Preparation method of biocompatible porous material

Abstract

The invention discloses a preparation method of a biocompatible porous material, and belongs to the technical field of biological materials and functional materials. The technical problem that an existing porous material is poor in biocompatibility due to the fact that a porous structure is formed by using strong acid or a toxic solution is solved. According to the technical scheme, the preparation method comprises the steps of self-assembly of a two-dimensional material and microcrystal particles, sectional temperature control drying treatment, dissolution treatment and vacuum freeze drying. The method has the beneficial effects that by utilizing a microcrystal dissolution differentiation technology, the precise construction of a porous structure is realized under the condition that strong acid or toxic solution is not used, and harmful chemicals are not used, so that the biocompatibility and the biological activity of the material are reserved.

Description

Technical Field

[0001] The invention belongs to the technical field of biomaterials and functional materials, and particularly relates to a method for preparing a biocompatible porous material. Background Art

[0002] In recent years, with the rapid development of new materials science and the increasing demand for biomedicine, the application prospects of biocompatible porous materials in the fields of drug delivery, tissue engineering and biosensing have become increasingly broad. These materials can effectively improve chemical reactivity, adsorption capacity and material transfer efficiency through their unique pore structure and high specific surface area.

[0003] Two-dimensional materials, especially graphene and transition metal sulfides such as molybdenum disulfide, have unique advantages in the preparation of porous materials due to their excellent electrical, optical and mechanical properties. These materials have high specific surface area and abundant surface active sites, which enable them to better control the pore size and improve the material performance during the construction of porous structures. However, the existing methods for preparing porous structures of two-dimensional materials often face the following technical difficulties: (1) Difficulty in pore size control: Due to the high conductivity and high surface energy of the two-dimensional materials themselves, they are prone to agglomeration during the preparation process, resulting in uneven pore size distribution; (2) Insufficient material structure stability: In some porous structures, the sheets of two-dimensional materials are prone to stacking or separation, affecting the long-term performance of the materials.

[0004] In response to the above technical problems, the current common technical solutions include introducing a multilayer structure or improving the agglomeration behavior of two-dimensional materials by chemical modification. For example, the invention patent CN118027502A discloses a method for preparing a porous graphene material by surface modification technology, which inhibits the agglomeration behavior of graphene sheets by chemical bonding, significantly improving the pore size distribution uniformity and structural stability of the material. Another typical solution is the invention patent CN108889326A, which discloses a method for constructing a porous molybdenum disulfide material by layered assembly. The method successfully realizes the porous structure of the material by regulating the assembly process. However, the existing methods for preparing porous materials often rely on the use of strong acids or toxic solutions to remove the material templates that form the porous structure (CN109021282B), which may have an adverse effect on the biocompatibility and biological activity of the material, limiting its application in the biomedical field. Summary of the invention

[0005] In response to the technical problem that existing porous materials use strong acids or toxic solutions to form porous structures, which may have poor biocompatibility, the purpose of the present invention is to provide a method for preparing biocompatible porous materials. By utilizing the differentiated crystallite dissolution technology, the porous structure can be accurately constructed without using strong acids or toxic solutions, and no harmful chemicals are used, so as to retain the biocompatibility and biological activity of the material.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing a biocompatible porous material, comprising the following steps:

[0007] (1) Self-assembly of two-dimensional materials and microcrystalline particles: dissolving the two-dimensional material in a polar solvent to obtain a two-dimensional material solution; dispersing the microcrystalline particles in a polar solvent to obtain a microcrystalline particle solution; adding the two-dimensional material solution to the microcrystalline particle solution for adsorption treatment, and then standing to obtain a self-assembled complex;

[0008] (2) Segmented temperature-controlled drying treatment: separating and washing the self-assembled composite obtained in step (1), and then performing segmented temperature-controlled drying treatment to obtain a two-dimensional material-microcrystal composite;

[0009] (3) dissolution treatment: immersing the two-dimensional material-microcrystal composite obtained in step (2) in an organic solvent to dissolve the microcrystal particles to obtain a composite with a porous structure;

[0010] (4) Vacuum freeze drying: The porous structured composite obtained in step (3) is subjected to vacuum freeze drying to remove the organic solvent and obtain a biocompatible porous material.

