Srco3@zif-8 / polymer composite bone scaffold and preparation method thereof

Abstract

The application discloses a SrCO3@ZIF-8 / polymer composite bone scaffold and a preparation method thereof, and comprises the following steps: growing zeolite imidazolate framework-8 (ZIF-8) on the surface of SrCO3 in situ to prepare SrCO3@ZIF-8 microrods, uniformly mixing the SrCO3@ZIF-8 microrods and a polymer material through grinding, and preparing the SrCO3@ZIF-8 / polymer composite bone scaffold by using a selective laser sintering technology. The SrCO3@ZIF-8 / polymer composite bone scaffold obtained by the application is applied to bone defect repair, and the Zn ions and Sr ions generated by in-vivo degradation of the scaffold can promote the differentiation of stem cells into osteoblasts, endow the scaffold with osteogenic activity, promote the polarization of macrophages into M2 type and the expression of related anti-inflammatory factors, and strengthen the anti-inflammatory performance of the scaffold. In addition, the ZIF-8 contains a large number of 2-methyl imidazole organic ligands, can form a strong interface with the molecular chain of the polymer, solves the problem of interface incompatibility between SrCO3 and the polymer, and thus improves the mechanical performance of the scaffold.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biomedical materials, more particularly, the present application relates to a SrCO3@ZIF-8 / polymer composite bone scaffold and a preparation method thereof. BACKGROUND

[0002] Bone defect as a common orthopedic disease is often repaired and treated by bone transplantation. Although autologous bone transplantation is the "gold standard" for bone defect repair, it has problems such as scarcity of quantity and increase of surgical time, which increases the risk of iatrogenic injury. Therefore, bone defect repair by allogeneic bone transplantation has great prospects. In allogeneic bone transplantation, artificial bone scaffold is undoubtedly an ideal substitute, which can be prepared by 3D printing and other technologies. Such scaffold can be completely matched with the shape of bone defect.

[0003] At present, high molecular materials are often selected to prepare bone scaffolds, which have high mechanical strength and rigidity, and the degradation products can be metabolized by the human body. However, since the high molecular material has no active group, it does not have osteogenic activity, which limits its application in bone defect repair. Strontium carbonate (SrCO3) as a biological ceramic material has good biological activity and osteogenic ability. The Sr ion in it can promote the differentiation of stem cells into osteoblasts and inhibit the production of osteoclasts. However, there is a big gap in the physical and chemical properties between SrCO3 and high molecular, which can easily cause adverse interface bonding, resulting in the decrease of the mechanical properties of the prepared bone scaffold.

[0004] In order to solve this problem, in recent years, people have proposed many strategies, such as surface coating of compatible phase and grafting of active groups. Although these strategies can increase the interface bonding between ceramic particles and polymer matrix to some extent, the new interface produced by coating and the short interaction time produced by grafting weaken the strengthening effect.

[0005] In-situ growth technology is a method that uses the surface of a pretreated carrier as a chemical reaction zone, places it in a reaction environment, and synchronously nucleates, grows and films on the substrate surface by hydrothermal or solvothermal synthesis. Since the compatible phase grown in-situ does not produce a new interface and does not have the problem of short interaction time, it is a promising method to realize strong interface bonding between ceramic materials and high molecular matrix by growing compatible phase on the surface of ceramic particles. Metal organic framework (MOFs) is an excellent interface compatible phase. In MOFs, zeolitic imidazolate framework-8 (ZIF-8) has attracted widespread attention in biomedical applications due to its good biocompatibility, degradability and high specific surface area. SUMMARY

[0006] An object of the present application is to solve at least the above problems and / or disadvantages and to provide at least the advantages described later.

