Fused deposition modeling printed ferroferric oxide functionalized biodegradable polymer nano-composite bone scaffold with near-infrared light / magnetic field activated shape memory and thermal therapy functions and preparation method of fused deposition modeling printed ferroferric oxide functionalized biodegradable polymer nano-composite bone scaffold

Abstract

The invention belongs to the field of biomedical polymer material and additive manufacturing, and discloses a fused deposition modeling printed ferroferric oxide functionalized biodegradable polymer nano composite bone scaffold with near-infrared light / magnetic field activated shape memory and thermal therapy functions, PLA is used as a matrix, TBC is used for adjusting the glass transition temperature, Fe3O4 nano particles are doped, and the composite bone scaffold is prepared. And carrying out fused deposition modeling printing preparation. Fe3O4 endows the stent with near-infrared light / magnetic field dual response, wireless control shape memory is achieved, the compressed and implanted stent recovers the form in vivo to adaptively fill complex bone defects, and meanwhile controllable local high temperature is generated through the photo-thermal / magnetothermal effect to inhibit tumor cells. The stent has a communicated porous structure, and the compression strength is matched with cancellous bone; tBC improves hydrophilicity and degradability, Fe3O4 degrades and releases iron ions, and proliferation, differentiation and biomineralization of osteoblasts are promoted synergistically. The stent has minimally invasive, tumor treatment and bone repair capabilities, and provides a new strategy for complex bone defects.

Description

TECHNICAL FIELD

[0001] The application relates to the field of biomedical polymer materials and additive manufacturing technology, in particular to a fused deposition modeling printing Fe3O4 functionalized biodegradable polymer nanocomposite bone scaffold with near-infrared light / magnetic field activated shape memory and thermotherapy functions and a preparation method thereof and application thereof in complex bone defect repair. BACKGROUND

[0002] In clinical medical practice, the treatment of bone tumors is mainly based on extensive resection. Although this method can effectively control tumor progression, it often forms complex and irregular bone defects after surgery, and the remaining tumor cells also have the risk of recurrence. In traditional bone repair methods, autologous bone transplantation will cause damage to the donor site, allogeneic bone transplantation faces the risk of immune rejection and disease transmission, and conventional artificial bone scaffolds not only are difficult to implant minimally invasively, but also lack synergistic anti-tumor function, and cannot meet the treatment needs of integrated defect repair and tumor inhibition.

[0003] Additive manufacturing (AM) technology, especially fused deposition modeling (FDM) 3D printing technology, has shown significant advantages in the field of customized bone scaffold preparation due to its wide material compatibility and convenient operation characteristics, and can accurately prepare scaffolds according to the specific morphology of patient bone defects. However, the polylactic acid (PLA) scaffold used in traditional FDM printing has the problem of too high glass transition temperature (Tg≈60℃), which is easy to cause thermal damage to the surrounding normal tissues when the shape memory function is activated by thermal stimulation; and the PLA scaffold without functional modification does not have tumor inhibition ability, and is difficult to meet the repair needs of tumor-related bone defects.

[0004] Tributyl citrate (TBC) as a non-toxic plasticizer can effectively reduce the glass transition temperature of PLA to the physiological temperature range (40-45℃), but the scaffold composed of only PLA and TBC lacks magnetic response or light response performance, and cannot realize non-contact function activation. Iron oxide (Fe3O4) nanoparticles have good biocompatibility, not only can generate magnetic heat / light heat effect through magnetic hysteresis loss or light absorption, but also can release iron ions to participate in bone metabolism and promote the growth of osteogenic-related cells during the degradation process. At present, there is no research on combining PLA, TBC and Fe3O4 to prepare a composite bone scaffold with shape memory, thermotherapy and osteogenesis promotion functions by FDM 3D printing technology, especially lacking of functional adaptation design for tumor-related bone defect repair.