[0011] Further, the microcrystalline particles are calcium oxalate, calcium carbonate, magnesium carbonate, magnesium hydroxide, strontium carbonate, barium sulfate, barium carbonate, calcium phosphate, magnesium phosphate, calcium silicate or magnesium silicate, and the diameter of the microcrystalline particles ranges from 100nm to 1000nm. The present invention selects microcrystalline particles with solubility differences and positive surface charges, and these microcrystals are insoluble in water but soluble in organic solvents.

[0012] Wherein, step (1) is specifically as follows:

[0013] (11) Material preparation: selecting a two-dimensional material and a polar solvent, wherein the two-dimensional material is graphene, transition metal disulfide or transition metal carbonitride; the polar solvent is one or more of water, ethanol, isopropanol and acetone; the required polar solvent needs to be able to fully disperse the two-dimensional material; the ratio of the mass of the two-dimensional material to the mass of the microcrystalline particles is 1:(3-5);

[0014] (12) Self-assembly:

[0015] (121) Preparation of two-dimensional material solution: slowly add the weighed two-dimensional material into a polar solvent and stir with a magnetic stirrer for 2 hours until the two-dimensional material is evenly dispersed in the polar solvent to obtain a two-dimensional material solution; if there are undissolved microcrystalline particles in the two-dimensional material solution, filter it through a microporous filter membrane to remove the undispersed particles to obtain a uniform two-dimensional material solution;

[0016] (122) Preparation of microcrystalline particle solution: slowly add microcrystalline particles into a polar solvent and stir with a magnetic stirrer to ensure that the microcrystals are evenly dispersed in the polar solvent to form a stable microcrystalline particle solution;

[0017] (123) Self-assembly: slowly pour the two-dimensional material solution into the microcrystalline particle solution, and the volume ratio of the two-dimensional material solution to the microcrystalline particle solution is 1:3; use a magnetic stirrer and an ultrasonic cleaner for alternating treatment, the stirring speed of the magnetic stirrer is 600 rpm, the treatment time of the magnetic stirrer is 30 min, and the treatment time of the ultrasonic cleaner is 10 min, to promote the uniform adsorption of the two-dimensional material on the surface of the microcrystal; after the self-assembly is completed, let the mixed solution stand for 1-2 hours to allow the self-assembled complex to settle to the bottom of the container;

[0018] Wherein, step (2) is specifically as follows:

[0019] (21) Centrifugal separation: Use a centrifuge to separate the self-assembled complex from the mixed solution of step (123) at a centrifugal speed of 5000 rpm for 10 minutes. Discard the supernatant and retain the deposited self-assembled complex.

[0020] (22) Washing and drying: The self-assembled composite is washed with deionized water; the washed self-assembled composite is subjected to a segmented temperature-controlled drying process to obtain a two-dimensional material-microcrystal composite.

[0021] The segmented temperature-controlled drying process is divided into eight stages, which include:

[0022] Stage 1: The temperature rises from 30°C to 60°C for 1 hour;

[0023] Stage 2: The temperature is maintained at 60°C for 2 hours;

[0024] Stage 3: The temperature drops from 60°C to 45°C for 1 hour;

[0025] Stage 4: The temperature is maintained at 45°C for 8 hours;

[0026] Stage 5: The temperature rises from 45°C to 55°C for 1 hour;

[0027] Stage 6: The temperature is maintained at 55°C for 3 hours;

[0028] Stage 7: The temperature drops from 55°C to 40°C for 1 hour;

[0029] Stage 8: The temperature is maintained at 40°C for 8 hours.

[0030] Wherein, step (3) is specifically as follows:

[0031] (31) Dissolving the microcrystals: soaking the two-dimensional material-microcrystal complex obtained in step (22) in an organic solvent to dissolve the microcrystal particles; wherein the soaking temperature is 50° C. and the soaking time is 6 to 24 hours; the organic solvent can effectively dissolve the microcrystal particles without destroying the structure of the two-dimensional material.

[0032] (32) Filtration and collection: The product after the dissolution treatment is filtered to obtain a composite with a porous structure.

[0033] Wherein, step (4) is specifically as follows:

[0034] (41) Pre-freezing treatment: The composite having a porous structure obtained in step (32) is pre-frozen at a low temperature of -50°C to -80°C until the sample is completely frozen.

[0035] (42) Vacuum freeze drying: The pre-frozen product is placed in a vacuum freeze drying device and dried at a pressure of 0.01 atm to 0.1 atm for 24 to 48 hours to completely remove the organic solvent and form a porous material with controllable pore size.