[0007] To achieve these objects and other advantages and in view of its purposes, the present application provides a SrCO3@ZIF-8 / polymer composite bone scaffold and a preparation method thereof. First, a zinc-based metal organic framework ZIF-8 is wrapped on the surface of SrCO3 to prepare a SrCO3@ZIF-8 microrod by in-situ growth. Then, the SrCO3@ZIF-8 microrod and a polymer material are uniformly mixed by grinding in a predetermined ratio. Finally, a SrCO3@ZIF-8 / polymer composite bone scaffold is prepared by selective laser sintering.

[0008] Preferably, the polymer material is at least one of a poly-L-lactic acid (PLLA) powder, a poly-D-lactic acid (PDLA) powder, a polyglycolic acid (PGA) powder, a polycaprolactone (PCL) powder, a poly-lactic-co-glycolic acid (PLGA) powder, and a poly-p-dioxanone (PPDO) powder.

[0009] Preferably, in the SrCO3@ZIF-8 / polymer composite bone scaffold, the mass fraction of SrCO3@ZIF-8 is 0.7-2.8 wt%, the mass fraction of the polymer is 97.2-99.3 wt%, the diameter of the SrCO3@ZIF-8 microrod is 1-3 μm, the length of the SrCO3@ZIF-8 microrod is 8-16 μm, and the particle size of the polymer material is 0.1-100 μm.

[0010] A preparation method of a SrCO3@ZIF-8 / polymer composite bone scaffold includes the following steps.

[0011] In step one, ZIF-8 is grown on the surface of strontium carbonate to synthesize a SrCO3@ZIF-8 microrod. The specific method includes: adding strontium carbonate to methanol, dispersing by ultrasonic, and obtaining a mixed solution, denoted as solution A; dissolving zinc nitrate hexahydrate in methanol, denoted as solution B; dissolving 2-methylimidazole in methanol, denoted as solution C; stirring solution A, adding solution B to solution A, and then slowly adding solution C to the mixed solution of solutions A and B at a rate of 500 μL per minute, continuing to stir for 5-6 hours after the addition is completed, obtaining a white suspension, and washing the obtained product by high-speed centrifugation with methanol for three times, and drying to obtain a SrCO3@ZIF-8 microrod.

[0012] In step two, a certain amount of SrCO3@ZIF-8 microrod and polymer material are weighed in a predetermined mass ratio, placed in a grinding bowl, and ground for 20-30 min to fully mix the powders, obtaining a SrCO3@ZIF-8 / polymer composite powder.

[0013] Step three, the SrCO3@ZIF-8 / polymer composite powder is placed in a selective laser sintering system, an appropriate three-dimensional model is selected, the composite powder is uniformly laid on the substrate, and layer-by-layer sintering is performed, and after sintering is completed, the unsintered powder is removed, and finally a SrCO3@ZIF-8 / polymer composite bone scaffold is obtained.

[0014] Preferably, in the step one, the mass-volume ratio of strontium carbonate and methanol in solution A is 0.122g:70-90mL; the mass-volume ratio of zinc nitrate hexahydrate and methanol in solution B is 0.192g:10-20mL; the mass-volume ratio of 2-methylimidazole and methanol in solution C is 0.212g:50-70mL; the stirring speed is 500-1500r / min, the centrifugal washing speed is 11000-12000r / min, and the drying temperature is 50-70℃, and the drying time is 22-26 hours.

[0015] Preferably, in the step three, in the selective laser sintering process, the process parameters of selective laser sintering are as follows: the laser power is 1-3W, the scanning speed is 200-300mm / s, the scanning interval is 0.1-1.0mm, the spot diameter is 0.3-1.0mm, and the powder laying thickness of the composite powder is 0.05-0.1mm.

[0016] Preferably, the porosity of the prepared SrCO3@ZIF-8 / polymer composite bone scaffold is 50-60%, and the pore size is 200-500μm.

[0017] Preferably, the prepared SrCO3@ZIF-8 / polymer composite bone scaffold is applied to bone defect repair.