[0005] The core deficiencies of the prior art are as follows: firstly, for complex bone defect repair, the traditional bracket needs to be implanted by expanding the surgical incision, which is poor in minimally invasive and difficult to accurately match the irregular defect boundary; secondly, the bracket does not have a hyperthermia function and cannot inhibit residual tumor cells after surgery, which may cause recurrence; thirdly, the T g of the PLA-based bracket is too high, which may easily damage the surrounding tissue when the shape memory is activated by heat; fourthly, there is no scheme to combine Fe3O4 functionalization with 3D printing technology to realize the preparation of a multifunctional bone bracket. Therefore, the development of a composite bone bracket with minimally invasive implantation capacity, double-response activation characteristics, and the ability to simultaneously achieve tumor inhibition and bone repair has become the key to solving the problem of tumor-related bone defect repair. SUMMARY

[0006] In view of the problems of poor minimally invasive, lack of anti-tumor function of the bracket, and high glass transition temperature of the PLA bracket which may easily damage the surrounding tissue in the prior art for complex tumor-related bone defect repair, the present application provides a fused deposition modeling printing Fe3O4 functionalized biodegradable polymer nanocomposite bone bracket with near-infrared light / magnetic field activated shape memory and hyperthermia function and a preparation method thereof. The TBC adjusts the glass transition temperature of the PLA to the physiological range, and the Fe3O4 gives the bracket a near-infrared / magnetic field double-response performance. As an implant material for bone defect after tumor resection, the bracket is implanted by minimally invasive compression, expands to fill the defect under the body light / magnetic stimulation, and simultaneously plays multiple functions of hyperthermia tumor inhibition, bone regeneration promotion, and biodegradable absorption, thereby providing a new technical solution for complex tumor-related bone defect repair.

[0007] To achieve the above object, the core technical scheme of the present application is: taking PLA as the matrix material, TBC as the plasticizer, and Fe3O4 as the functional filler, the PLA particles, TBC and Fe3O4 powder are dispersed and mixed in an organic solvent, then dried, cast into a film, crushed and granulated, and then a composite bone scaffold is prepared by FDM 3D printing technology. By adjusting the proportion of each component and the process parameters, the precise matching of the function and performance of the scaffold is realized. Fe3O4 nanoparticles are superparamagnetic, and the saturation magnetization linearly adjustable with the content of Fe3O4 reaches 0.1-0.3 emu / g under the detection of a vibrating sample magnetometer with a maximum magnetic field of 2.5T. The present application believes that when the composite bone scaffold is irradiated by near-infrared light or placed in an alternating magnetic field environment, the Fe3O4 nanoparticles will absorb energy and convert it into heat, causing the overall temperature of the scaffold to rise above the glass transition temperature (40-42℃) of the PLA-TBC / Fe3O4 composite scaffold. At this time, the PLA-TBC / Fe3O4 composite scaffold molecular chain restores its movement ability, and the scaffold can recover from the temporary shape compressed before the operation to the initial design shape, realizing the self-adaptive filling of complex irregular bone defects. At the same time, the magnetocaloric effect and photothermal effect of Fe3O4 can precisely raise the temperature of the scaffold to 45-50℃, which can effectively destroy the structure and function of tumor cells and inhibit the proliferation of tumor cells, while not causing significant damage to the surrounding normal tissues, and can be used to remove residual tumor cells after the operation, reducing the risk of recurrence. During the degradation of the scaffold, TBC improves the hydrophilicity and degradability, while Fe3O4 slowly releases iron ions, which are essential trace elements for the human body and can participate in bone metabolism, promoting the proliferation and differentiation of osteogenic-related cells; at the same time, the interconnected porous structure of the scaffold provides sufficient space for cell growth, and a mineralized layer containing Ca and P elements can be formed in the simulated body fluid (SBF), further promoting new bone formation.

[0008] As a preferred scheme, the material composition of the PLA-TBC / Fe3O4 composite bone scaffold according to the present application is designed as follows: the mass percentage of PLA, TBC and Fe3O4 is set to (85-95):(5-10):(5-15). Among them, TBC accounts for 5-10%, which can reduce the glass transition temperature of PLA to 40-42℃, avoiding damage to the surrounding tissues when heat-activated shape memory; Fe3O4 accounts for 5-15%, which can ensure that the scaffold has excellent near-infrared / magnetic field response performance, and will not affect the material flowability and molding quality during FDM printing.