[0036] Furthermore, the method for preparing the microcrystalline particles comprises the following steps:

[0037] (100) Material selection: Select microcrystalline particles with different solubility and positive surface charge; poorly soluble in polar solvents but soluble in organic solvents;

[0038] (101) Solution preparation: Mix a metal salt solution with a weak acid solution to form a uniform solution; the metal salt solution is a calcium salt solution, a magnesium salt solution or a barium salt solution, and the weak acid solution is an oxalic acid solution, a carbonic acid solution, an ammonia solution, a phosphoric acid solution or a silicic acid solution.

[0039] (102) Spray drying: using a spray drying device to atomize the solution into tiny droplets, and drying in a high-temperature airflow, the droplets evaporate during the drying process and naturally settle to form microcrystalline products; wherein the nozzle diameter of the spray drying device is 0.2-0.5 mm to control the droplet size and drying speed; the high-temperature airflow is a high-temperature airflow of 350°C generated by an air heater with a flow rate of 1.0 m / s to ensure that the droplets evaporate and form microcrystalline products;

[0040] (103) Microcrystal collection and surface treatment: The microcrystal products after spray drying are collected, and then cleaned and activated to obtain microcrystal particles; the surface impurity removal and activation are carried out in a plasma cleaning device with a cleaning pressure of 50 mTorr and high-purity argon as the protective gas. The cleaning time is 30 seconds, which can effectively remove organic matter and oxide layers on the surface of the microcrystals and improve the surface energy and bonding strength of the material.

[0041] The pore size of the porous material is controlled by adjusting the initial particle size of the microcrystalline particles and the nozzle diameter. When the target is a nano-scale pore size, a nozzle smaller than 0.5 mm is selected; when the target is a micron-scale pore size, a nozzle between 0.5 mm and 1.0 mm is selected; when the target is a large pore size, a nozzle larger than 1.0 mm is selected.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] (1) The present invention can precisely control the pore size of porous materials through the differentiated microcrystal dissolution technology; by selecting different microcrystal particles and adjusting the initial particle size of the microcrystal particles and the dissolution conditions, precise control of the pore size from nanometer to micrometer level can be achieved;

[0044] (2) The present invention uses biocompatible microcrystalline materials and controls their dissolution process to avoid the use of strong acids or toxic solvents, thereby significantly improving the biocompatibility of the final porous material;

[0045] (3) The present invention simplifies the preparation process of traditional porous materials through the microcrystal dissolution differentiation technology, reduces the process steps and the use of chemical reagents; compared with the traditional multi-step complex chemical treatment, the present invention not only reduces environmental pollution, but also reduces production costs;

[0046] (4) The present invention ensures a stable structure between the two-dimensional material and the microcrystals during the low-temperature drying and vacuum freeze-drying steps; after the precise dissolution of the microcrystals, the formed porous material has excellent structural stability and uniformity. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 This is a SEM microscopic morphology image of the biocompatible porous material of Example 1;

[0048] Figure 2 This is a schematic diagram of the process of segmented low-temperature drying in Example 1. DETAILED DESCRIPTION

[0049] The present invention is further described below in conjunction with the accompanying drawings and embodiments.

[0050] The present invention provides a method for preparing a biocompatible porous material, which is divided into four steps: self-assembly of two-dimensional materials and microcrystalline particles, segmented temperature-controlled drying treatment, dissolution treatment and vacuum freeze-drying, wherein the segmented temperature-controlled drying treatment is divided into eight stages, as shown in Table 1.

[0051] Generally speaking, higher temperatures are not conducive to the stability of two-dimensional material-microcrystal composites, because higher temperatures often lead to the destruction of the adsorption relationship at the interface, resulting in structural failure, so a lower drying temperature should be used as much as possible (the most common temperature is 50°C). However, low drying temperatures still cannot ensure stability, which is contrary to common sense and intuition.

