Preparation method of bionic layered calcium phosphate composite material with unburned shell structure

Abstract

The invention discloses a method for preparing a bionic layered calcium phosphate composite material with a shell structure without firing, comprising: mixing solid phase powder of calcium phosphate bone cement with a liquid phase to obtain a semi-dry slurry of calcium phosphate bone cement, rolling the semi-dry slurry of calcium phosphate bone cement on a roller press to obtain a calcium phosphate bone cement blank; coating the calcium phosphate bone cement blank with an organic biomaterial, and then repeatedly folding and rolling the blank for multiple times to obtain a sheet-like composite material with a uniformly dispersed organic biomaterial; folding the sheet-like composite material for multiple times to obtain a block composite material; and performing pressure-maintaining molding on the block composite material to obtain a shell-structured bionic layered calcium phosphate composite material. The mechanical properties of calcium phosphate bone cement are improved.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical materials and relates to a method for preparing a bionic layered calcium phosphate composite material with a non-fired shell structure. Background Art

[0002] At present, the bone defects caused by aging, traffic accidents, trauma, etc. are increasing, which brings great pain to patients and the demand for bone defect repair materials is also increasing. Bioactive ceramics, as a bone transplant substitute with excellent performance, have good biocompatibility, mechanical compatibility, degradability and chemical stability, but their inherent brittleness hinders their application in load-bearing parts. Therefore, improving the toughness of bioceramic materials and improving their reliability have become current research hotspots. Studies have found that the shell nacre in nature is a high-performance biomaterial, which is composed of 95wt% highly oriented aragonite platelets (mainly CaCO3) and 5wt% of a small amount of organic biopolymers (mainly proteins and polysaccharides). The shell nacre structure can be described as a multi-layered "brick-mud structure", with flaky calcium carbonate as bricks, regularly staggered and stacked, and a small amount of organic matter filled between bricks as "mud" to play a bonding role. When subjected to a large impact, the interlayer will undergo a large plastic deformation to consume and absorb energy, while at the same time, the crack will be blunted and deflected, and will expand in a step-like manner along the propagation direction from the starting point, increasing the crack expansion path and improving the fracture strength. Therefore, a high-toughness layered composite material can be prepared by imitating the structure of the shell nacre. The existing layered composite material is formed by alternately stacking the substrate layer and the organic biological interface layer, and sintering them through a certain process. However, high-temperature sintering causes the organic polymer material to volatilize and no longer exist, and the subsequent infusion is subject to dimensional restrictions such as the thickness and spacing of the layer, and the carbon and other substances produced by the sintering aid during the vacuum sintering process affect the mechanical and biological properties of the material. The use of sinter-free, self-solidified calcium phosphate ceramics (CPC) can effectively solve this problem. Therefore, developing a composite material that combines high strength and high toughness through shell structure biomimetic is one of the current research focuses in this field.

[0003] The Chinese patent "A composite bionic bone and its preparation method" (application number: 202111344147.9, publication number: CN 114010838 A, publication date: 2022.02.08) discloses a composite bionic bone and its preparation method, which uses nano-hydroxyapatite and type I collagen to restore the inorganic and organic components of the bone respectively. At the same time, the mixture composed of the two can better restore the physical properties of the bone such as hardness. Secondly, the pH value of the composite material can be adjusted by vancomycin hydrochloride and sodium hydroxide to make it closer to the human body environment, so that the composite bionic bone is closer to the properties of the bone, solving the problem that the existing replacement bones are difficult to meet the higher use requirements. However, this method cannot achieve a significant improvement in mechanical properties by physically blending and structurally disordering the inorganic and organic components.

[0004] The Chinese patent "A bone regeneration multiple bionic scaffold material and its preparation method" (application number: 202110021590.6, publication number: CN 112870447 B, publication date: 2022.03.11) discloses a bone regeneration multiple bionic scaffold material and its preparation method, which uses a mixed solution of bioactive nano inorganic particles, water-soluble natural proteins and nano fiber bundles as raw materials, and through a process of pre-freezing-freezing treatment-freeze drying-post-treatment, a bone regeneration multiple bionic scaffold material including a sheet material and an intercalated structure dispersed between the sheets of the sheet material is prepared. However, its mechanical properties are poor and cannot meet actual needs.

