Bone filling scaffold with near-infrared light and magnetic field double responsiveness and preparation method thereof

Abstract

The invention discloses a bone filling scaffold with near-infrared light and magnetic field double responsiveness, and relates to the technical field of biomedical materials, the bone filling scaffold comprises a 3D printing scaffold and a filler filled in the 3D printing scaffold; wherein the raw materials of the 3D printing stent are polyetherimide and nano ferroferric oxide; and the filler is methacrylic anhydride gelatin. After the bone filling scaffold prepared by the preparation method is irradiated by near-infrared light, infection can be controlled, infectious bone defect bone repair can be promoted, and revascularization can be promoted and bone repair can be accelerated under combined stimulation of a static magnetic field; meanwhile, the infection problem and the revascularization problem after the bone implant is implanted are solved, the intensity and frequency of exogenous near-infrared light and magnetic field treatment can be regulated and controlled according to the actual illness state, and the treatment strategy is adjusted.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a bone filling scaffold with dual responsiveness to near-infrared light and magnetic field and a preparation method thereof. Background Art

[0002] Bone defects are usually caused by trauma, infection and bone tumors, and bone defects are a difficult problem in clinical treatment. Bone transplant materials include autologous bone, allogeneic bone and artificial bone. The source of autologous bone is limited, and allogeneic bone can cause immune response, limiting its clinical application. Therefore, 3D printed bone filling scaffolds have broad application prospects in the field of bone tissue engineering.

[0003] However, conventional 3D printed bone-filling scaffolds often lack bioactivity and cannot cope well with complex bone defects accompanied by vascular damage and infection. Currently, some scaffolds are loaded with cytokines or antibiotics to promote angiogenesis and prevent infection, but their limited drug loading capacity and unstable drug activity make them ineffective and cannot maintain long-term bioactivity. In addition, after the scaffold is implanted in the body, it is impossible to adjust the treatment strategy according to the condition of the disease. Therefore, the development of stable, adjustable bone-filling scaffolds that promote angiogenesis and resist infection is a research hotspot in the field of bone repair materials.

[0004] Therefore, providing a stable and adjustable bone filling scaffold that promotes angiogenesis and resists infection is a technical problem that urgently needs to be solved in the art. Summary of the invention

[0005] The present invention proposes a bone filling scaffold with dual responsiveness to near-infrared light and magnetic field and a preparation method thereof. The bone filling scaffold prepared by the preparation method can control infection and promote bone repair of infected bone defects after being irradiated with near-infrared light, and promote blood vessel regeneration and accelerate bone repair under the combined stimulation of a static magnetic field; at the same time, the infection problem and blood vessel regeneration problem after bone implantation are solved, and the intensity and frequency of exogenous near-infrared light and magnetic field treatment can be regulated according to the actual condition of the disease, and the treatment strategy can be adjusted.

[0006] In order to achieve the above object, the present invention adopts the following technical solution:

[0007] A bone filling scaffold with dual responsiveness to near-infrared light and magnetic field, the bone filling scaffold comprising a 3D printed scaffold and a filler filled inside the 3D printed scaffold;

[0008] The raw materials of the 3D printed bracket are polyetherimide and nano-ferroferric oxide;

[0009] The filler is methacrylic anhydride gelatin.

[0010] Preferably, the mass ratio of the polyetherimide to the nano-ferroferric oxide is 1:0.01-0.05;

[0011] The filling amount of the filler in the 3D printed bracket is 0.5-1.5 mL / mm 3 .

[0012] Preferably, the methacrylic anhydride gelatin is loaded with active substances, and the active substances include silver nanoparticles or vascular endothelial growth factor.

[0013] Preferably, the concentration of the silver nanoparticles is 0.01-0.05 wt %, and the concentration of the vascular endothelial growth factor is 25 ng / mL.

[0014] Preferably, the bone-filled scaffold further comprises a polydopamine connecting layer between the 3D printed scaffold and the filler.

[0015] In order to make the soft hydrogel and the hard 3D printed stent more tightly and firmly combined, the present invention further prepares a polydopamine coating on the surface of the polyetherimide-ferroferric oxide stent. Dopamine undergoes oxidative polymerization reaction in a weakly alkaline environment to cover almost all material surfaces to form a polydopamine coating. Methacrylated gelatin contains a large number of amino groups and can be covalently grafted onto the PDA coating. Therefore, the methacrylated gelatin and the 3D printed polyetherimide-ferroferric oxide stent are connected by preparing a polydopamine coating on the stent surface as a connecting layer.