[0052] In-depth research has found that this is related to the evaporation process of organic solvents on the surface of the material and the stress release process inside the material. In order to enhance stability, the drying temperature needs to be precisely controlled; mainly to solve the following two problems:

[0053] a. Control of organic solvent residues:

[0054] During the low-temperature drying process, if the temperature is too low, the organic solvent cannot evaporate effectively, resulting in residual organic solvent inside the material. This will cause uneven pore structure and reduce the stability of the material. Through the staged temperature control technology, the temperature is gradually increased and decreased, which can optimize the evaporation rate of the organic solvent in each temperature range, so that the organic solvent can escape from the material more evenly and reduce the residue;

[0055] b. Control of stress release:

[0056] During the drying process, due to temperature changes, thermal stress and shrinkage stress will be generated inside the material. If the temperature change is too drastic and the stress cannot be effectively released, micro cracks may be generated inside the material, which will in turn affect the compressive strength of the material. Through staged temperature control, stress can be gradually released in different temperature ranges to avoid stress concentration, thereby maintaining the structural integrity of the material.

[0057] Table 1 Time and temperature of each stage of segmented temperature-controlled drying treatment

[0058]

[0059] Example 1

[0060] The biocompatible porous material of this embodiment is prepared by the following steps:

[0061] (1) Self-assembly of two-dimensional materials and microcrystalline particles: dissolving the two-dimensional material in a polar solvent to obtain a two-dimensional material solution; dispersing the microcrystalline particles in a polar solvent to obtain a microcrystalline particle solution; adding the two-dimensional material solution to the microcrystalline particle solution for adsorption treatment, and then standing to obtain a self-assembled complex;

[0062] (2) Segmented temperature-controlled drying treatment: separating and washing the self-assembled composite obtained in step (1), and then performing segmented temperature-controlled drying treatment to obtain a two-dimensional material-microcrystal composite;

[0063] (3) dissolution treatment: immersing the two-dimensional material-microcrystal composite obtained in step (2) in an organic solvent to dissolve the microcrystal particles to form a composite with a porous structure;

[0064] (4) Vacuum freeze drying: The porous structured composite obtained in step (3) is subjected to vacuum freeze drying to remove the organic solvent and obtain a biocompatible porous material.

[0065] Wherein, step (1) is specifically as follows:

[0066] (11) Material preparation: Graphene is selected as the two-dimensional material, and the graphene is dissolved in deionized water to ensure that the graphene is evenly dispersed; the ratio of the mass of graphene to the mass of calcium oxalate microcrystalline particles is 1:4;

[0067] (12) Self-assembly:

[0068] (121) Preparation of two-dimensional material solution: weighed graphene is slowly added into deionized water and stirred with a magnetic stirrer for 2 h until the two-dimensional material is evenly dispersed in the deionized water to obtain a graphene solution; if undissolved calcium oxalate microcrystalline particles exist in the graphene solution, the solution is filtered through a 0.2 μm microporous filter membrane to obtain a uniform graphene solution;

[0069] (122) Preparation of microcrystalline particle solution: Calcium oxalate microcrystalline particles were slowly added into deionized water and stirred using a magnetic stirrer to ensure that the microcrystals were evenly dispersed in the deionized water to form a stable calcium oxalate microcrystalline particle solution.

[0070] (123) Self-assembly: The graphene solution was slowly poured into the calcium oxalate microcrystalline particle solution, and the stirring speed was maintained at 600 rpm to ensure uniform mixing; a magnetic stirrer and an ultrasonic cleaner were used for alternating treatments, the stirring speed of the magnetic stirrer was 600 rpm, the treatment time of the magnetic stirrer was 30 minutes, and the treatment time of the ultrasonic cleaner was 10 minutes, so as to promote the uniform adsorption of graphene on the surface of the calcium oxalate microcrystalline particles; after the self-assembly was completed, the mixed solution was allowed to stand for 1 to 2 hours to allow the self-assembled complex to settle to the bottom of the container; the volume ratio of the graphene solution to the calcium oxalate microcrystalline particle solution was 1:3;

[0071] Wherein, step (2) is specifically as follows:

[0072] (21) Centrifugal separation: The self-assembled complex is separated from the mixed solution using a centrifuge at a speed of 5000 rpm for 10 min. The supernatant is discarded and the deposited self-assembled complex is retained.

[0073] (22) Washing and drying: The self-assembled complex is washed with deionized water; the washed self-assembled complex is subjected to a stepwise temperature-controlled drying process, as shown in the flow chart. Figure 2 As shown, a graphene-calcium oxalate microcrystalline particle composite was obtained.