[0018] The present application at least includes the following beneficial effects: the SrCO3@ZIF-8 / polymer composite bone scaffold provided by the present application can generate Zn ions and Sr ions in vivo degradation, the Zn ions and Sr ions can synergistically promote the differentiation of stem cells into osteoblasts, inhibit the generation of osteoclasts, and can promote the polarization expression of M2 type related anti-inflammatory factors of macrophages, prevent excessive inflammatory reaction from affecting bone regeneration and repair, and solve the problem that the polymer does not have osteogenic and anti-inflammatory properties. At the same time, because ZIF-8 contains a large amount of organic ligand, it can solve the problem of interface incompatibility between SrCO3 and polymer, so that it has good mechanical properties. The scaffold prepared by using selective laser sintering technology can meet the customized demand, and a bone scaffold with suitable porosity and pore size can be designed, which is beneficial to the degradation, cell adhesion and exchange of nutrients and metabolites after implantation.

[0019] An object of the present application is to solve the problem of interface incompatibility between ceramic materials and polymer materials. By in-situ growth technology, ZIF-8 is wrapped on SrCO3, and because ZIF-8 contains a large amount of 2-methyl imidazole organic ligand, the imidazole ring can form a strong interface with the molecular chain of the polymer, and at the same time, the negative Zeta potential of SrCO3 in the solution can adsorb positively charged zinc ions, promoting the heterogeneous nucleation and in-situ growth of ZIF-8 on SrCO3, thereby solving the problem of significant reduction in the mechanical properties of the scaffold due to the interface incompatibility between SrCO3 and the polymer.

[0020] Another object of the present application is to improve the osteogenesis and anti-inflammatory performance of the scaffold. Because the SrCO3@ZIF-8 / polymer composite bone scaffold generates Zn ions and Sr ions during in-vivo degradation, the Zn ions and Sr ions can promote the differentiation of stem cells into osteoblasts, so that the scaffold has osteogenesis performance; furthermore, the Zn ions and Sr ions can also synergistically promote the polarization of macrophages into M2 type and express related anti-inflammatory factors, prevent the inflammation reaction caused by the 'protection mechanism' of macrophages when the scaffold is implanted into the bone defect, and because excessive inflammation reaction can promote the differentiation of inflammatory osteoclast precursors into highly active osteoclasts, the scaffold prepared by the present application has certain anti-inflammatory performance and can also inhibit the formation of osteoclasts to prevent the surface of the scaffold from being dissolved by true bone.

[0021] Other advantages, objects and features of the present application will be partly embodied in the following description, and will also be understood by those skilled in the art through research and practice of the present application. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 A scanning electron microscope image of the SrCO3@ZIF-8 microrod prepared in Example 1;

[0023] Figure 2 A schematic diagram of the model of the bone scaffold prepared in Example 1;

[0024] Figure 3 A scanning electron microscope image of the section of the PLLA bone scaffold prepared in Comparative Example 1;

[0025] Figure 4 A scanning electron microscope image of the section of the SrCO3 / PLLA bone scaffold prepared in Comparative Example 2;

[0026] Figure 5 A scanning electron microscope image of the section of the SrCO3@ZIF-8 / PLLA bone scaffold prepared in Example 1;

[0027] Figure 6Compression stress-strain curves of SrCO3@ZIF-8 / PLLA bone scaffold prepared in Example 1, PLLA bone scaffold of Comparative Example 1 and SrCO3 / PLLA bone scaffold of Comparative Example 2;

[0028] Figure 7 Expression of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) of SrCO3@ZIF-8 / PLLA bone scaffold prepared in Example 1, PLLA bone scaffold of Comparative Example 1 and SrCO3 / PLLA bone scaffold of Comparative Example 2 after co-cultured with mouse monocyte macrophage leukemia cells (RAW264.7) for 3 days was detected by RT-qPCR;

[0029] Figure 8 Cell counting (CCK-8) results of SrCO3@ZIF-8 / PLLA bone scaffold prepared in Example 1, PLLA bone scaffold of Comparative Example 1 and SrCO3 / PLLA bone scaffold of Comparative Example 2 after co-cultured with mouse bone marrow mesenchymal stem cells (mBMSCs) for 1 day and 3 days;