[0016] According to the above-mentioned method for preparing a bone filling scaffold having dual responsiveness to near-infrared light and magnetic field, it is characterized by comprising the following steps:

[0017] (1) Weighing polyetherimide and nano-ferroferric oxide powder according to the mass ratio, mixing them evenly, and then using a twin-screw extruder to prepare polyetherimide-ferroferric oxide 3D printing filaments, and then preparing a porous polyetherimide-ferroferric oxide scaffold by 3D printing the polyetherimide-ferroferric oxide 3D printing filaments;

[0018] (2) Methacrylic gelatin is prepared into a hydrogel solution, and the hydrogel solution is injected into the porous polyetherimide-ferroferric oxide scaffold, and then cured and dried to obtain a bone filling scaffold with dual responsiveness to near-infrared light and magnetic field.

[0019] The present invention heats and melts polyetherimide particles and ferroferric oxide nanoparticles with photothermal and magnetic properties through a twin-screw extruder, mixes and extrude, prepares filaments for 3D printing, places the filaments into a 3D printer for 3D printing, and prints out a 3D polyetherimide-ferroferric oxide scaffold with a macroporous structure. The polyetherimide-ferroferric oxide scaffold is photoresponsive under near-infrared light irradiation, produces a photothermal effect, and the temperature of the scaffold increases, producing an antibacterial effect; the ferroferric oxide located on the surface of the 3D printed scaffold constitutes a magnetic response module. Under the action of an external magnetic field, the magnetic nanoparticles can stimulate the proliferation and differentiation of bone marrow mesenchymal stem cells adhered to the surface of the scaffold to promote bone repair; stimulate the proliferation and differentiation of venous endothelial cells adhered to the surface of the scaffold to promote vascular regeneration.

[0020] Then, a composite scaffold was prepared by preparing methacrylated gelatin hydrogel and injecting it into a 3D printed scaffold. Silver nanoparticles and vascular endothelial growth factor were added to the hydrogel to prepare a mixed hydrogel, which can release silver nanoparticles and vascular endothelial growth factor to increase the antibacterial and angiogenesis properties of the scaffold. The microporous structure formed by the hydrogel, namely the microporous channel, can guide the growth of blood vessels in these microporous channels; the macroporous channel scaffold of the 3D printed scaffold guides bone regeneration. The load module refers to the hydrogel filled inside the scaffold, which can load bioactive substances, the light response module refers to the crossbeam of the 3D printed scaffold, and the magnetic response module refers to the ferroferric oxide nanoparticles on the surface of the scaffold;

[0021] In summary, the antibacterial effect of the present invention is achieved by irradiating the stent with near-infrared light, which increases the temperature of the stent, produces a thermal killing effect on bacteria, and produces an antibacterial effect. In addition, silver nanoparticles have an antibacterial effect, and the thermal killing combined with the antibacterial effect of silver nanoparticles produces an antibacterial effect; at the same time, the external magnetic field is combined with the magnetic response module to stimulate the proliferation and differentiation of venous endothelial cells, and the venous endothelial cells generate new blood vessels in the microporous channels of the stent, thereby promoting angiogenesis. In addition, the vascular endothelial growth factor loaded in the hydrogel increases the angiogenesis-promoting performance of the stent; the bone regeneration effect is promoted by stimulating the proliferation and differentiation of bone marrow mesenchymal stem cells through the external magnetic field combined with the magnetic response module, and the bone marrow mesenchymal stem cells form new bone tissue in the macroporous channels of the stent, thereby accelerating bone repair.

[0022] Preferably, the diameter of the polyetherimide-ferroferric oxide 3D printing filament in step (1) is 1.50-2.00 mm, the nozzle temperature of the 3D printing is 330-405° C., and the base plate temperature is 120-200° C.;

[0023] The 3D printing has a porosity of 35-65% and a layer height of 0.1-0.3 mm.