[0009] As a preferred scheme, the molecular weight of PLA according to the present application is about 1.5×10 5 g / mol; the molecular weight of TBC is about 360.44 g / mol; the particle size of Fe3O4 is 200-500 nm, and the purity is ≥99%.

[0010] As a preferred solution, the organic solvent used in the application is dichloromethane (DCM).

[0011] As a preferred solution, the dispersion method used in the application is ultrasonic dispersion. The ultrasonic dispersion temperature is 25-37℃, and the dispersion time is 10-30min.

[0012] As a preferred solution, the mixing method used in the application is magnetic stirring, the temperature is 30-37℃, and the stirring time is 1-2h.

[0013] As a preferred solution, the slurry drying film casting form used in the application is placed at room temperature for 12-24h to form a film, and the pulverization and granulation form used is granulated by a paper shredder, and then placed in a vacuum drying oven for drying for 24h.

[0014] As a preferred solution, the extrusion method used in the application is to use a single screw extruder to extrude, set the feeding end temperature to 165-175℃, the discharging end temperature to 170-180℃, and the rotation speed to 20-50 rpm, and extrude to form FDM printing wire with a diameter of 1.75±0.1mm.

[0015] As a preferred solution, the application uses computer aided design (CAD) software to design a model, then converts the model into STL format and imports it into an FDM 3D printer; the prepared printing wire is loaded into the printer, the heating bed temperature is set to 40-50℃ to ensure stable adhesion of the wire, the nozzle temperature is set to 175-180℃ to ensure sufficient melting of the wire, the printing path adopts 0 / 90° orthogonal filling, the printing speed is 20-30mm / s, and the layer thickness is 0.1-0.2mm to balance the forming precision and efficiency, the three-dimensional model is printed layer by layer, and after printing is completed, it is naturally cooled to room temperature to obtain a 3D printed iron oxide functionalized degradable PLA-TBC / Fe3O4 composite bone scaffold.

[0016] The 3D printed iron oxide functionalized degradable PLA-TBC / Fe3O4 composite bone scaffold provided by the application has the following outstanding advantages compared with the prior art.

[0017] (1) The composite bone scaffold prepared by the application has minimally invasive implantation and precise adaptability: the scaffold can generate a photothermal / magnetic thermal temperature rise of >45 DEG C under the action of 808 nm near-infrared laser or 55 kHz alternating magnetic field, realize the shape memory behavior of light-magnetic double response, the shape fixing rate is >90%, the shape recovery rate is >90%, and the recovery time is <90 s. Before the operation, the scaffold can be compressed to 1 / 3-1 / 2 of the original volume, implanted into the bone defect site through a minimally invasive incision, and the shape memory function is activated by means of near-infrared light or alternating magnetic field after the operation, so that the scaffold can automatically recover to the original shape and precisely match the complex irregular defect boundary, without the need to enlarge the surgical incision, reduce surgical trauma and reduce the risk of infection.

[0018] (2) The composite bone scaffold prepared by the application has a double-response hyperthermia tumor inhibition function: relying on the magnetic and photothermal properties of Fe3O4, the scaffold has a near-infrared (808 nm, 0.4-1.2 W / cm 2 ) / alternating magnetic field (55 kHz, 500-600A) double-response capability, and the hyperthermia temperature can be controlled at 45-50 DEG C. After co-culturing with A673 tumor cells, the cell survival rate is reduced to <41% and <11% respectively after photothermal or magnetic thermal treatment for 10 min, which to some extent inhibits the activity of tumor cells.

[0019] (3) The mechanical properties of the composite bone scaffold prepared by the application match the human bone tissue: the Fe3O4 nanoparticles are uniformly dispersed in the PLA matrix, play a dispersion strengthening role, and make the compression strength of the scaffold reach 16.4 MPa and the elastic modulus reach 346.8 MPa, which are highly matched with the mechanical properties (compression strength 2-18 MPa) of human cancellous bone, and can meet the mechanical support requirements in the bone defect repair process, avoiding implantation failure caused by insufficient strength of the scaffold.