[0074] Wherein, step (3) is specifically as follows:

[0075] (31) Dissolving microcrystals: Soaking the dried graphene-calcium oxalate microcrystal particle complex in glycerol to dissolve the calcium oxalate microcrystal particles; the soaking temperature is controlled at 50°C and the soaking time is 24 hours. Glycerol can effectively dissolve the calcium oxalate microcrystal particles without destroying the structure of graphene.

[0076] (32) Filtration and collection: The product after the dissolution treatment is filtered to obtain a composite with a porous structure.

[0077] Wherein, step (4) is specifically as follows:

[0078] (41) Prefreezing treatment: The composite with a porous structure is prefrozen at a low temperature of -50°C to -80°C until the sample is completely frozen.

[0079] (42) Vacuum freeze drying: The pre-frozen product is placed in a vacuum freeze drying device and dried at a pressure of 0.01 atm to 0.1 atm for 24 to 48 hours to completely remove the glycerol and form a porous material with controllable pore size.

[0080] The method for preparing microcrystalline particles comprises the following steps:

[0081] (100) Material selection: Calcium oxalate (CaC2O4) was selected as microcrystalline particles with different solubility and positive surface charge; calcium oxalate microcrystalline particles are poorly soluble in water but soluble in glycerol;

[0082] (101) Solution preparation: Mix 0.1 mol / L calcium chloride solution and 0.2 mol / L oxalic acid solution to form a uniform solution;

[0083] (102) Spray drying: A spray drying device is used to atomize the solution into tiny droplets; the nozzle diameter is set to 0.2-0.5 mm to control the droplet size and drying speed; during the drying process, an air heater is used to generate a high-temperature airflow of 350°C, and the flow rate is set to 1.0 m / s to ensure that the droplets evaporate quickly to generate calcium oxalate microcrystalline products;

[0084] (103) Microcrystal collection and surface treatment: Collect the calcium oxalate microcrystal product after spray drying; use a low-temperature plasma cleaning method to clean and activate the surface of the calcium oxalate microcrystal product to obtain calcium oxalate microcrystal particles; the cleaning pressure is set to 50 mTorr, high-purity argon is used as the protective gas, and the cleaning time is 30 seconds; this step can effectively remove organic matter and oxide layers on the surface of the microcrystal, thereby improving the surface energy and bonding strength of the material.

[0085] Embodiments 2 to 11

[0086] Same as Example 1, except that the microcrystalline particles and the organic solvent are different, see Table 2 for details.

[0087] Comparative Example 1

[0088] The same as Example 1, except that: in step (2), instead of using a segmented temperature-controlled drying process, drying is performed at 50° C. for 24 h, as shown in Table 3.

[0089] Comparative Examples 2 to 11

[0090] The same as Comparative Example 1, except that the microcrystalline particles and the organic solvent are different, see Table 3 for details.

[0091] The biocompatible porous materials of Examples 1 to 11 and Comparative Examples 1 to 11 were characterized by testing pore size distribution, mechanical strength and biocompatibility, respectively. The test results are shown in Tables 2 and 3. The microscopic morphology of the biocompatible porous material of Example 1 is shown in Figure 1 shown.

[0092] Table 2 Performance results of microcrystalline particles and organic solvents used in Examples 1 to 11 and the prepared porous materials

[0093] Example Microcrystalline particles Organic solvents Pore ​​size distribution / nm Mechanical strength / MPa Biocompatibility 1 <![CDATA[Calcium oxalate (CaC2O4)]]> glycerin 200-400 3.5 excellent 2 <![CDATA[Calcium carbonate (CaCO3)]]> Ethylene glycol 150-350 2.8 good 3 <![CDATA[Magnesium carbonate (MgCO3)]]> glycerin 300-500 3.2 excellent 4 <![CDATA[Magnesium hydroxide (Mg(OH)2)]]> Propylene glycol 400-600 2.5 good 5 <![CDATA[Strontium carbonate (SrCO3)]]> Propylene glycol 600-800 2.4 good 6 <![CDATA[Barium sulfate (BaSO4)]]> Ethanol 500-700 4 medium 7 <![CDATA[Barium carbonate (BaCO3)]]> Ethanol 300-500 3.8 good 8 <![CDATA[Calcium phosphate (Ca3(PO4)2)]]> Dimethyl sulfoxide 200-400 4.2 excellent 9 <![CDATA[Magnesium phosphate (Mg3(PO4)2)]]> glycerin 500-1000 3 excellent 10 <![CDATA[Calcium silicate (CaSiO3)]]> Dimethyl sulfoxide 1000-1500 3.1 good 11 <![CDATA[Magnesium silicate (MgSiO3)]]> Ethylene glycol 200-400 2.9 good