[0024] Preferably, the specific steps of the polyetherimide-ferroferric oxide 3D printing filament preparation method are:

[0025] 1) Place the polyetherimide particles in a drying oven and dry them at 120°C for 2-4 hours;

[0026] 2) using a powder grinder to fully crush the polyetherimide particles and mix them with ferrosoferric oxide powder for 10-15 minutes to obtain a mixed powder;

[0027] 3) Add the mixed powder into the feed barrel of a twin-screw extruder, set the melting temperature of zone 1 to 250°C-280°C, the heating temperature of zone 2 to 280°C-320°C, the speed of the wire drawing machine to 10-25r / min, and maintain the wire diameter to 1.50-2.00mm to obtain polyetherimide-iron tetroxide wire, and then put the prepared polyetherimide-iron tetroxide wire into a drying oven at 120°C and dry it for 2-4h.

[0028] Preferably, step (1) further comprises preparing a polydopamine connecting layer on the surface of the porous polyetherimide-ferroferric oxide scaffold, and the specific method is: immersing the polyetherimide-ferroferric oxide scaffold in a dopamine solution, stirring at 600-800 rpm for 12-24 hours under light-proof conditions, and then washing and drying;

[0029] The method for preparing the dopamine solution is to add dopamine into a Tris-HCl buffer solution with a concentration of 10 mmol / L and P=8.5 to prepare a dopamine solution with a concentration of 2 mg / mL.

[0030] Preferably, the concentration of the hydrogel solution in step (2) is 5-15% w / v;

[0031] The preparation method of the hydrogel solution is as follows: adding LAP (phenyl (2,4,6-trimethylbenzoyl) lithium phosphate) photoinitiator into phosphate buffer and stirring to dissolve to obtain a photoinitiator standard solution with a concentration of 0.25% (w / v), adding methacrylic anhydride gelatin into the photoinitiator standard solution and stirring to dissolve at 60-70° C. to obtain a hydrogel solution;

[0032] The curing is performed by irradiating with a 405 nm light source for 15-30 seconds.

[0033] The drying is freeze-drying at -80°C for 48-72h.

[0034] Preferably, step (2) further comprises adding active substances into the hydrogel solution for loading.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] (1) The present invention adds nano-iron tetroxide particles to the 3D printed stent, so that the main body of the stent has near-infrared responsiveness to form a light response module. Under the irradiation of near-infrared light, the temperature of the main body of the stent rises, producing a photothermal antibacterial effect. In the early stage of infection, killing bacteria as early as possible is the primary task. Therefore, in the early stage, the near-infrared light of the present invention can be used to irradiate the stent to produce a photothermal antibacterial effect and inhibit bacterial growth;

[0037] At the same time, the nano-iron tetroxide particles on the surface of the stent of the present invention constitute a magnetic response module, which can move in a directed manner under the action of the magnetic field, stimulate the proliferation and differentiation of bone marrow mesenchymal stem cells and venous endothelial cells in the bone defect site, accelerate bone repair and angiogenesis, and tissue reconstruction is required after killing bacteria. Angiogenesis provides nutrients for bone regeneration. Therefore, the size of the magnetic field can be adjusted during this period to make it suitable for angiogenesis and restore blood supply as soon as possible. Bone regeneration takes about 3 months. During this period, treatment can be carried out on demand by adjusting the magnetic force of the external magnetic field to accelerate bone repair.

[0038] (3) The hydrogel filled inside the 3D printed stent of the present invention constitutes a loading module, which can load active substances. For example, the loaded silver nanoparticles can destroy the bacterial membrane structure and increase the photothermal antibacterial performance of the stent. The loaded vascular endothelial growth factor can increase the angiogenesis performance of the stent.

[0039] (3) The macroporous channels of the 3D printed scaffold of the present invention serve as bone channels to provide space for new bone tissue, so that the scaffold is closely combined with the new bone tissue to avoid loosening after implantation; at the same time, the macroporous structure of the scaffold can be filled with hydrogel, and the microporous channels of the hydrogel after freeze-drying. These soft microporous channels provide a suitable growth environment for venous endothelial cells and serve as vascular channels to guide vascular regeneration. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. The drawings in this description are only embodiments of the present invention.