[0030] Figure 9 Alkaline phosphatase (ALP) staining results of PLLA bone scaffold prepared in Comparative Example 1 after co-cultured with mBMSCs for 7 days;

[0031] Figure 10 Alkaline phosphatase (ALP) staining results of SrCO3 / PLLA bone scaffold prepared in Comparative Example 2 after co-cultured with mBMSCs for 7 days;

[0032] Figure 11 Alkaline phosphatase (ALP) staining results of SrCO3@ZIF-8 / PLLA bone scaffold prepared in Example 1 after co-cultured with mBMSCs for 7 days. DETAILED DESCRIPTION

[0033] The application will be further described in conjunction with the accompanying drawings, so that those skilled in the art can implement the application according to the description and drawings.

[0034] It should be understood that the terms such as "have", "contain" and "include" used herein do not exclude the presence or addition of one or more other elements or combinations thereof.

[0035] Example 1:

[0036] The present embodiment provides a preparation method of SrCO3@ZIF-8 / polymer composite bone scaffold, comprising the following steps:

[0037] Step one, preparation of SrCO3@ZIF-8 microrods by in-situ growth: 0.122 g of strontium carbonate was added to 80 mL of methanol and dispersed by ultrasonic, and the resulting mixed solution was denoted as solution A. 0.192 g of zinc nitrate hexahydrate was dissolved in 15 mL of methanol solution, denoted as solution B. 0.212 g of 2-methylimidazole was dissolved in 60 mL of methanol solution, denoted as solution C. Solution A was stirred at a speed of 1000 r / min, and solution B was added to solution A, and solution C was slowly added to the mixed solution of solution A and B at a speed of 500 μL per minute, and after the addition was completed, the stirring was continued for 5-6 hours to obtain a white suspension. The obtained product was washed by high-speed centrifugation with methanol for three times, and dried at 60°C for 24 hours to obtain SrCO3@ZIF-8 microrods. The scanning electron microscope image of the SrCO3@ZIF-8 microrods is shown in Figure 1

[0038] Step two, preparation of composite powder: SrCO3@ZIF-8 microrods and poly-L-lactic acid (PLLA) were mixed according to a mass ratio of 7:993 (the content of SrCO3@ZIF-8 was 0.7%), and placed in a grinding bowl for grinding for 20 min to fully mix the powders, to obtain SrCO3@ZIF-8 / PLLA composite powder;

[0039] Step three, 3D printing step: an Autodesk Inventor three-dimensional modeling software was used to design a scaffold model with a size of Φ6×1.5 mm and a porosity of 50%, as shown in Figure 2 The scaffold model was saved in the.stl format. The scaffold model was imported into the control software 3DPrinter of the selective laser sintering printing system, and the printing parameters were set as follows: spot diameter 300 μm, laser power 1.2 W, and scanning speed 300 mm / s. The uniformly mixed composite powder was uniformly spread on the substrate, and the powder spreading thickness was 0.05 mm. After layer-by-layer sintering, a 0.7% SrCO3@ZIF-8 / PLLA composite bone scaffold was obtained.

[0040] Example 2

[0041] The present embodiment provides a preparation method of a SrCO3@ZIF-8 / polymer composite bone scaffold, comprising the following steps:

[0042] ​Step one, preparation of SrCO3@ZIF-8 microrods by in-situ growth: 0.122g of strontium carbonate was added to 80mL of methanol and dispersed by ultrasonic, and the resulting mixed solution was denoted as solution A. 0.192g of zinc nitrate hexahydrate was dissolved in 15mL of methanol solution, denoted as solution B. 0.212g of 2-methylimidazole was dissolved in 60mL of methanol solution, denoted as solution C. Solution A was stirred at a speed of 1500r / min, and solution B was added to solution A, and solution C was slowly added to the mixed solution of solution A and B at a speed of 500μL per minute, and after the addition was completed, the stirring was continued for 5-6 hours to obtain a white suspension. The obtained product was washed by high-speed centrifugation with methanol for three times, and dried at 60℃ for 24 hours to obtain SrCO3@ZIF-8 microrods;