[0020] (4) The composite bone scaffold prepared by the application has good biocompatibility and osteogenic activity: the introduction of TBC reduces the glass transition temperature of PLA to the physiological range, avoiding damage to the surrounding tissue during thermal activation; the iron ions released during the degradation of the scaffold can promote the proliferation of osteoblasts, and can form a uniform calcium and phosphorus deposition mineralization layer in the simulated body fluid. The cell proliferation density of the scaffold co-cultured with MC3T3-E1 cells for 7 days is higher than that of the pure PLA-TBC control, and the alkaline phosphatase (ALP) staining area and intensity are significantly higher than those of the pure PLA-TBC control after 14 days, which significantly promotes osteogenic differentiation.

[0021] (5) The prepared composite bone scaffold has controllable degradation rate: the scaffold is soaked in PBS solution containing protease K for 3 weeks, the weight loss rate is 10-17%, iron ions are continuously released, the degradation rate can be regulated by the content of Fe3O4, can match the rate of new bone formation, avoid insufficient support due to too fast degradation or affect new bone integration due to too slow degradation, and has no long-term implantation risk. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 : Figure 1 Surface morphology diagrams of Comparative Example 1 and Examples 1, 2 and 3.

[0023] Figure 2 : Figure 1 In vitro degradation and in vitro mineralization diagrams of Comparative Example 1 and Examples 1, 2 and 3.

[0024] Figure 3 : Figure 1 7-day cell proliferation and 14-day alkaline phosphatase staining (ALP) staining of Comparative Example 1 and Examples 1, 2 and 3.

[0025] Figure 4 : Figure 1 Photothermal shape memory and magnetic heat shape memory case recovery process diagram of Example 2.

[0026] Figure 5 : Figure 1 Photothermal and magnetic heat tumor cell inhibition diagram of Comparative Example 1 and Example 2. DETAILED DESCRIPTION

[0027] The technical solutions of the present application are further described below in combination with the drawings, specific examples and comparative examples. The raw materials and equipment used are commercially available conventional products. Unless otherwise specified, the experimental methods are conventional experimental methods. It should be noted that the examples and comparative examples described below are part of the present application, not all. Unless otherwise defined, all technical terms used in the following examples have the same meaning as generally understood by those skilled in the art in the field described.

[0028] The surface morphology characterization process of the comparative examples and examples of the present application is as follows: the macroscopic morphology of the scaffold is observed using an industrial microscope; the microscopic surface morphology of the scaffold is observed using a scanning electron microscope.

[0029] The in vitro degradation and in vitro mineralization processes of the inventive examples and the comparative examples are as follows: in the in vitro degradation experiment, the degradation performance of the inventive examples and the comparative examples was evaluated by immersing them in a phosphate buffer solution (PBS) containing protease K at 37°C, and the degradation morphology was observed under a scanning electron microscope after the immersion was completed; in the in vitro mineralization experiment, the prepared inventive examples and the comparative examples were immersed in a simulated body fluid (SBF) solution and kept at 37°C, and the SBF solution was replaced every 1 week. After reaching the set time point, the scaffold was taken out of the SBF, rinsed with deionized water, and dried in an electric heating drying box. Subsequently, the surface deposition of the scaffold after immersion in the SBF was observed using a scanning electron microscope (SEM).

[0030] The cell proliferation and ALP staining experiment processes of the inventive examples and the comparative examples are as follows: before cell culture, the scaffold was sterilized by ethylene oxide and then immersed in culture medium for humidification. The cell suspension was inoculated onto the scaffold in a 24-well plate containing 10% fetal bovine serum (FBS) and 1% antibiotics in DMEM medium, and incubated at 37°C. The proliferation and osteogenic differentiation of MC3T3-E1 cells on the inventive examples and the comparative examples were evaluated by nuclear / F-actin immunofluorescence staining and alkaline phosphatase (ALP) staining. Cell proliferation was cultured for a specified number of days after inoculation, stained with a specific reagent, observed and photographed under a fluorescence microscope, and the images were combined; the latter was cultured in osteogenic induction medium after cell adhesion, cultured for a specified number of days, and photographed under an inverted microscope after BCIP / NBT staining.