[0041] Figure 1 This is a structural diagram of a 3D printed bone filling scaffold of the present invention that has dual responsiveness to infrared light and magnetic field;

[0042] Figure 2 The actual images are of the 3D printed stents prepared in Comparative Example 1 (PEI), Example 1 (P-1% Fe3O4) and Example 2 (P-2% Fe3O4) of the present invention;

[0043] Figure 3 It is a temperature rise diagram of Comparative Example 1 (PEI), Example 1 (P-1% Fe3O4) and Example 2 (P-2% Fe3O4) of the present invention after being irradiated with near-infrared light;

[0044] Figure 4 These are the magnetic detection diagrams of the vibrating sample ferromagnetometer of the brackets of Example 1 (P-1% Fe3O4) and Example 2 (P-2% Fe3O4) of the present invention. DETAILED DESCRIPTION

[0045] Embodiments of the present invention are described below. Examples of the embodiments are shown in the accompanying drawings. The embodiments described with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, but are not to be construed as limiting the present invention.

[0046] Example 1

[0047] The present invention provides a method for preparing a bone filling scaffold having dual responsiveness to near-infrared light and magnetic field, comprising the following steps:

[0048] (1) Weighing polyetherimide and nano-iron tetroxide particles in a mass ratio of 1:0.01, placing the polyetherimide particles in a drying oven at 120° C. and drying for 2 days, using a powder grinder to fully crush the polyetherimide particles and mix them with the iron tetroxide powder for 10 minutes, mixing evenly to obtain a mixed powder, adding the mixed powder to a feed barrel of a twin-screw extruder, setting the melting temperature of the first zone to 250° C., the heating temperature of the second zone to 280° C., the speed of the wire drawing machine to 10 r / min, and maintaining the wire diameter at 1.74-1.76 mm to obtain a polyetherimide-iron tetroxide wire, and then placing the prepared polyetherimide-iron tetroxide wire in a drying oven at 120° C. and drying for 2 hours for standby use;

[0049] (2) The dried polyetherimide-iron tetroxide wire was placed into a high-temperature 3D printer, and the temperature of the printer nozzle was set to 380°C and the temperature of the base plate was set to 120°C. 3D printing was performed according to the set program, and the printing porosity was set to 65%, the diameter was 15 mm, the height was 3 mm, and the layer height was 0.2 mm. Printing was performed to obtain a 3D printed polyetherimide-iron tetroxide scaffold.

[0050] Example 2

[0051] The present invention provides a method for preparing a bone filling scaffold with dual responsiveness to near-infrared light and magnetic field, which differs from Example 1 in that in step (1), polyetherimide and nano-iron tetroxide particles are weighed in a mass ratio of 1:0.02, and the remaining operations are exactly the same as in Example 1.

[0052] Example 3

[0053] The present invention provides a method for preparing a bone filling scaffold having dual responsiveness to near-infrared light and magnetic field, wherein steps (1) and (2) are exactly the same as those in Example 2;

[0054] (3) Add LAP photoinitiator to pH = 7.4 phosphate buffer and stir to dissolve to obtain a photoinitiator standard solution with a concentration of 0.25% (w / v). Weigh methacrylic anhydride gelatin and add it to the photoinitiator standard solution and stir at 60°C for 30 min to dissolve to obtain a methacrylic anhydride gelatin solution with a concentration of 10% w / v. Immediately filter the methacrylic anhydride gelatin solution using a 0.22 μm bacteria filter in an ultra-clean workbench to obtain a hydrogel solution. Inject 500 μL of the hydrogel solution into a 3D-printed polyetherimide-iron tetroxide scaffold, then use a 405 nm light source to irradiate for 15 s to photocured hydrogel. Put the scaffold loaded with hydrogel into a freeze dryer and freeze-dry at -80°C for 72 h to obtain a 3D-printed bone filling scaffold with dual responsiveness to infrared light and magnetic field. The structural diagram of the relevant scaffold is shown in FIG. Figure 1 , wherein 1 is a light response module, 2 is a magnetic response module, 3 is a load module, 4 is a macroporous channel, and 5 is a microporous channel. It can be seen from the figure that after the nano-iron tetroxide particles are added to the 3D printed stent of the present invention, the main body of the stent has near-infrared responsiveness to constitute a light response module, the nano-iron tetroxide particles on the surface of the stent constitute a magnetic response module, and the hydrogel filled inside constitutes a load module. The macroporous channel of the 3D printed stent serves as a bone channel to provide space for the new bone tissue, so that the stent is closely combined with the new bone tissue to avoid loosening after implantation. At the same time, the macroporous structure of the stent is filled with hydrogel, and microporous channels exist after the hydrogel is freeze-dried. These soft microporous channels provide a suitable growth environment for venous endothelial cells and serve as vascular channels to guide vascular regeneration.