[0094] Table 3 Performance results of the microcrystalline particles and organic solvents used in Comparative Examples 1 to 11 and the prepared porous materials

[0095] Comparative Example Microcrystalline particles Organic solvents Pore ​​size distribution nm Mechanical strength MPa Biocompatibility 1 <![CDATA[Calcium oxalate (CaC2O4)]]> glycerin 200-400 1.56 excellent 2 <![CDATA[Calcium carbonate (CaCO3)]]> Ethylene glycol 150-350 1.24 good 3 <![CDATA[Magnesium carbonate (MgCO3)]]> glycerin 300-500 1.62 excellent 4 <![CDATA[Magnesium hydroxide (Mg(OH)2)]]> Propylene glycol 400-600 1.21 good 5 <![CDATA[Strontium carbonate (SrCO3)]]> Propylene glycol 600-800 1.16 good 6 <![CDATA[Barium sulfate (BaSO4)]]> Ethanol 500-700 2.17 medium 7 <![CDATA[Barium carbonate (BaCO3)]]> Ethanol 300-500 2.06 good 8 <![CDATA[Calcium phosphate (Ca3(PO4)2)]]> Dimethyl sulfoxide 200-400 2.16 excellent 9 <![CDATA[Magnesium phosphate (Mg3(PO4)2)]]> glycerin 500-1000 1.31 excellent 10 <![CDATA[Calcium silicate (CaSiO3)]]> Dimethyl sulfoxide 1000-1500 1.48 good 11 <![CDATA[Magnesium silicate (MgSiO3)]]> Ethylene glycol 200-400 1.43 good

[0096] By comparing Table 2 and Table 3, it can be found that the porous materials in the embodiments using segmented temperature-controlled drying are generally higher than those in the control group in terms of mechanical strength. Specifically, the mechanical strength range in Table 2 is 2.4-4MPa, while the mechanical strength of the control group in Table 3 is only 1.16-2.17MPa. This shows that the segmented temperature-controlled drying process effectively reduces the residual stress inside the material and promotes the formation of a more uniform pore structure, thereby significantly improving the compressive strength of the material. Segmented low-temperature drying helps to better control the pore size distribution. The pore size distribution ranges in Table 2 and Table 3 are basically the same, indicating that the process can achieve a better balance between high mechanical strength and pore structure stability while maintaining the desired pore size distribution. This means that segmented low-temperature drying does not sacrifice the uniformity of pore size distribution, but rather better maintains the stability of the pore structure by optimizing the evaporation of organic solvents and stress release during the drying process. Whether it is an embodiment or a comparative example using segmented low-temperature drying, its biocompatibility evaluation is "excellent" or "good", indicating that segmented low-temperature drying will not have a negative impact on the biocompatibility of the material. Instead, it ensures that the material retains high mechanical strength while still maintaining good biocompatibility.

[0097] In addition, the segmented temperature-controlled drying process optimizes the evaporation rate of the organic solvent and reduces the possibility of organic solvent residue by adjusting the temperature at different stages. Excessive organic solvent residue may lead to uneven pore structure and decreased mechanical strength, and the data in Table 2 show that this process significantly reduces these negative effects, thereby enhancing the mechanical properties of the final material. Segmented low-temperature drying makes stress release during the drying process more uniform. Through slow temperature changes, stress concentration and microcrack formation inside the material are reduced, which is of great significance in improving the mechanical strength and long-term stability of the material. The mechanical strength data in Table 2 is higher than that of the control group in Table 3, which is the result of effective stress release by the segmented temperature-controlled drying process.

[0098] The segmented temperature-controlled drying process provides a high degree of process controllability, and the temperature settings of each stage can be flexibly adjusted according to the characteristics of different materials (such as the type of microcrystalline particles, the properties of organic solvents, etc.), thereby achieving precise control of the final material properties. This makes the process have a wide range of application potentials and can meet the preparation needs of a variety of biocompatible porous materials.

