Strontium-doped inorganic nanofiber composite 3D printing scaffold for bone defect repair and preparation method thereof

Abstract

The application discloses a strontium-doped inorganic nanofiber composite 3D printing scaffold for bone defect repair and a preparation method thereof, and belongs to the field of bone defect repair biomaterials. The preparation method comprises the following steps: dissolving strontium nitrate in a mixed solution of tetraethyl orthosilicate, phosphoric acid and deionized water, stirring and mixing the obtained SiO2-SrO sol with a PVA solution, electrospinning, high-temperature calcination, obtaining a SiO2-SrO nanofiber membrane, cutting small pieces, high-speed stirring and dispersing, adding deionized water, high-speed homogenizing, freeze-drying, mixing with deionized water, grinding and freeze-drying, obtaining SiO2-SrO nanofiber as a dispersed phase, magnetically stirring and uniformly mixing CS solution and HA solution as a continuous phase, fully mixing and uniformly mixing to obtain a biological ink, and then 3D printing, freeze-drying and ultraviolet sterilization of the obtained scaffold, and immersion in a crosslinking agent solution for crosslinking reaction. The application realizes macroscopic and microscopic double-layer repair functions of the scaffold by combining electrospinning with 3D printing, and is used for bone defect repair.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials for bone defect repair, specifically relating to a strontium-doped inorganic nanofiber composite 3D printed scaffold for bone defect repair and its preparation method. Background Technology

[0002] Bone defects are a common clinical orthopedic condition, often caused by severe trauma, tumor resection, infection and necrosis, and congenital developmental abnormalities. They not only disrupt the integrity and mechanical stability of bone tissue but can also lead to limb dysfunction, malunion, and even disability, severely impacting patients' physical and mental well-being and quality of life. Currently, bone defect repair has become a key research area in orthopedics, with commonly used clinical repair methods including autologous bone grafting, allogeneic bone grafting, and artificial scaffold implantation. Among these, biomimetic 3D scaffolds, with their customizable structure, biomimetic microenvironment construction capabilities, and excellent tissue compatibility, are gradually becoming one of the core technologies replacing traditional repair methods. By mimicking the structure and function of natural bone tissue, they provide support for osteoblast proliferation, differentiation, and bone matrix deposition, promoting bone tissue regeneration and repair.

[0003] Existing biomimetic 3D scaffolds still have many shortcomings in key technical aspects such as structural biomimicry, bioactivity regulation, degradation rate matching, and vascularization induction, making it difficult to fully meet the clinical demand for efficient repair of bone defects. These shortcomings mainly include:

[0004] 1. Insufficient precision in structural biomimicry: Existing 3D scaffolds mostly employ a single-pore design, which cannot accurately simulate the multi-level porous interconnected structure of trabeculae in natural bone tissue (such as the synergistic distribution of micron-level interconnected channels and nano-level matrix pores). This results in limited osteocyte infiltration depth and impaired nutrient exchange, hindering the three-dimensional regeneration of bone tissue. Although some scaffolds attempt to construct porous structures, poor pore connectivity and difficulty in controlling porosity prevent them from matching the structural characteristics of bone tissue in different locations.

[0005] 2. Poor compatibility between bioactivity and degradability: Existing scaffold materials are mostly single polymers (such as PLA and PGA) or inorganic ceramics (such as hydroxyapatite). Polymer scaffolds lack sufficient bioactivity and are difficult to effectively induce osteoblast adhesion and differentiation; ceramic scaffolds are brittle and have a slow degradation rate, easily remaining after bone regeneration, triggering inflammatory responses or affecting bone tissue mechanical reconstruction. In addition, some composite scaffolds do not achieve a precise match between material degradation rate and bone regeneration rate, or produce toxic metabolites during degradation, affecting the repair effect.

[0006] 3. Mismatch between mechanical properties and natural bone tissue: The existing scaffold is unable to provide effective mechanical support for large bone defects due to insufficient mechanical strength, resulting in deformation and collapse of the scaffold during the repair process; some parts have excessive mechanical stiffness, which is significantly different from the elastic modulus of natural bone tissue, causing a "stress shielding effect" that inhibits the normal regeneration and remodeling of bone tissue, resulting in weak mechanical properties of the repaired bone tissue.

