably, in step S2, the hydrogel is composed of water and organic matter, and its freezing point is higher than that of the ceramic slurry.

[0014] Preferably, the organic material is one or more of sodium alginate, gelatin, cellulose, and chitosan.

[0015] The present invention proposes a method for manufacturing a bioceramic green body with a macro-micro multi-level porous structure, the advantages of which are as follows: 1. This invention achieves integrated and controllable fabrication of bioceramics with macroscopic and microscopic multi-level porous structures by constructing macroscopic frozen gel templates and microscopic ice crystal templates.

[0016] 2. This invention adopts a layer-by-layer material laying method, which does not have high requirements for material rheology, allows for more freedom in material system design, and has a wide range of material applications.

[0017] 3. The present invention adopts a layer-by-layer freezing method, with the lower layer providing solid support for the upper layer, reducing the deformation of the cantilever structure, eliminating the need to design supports for the cantilever structure, and facilitating the manufacture of cantilever / tilted structures.

[0018] 3. This invention uses contact freezing to solidify the material layer. The freezing conditions are easy to control, and the micropore size can be adjusted by multiple parameters through the slurry system and freezing conditions.

[0019] 4. The main pores manufactured by the low-temperature direct-writing hydrogel template of this invention have a circular structure, which can effectively avoid stress concentration under load. The layer-by-layer freezing process allows the interlayer materials to be connected into a whole after "micro-melting-crystallization", which ensures the firmness of the interlayer bonding and improves the mechanical properties of the scaffold.

[0020] 5. This invention is based on a 3D printing method using water-based slurry freeze-drying. The processing does not require molds, which shortens the research and development and production cycle, and is low in cost and environmentally friendly. Attached Figure Description

[0021] Figure 1 This is a schematic flowchart of a method for manufacturing a bioceramic preform with a macro-micro multi-level porous structure according to the present invention. Detailed Implementation

[0022] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] Example 1: like Figure 1 As shown, the process of this invention includes the step of preparing a macro-microporous structured bioceramic green body: Step (1): Use design software such as Pro / E or UG, or a 3D scanner to create an STL format model of the target blank; Step (2): Use computer software to perform layering processing on the three-dimensional model along the Z-axis, with each layer having a thickness of 0.2 mm; establish the outer contour of the sliced ​​two-dimensional graphic and the milling path data of the macro-hole channel; Step (3): Prepare a ceramic slurry with freeze-drying properties: Weigh 140g of alumina powder (analytical grade, passed through 325 mesh); weigh 50g of PVA solution (4wt%); weigh 1.4g of ammonium polyacrylate (dispersant); and measure 8.6ml of distilled water. Add the above raw materials to a corundum ball mill jar and ball mill at high speed for 2 hours. Step (4): Place the ball-milled slurry in a vacuum defoamer for 10 minutes to defoam; Step (5): Control the low-temperature environment temperature to -15 to -30°C, add the defoamed slurry to the barrel, keep stirring the slurry in the barrel to prevent the slurry from settling; spread a layer of slurry on the printing platform with a scraper, the thickness of which is the same as the layer thickness during computer layer processing; use a -40°C freezing plate to contact the slurry layer from top to bottom to make it freeze quickly and form a dense ice crystal structure; Step (6): Remove the freezing plate and use a ball end mill to mill the groove along the two-dimensional milling path. The ball end mill has a radius of 0.1 mm and the milling depth is the same as the ball end radius size to ensure that the adjacent layer channels are connected vertically.

[0024] Step (7): Sodium alginate hydrogel material is used. The hydrogel solution is extruded along the milling groove through a three-dimensional extrusion device. The radius of the extruded filament is the same as the radius of the milling cutter ball head. The hydrogel is naturally frozen and solidified in a low temperature environment. Step (8) Repeat steps (5) to (7) to obtain a solidified ceramic body surrounded by solidified slurry; Step (9): The solidified ceramic body surrounded by the solidified slurry is placed in a freeze dryer for low-pressure drying to obtain a microporous structure with the same structure as ice crystals.

[0025] Step (10): Place the dried preform into a degreasing oven and degrease it at 600°C for 60 minutes to obtain a macroscopic pore structure that is the same as the frozen gel structure. Step (11): Remove excess material from the periphery to obtain a bioceramic body with a macro-micro multi-level porous structure, characterized by large pores running vertically between layers and fine pores within the layers.

[0026]

[0027] Based on the data given above, the following conclusions can be drawn: The data provided in Example 1 reflects some key properties of the macro- and microporous bioceramic preforms. The effects of these data are summarized below: 1. Porosity of 40%: The macro- and microporous structure of the bioceramic preform has a high porosity, which means that the material may have good permeability, adsorption and other properties in application; 2. Pore size distribution: By analyzing the distribution data of multiple pore size ranges, it can be determined that the material contains a multi-scale pore structure. Smaller pores are suitable for adsorbing small molecules and are beneficial for cell adhesion and climbing, while larger pores are beneficial for applications such as liquid transport and cell growth. 3. Compressive strength of 50MPa: This material has relatively high compressive strength and can withstand high compressive loads, making it suitable for applications requiring high compressive strength. 4. Specific surface area of ​​10 square meters / gram: A relatively high specific surface area indicates that the material has a larger surface area, which helps to increase the contact area with the surrounding environment and may promote processes such as adsorption and reaction. 5. The pore morphology is a composite shape: the primary pores are circular, which can improve the mechanical properties of the material, while the secondary pores are layered biomimetic structures. This structural morphology may provide the material with more surface area, which is in line with the natural growth law of ice crystals. 6. High pore connectivity: The pores in the material have good connectivity, which allows liquids and gases to move freely inside the material, facilitating processes such as liquid permeation and cell diffusion.