[0043] Step two, preparation of composite powder: SrCO3@ZIF-8 microrods and poly-L-lactic acid (PLLA) were mixed according to a mass ratio of 7:493 (the content of SrCO3@ZIF-8 was 1.4%), and placed in a grinding bowl for grinding for 30min to fully mix the powders, to obtain SrCO3@ZIF-8 / PLLA composite powder;

[0044] Step three, 3D printing step: a scaffold model with a size of Φ6×1.5mm and a porosity of 50% was designed by Autodesk Inventor three-dimensional modeling software, and the scaffold model was saved as a.stl format. The scaffold model was imported into the control software 3DPrinter of the selective laser sintering printing system, and the printing parameters were set as follows: spot diameter 700μm, laser power 2W, scanning speed 200mm / s. The uniformly mixed composite powder was uniformly spread on the substrate, and the powder thickness was 0.05mm. After layer-by-layer sintering, a 1.4% SrCO3@ZIF-8 / PLLA composite bone scaffold was obtained.

[0045] Example 3:

[0046] The embodiment provides a preparation method of a SrCO3@ZIF-8 / polymer composite bone scaffold, comprising the following steps:

[0047] Step one, preparation of SrCO3@ZIF-8 microrods by in-situ growth: 0.122 g of strontium carbonate was added to 80 mL of methanol and dispersed by ultrasonic, and the resulting mixed solution was denoted as solution A. 0.192 g of zinc nitrate hexahydrate was dissolved in 15 mL of methanol solution, denoted as solution B. 0.212 g of 2-methylimidazole was dissolved in 60 mL of methanol solution, denoted as solution C. Solution A was stirred at a speed of 1000 r / min, and solution B was added to solution A, and solution C was slowly added to the mixed solution of solution A and B at a rate of 500 μL per minute, and after the addition was completed, the stirring was continued for 5-6 hours to obtain a white suspension. The obtained product was washed by high-speed centrifugation with methanol for three times, and dried at 60°C for 24 hours to obtain SrCO3@ZIF-8 microrods;

[0048] Step two, preparation of composite powder: SrCO3@ZIF-8 microrods and poly-L-lactic acid (PLLA) were mixed according to a mass ratio of 7:243 (the content of SrCO3@ZIF-8 was 2.8%), and placed in a grinding bowl for grinding for 20 min to fully mix the powders, to obtain SrCO3@ZIF-8 / PLLA composite powder;

[0049] Step three, 3D printing step: an Autodesk Inventor three-dimensional modeling software was used to design a scaffold model with a size of Φ6×1.5 mm and a porosity of 50%, and the scaffold model was saved in the.stl format. The scaffold model was imported into the control software 3DPrinter of the selective laser sintering printing system, and the printing parameters were set as follows: light spot diameter 1.0 mm, laser power 3 W, scanning speed 300 mm / s. The uniformly mixed composite powder was evenly spread on the substrate, and the powder thickness was 0.1 mm. After layer-by-layer sintering, a 2.8% SrCO3@ZIF-8 / PLLA composite bone scaffold was obtained.

[0050] Comparative Example 1

[0051] This comparative example provides a preparation method of a PLLA (poly-L-lactic acid) bone scaffold. In this comparative example, 100 wt% of PLLA was used as a raw material to prepare a PLLA bone scaffold, which comprises the following steps:

[0052] Step one, the PLLA powder was placed in a grinding bowl and ground for 10 min to fully mix the powders, to obtain uniformly mixed PLLA powder;

[0053] Step two, 3D printing step: a scaffold model with a size of Φ6x1.5mm and a porosity of 50% is designed by Autodesk Inventor three-dimensional modeling software, and the scaffold model is saved in.stl format. The scaffold model is imported into the control software 3DPrinter of the selective laser sintering printing system, and the printing parameters are set as follows: spot diameter 300μm, laser power 1.2W, and scanning speed 300mm / s. The uniformly mixed PLLA powder is uniformly laid on the substrate, and the powder laying thickness is 0.05mm. After layer-by-layer sintering, the PLLA bone scaffold is obtained.