[0007] 4. Weak Vascularization Induction Capacity: Bone tissue regeneration depends on a sufficient blood supply. Existing biomimetic 3D scaffolds often lack targeted vascularization induction designs, failing to effectively recruit vascular endothelial cells and promote angiogenesis. This leads to cell necrosis in deep areas within the scaffold due to ischemia and hypoxia, making complete repair of large bone defects difficult. While some scaffolds are loaded with bioactive factors such as vascular endothelial growth factor (VEGF), problems exist including easy loss of growth factors, uncontrolled release rates, and easy attenuation of bioactivity, preventing long-term vascularization induction.

[0008] 5. Mismatch between the bioactivity and osteogenic efficiency of strontium-doped scaffolds: Some existing strontium-doped scaffolds simply physically mix strontium salts into the substrate, resulting in an uncontrolled release rate of strontium (initial burst release or long-term insufficient release), which cannot continuously exert its osteogenic regulatory effect. In addition, the scaffold surface lacks a biomimetic mineralization layer or active sites, which has limited effect on osteoblast adhesion and proliferation induction, resulting in a long bone defect repair cycle. Summary of the Invention

[0009] To overcome the above-mentioned shortcomings of the prior art, the main objective of this invention is to provide a method for preparing a strontium-doped inorganic nanofiber composite 3D-printed scaffold for bone defect repair. The scaffold is prepared by combining electrospinning technology with 3D printing technology. The process is simple and controllable, and the scaffold can achieve dual-layer repair function at both the macroscopic and microscopic levels.

[0010] Another objective of this invention is to provide a strontium-doped inorganic nanofiber composite 3D printed scaffold, which is prepared by the above-described method for preparing a strontium-doped inorganic nanofiber composite 3D printed scaffold for bone defect repair.

[0011] Another object of the present invention is to provide the application of the aforementioned strontium-doped inorganic nanofiber composite 3D printed scaffold in the preparation of products for bone defect repair.

[0012] To achieve the above objectives, the present invention adopts the following technical solution:

[0013] A first aspect of the present invention provides a method for preparing a strontium-doped inorganic nanofiber composite 3D-printed scaffold for bone defect repair, comprising the following steps:

[0014] S1: Strontium nitrate is dissolved in a mixed solution of tetraethyl orthosilicate (TEOS), phosphoric acid (H3PO4), and deionized water and stirred to obtain SiO2-SrO sol. This sol is then stirred and mixed evenly with PVA solution to obtain an electrospinning solution.

[0015] S2: The electrospinning solution is electrospinned to obtain a nanofiber membrane, which is then calcined at high temperature to obtain a flexible silica-strontium oxide (SiO2-SrO) nanofiber membrane;

[0016] S3: Cut the SiO2-SrO nanofiber membrane into small pieces, stir at high speed to disperse the nanofiber fragments evenly, add deionized water to homogenize at high speed, freeze dry, mix with deionized water, add grinding steel balls, put into a planetary ball mill for grinding and freeze dry to obtain SiO2-SrO nanofibers.

[0017] S4: Chitosan CS powder is dissolved in dilute acetic acid solution and magnetically stirred until completely dissolved to obtain CS solution; hyaluronic acid HA powder is dissolved in double-distilled water and magnetically stirred until uniform to obtain HA solution; CS solution and HA solution are mixed and magnetically stirred until uniform to obtain hydrogel containing CS and HA, and then the SiO2-SrO nanofibers are added and fully dispersed to obtain bio-ink;

[0018] S5: Transfer the bio-ink into the extrusion cylinder of the 3D printer, install the 21-G printing needle and 3D print the scaffold. After printing, freeze-dry and sterilize the obtained 3D printed scaffold with ultraviolet light.

[0019] S6: Immerse the 3D printed scaffold in the crosslinking agent solution and carry out the crosslinking reaction at room temperature for 6 hours. First rinse with PBS buffer, then rinse repeatedly with deionized water to remove residual crosslinking agent solution. After thorough cleaning, freeze-dry and sterilize with ultraviolet light.

[0020] Preferably, in step S1, the mass fraction of strontium nitrate is 0.1%-1%.

[0021] Preferably, in step S1, the volume ratio (v / v) of tetraethyl orthosilicate, phosphoric acid, and deionized water is 10:0.07:10.

[0022] And / or the mass ratio of PVA to deionized water in the PVA solution is 1:9;

[0023] And / or the mass ratio of the SiO2-SrO sol to the PVA solution is 1:1, and the mixture is stirred at 15°C for 20 hours.