[0031] The photothermal shape memory and magneto-thermal shape memory case recovery experiment processes of the inventive examples and the comparative examples are as follows: in the photothermal shape memory case, 808 nm near-infrared (NIR) laser was used to irradiate the strip-shaped sample at a power density of 0.4 W / cm 2 ; in the magneto-thermal shape memory case, each group of samples was first placed in hot water above the glass transition temperature (T g ) to release the internal stress generated during printing; then the sample was placed back in the hot water and reduced to a certain shape under external force, and then placed in ice water while keeping the external force unchanged to cool and set. After the set sample was taken out and stored at room temperature, it was placed in an alternating magnetic field, and the recovery time and process of the sample were recorded.

[0032] The photothermal and magneto-thermal tumor cell inhibition experiment processes of the inventive examples and the comparative examples are as follows: A673 cells were inoculated onto the samples for co-culture for 24 hours, and then 808 nm near-infrared (NIR) laser (power density 0.4 W / cm 2) and an alternating magnetic field generator (600A) to heat the scaffold until the temperature reaches 45℃, and each sample is heated for 10 minutes. After the treatment is completed, the culture plate is returned to the incubator for continuous culture for 12 hours. Then, live cells and dead cells are stained with Calcein and propidium iodide (PI), respectively, and the stained images are taken by fluorescence microscopy. Example 1

[0033] (1) PLA and TBC were weighed in a mass ratio of 9:1, PLA was added to dichloromethane (mass-volume ratio of 1 g / 10 mL), and stirred in a magnetic stirrer until completely dissolved, then TBC was added and stirred for 1 h to obtain a PLA-TBC mixture; (2) Fe3O4 powder with a mass ratio of 95:5 to PLA-TBC was weighed and dispersed in dichloromethane (mass-volume ratio of 1 g / 10 mL) at a temperature of 25℃ for 30 min, then the Fe3O4 dispersion was added to the PLA-TBC mixture and stirred for 2 h to obtain a uniform mixed slurry; (3) the mixed slurry was dried at room temperature for 12 h to form a solid film; the solid film was cut into small pieces and dried in a vacuum drying oven for 24 h, then the pieces were added to a screw extruder, the feeding end temperature was set to 165-175℃, the discharge end temperature was set to 170-180℃, and the rotation speed was set to 20-50 rpm, and the extrusion formed a printing filament with a diameter of 1.75±0.1 mm; (4) a three-dimensional model of the composite bone scaffold was designed using CAD software and converted to STL format, and imported into the FDM 3D printer; the printing filament was loaded into the printer, the heating bed temperature was set to 40-50℃, the nozzle temperature was set to 175-180℃, the printing speed was set to 20-30 mm / s, and the layer thickness was set to 0.1-0.2 mm, and the model was printed layer by layer, and after printing, it was naturally cooled to room temperature to obtain Example 1.

[0034] According to the surface topography observation, the overall scaffold of Example 1 was black, the surface was smooth, the struts were well overlapped, and the side showed the characteristics of layer-by-layer stacking of fused deposition modeling.

[0035] According to the in vitro degradation and in vitro mineralization experiments, Example 1 was stable in degradation in phosphate buffer solution (PBS) containing protease K (37℃), and large corrosion cavities were formed on the surface after 3 weeks, with a mass loss lower than that of Examples 2 and 3 and higher than that of Comparative Example 1; after soaking in simulated body fluid (SBF), a calcium and phosphorus deposition layer was formed on the surface, but the deposition particle density and uniformity were lower than those of Examples 2 and 3 and significantly higher than that of Comparative Example 1, and the addition of Fe3O4 promoted the biological mineralization ability of the scaffold.

[0036] Through cell proliferation and ALP staining experiments, the MC3T3-E1 cells can normally adhere, spread and proliferate on the surface of the scaffold of Example 1, the cell density is higher than that of Comparative Example 1, but lower than that of Examples 2 and 3; after 14 days of culture, ALP staining is performed, the staining intensity and area of Example 1 are higher than those of Comparative Example 1, but lower than those of Examples 2 and 3, indicating that it has the ability to promote the early differentiation of osteoblasts, and the ability improves with the increase of the content of Fe3O4. Example 2

[0037] The difference between this example and Example 1 is only that the mass ratio of Fe3O4 to PLA-TBC is 10:90; the specifications of the remaining raw materials, the preparation steps and the process parameters are consistent with those of Example 1, and finally Example 2 is obtained.