[0099] The test methods of the present invention for pore size distribution, mechanical strength and biocompatibility are as follows:

[0100] (1) Pore size distribution test of porous materials

[0101] The BET (Brunauer-Emmett-Teller) method is a commonly used surface area and pore analysis method that can be used to measure the porosity of thin film materials. Ensure that the BET instrument is operating properly and calibrated and debugged according to the instrument instructions. Prepare the film sample to be tested and cut it into appropriate sizes to fit the sample holder of the test instrument. Place the film sample on the sample holder of the BET instrument, ensuring that the sample surface is smooth and has no obvious defects. Start the nitrogen adsorption process and gradually inject nitrogen into the sample at a low temperature (usually liquid nitrogen temperature) so that nitrogen is adsorbed on the sample surface. Control the gas flow rate and pressure during the adsorption process to ensure the appropriate adsorption amount and steady state. During the adsorption process, record the data of nitrogen pressure and adsorption amount to draw the adsorption isotherm curve. According to the adsorption isotherm curve, determine the relationship between the adsorption amount and the relative pressure of nitrogen for subsequent calculation of surface area and porosity. Use the BET theory to calculate the specific surface area of ​​the film material. Based on the definition of porosity (the ratio of pore volume to total volume), the porosity of the film is calculated according to the specific surface area and film thickness.

[0102] (2) Mechanical strength test of porous materials

[0103] The mechanical strength test of porous materials usually adopts the compressive strength test method. First, prepare the porous material powder sample to be tested, seal it into a regular geometric shape (such as a cube or cylinder), ensure that the sample surface is smooth and has no obvious defects, and use a multifunctional material mechanical properties testing platform for testing. Calibrate and debug according to the instrument instructions, including applying the initial load and adjusting the measuring device to ensure accuracy. Place the prepared sample on the test bench of the compression testing machine, ensure that the position of the sample is correct and stable, and align its axial direction with the direction of applied pressure. Start the compression testing machine, gradually apply pressure at the set loading speed (1-5mm / min), and record the change of pressure over time. Observe and record the deformation behavior of the sample under gradually increasing pressure until the sample breaks or reaches the preset deformation standard. According to the maximum destructive force (N) and the cross-sectional area (m 2 ), the compressive strength (MPa) of the material is calculated to indicate its mechanical strength under the porous structure. By comparing the compressive strength of different samples, the mechanical properties of the porous material are evaluated to ensure its reliability and stability in practical applications.

[0104] (3) Biocompatibility testing

[0105] First, select a suitable cell line (L929 mouse fibroblasts) for culture, use an appropriate culture medium (DMEM culture medium) and keep the cells cultured at 37°C and 5% CO2 to maintain normal cell growth. Prepare the porous material sample to be tested into an appropriate size, ensure that the sample surface is free of contamination, and perform sterilization (such as by ultraviolet irradiation or sterilization with ethylene oxide). Soak the porous material sample in sterile saline or cell culture medium, and follow the liquid volume to sample surface area ratio specified in the ISO 10993 standard (1mL extract: 1cm 2 The sample area) is extracted, and the extraction time is usually 24 hours, and the temperature is maintained at 37°C. Then, the extract is mixed with the cultured cells to ensure that the extract covers all cells in the cell culture plate, and positive and negative controls are set to ensure the accuracy of the test results. After 24 hours of exposure, an inverted microscope is used to observe cell morphological changes, such as cell contraction, changes in cell membrane integrity and cell density, and the observed cell responses are recorded. Subsequently, the metabolic activity of the cells is determined using the MTT method or other colorimetric methods, and the cell survival rate is determined by measuring the cell absorbance value. The cell survival rate of the experimental group is compared with that of the control group, and the effect of the porous material on cell activity is analyzed to determine the biocompatibility of the material. If the survival rate is 60% to 70%, the biocompatibility of the material is considered to be moderate. If the survival rate is 70% to 80%, the biocompatibility of the material is considered to be good. If the survival rate is higher than 80%, the biocompatibility of the material is considered to be excellent.

Claims

1. A method for preparing a biocompatible porous material, characterized in that: The steps include: (1) Self-assembly of two-dimensional materials and microcrystalline particles: dissolving the two-dimensional material in a polar solvent to obtain a two-dimensional material solution; dispersing the microcrystalline particles in a polar solvent to obtain a microcrystalline particle solution; adding the two-dimensional material solution to the microcrystalline particle solution for adsorption treatment, and then standing to obtain a self-assembled complex; (2) Segmented temperature-controlled drying treatment: separating and washing the self-assembled composite obtained in step (1), and then performing segmented temperature-controlled drying treatment to obtain a two-dimensional material-microcrystal composite; (3) dissolution treatment: immersing the two-dimensional material-microcrystal composite obtained in step (2) in an organic solvent to dissolve the microcrystal particles to obtain a composite with a porous structure; (4) Vacuum freeze drying: The porous structured composite obtained in step (3) is subjected to vacuum freeze drying to remove the organic solvent and obtain a biocompatible porous material.