[0024] Preferably, in step S2, the nanofiber membrane is calcined in a muffle furnace at 800°C for 2 hours.

[0025] Preferably, in step S3, the SiO2-SrO nanofiber membrane is cut into small pieces of 1cm×1cm;

[0026] And / or the high-speed stirring and high-speed homogenization mentioned above both refer to stirring at a speed of 10,000 rpm / min for 30 min;

[0027] And / or grind for 5 minutes at 4°C and 60 Hz.

[0028] Preferably, in step S4, the bio-ink contains only CS, HA and SiO2-SrO nanofibers, wherein the mass ratio of CS to HA is 1:0.01-0.1, the SiO2-SrO nanofibers account for 1% of the total dry weight, and the volume concentration of the dilute acetic acid solution is 2% (v / v).

[0029] Preferably, in step S5, the process parameters of the 3D printing bracket include: the temperature of the barrel and the tip is 15-25℃, the temperature of the receiving platform is 5℃, the printing speed is 8mm / s, and the extrusion pressure is 0.2MPa.

[0030] And / or the freeze-drying process includes: the 3D printed scaffold is first pre-frozen at -20°C for 12 hours, then rapidly transferred to an environment at -80°C for freeze-drying for 12 hours, thoroughly cleaned, and then transferred to an environment at -80°C for freeze-drying for 12 hours.

[0031] Preferably, in step S6, the crosslinking agent solution is a buffer solution containing 50 mM EDC and 25 mM NHS with a pH of 5.5; and / or the concentration of the PBS buffer is 0.1 mol / L.

[0032] In a second aspect, the present invention provides a strontium-doped inorganic nanofiber composite 3D-printed scaffold, which is prepared by any of the above-described methods for preparing a strontium-doped inorganic nanofiber composite 3D-printed scaffold for bone defect repair.

[0033] A third aspect of the present invention provides the application of the strontium-doped inorganic nanofiber composite 3D printed scaffold in the preparation of products for bone defect repair.

[0034] Compared with existing technologies, this invention utilizes electrospinning technology to prepare TEOS / SrO / PVA nanofiber membranes. PVA acts as a spinning aid to increase the spinnability of the sol and provides support for the inorganic materials. After freeze-drying, the membrane is pyrolyzed at high temperature in a muffle furnace to remove PVA and promote the gradual dehydration of TEOS to form SiO2, resulting in a SiO2-SrO nanofiber membrane. This membrane is then mixed with deionized water and freeze-dried in a high-speed homogenizer and ball mill to obtain SiO2-SrO nanofibers as the dispersed phase. CS solution and HA solution are magnetically stirred to form the continuous phase. After thorough mixing, a bio-ink is prepared and 3D printed. The resulting 3D printed scaffold is freeze-dried and sterilized under ultraviolet light, then immersed in a crosslinking agent solution for crosslinking reaction. It is then freeze-dried and sterilized again under ultraviolet light to obtain a strontium-doped inorganic nanofiber composite 3D printed scaffold, suitable for bone defect repair applications, and has the following beneficial effects:

[0035] (1) Combining electrospinning technology with 3D printing technology to achieve dual-layer repair of the scaffold at both the macroscopic and microscopic levels.

[0036] (2) Chitosan (CS), hyaluronic acid (HA) and electrospun short fibers are mixed as bio-ink for 3D printing. The strontium-doped short fibers of electrospun fibers can effectively enhance the mechanical properties of the scaffold as a reinforcing phase. A fiber-matrix interlocking structure is formed in the chitosan-hyaluronic acid matrix. Combined with network reinforcement by chemical cross-linking (such as EDC / NHS cross-linking), pores are provided at the micro level for material transport and cell adhesion and proliferation. Strontium ions can mimic the dual advantages of calcium ions in promoting bone formation and inhibiting bone resorption through calcium-sensitive receptors in bone tissue. Furthermore, strontium ions can promote the formation of new bone by enhancing bone activity.

[0037] (3) The porous structure constructed by 3D printing combines the porous morphology of silica with the spatial support of short fibers to form a continuous and interconnected network of pores, which can guide the migration, proliferation and formation of new blood vessels of vascular endothelial cells. It has strong vascularization ability and can provide sufficient nutrition for bone repair, overcoming the problems of difficult vascular ingrowth and easy bone tissue ischemia and necrosis caused by traditional dense or low porosity stents.