[0038] Through surface morphology observation, the scaffold of Example 2 is black as a whole, the surface photographed by scanning electron microscope is slightly rougher than that of Example 1, the struts are well overlapped, the side clearly presents the printing characteristics of layer-by-layer stacking of fused deposition modeling, and there is no obvious crack or defect.

[0039] Through in vitro degradation and in vitro mineralization experiments, after Example 2 scaffold is soaked in PBS buffer solution for 1 week, the corrosion morphology is more significant than that of Example 1 and Comparative Example 1, the weight loss also increases, and after soaking in simulated body fluid (SBF), more deposits appear on the surface, and its biological mineralization ability is better than that of Example 1.

[0040] Through cell proliferation and ALP staining experiments, the MC3T3-E1 cells adhere, spread and proliferate well on the surface of the scaffold of Example 2, and the cell density is higher than that of Example 1 and Comparative Example 1; after 14 days of culture, the ALP staining results show that the staining intensity is significantly higher than that of Example 1 and Comparative Example 1.

[0041] Through photothermal shape memory and magnetic shape memory experiments, Example 2 exhibits certain remote light-driven shape memory recovery performance under 808 nm near-infrared light irradiation; in an alternating magnetic field, Example 2 can expand from a tight spherical shape to the original snowflake shape under the action of the magnetic field, to a certain extent, verifying the feasibility of magnetic field-driven shape memory.

[0042] Through photothermal and magnetic thermal inhibition of tumor cells, after Example 2 is irradiated by 808 nm near-infrared light (temperature 45℃, 10min), the survival rate of A673 cells decreases to about 41% of the control group; after being treated by 600A alternating magnetic field (temperature 45℃, 10min), the cell survival rate decreases to about 11% of the control group, and the magnetic thermal inhibition effect is the best among all groups, and Comparative Example 1 has no tumor inhibition effect. Example 3

[0043] The difference between this embodiment and Example 1 is only that the mass ratio of Fe3O4 to PLA-TBC is 15:80; the specifications of the remaining raw materials, the preparation steps and the process parameters are consistent with those of Example 1, and finally a P-T / 15Fe composite bone scaffold is obtained.

[0044] Through surface morphology observation, the scaffold of Example 3 as a whole presents a deep black color, and the scanning electron microscope shows that there is a trace of Fe3O4 particle agglomeration on the surface, but the strut lap integrity is good, and the side still maintains the printing characteristics of layer-by-layer stacking of fused deposition forming, without obvious structural damage.

[0045] Through in vitro degradation and in vitro mineralization experiments, the corrosion morphology of Example 3 in the PBS solution containing protease K (37°C) is the most serious within 3 weeks, and the mass loss is the highest among all groups; after soaking in the simulated body fluid (SBF), the surface calcium and phosphorus deposition particle density is higher than that of Example 1 and Comparative Example 1.

[0046] Through cell proliferation and ALP staining experiments, MC3T3-E1 cells can normally adhere and proliferate on the surface of the scaffold of Example 3, and the cell density after 7 days of culture is higher than that of Example 1, 2 and Comparative Example 2; the ALP staining intensity and positive area after 14 days of culture are higher than those of Example 1, 2 and Comparative Example 1. Comparative Example 1

[0047] The difference between this comparative example and Example 1 is only that Fe3O4 is not added, and only a PLA-TBC scaffold is prepared; the specifications of the remaining raw materials, the preparation steps and the process parameters are consistent with those of Example 1.

[0048] Through surface morphology observation, the scaffold of Comparative Example 1 as a whole presents a milky white color, and the smoothness of the surface observed by scanning electron microscope is better than that of Examples 1-3, the struts are well lapped, and the side presents the printing characteristics of layer-by-layer stacking of fused deposition forming, without color change related to pigments.

[0049] Through in vitro degradation and in vitro mineralization experiments, the weight loss rate of Comparative Example 1 in the PBS solution containing protease K (37°C) within 3 weeks is the lowest among all groups; after soaking in the simulated body fluid (SBF), only a trace of calcium and phosphorus deposition is formed on the surface, and the deposition particle density and thickness are significantly lower than those of Examples 1-3, without the promotion effect of Fe3O4-mediated biomineralization.