2. The preparation method according to claim 1, characterized in that: The microcrystalline particles are calcium oxalate, calcium carbonate, magnesium carbonate, magnesium hydroxide, strontium carbonate, barium sulfate, barium carbonate, calcium phosphate, magnesium phosphate, calcium silicate or magnesium silicate; the diameter of the microcrystalline particles ranges from 100nm to 1000nm.

3. The preparation method according to claim 1, characterized in that: The method for preparing the microcrystalline particles comprises the following steps: (101) mixing the metal salt solution and the weak acid solution to form a uniform solution; (102) Using a spray drying device, the solution is atomized into tiny droplets through a nozzle and dried in a high-temperature airflow. The droplets evaporate during the drying process and naturally settle to form microcrystalline products; (103) The microcrystalline product obtained in step (102) is collected, and then surface impurities are removed and activated to obtain microcrystalline particles.

4. The preparation method according to claim 3, characterized in that: In step (102), the nozzle diameter of the spray drying equipment is 0.2-0.5 mm, and the high-temperature airflow is a high-temperature airflow of 350° C. generated by an air heater with a flow rate of 1.0 m / s; in step (103), the surface decontamination and activation are carried out in a low-temperature plasma cleaning equipment, the cleaning pressure is 50 mTorr, the protective gas is high-purity argon, and the cleaning time is 30 s.

5. The preparation method according to claim 1, characterized in that: In step (1), the two-dimensional material is graphene, transition metal disulfide or transition metal carbonitride, the polar solvent is one or more of water, ethanol, isopropanol and acetone; the ratio of the mass of the two-dimensional material to the mass of the microcrystalline particles is 1:(3-5); the volume ratio of the two-dimensional material solution to the microcrystalline particle solution is 1:3; the dissolution is to slowly add the two-dimensional material into the polar solvent and stir it with a magnetic stirrer for 2 hours; The dispersion is stirred using a magnetic stirrer; the adsorption treatment is performed by alternating treatment using a magnetic stirrer and an ultrasonic cleaner, the stirring speed of the magnetic stirrer is 600 rpm, the treatment time of the magnetic stirrer is 30 minutes, and the treatment time of the ultrasonic cleaner is 10 minutes; the standing time is 1 to 2 hours.

6. The preparation method according to claim 1, characterized in that: Step (1) also includes filtering the two-dimensional material solution using a microporous filter membrane to remove undispersed microcrystalline particles; the pore size of the microporous filter membrane is 0.2 μm.

7. The preparation method according to claim 1, characterized in that: In step (2), the separation is performed using a centrifuge at a speed of 5000 rpm for 10 minutes, the supernatant after centrifugation is discarded, and the deposited complex is retained; and the washing is performed by washing the self-assembled complex with deionized water.

8. The preparation method according to claim 1, characterized in that: In step (2), the segmented temperature-controlled drying process is divided into eight stages, which include: Stage 1: The temperature rises from 30°C to 60°C for 1 hour; Stage 2: The temperature is maintained at 60°C for 2 hours; Stage 3: The temperature drops from 60°C to 45°C for 1 hour; Stage 4: The temperature is maintained at 45°C for 8 hours; Stage 5: The temperature rises from 45°C to 55°C for 1 hour; Stage 6: The temperature is maintained at 55°C for 3 hours; Stage 7: The temperature drops from 55°C to 40°C for 1 hour; Stage 8: The temperature is maintained at 40°C for 8 hours.

9. The preparation method according to claim 1, characterized in that: In step (3), the organic solvent is glycerol, ethylene glycol, propylene glycol or dimethyl sulfoxide; the soaking temperature is room temperature to 50° C., and the soaking time is 6 to 12 hours.

10. The preparation method according to claim 1, characterized in that: In step (4), the vacuum freeze drying is carried out at a temperature of -50°C to -80°C, a pressure of 0.01atm to 0.1atm, and a drying time of 24 to 48 hours.

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