[0038] (4) The scaffold has a slow-release effect on silicon and strontium ions, and the Sr released from strontium oxide 2+ It can activate the Wnt / β-catenin signaling pathway in osteoblasts and promote osteogenic differentiation; the silicon ions in silica can stimulate osteoblast proliferation and mineralization. The two ions work together to provide sustained and stable stimulation to osteoblasts throughout the bone repair cycle, which can maintain biological activity for a long time, promote bone tissue regeneration, and improve the bone repair effect.

[0039] (5) The raw materials are widely available. Chitosan can be extracted on a large scale from aquatic waste such as shrimp and crab shells. Hyaluronic acid can be extracted through microbial fermentation (such as streptococcal fermentation) or animal tissue (such as chicken comb). Silica and strontium oxide are common inorganic chemical raw materials with large output and low cost. Attached Figure Description

[0040] Figure 1 The images shown are scanning electron microscope images of the nanofiber membranes and strontium-doped silica nanofiber membranes prepared in the examples.

[0041] Figure 2 The results of the proliferation test of NIH-3T3 cells on strontium-doped silica nanofiber membranes in the examples are shown.

[0042] Figure 3 This is a flowchart illustrating the fabrication process of the strontium-doped inorganic nanofiber composite 3D printing scaffold in the embodiments. Detailed Implementation

[0043] To more fully understand and demonstrate the technical solutions, objectives, and advantages of the present invention, the technical effects produced by the present invention will be further described in detail and completely below with reference to the accompanying drawings and specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. It should be noted that other embodiments obtained by those skilled in the art without departing from the concept of the present invention are all within the protection scope of the present invention.

[0044] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0045] Example 1

[0046] like Figure 3 As shown in the figure, this embodiment prepares a strontium-doped inorganic nanofiber composite 3D printed scaffold for bone defect repair. The specific steps are as follows:

[0047] Step 1: Preparation of electrospinning solution

[0048] Strontium nitrate was dissolved in a TEOS / H3PO4 / H2O (10:0.07:10, v / v) solution and stirred for 10 h, with a strontium nitrate mass concentration of 0.1%, to obtain a SiO2-SrO sol. PVA was dissolved in deionized water at a mass ratio of 1:9 to obtain a PVA solution. Subsequently, the SiO2-SrO sol and the PVA solution were mixed at a mass ratio of 1:1 and stirred at 15 °C for 30 h.

[0049] Step 2: Preparation of SiO2-SrO fiber membrane

[0050] After uniformly mixing PVA solution with SiO2-SrO-0.1% sol, nanofiber membranes were prepared by electrospinning. The PVA was removed by calcination in a muffle furnace at 800℃ for 3 hours to obtain flexible SiO2-SrO fiber membranes.

[0051] Step 3: Preparation of SiO2-SrO nanofibers

[0052] The SiO2-SrO fiber membrane was cut into small pieces of approximately 1cm × 1cm and stirred for 30 minutes at 10,000 rpm / min using a high-speed mixer (IKAT18, Germany) to uniformly disperse the nanofiber fragments. Deionized water was added, and the mixture was stirred for 30 minutes at 10,000 rpm / min in a high-speed homogenizer. The mixture was then transferred to a -80℃ environment for freeze-drying. After mixing with deionized water again, grinding balls were added, and the mixture was ground in a planetary ball mill (4℃, 60Hz, 5 minutes). The mixture was then transferred to a -80℃ environment for freeze-drying to obtain SiO2-SrO nanofibers.

[0053] Step 4: Preparation of 3D Printing Bio-Ink

[0054] Chitosan (CS) solution: Dissolve CS powder in 2% (v / v) dilute acetic acid solution and stir magnetically until completely dissolved.

[0055] Hyaluronic acid (HA) solution: Dissolve HA powder in double-distilled water and stir magnetically until homogeneous.

[0056] Bio-ink preparation: Mix 1% (w / v) CS solution with 0.02% (w / v) HA solution and stir thoroughly with a magnetic stirrer until homogeneous to obtain a hydrogel containing only Cs and HA.

[0057] The SiO2-SrO nanofibers obtained in step three are mixed with hydrogel and magnetically stirred until fully mixed to obtain bio-ink.