[0054] Comparative Example 2:

[0055] The present comparative example provides a preparation method of SrCO3 / PLLA bone scaffold. The present comparative example uses 99.58wt% PLLA and 0.42wt% SrCO3 as raw materials to prepare the SrCO3 / PLLA bone scaffold, which comprises the following steps:

[0056] Step one, the PLLA powder and the SrCO3 powder are placed in a grinding bowl and ground for 20min to fully mix the powders, obtaining uniformly mixed SrCO3 / PLLA powder;

[0057] Step two, 3D printing step: a scaffold model with a size of Φ6x1.5mm and a porosity of 50% is designed by Autodesk Inventor three-dimensional modeling software, and the scaffold model is saved in.stl format. The scaffold model is imported into the control software 3DPrinter of the selective laser sintering printing system, and the printing parameters are set as follows: spot diameter 300μm, laser power 1.2W, and scanning speed 300mm / s. The uniformly mixed SrCO3 / PLLA powder is uniformly laid on the substrate, and the powder laying thickness is 0.05mm. After layer-by-layer sintering, the SrCO3 / PLLA bone scaffold is obtained.

[0058] The SrCO3@ZIF-8 / PLLA bone scaffold prepared in the present example 1 and the PLLA bone scaffold and the SrCO3 / PLLA bone scaffold prepared in the comparative example are respectively subjected to brittle fracture in liquid nitrogen, and the fracture surfaces are photographed by scanning electron microscopy. The fracture surface electron micrographs of the scaffolds in each group are shown in Figures 3-5 As can be seen from the photographs, the surface of the PLLA bone scaffold at the fracture surface is smooth; SrCO3 particles can be observed at the fracture surface of the SrCO3 / PLLA bone scaffold, and there is no obvious combination and interaction between the SrCO3 particles and the PLLA matrix; SrCO3@ZIF-8 particles can be observed embedded in the PLLA matrix at the fracture surface of the SrCO3@ZIF-8 / PLLA bone scaffold. The results show that ZIF-8 as an interfacial compatible phase can solve the problem of interfacial incompatibility between SrCO3 and the PLLA matrix.

[0059] The compressive strength of the SrCO3@ZIF-8 / PLLA bone scaffold prepared in this Example 1 and the PLLA bone scaffold and the SrCO3 / PLLA bone scaffold prepared in the comparative example were tested by a universal mechanical testing machine, wherein the loading rate was set to 1.0 mm / min during the test, and the stress-strain curve results of each group of scaffolds are shown in Figure 6 It can be seen that the compressive stress of the three groups of scaffolds first increases with the increase of strain until the yield strength is reached, and then gradually decreases. In addition, the compressive strength of the PLLA, SrCO3 / PLLA and SrCO3@ZIF-8 / PLLA bone scaffolds can be obtained from the stress-strain curve, which is 20.07 Mpa, 15.21 Mpa and 21.93 Mpa, respectively. The compressive strength of the SrCO3 / PLLA bone scaffold is the worst, which is due to the incompatibility of the interface between SrCO3 and the PLLA matrix, while the compressive strength of the SrCO3@ZIF-8 / PLLA bone scaffold is significantly higher than that of the SrCO3 / PLLA bone scaffold, which can be inferred that there is a good interface between SrCO3@ZIF-8 and the PLLA matrix.