[0055] Example 4

[0056] The present invention provides a method for preparing a bone filling scaffold with dual responsiveness to near-infrared light and magnetic field. The method differs from Example 3 in that a polydopamine coating is prepared on the surface of a 3D printed polyetherimide-ferroferric oxide scaffold. The specific operation is as follows: dopamine is added to a Tris-HCl buffer solution with a concentration of 10 mmol / L and a pH of 8.5 to prepare a dopamine solution with a concentration of 2 mg / mL; the 3D printed polyetherimide-ferroferric oxide scaffold obtained in step (2) is immersed in 100 mL of the dopamine solution; the 3D printed polyetherimide-ferroferric oxide scaffold is stirred in a dark environment at a constant temperature of 37° C. and in full contact with air; the stirring speed is 600 rpm for 24 hours to obtain a polyetherimide-ferroferric oxide scaffold with a surface modified by dopamine; the dopamine-modified scaffold is washed with deionized water for 3 times; and the scaffold is dried at 37° C. for 24 hours. Step (3) and the operation are exactly the same as those in Example 3.

[0057] Example 5

[0058] The present invention provides a method for preparing a bone filling scaffold having dual responsiveness to near-infrared light and magnetic field, comprising the following steps:

[0059] (1) Weighing polyetherimide and nano-iron tetroxide particles in a mass ratio of 1:0.05, placing the polyetherimide particles in a drying oven at 120° C. and drying for 2 days, using a powder grinder to fully crush the polyetherimide particles and mix them with the iron tetroxide powder for 10 minutes, mixing evenly to obtain a mixed powder, adding the mixed powder to a feed barrel of a twin-screw extruder, setting the melting temperature of the first zone to 300° C., the heating temperature of the second zone to 330° C., the speed of the wire drawing machine to 10 r / min, and maintaining the wire diameter at 1.60-2.00 mm to obtain a polyetherimide-iron tetroxide wire, and then placing the prepared polyetherimide-iron tetroxide wire in a drying oven at 120° C. and drying for 2 hours for standby use;

[0060] (2) The dried polyetherimide-iron tetroxide wire was placed into a high-temperature 3D printer, and the temperature of the printer nozzle was set to 405°C and the temperature of the base plate was set to 180°C. 3D printing was performed according to the set program, and the printing porosity was set to 55% and the layer height was 0.2 mm. The 3D printed polyetherimide-iron tetroxide scaffold was obtained.

[0061] The remaining operations are the same as in Example 4.

[0062] Example 6

[0063] The present invention provides a method for preparing a bone filling scaffold with dual responsiveness to near-infrared light and magnetic field. The method differs from Example 2 in that silver nanoparticles are added to the methacrylic anhydride gelatin solution obtained in step (3) so that the concentration of the silver nanoparticles is 0.01wt%. The remaining operations are exactly the same as those in Example 4.

[0064] Example 7

[0065] The present invention provides a method for preparing a bone filling scaffold with dual responsiveness to near-infrared light and magnetic field. The method differs from Example 5 in that vascular endothelial growth factor is added to the methacrylic anhydride gelatin solution obtained in step (3) so that the concentration of the vascular endothelial growth factor is 25 ng / mL, and the remaining operations are exactly the same as those in Example 5.

[0066] Comparative Example 1

[0067] The difference from Example 1 is that nano-iron tetroxide particles are not added in step (1), and the remaining operations are exactly the same as in Example 1.

[0068] The product pictures of 3D printed polyetherimide-ferroferric oxide scaffolds prepared in Example 1 (P-1% Fe3O4), Example 2 (P-2% Fe3O4) and Comparative Example 1 (PEI) are as follows: Figure 2 .

[0069] Figure 3The temperature rise diagram of the 3D printed polyetherimide-ferroferric oxide stents prepared in Example 1 (P-1% Fe3O4), Example 2 (P-2% Fe3O4) and Comparative Example 1 (PEI) after near-infrared light irradiation. It can be seen from the figure that after the stent prepared by the present invention is irradiated with near-infrared light, the surface temperature of the stent gradually increases with time and then tends to be stable, which can reach above 60°C, and has strong photothermal properties, which is sufficient to kill bacteria.