[0005] The Chinese patent "A multi-layer alternating structure composite bone repair material and preparation method" (application number: 202010281473.9, publication number: CN 111603612 B, publication date: 2022.05.13) discloses a multi-layer alternating structure composite bone repair material and preparation method, through the uniform growth of calcium hydrogen phosphate micro-belts on the surface of carbon cloth to form a ribbon-shaped modified cloth, calcium hydrogen phosphate micro-belts can give the composite material biological activity on the one hand, and on the other hand can be used as a ribbon nanobody to enhance the strength of the composite material. However, this method cannot achieve a synergistic improvement in strength and toughness. Summary of the invention

[0006] The purpose of the present invention is to provide a method for preparing a non-fired shell structure bionic layered calcium phosphate composite material, which solves the problem of poor mechanical properties of calcium phosphate bone cement in the prior art.

[0007] The technical solution adopted by the present invention is a method for preparing a non-fired shell structure bionic layered calcium phosphate composite material, comprising the following steps:

[0008] Step 1, mixing the solid phase powder of calcium phosphate bone cement with the liquid phase to obtain a semi-dry slurry of calcium phosphate bone cement, and rolling the semi-dry slurry of calcium phosphate bone cement on a roller press to obtain a calcium phosphate bone cement green sheet;

[0009] Step 2, coating the calcium phosphate bone cement blank with organic biomaterials, and then repeatedly folding and rolling the blank for multiple times to obtain a sheet-like composite material in which the organic biomaterials are evenly dispersed;

[0010] Step 3, folding the sheet composite material in half for multiple times to obtain a block composite material;

[0011] Step 4: Perform pressure-maintaining molding on the block composite material to obtain a shell-structured bionic layered calcium phosphate composite material.

[0012] The present invention is also characterized in that:

[0013] Calcium phosphate bone cement solid phase powder includes the following components in terms of mass percentage:

[0014] 40-70% tetracalcium phosphate, 10-40% calcium hydrogen phosphate dihydrate, 5-20% sodium citrate, the total mass percentage of the above components is 100%.

[0015] The liquid phase is any one of distilled water, blood, physiological saline, dilute acid, serum, and phosphate solution.

[0016] The solid-liquid ratio of calcium phosphate solid phase powder to liquid phase is 1:0.2-2.0 g / ml.

[0017] The thickness of calcium phosphate bone cement blank is 0.2-1.5mm.

[0018] The organic biological material is any one of medical resin, sodium alginate, gelatin, polyvinyl alcohol, pectin, agarose, starch and sodium carboxymethyl cellulose.

[0019] The organic biological material accounts for 2-10% of the total mass of the shell structure bionic layered calcium phosphate composite material.

[0020] Step 4 is specifically as follows: at 37° C., 100% humidity, and 1-4 MPa pressure, the block composite material is pressure-formed for a curing time of 6-24 hours to obtain a shell-structured bionic layered calcium phosphate composite material.

[0021] The beneficial effects of the present invention are as follows: the preparation method of the bionic layered calcium phosphate composite material with a firing-free shell structure of the present invention adopts a roller pressing and rolling process to quickly and efficiently realize the uniform and alternating distribution of calcium phosphate and organic biomaterials; when the material is bent or impacted, the main crack expands in the vertical direction and penetrates the calcium phosphate layer to reach the organic interface layer. Since the average strength of the organic interface layer is relatively low, the main crack tends to expand along the interface between the two, so that the crack expansion is deflected, resulting in a step-like fracture mode, which increases the crack expansion path, and energy is released during the crack expansion, thereby achieving a toughening effect and having higher mechanical properties; at the same time, the composition of the calcium phosphate after hydration is the same as that of human bones, and no sintering is required, the degree of crystallization is also similar to that of human bones, and the degradation performance and biocompatibility are more compatible with human bones. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is a schematic structural diagram of a composite material obtained by the method for preparing the unfired shell structure bionic layered calcium phosphate composite material of the present invention. DETAILED DESCRIPTION

[0023] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0024] The method for preparing a non-fired shell structure bionic layered calcium phosphate composite material comprises the following steps:

[0025] Step 1, mixing the solid phase powder of calcium phosphate bone cement with the liquid phase to obtain a semi-dry slurry of calcium phosphate bone cement, and rolling the semi-dry slurry of calcium phosphate bone cement on a roller press to obtain a calcium phosphate bone cement green sheet;

[0026] Calcium phosphate bone cement solid phase powder includes the following components in terms of mass percentage:

[0027] 40-70% tetracalcium phosphate, 10-40% calcium hydrogen phosphate dihydrate, 5-20% sodium citrate, the total mass percentage of the above components is 100%.