[0060] The SrCO3@ZIF-8 / PLLA bone scaffold prepared in this Example 1 and the PLLA bone scaffold and the SrCO3 / PLLA bone scaffold prepared in the comparative example were used for the experiment of the expression of inflammation-related genes of mouse mononuclear macrophage leukemia cells (RAW264.7). First, 150 mg of sterilized PLLA bone scaffold, SrCO3 / PLLA bone scaffold and SrCO3@ZIF-8 / PLLA bone scaffold were added to 6 mL of high-sugar medium containing 10% fetal bovine serum (FBS), and soaked in a 37°C environment for 1 day. The scaffolds were taken out to obtain the extraction solution. RAW264.7 cells were seeded in a 6-well plate at a density of 2.0×10 5 Figure 7 ​The results are shown in FIG. 6. It can be seen that TNF-a, as a pro-inflammatory factor, was down-regulated in the PLLA, SrCO3 / PLLA and SrCO3@ZIF-8 / PLLA groups in turn, and IL-10, as an anti-inflammatory factor, was up-regulated in the PLLA, SrCO3 / PLLA and SrCO3@ZIF-8 / PLLA groups in turn, and the up-regulation in the SrCO3@ZIF-8 / PLLA group was more significant. It can be inferred that the SrCO3 / PLLA bone scaffold and the SrCO3@ZIF-8 / PLLA bone scaffold both have anti-inflammatory properties, and the anti-inflammatory effect of the SrCO3@ZIF-8 / PLLA bone scaffold is more excellent due to the synergistic effect of Sr ions and Zn ions during the degradation of the SrCO3@ZIF-8 / PLLA bone scaffold.

[0061] Biocompatibility experiments and pro-osteogenic experiments were performed on the SrCO3@ZIF-8 / PLLA bone scaffold prepared in Example 1 and the PLLA bone scaffold and the SrCO3 / PLLA bone scaffold prepared in the comparative example, and mouse bone marrow mesenchymal stem cells (mBMSCs) were selected as the cells. Biocompatibility experiment: first, 150 mg of sterilized PLLA bone scaffold, SrCO3 / PLLA bone scaffold and SrCO3@ZIF-8 / PLLA bone scaffold were added to 6 mL of high-sugar medium containing 10% fetal bovine serum (FBS) and soaked in a 37°C environment for 1 day. The scaffolds were taken out to obtain the extraction solution. The mBMSCs cells were seeded in a 96-well plate at a density of 1500 cells per well, and after 1 day of culture, the culture medium was aspirated, the extraction solution was added, and the culture was continued for 1 day and 3 days. Cell counting reagent (CCK-8) was added, and the absorbance was measured at 450 nm. The results are shown in FIG. 5. Figure 8 It can be seen that the three groups of scaffolds all have good biocompatibility. At 3 days, the OD values of the SrCO3 / PLLA and SrCO3@ZIF-8 / PLLA groups are greater than that of the PLLA group, and the OD value of the SrCO3@ZIF-8 / PLLA group is the largest. The results show that Sr ions have a good effect of promoting the proliferation of mBMSCs cells, and the synergistic effect of Sr ions and Zn ions is more significant. Alkaline phosphatase (ALP) staining experiment: mBMSCs cells were seeded in a 48-well plate at a density of 1.0 x 10 4 absorbed, washed with PBS, and then stained with ALP staining agent. The staining results are shown in FIG. 6. Figures 9-11The results are shown in the figure. It can be seen that the expression of ALP in the SrCO3 / PLLA and SrCO3@ZIF-8 / PLLA groups is significantly higher than that in the PLLA group, and the expression of ALP in the SrCO3@ZIF-8 / PLLA group is the highest, which proves that the synergistic effect of Sr ions and Zn ions can better promote the differentiation of stem cells into osteoblasts.

[0062] While embodiments of the application have been disclosed in connection with the above specification and drawings, it will be understood that it is not intended to limit the application to the details described therein, rather it is intended to cover all modifications and equivalents thereof falling within the scope of the application. Additional modifications will readily occur to those skilled in the art. The application is not limited to a particular detail set forth in the description above and drawings.