[0028] Example 2: The difference between this embodiment and embodiment 1 is that the ceramic powder used in step (3) is tricalcium phosphate powder and the binder is carboxymethyl cellulose; in step (5), a -15°C freezing plate is used to contact the material layer from top to bottom to slowly freeze it and form a coarse ice crystal structure; in step (11), a bioceramic blank with a macro-micro multi-level pore structure with large pores between layers and large small pores inside the layers is obtained.

[0029]

[0030] The data provided in Example 2 reflect some key properties of the macro- and microporous bioceramic preforms. The effects of these data are summarized below: 1. Pore size distribution: Through the distribution data of multiple pore size ranges, it can be known that there is a multi-scale pore structure in the material. By increasing the temperature of the freezing plate, ice crystals can grow fully, thereby forming a 10.3-micron secondary pore that is larger than that in Example 1. 2. Compressive strength is 40 MPa: Compared with Example 1, the compressive strength of the material is slightly reduced, but it still has a certain compressive strength. 3. Specific surface area of ​​5 square meters / gram: The relatively low specific surface area indicates that the surface area of ​​the material is small, but it can still provide a certain degree of active surface, which can promote certain reactions and effects. Example 3: The difference between this embodiment and embodiment 1 is that in step (6), two types of milling cutters are used for milling: a milling cutter with a ball head radius of 0.1 mm mills the groove along the two-dimensional graphic contour path, and the milling depth is the same as the ball head radius; a milling cutter with a ball head radius of 0.08 mm mills the macroscopic channel, and the milling depth is the same as the ball head radius; in step (7), gelatin hydrogel material is used, and the radius of the extruded filament is the same as the ball head radius of the milling cutter used for milling the macroscopic channel; in step (11), a bioceramic blank with a macro-micro multi-level porous structure with interlayer macropores that are not interconnected is obtained.

[0031]

[0032] The data provided in Example 3 reflect some key properties of the macro- and microporous bioceramic preforms. The effects of these data are summarized below: 1. Porosity of 35%: Compared with Examples 1 and 2, the macro-microporous structure bioceramic preform has a lower porosity, with fewer voids in the material, which may result in lower permeability and adsorption. 2. Primary pore size distribution: By analyzing the distribution data of multiple pore size ranges, it can be determined that the material contains a multi-scale pore structure. Compared with Example 1, the primary pore size is 160 micrometers due to the use of a smaller milling cutter. 3. Compressive strength of 60 MPa: Compared with Examples 1 and 2, the compressive strength of the material is significantly increased, and it has higher compressive resistance in applications; 4. Primary pore connectivity is not interlayer connectivity: Unlike Examples 1 and 2, the primary pores in the material are not interconnected between layers, which limits the transport capacity of liquids and gases within the material.

[0033] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for manufacturing a bioceramic green body with a macro-micro multi-level porous structure, characterized in that, Includes the following steps: S1: Prepare a slurry with freeze-drying properties; establish a three-dimensional model of the printing target; perform layer processing on the three-dimensional model; extract the contour and main channel data of each layer as the milling path for the milling cutter. S2: In a low-temperature environment, which refers to a temperature below the freezing point of the ceramic slurry, a layer of slurry is laid on the printing platform using a scraper. A freezing plate is then used to contact the slurry layer from top to bottom to freeze it. Then, a milling machine is used to mill the frozen slurry layer according to the milling path obtained in step S1, removing the frozen slurry at the contour and main channel to form a groove network. Continuing in the low-temperature environment, according to the milling path data in S1, an extrusion molding machine is used to extrude hydrogel along the groove network, so that the grooves are filled with hydrogel. After the hydrogel freezes, the printer platform is adjusted to descend one layer. S3: Repeat step S2 continuously to obtain a solidified green body surrounded by the frozen solidification slurry layer by layer; S4: The ice in the solidified green body is sublimated and removed by freeze dryer to form a dried green body surrounded by dry slurry; the dried green body is placed in a degreasing furnace for degreasing to obtain a green body without organic matter; then the excess material on the outside of the dried green body is removed to obtain a porous ceramic green body.

2. The method for manufacturing a bioceramic green body with a macro-micro multi-level porous structure according to claim 1, characterized in that: The slurry is a slurry with freeze-drying properties, and its components include 5 to 90 parts by weight of bioceramic powder, 1 to 30 parts by weight of binder, and the remainder being solvent.

3. The method for manufacturing a bioceramic green body with a macro-micro multi-level porous structure according to claim 2, characterized in that: The solvent is water, and the ceramic powder is composed of one or more of alumina ceramics, zirconium oxide ceramics, hydroxyl lime ceramics, and tricalcium phosphate ceramics.

4. The method for manufacturing a bioceramic green body with a macro-micro hierarchical porous structure according to claim 3, characterized in that: The adhesive is a water-soluble organic adhesive, and is one or more of carboxymethyl cellulose, polyvinyl alcohol, acrylic acid, epoxy resin, and polyurethane.

5. The method for manufacturing a macro-micro multi-level porous bioceramic preform according to claim 4, characterized in that: In step S2, the temperature of the freezing plate is -10 to -60°C.

6. The method for manufacturing a bioceramic green body with a macro-micro multi-level porous structure according to claim 5, characterized in that: In step S2, the milling cutter is a ball end mill.

7. The method for manufacturing a bioceramic green body with a macro-micro hierarchical porous structure according to claim 6, characterized in that: In step S2, the hydrogel is composed of water and organic matter, and its freezing point is higher than that of the ceramic slurry.

8. The method for manufacturing a macro-micro multi-level porous bioceramic preform according to claim 7, characterized in that: The organic matter is one or more of sodium alginate, gelatin, cellulose, and chitosan.

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