[0028] The liquid phase is any one of distilled water, blood, physiological saline, dilute acid, serum, and phosphate solution.

[0029] Specifically, 40-70% tetracalcium phosphate, 10-40% dibasic calcium phosphate and 5-20% sodium citrate are ball-milled for 2 hours according to their mass fractions and mixed evenly, and then mixed with a liquid phase at a solid-liquid ratio of 1:0.2-2.0 g / ml for 10 minutes to obtain a semi-dry slurry of calcium phosphate bone cement. The semi-dry slurry of calcium phosphate bone cement is repeatedly rolled on a roller press. During the rolling, the green sheet is continuously inverted 90 degrees and folded repeatedly to ensure that the calcium phosphate solid phase powder and the solidifying liquid are mixed highly evenly and bubbles are discharged to obtain a 0.2-1.5 mm calcium phosphate bone cement green sheet.

[0030] Step 2, coating the calcium phosphate bone cement blank with organic biomaterials, and then repeatedly folding and rolling the blank for multiple times to obtain a sheet-like composite material in which the organic biomaterials are evenly dispersed;

[0031] The organic biological material is any one of medical resin, sodium alginate, gelatin, polyvinyl alcohol, pectin, agarose, starch and sodium carboxymethyl cellulose.

[0032] Specifically, a calcium phosphate bone cement green sheet is placed on a roller press, and an organic biomaterial accounting for 2-10% of the total mass percentage of the composite material is coated on the calcium phosphate bone cement green sheet, and the mass fraction of the organic biomaterial is 3%. Then, the green sheet is repeatedly folded in half and rolled, and the folding and rolling are controlled within 10 minutes in total, and the number of rolling is 10-40 times, so as to obtain a sheet-like composite material with the organic biomaterial dispersed and evenly distributed.

[0033] Step 3, folding the sheet composite material in half for multiple times to obtain a block composite material;

[0034] Step 4: Under the conditions of 37° C., 100% humidity and 1-4 MPa pressure, the block composite material is subjected to pressure-maintaining molding for a curing time of 6-24 hours to obtain a shell-structured bionic layered calcium phosphate composite material.

[0035] Through the above methods, the preparation method of the unfired shell structure bionic layered calcium phosphate composite material of the present invention adopts a roller rolling process to quickly and efficiently achieve the uniform and alternating distribution of calcium phosphate and organic biomaterials; when the material is bent or impacted, the toughening effect can be achieved through crack deflection and the bridging of organic matter, and it has higher mechanical properties; at the same time, its inorganic component is the same as that of human bone, and no sintering is required, the degree of crystallization is also similar to that of human bone, and the degradation performance and biocompatibility are more matched with human bone.

[0036] Example 1

[0037] Step 1. Ball-mill 70% tetracalcium phosphate, 10% dibasic calcium phosphate dihydrate, and 20% sodium citrate by mass for 2 hours to mix evenly, and then mix with distilled water at a solid-liquid ratio of 1:0.35 g / ml, and stir for 10 minutes to obtain a semi-dry slurry of calcium phosphate bone cement. The semi-dry slurry of calcium phosphate bone cement is repeatedly rolled on a roller press. During rolling, the green sheet is continuously turned 90 degrees and folded repeatedly to ensure that the calcium phosphate solid phase powder and the solidifying liquid are mixed highly evenly and bubbles are discharged to obtain a 0.8 mm calcium phosphate bone cement green sheet.

[0038] Step 2: Place the calcium phosphate bone cement green sheet on a roller press, coat the calcium phosphate bone cement green sheet with 10% sodium alginate accounting for 3% of the total mass percentage of the composite material, and then repeatedly fold and roll the green sheet, the folding and rolling are controlled within 10 minutes, the rolling number is 10 times, and a sheet composite material with uniformly dispersed organic biomaterials is obtained.

[0039] Step 3, folding the sheet composite material in half for multiple times to obtain a block composite material;

[0040] Step 4: The block composite material is subjected to pressure-maintaining molding at 37° C., 100% humidity, and 4 MPa pressure for 6 hours to obtain a shell-structured bionic layered calcium phosphate composite material, such as Figure 1 shown.