Claims

1. A method for preparing a SrCO3@ZIF-8 / polymer composite bone scaffold, characterized in that, Includes the following steps: Step 1: In situ growth of ZIF-8 on the surface of SrCO3 to synthesize SrCO3@ZIF-8 microrods. The specific method includes: adding strontium carbonate to methanol and dispersing it by ultrasound to obtain a mixed solution, denoted as solution A; dissolving zinc nitrate hexahydrate in methanol, denoted as solution B; dissolving 2-methylimidazole in methanol, denoted as solution C; stirring solution A, adding solution B to solution A, and then slowly adding solution C dropwise to the mixed solution of solutions A and B at a rate of 500 μL per minute. After the addition is complete, stirring is continued for 5-6 hours to obtain a white suspension. The obtained product is then washed three times by high-speed centrifugation with methanol and dried to obtain SrCO3@ZIF-8 microrods. Step 2: Weigh a certain amount of SrCO3@ZIF-8 micron rods and polymer materials according to a preset mass ratio, place them in a grinding mortar and grind for 20-30 minutes to ensure thorough mixing of the powders, thereby obtaining SrCO3@ZIF-8 / polymer composite powder; wherein, the polymer material is at least one of the following: L-polylactic acid (PLLA) powder, D-polylactic acid (PDLA) powder, polyglycolic acid (PGA) powder, polycaprolactone (PCL) powder, polylactic acid-carboxylic acid copolymer (PLGA) powder, and poly(p-dioxanone) (PPDO) powder; Step 3: Place the SrCO3@ZIF-8 / polymer composite powder in a selective laser sintering system, select an appropriate three-dimensional model, spread the composite powder evenly on the substrate, and sinter layer by layer. After sintering, remove the unsintered powder to finally obtain the SrCO3@ZIF-8 / polymer composite bone scaffold.

2. The method for preparing the SrCO3@ZIF-8 / polymer composite bone scaffold as described in claim 1, characterized in that, In the SrCO3@ZIF-8 / polymer composite bone scaffold, the mass fraction of SrCO3@ZIF-8 is 0.7~2.8wt%, the mass fraction of polymer is 97.2~99.3wt%, the diameter of the SrCO3@ZIF-8 microrods is 1~3μm, the length is 8~16μm, and the particle size of the polymer material is 0.1~100μm.

3. The method for preparing the SrCO3@ZIF-8 / polymer composite bone scaffold as described in claim 1, characterized in that, In step one, the mass-to-volume ratio of strontium carbonate to methanol in solution A is 0.122 g: 70-90 mL; the mass-to-volume ratio of zinc nitrate hexahydrate to methanol in solution B is 0.192 g: 10-20 mL; the mass-to-volume ratio of 2-methylimidazole to methanol in solution C is 0.212 g: 50-70 mL; the stirring speed is 500-1500 r / min; the centrifugal washing speed is 11000-12000 r / min; the drying temperature is 50-70℃; and the drying time is 22-26 hours.

4. The method for preparing the SrCO3@ZIF-8 / polymer composite bone scaffold as described in claim 1, characterized in that, In step three, the selective laser sintering process parameters are as follows: laser power of 1~3W, scanning speed of 200~300mm / s, scanning spacing of 0.1~1.0mm, spot diameter of 0.3~1.0mm, and the thickness of the composite powder is 0.05~0.1mm.

5. The method for preparing the SrCO3@ZIF-8 / polymer composite bone scaffold as described in claim 1, characterized in that, The prepared SrCO3@ZIF-8 / polymer composite bone scaffold has a porosity of 50-60% and a pore size of 200-500 μm.

6. The application of the SrCO3@ZIF-8 / polymer composite bone scaffold prepared by the method described in claim 1, characterized in that, The prepared SrCO3@ZIF-8 / polymer composite bone scaffold was used to prepare bone defect repair materials.

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