[0070] Figure 4 The vibrating sample strong magnetometer magnetic detection diagram of the 3D printed polyetherimide-ferroferric oxide bracket prepared in Example 1 (P-1% Fe3O4) and Example 2 (P-2% Fe3O4). It can be seen from the figure that the higher the Fe3O4 content, the stronger the magnetism of the bracket.

[0071] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A bone filling scaffold with dual responsiveness to near-infrared light and magnetic field, characterized in that: The bone filling scaffold includes a 3D printed scaffold and a filler filled inside the 3D printed scaffold; The raw materials of the 3D printed bracket are polyetherimide and nano-ferroferric oxide; The filler is methacrylic anhydride gelatin.

2. According to claim 1, a bone filling scaffold having dual responsiveness to near-infrared light and magnetic field, characterized in that: The mass ratio of the polyetherimide to the nano-ferroferric oxide is 1:0.01-0.05; The filling amount of the filler in the 3D printed bracket is 0.5-1.5 mL / mm 3 .

3. The bone filling scaffold with dual responsiveness to near infrared light and magnetic field according to claim 1, characterized in that: The methacrylic anhydride gelatin is loaded with active substances, and the active substances include silver nanoparticles or vascular endothelial growth factor.

4. A bone filling scaffold with dual responsiveness to near infrared light and magnetic field according to claim 3, characterized in that: The concentration of the silver nanoparticles is 0.01-0.05wt%, and the concentration of the vascular endothelial growth factor is 25ng / mL.

5. The bone filling scaffold with dual responsiveness to near infrared light and magnetic field according to claim 1, characterized in that: The bone filling scaffold also includes a polydopamine connecting layer between the 3D printed scaffold and the filler.

6. A method for preparing a bone filling scaffold having dual responsiveness to near infrared light and magnetic field according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) weighing polyetherimide and nano-iron tetroxide powder according to the mass ratio, mixing them evenly, and then preparing polyetherimide-iron tetroxide 3D printing filaments through a twin-screw extruder, and then preparing the polyetherimide-iron tetroxide 3D printing filaments through 3D printing to obtain a porous polyetherimide-iron tetroxide scaffold; (2) Methacrylic gelatin is prepared into a hydrogel solution, and the hydrogel solution is injected into the porous polyetherimide-ferroferric oxide scaffold, and then cured and dried to obtain a bone filling scaffold with dual responsiveness to near-infrared light and magnetic field.

7. A method for preparing a bone filling scaffold having dual responsiveness to near infrared light and magnetic field according to claim 6, characterized in that: The diameter of the polyetherimide-ferroferric oxide 3D printing filament in step (1) is 1.50-2.00 mm, the nozzle temperature of the 3D printing is 330-405° C., and the base plate temperature is 120-200° C.; The 3D printing has a porosity of 35-65% and a layer height of 0.1-0.3 mm.

8. The method for preparing a bone filling scaffold having dual responsiveness to near infrared light and magnetic field according to claim 6, characterized in that: Step (1) also includes preparing a polydopamine connecting layer on the surface of the porous polyetherimide-ferroferric oxide scaffold, and the specific method is: immersing the polyetherimide-ferroferric oxide scaffold in a dopamine solution, stirring at 600-800 rpm for 12-24 hours under light-proof conditions, and then washing and drying; The method for preparing the dopamine solution is to add dopamine into a Tris-HCl buffer solution with a concentration of 10 mmol / L and a pH of 8.5 to prepare a dopamine solution with a concentration of 2 mg / mL.

9. The method for preparing a bone filling scaffold having dual responsiveness to near infrared light and magnetic field according to claim 6, characterized in that: The concentration of the hydrogel solution in step (2) is 5-15% w / v; The preparation method of the hydrogel solution is as follows: adding LAP (phenyl (2,4,6-trimethylbenzoyl) lithium phosphate) photoinitiator into phosphate buffer and stirring to dissolve to obtain a photoinitiator standard solution with a concentration of 0.25% w / v, adding methacrylic anhydride gelatin into the photoinitiator standard solution and stirring to dissolve at 60-70° C. to obtain a hydrogel solution; The curing is performed by irradiating with a 405nm light source for 15-30s. The drying is freeze-drying at -80°C for 48-72h.

10. The method for preparing a bone filling scaffold having dual responsiveness to near infrared light and magnetic field according to claim 6, characterized in that: Step (2) also includes adding active substances into the hydrogel solution for loading.

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