[0041] Example 2

[0042] Step 1. Ball-mill 40% tetracalcium phosphate, 40% dibasic calcium phosphate dihydrate, and 20% sodium citrate by mass for 2 hours to mix evenly, and then mix with physiological saline at a solid-liquid ratio of 1:0.2 g / ml, and stir for 5 minutes to obtain a semi-dry slurry of calcium phosphate bone cement. The semi-dry slurry of calcium phosphate bone cement is repeatedly rolled on a roller press. During rolling, the green sheet is continuously inverted 90 degrees and folded repeatedly to ensure that the calcium phosphate solid phase powder and the solidifying liquid are mixed highly evenly and bubbles are discharged to obtain a 0.4 mm calcium phosphate bone cement green sheet.

[0043] Step 2: Place the calcium phosphate bone cement green sheet on a roller press, coat the calcium phosphate bone cement green sheet with 5% polyvinyl alcohol accounting for 15% of the total mass percentage of the composite material, and then repeatedly fold and roll the green sheet, the folding and rolling are controlled within 10 minutes, the rolling number is 20 times, and a sheet composite material with uniformly dispersed organic biomaterials is obtained.

[0044] Step 3, folding the sheet composite material in half for multiple times to obtain a block composite material;

[0045] Step 4: Under the conditions of 37° C., 100% humidity and 4 MPa pressure, the block composite material is subjected to pressure-maintaining molding and the curing time is 24 hours to obtain a shell-structured bionic layered calcium phosphate composite material.

[0046] Example 3

[0047] Step 1. Ball-mill 60% tetracalcium phosphate, 35% dibasic calcium phosphate dihydrate, and 5% sodium citrate by mass for 2 hours to mix evenly, and then mix with a dilute acid solution at a solid-liquid ratio of 1:1.0 g / ml, and stir for 20 minutes to obtain a semi-dry slurry of calcium phosphate bone cement. The semi-dry slurry of calcium phosphate bone cement is repeatedly rolled on a roller press. During rolling, the green sheet is continuously turned 90 degrees and folded repeatedly to ensure that the calcium phosphate solid phase powder and the solidifying liquid are mixed highly evenly and bubbles are discharged to obtain a 1.0 mm calcium phosphate bone cement green sheet.

[0048] Step 2: Place the calcium phosphate bone cement green sheet on a roller press, coat the calcium phosphate bone cement green sheet with gelatin accounting for 10% of the total mass percentage of the composite material, and the mass fraction of gelatin is 4%, and then repeatedly fold and roll the green sheet, the folding and rolling are controlled within 10 minutes, the rolling number is 40 times, and a sheet composite material with uniformly dispersed organic biomaterials is obtained.

[0049] Step 3, folding the sheet composite material in half for multiple times to obtain a block composite material;

[0050] Step 4: Under the conditions of 37° C., 100% humidity and 4 MPa pressure, the block composite material is subjected to pressure-maintaining molding and the curing time is 12 hours to obtain a shell-structured bionic layered calcium phosphate composite material.

[0051] Example 4

[0052] Step 1. Ball-mill 60% tetracalcium phosphate, 30% dibasic calcium phosphate dihydrate, and 10% sodium citrate by mass for 2 hours to mix evenly, and then mix with the serum solution at a solid-liquid ratio of 1:0.2 g / ml, and stir for 30 minutes to obtain a semi-dry slurry of calcium phosphate bone cement. The semi-dry slurry of calcium phosphate bone cement is repeatedly rolled on a roller press. During rolling, the green sheet is continuously inverted 90 degrees and folded repeatedly to ensure that the calcium phosphate solid phase powder and the solidifying liquid are mixed highly evenly and bubbles are discharged to obtain a 0.2 mm calcium phosphate bone cement green sheet.

[0053] Step 2, placing the calcium phosphate bone cement green sheet on a roller press, coating the calcium phosphate bone cement green sheet with 5% agarose accounting for the total mass percentage of the composite material, the mass fraction of agarose is 8%, and then repeatedly folding and rolling, the folding and rolling are controlled within 10 minutes, the rolling number is 30 times, and a sheet composite material with uniformly dispersed organic biomaterials is obtained.

[0054] Step 3, folding the sheet composite material in half for multiple times to obtain a block composite material;

[0055] Step 4: Under the conditions of 37° C., 100% humidity and 4 MPa pressure, the block composite material is subjected to pressure-maintaining molding and the curing time is 18 hours to obtain a shell-structured bionic layered calcium phosphate composite material.