[0058] Step 5: 3D Printing the Support

[0059] The bio-ink was transferred into the extrusion barrel of the 3D printer, and a 21-G printing needle was installed. The barrel and needle tip temperature was 15-25℃, the receiving platform temperature was 5℃, the printing speed was 8mm / s, and the extrusion pressure was 0.2MPa. After the scaffold was printed, it was pre-frozen at -20℃ for 12 hours, then rapidly transferred to a -80℃ environment for freeze-drying for 12 hours. Finally, the thoroughly cleaned scaffold was freeze-dried at -80℃ for 12 hours, sterilized with ultraviolet light, and then stored.

[0060] Step Six: Crosslinking of the 3D Printed Scaffold

[0061] Prepare a buffer solution (pH 5.5) containing 50 mMMEDC and 25 mMMNHS as the cross-linking agent solution. Immerse the scaffold in the cross-linking agent solution and react at room temperature for 6 h. Rinse three times with 0.1 mol / L PBS buffer, followed by repeated rinsing with deionized water to remove residual cross-linking agent. Transfer the thoroughly cleaned scaffold to -80°C for freeze drying, sterilize with ultraviolet light, and store.

[0062] (1) Microscopic morphological characterization

[0063] The nanofiber membrane samples prepared above before and after muffle furnace calcination were cut into 5 mm × 5 mm sizes, fixed on the scanning electron microscope (SEM) sample stage with conductive adhesive, and after being sputtered with gold for 60 seconds, the fiber micromorphology was observed under the SEM.

[0064] See Figure 1 As shown, by comparing the scanning electron microscope images of the fiber membrane prepared in this embodiment before and after muffle furnace calcination, it can be seen that the surface of the sample membrane after muffle furnace calcination is smooth, the fiber diameter is uniformly distributed and presents a three-dimensional interconnected network structure. This porous structure is conducive to the transport of nutrients and the migration and replacement of cells, further confirming from the microstructure that it is suitable as a scaffold material for bone tissue engineering.

[0065] (2) Biocompatibility experiment

[0066] The strontium-doped silica nanofiber membrane prepared in Example 1 was cut into 14 mm diameter discs, sterilized, and placed in a 24-well plate. NIH-3T3 cells were then introduced at a concentration of 1 × 10⁻⁶. 5 Inoculated onto the material surface at a density of 100 individuals / mL and cultured using standard methods. The absorbance at 450 nm was measured using the CCK-8 assay on days 1, 4, and 7.

[0067] The results are as follows Figure 2 As shown, the nanofiber membrane can effectively support cell adhesion and proliferation.

[0068] Example 2

[0069] This embodiment describes the fabrication of a strontium-doped inorganic nanofiber composite 3D-printed scaffold for bone defect repair. The specific steps are as follows:

[0070] The mass concentration of strontium nitrate was changed from 0.1% in the TEOS / H3PO4 / H2O (10:0.07:10, v / v) solution in Example 1 to 0.2%. The steps of preparing the electrospinning solution, preparing the SiO2-SrO fiber membrane, preparing the SiO2-SrO nanofibers, preparing the 3D printing bio-ink, and cross-linking the 3D printing scaffold with the scaffold were the same as in Example 1. Finally, a bone repair scaffold with a strontium content of 0.2% was obtained.

[0071] Example 3

[0072] This embodiment describes the fabrication of a strontium-doped inorganic nanofiber composite 3D-printed scaffold for bone defect repair. The specific steps are as follows:

[0073] The mass concentration of strontium nitrate was changed from 0.1% in the TEOS / H3PO4 / H2O (10:0.07:10, v / v) solution in Example 1 to 0.3%. The steps of preparing the electrospinning solution, preparing the SiO2-SrO fiber membrane, preparing the SiO2-SrO nanofibers, preparing the 3D printing bio-ink, and cross-linking the 3D printing scaffold with the scaffold were the same as in Example 1. Finally, a bone repair scaffold with a strontium content of 0.3% was obtained.