[0056] Example 5

[0057] Step 1. Ball-mill 70% tetracalcium phosphate, 20% dibasic calcium phosphate dihydrate, and 10% sodium citrate by mass for 2 hours to mix evenly, and then mix with phosphate solution at a solid-liquid ratio of 1:2.0 g / ml, and stir for 10 minutes to obtain a semi-dry slurry of calcium phosphate bone cement. The semi-dry slurry of calcium phosphate bone cement is repeatedly rolled on a roller press. During rolling, the green sheet is continuously turned 90 degrees and folded repeatedly to ensure that the calcium phosphate solid phase powder and the solidifying liquid are mixed highly evenly and bubbles are discharged to obtain a 1.5 mm calcium phosphate bone cement green sheet.

[0058] Step 2: Place the calcium phosphate bone cement green sheet on a roller press, coat the calcium phosphate bone cement green sheet with 2% sodium carboxymethyl cellulose accounting for 7% of the total mass percentage of the composite material, and then repeatedly fold and roll the green sheet, the folding and rolling are controlled within 10 minutes, the rolling number is 40 times, and a sheet composite material with uniformly dispersed organic biomaterials is obtained.

[0059] Step 3, folding the sheet composite material in half for multiple times to obtain a block composite material;

[0060] Step 4: Under the conditions of 37° C., 100% humidity and 4 MPa pressure, the block composite material is pressure-formed for 10 hours to obtain a shell-structured bionic layered calcium phosphate composite material.

[0061] The compressive strength of the conventional calcium phosphate (CPC) bone cement, after being processed by the folding and rolling method in step 2 of Examples 1-5, is compared with the shell structure bionic layered calcium phosphate composite material prepared in Examples 1 to 5 of the present invention as shown in Table 1:

[0062] Table 1 Comparison of compressive strength of the present invention and traditional calcium phosphate (CPC) bone cement

[0063]

[0064] It can be seen from the above table that, compared with traditional calcium phosphate (CPC) bone cement, the shell-structured bionic layered calcium phosphate composite material prepared by the present invention has higher compressive strength and its mechanical properties are improved to a certain extent.

Claims

1. A method for preparing a bionic layered calcium phosphate composite material with a shell structure that does not require burning, characterized in that: The following steps are involved: Step 1, mixing the solid phase powder of calcium phosphate bone cement with the liquid phase to obtain a semi-dry slurry of calcium phosphate bone cement, and rolling the semi-dry slurry of calcium phosphate bone cement on a roller press to obtain a calcium phosphate bone cement green sheet; The calcium phosphate bone cement solid phase powder comprises the following components in terms of mass percentage: 40-70% tetracalcium phosphate, 10-40% dibasic calcium phosphate dihydrate, and 5-20% sodium citrate, and the sum of the mass percentages of the above components is 100%; the solid-liquid ratio of the calcium phosphate bone cement solid phase powder to the liquid phase is 1:0.2-2.0 g / ml; Step 2, coating the calcium phosphate bone cement blank with organic biomaterials, and then repeatedly folding and rolling the blank for multiple times to obtain a sheet-like composite material in which the organic biomaterials are evenly dispersed; Specifically, a calcium phosphate bone cement green sheet is placed on a roller press, and an organic biomaterial accounting for 2-10% of the total mass percentage of the composite material is coated on the calcium phosphate bone cement green sheet, and the mass fraction of the organic biomaterial is 3%, and then the green sheet is repeatedly folded in half and rolled, the folding and rolling are controlled within 10 minutes in total, and the number of rolling is 10-40 times, so as to obtain a sheet-like composite material in which the organic biomaterial is dispersed and evenly distributed; The organic biological material is sodium alginate or gelatin; The organic biological material accounts for 2-10% of the total mass of the shell structure bionic layered calcium phosphate composite material; Step 3, folding the sheet-like composite material in half for multiple times to obtain a block composite material; Step 4: performing pressure-maintaining molding on the block composite material to obtain a shell-structured bionic layered calcium phosphate composite material.

2. The method for preparing the burn-free shell structure bionic layered calcium phosphate composite material according to claim 1, characterized in that: The liquid phase in step 1 is any one of distilled water, blood, physiological saline, dilute acid, serum, and phosphate solution.

3. The method for preparing the burn-free shell structure bionic layered calcium phosphate composite material according to claim 1, characterized in that: The thickness of the calcium phosphate bone cement blank is 0.2-1.5 mm.

4. The method for preparing the burn-free shell structure bionic layered calcium phosphate composite material according to claim 1, characterized in that: Step 4 is specifically as follows: at 37° C., 100% humidity, and 1-4 MPa pressure, the block composite material is subjected to pressure-maintaining molding for a curing time of 6-24 hours to obtain a shell-structured bionic layered calcium phosphate composite material.

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