[0074] The above are merely preferred embodiments of the present invention and are not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing a strontium-doped inorganic nanofiber composite 3D-printed scaffold for bone defect repair, characterized in that, Includes the following steps: S1: Strontium nitrate is dissolved in a mixed solution of tetraethyl orthosilicate, phosphoric acid, and deionized water and stirred to obtain SiO2-SrO sol. This sol is then stirred and mixed evenly with PVA solution to obtain an electrospinning solution. S2: The electrospinning solution is electrospinned to obtain a nanofiber membrane, which is then calcined at high temperature to remove PVA and obtain a flexible SiO2-SrO nanofiber membrane. S3: The SiO2-SrO nanofiber membrane is cut into small pieces, stirred at high speed to disperse the nanofiber fragments evenly, added to deionized water for high-speed homogenization, freeze-dried, then mixed with deionized water, added to grinding steel balls, placed in a planetary ball mill for grinding and freeze-drying to obtain SiO2-SrO nanofibers. S4: Chitosan CS powder is dissolved in dilute acetic acid solution and magnetically stirred until completely dissolved to obtain CS solution; Hyaluronic acid (HA) powder was dissolved in double-distilled water and magnetically stirred until homogeneous to obtain an HA solution. The CS solution and HA solution were mixed and magnetically stirred until homogeneous to obtain a hydrogel containing CS and HA. Then, the SiO2-SrO nanofibers were added and fully dispersed to obtain a bio-ink. S5: The bio-ink is transferred into the extrusion cylinder of the 3D printer, a 21-G printing needle is installed, and a 3D printing bracket is formed. After printing, the obtained 3D printing bracket is freeze-dried and sterilized with ultraviolet light. S6: The 3D printed scaffold is immersed in a crosslinking agent solution and subjected to a crosslinking reaction at room temperature for 6 hours. It is then rinsed with PBS buffer and repeatedly rinsed with deionized water to remove residual crosslinking agent solution. The thoroughly cleaned 3D printed scaffold is then freeze-dried and sterilized with ultraviolet light.

2. The method for preparing the strontium-doped inorganic nanofiber composite 3D printing scaffold according to claim 1, characterized in that, In step S1, the mass fraction of strontium nitrate is 0.1%-1%.

3. The method for preparing the strontium-doped inorganic nanofiber composite 3D printing scaffold according to claim 1, characterized in that, In step S1, the volume ratio of tetraethyl orthosilicate, phosphoric acid, and deionized water is 10:0.07:10; And / or the mass ratio of PVA to deionized water in the PVA solution is 1:9; And / or the mass ratio of the SiO2-SrO sol to the PVA solution is 1:1, and the mixture is stirred at 15°C for 20 h.

4. The method for preparing the strontium-doped inorganic nanofiber composite 3D printing scaffold according to claim 1, characterized in that, In step S2, the nanofiber membrane is calcined in a muffle furnace at 800°C for 2 hours.

5. The method for preparing the strontium-doped inorganic nanofiber composite 3D printing scaffold according to claim 1, characterized in that, In step S3, the SiO2-SrO nanofiber membrane is cut into small pieces of 1cm × 1cm; And / or the high-speed stirring and high-speed homogenization mentioned above both refer to stirring at a speed of 10,000 rpm / min for 30 min; And / or grind for 5 min at 4°C and 60 Hz.

6. The method for preparing the strontium-doped inorganic nanofiber composite 3D printing scaffold according to claim 1, characterized in that, In step S4, the bio-ink contains only CS, HA and SiO2-SrO nanofibers, wherein the mass ratio of CS to HA is 1:0.01-0.1, the SiO2-SrO nanofibers account for 1% of the total dry weight, and the volume concentration of the dilute acetic acid solution is 2% (v / v).

7. The method for preparing the strontium-doped inorganic nanofiber composite 3D printing scaffold according to claim 1, characterized in that, In step S5, the process parameters of the 3D printing bracket include: the temperature of the barrel and the tip is 15-25℃, the temperature of the receiving platform is 5℃, the printing speed is 8 mm / s, and the extrusion pressure is 0.2 MPa. And / or the freeze-drying process includes: the 3D printed scaffold is first pre-frozen at -20°C for 12 hours, then rapidly transferred to an environment at -80°C for freeze-drying for 12 hours, thoroughly cleaned, and then transferred to an environment at -80°C for freeze-drying for 12 hours.

8. The method for preparing the strontium-doped inorganic nanofiber composite 3D printing scaffold according to claim 1, characterized in that, In step S6, the crosslinking agent solution is a buffer solution containing 50 mM EDC and 25 mM NHS with a pH of 5.5; And / or the concentration of the PBS buffer is 0.1 mol / L.

9. A strontium-doped inorganic nanofiber composite 3D printed scaffold, prepared by the method for preparing a strontium-doped inorganic nanofiber composite 3D printed scaffold for bone defect repair as described in any one of claims 1-8.

10. The application of the strontium-doped inorganic nanofiber composite 3D printed scaffold of claim 9 in the preparation of products for bone defect repair.

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