[0050] Through cell proliferation and ALP staining experiments, the cell proliferation density and ALP staining intensity on Comparative Example 1 are lower than those of Examples 1, 2 and 3.

[0051] Through photothermal and magnetic thermal inhibition of tumor cells, the cell survival rate of Comparative Example 1 after 0.4 W / cm2 808nm near-infrared light or 600A alternating magnetic field treatment (temperature 45℃, 10min), A673 cell survival rate and before and after no significant difference, due to the lack of Fe3O4 photothermal / magnetic heat conversion ability, no tumor inhibition effect.

Claims

1. A fused deposition modeling (FDM) printed biodegradable polymer nanocomposite bone scaffold functionalized with magnetite (Fe3O4) and near-infrared light / magnetic field activated shape memory and thermotherapy functions, characterized in that, The composite bone scaffold comprises, by weight percentage: 85-95% polylactic acid (PLA), 5-10% tributyl citrate (TBC), and 5-15% iron(III) oxide (Fe3O4) nanoparticles; the Fe3O4 particles have a diameter of 200-500 nm and are uniformly dispersed in the PLA-TBC matrix; the composite bone scaffold is fabricated into an interconnected porous structure by fused deposition modeling (FDM) 3D printing, with a pore size of 600-800 μm, a porosity of 40-60%, a compressive strength ≥16 MPa, and a glass transition temperature T0. g It will drop to 40–42℃.

2. The fused deposition modeling printed iron(III) oxide functionalized biodegradable polymer nanocomposite bone scaffold with near-infrared light / magnetic field activated shape memory and thermotherapy functions according to claim 1, characterized in that, The Fe3O4 nanoparticles are superparamagnetic, and their saturation magnetization is linearly adjustable with the Fe3O4 content, reaching 0.1–0.3 emu / g under the detection of a vibrating sample magnetometer with a maximum magnetic field of 2.5T.

3. The fused deposition modeling printed iron(III) oxide functionalized biodegradable polymer nanocomposite bone scaffold with near-infrared light / magnetic field activated shape memory and thermotherapy functions according to claim 1, characterized in that, The bracket can generate a photothermal / magnetic temperature rise of ≥45℃ under the action of 808 nm near-infrared laser or 55 kHz alternating magnetic field, realizing shape memory behavior with dual photothermal and magnetic response, shape fixation rate ≥90%, shape recovery rate ≥90%, and recovery time ≤90 s.

4. The fused deposition modeling printed iron(III) oxide functionalized biodegradable polymer nanocomposite bone scaffold with near-infrared light / magnetic field activated shape memory and thermotherapy functions as described in claim 1, characterized in that, The mass loss rate was 10–17% after degradation at 37°C for 3 weeks in phosphate buffer, with continuous release of iron ions; a calcium phosphate deposit layer was formed on the surface after immersion in simulated body fluid for 3 weeks.

5. A fused deposition modeling (FDM) printed biodegradable polymer nanocomposite bone scaffold functionalized with near-infrared light / magnetic field activated shape memory and thermotherapy functions, as described in claim 1, is characterized in that... The scaffold co-cultured with MC3T3-E1 cells for 7 days showed a higher cell proliferation density compared to the pure PLA-TBC control. The alkaline phosphatase (ALP) staining area and intensity were significantly higher than those of the pure PLA-TBC control after 14 days. After co-culturing with A673 tumor cells, the cell viability decreased to ≤41% and ≤11% after photothermal or magnetothermal treatment for 10 min, respectively.

6. A method for preparing the fused deposition modeling printed iron(III) oxide functionalized biodegradable polymer nanocomposite bone scaffold with near-infrared light / magnetic field activated shape memory and thermotherapy functions as described in claim 1, comprising: (1) Dissolve PLA in dichloromethane according to the formula ratio, add TBC and mix well to obtain PLA / TBC solution; (2) After dispersing Fe3O4 nanoparticles in dichloromethane, mix them with PLA-TBC solution, evaporate the solvent, cut them into pieces, and extrude them into printing filaments with a diameter of 1.75±0.1 mm; (3) Use fused deposition modeling, with a nozzle temperature of 175-180℃, a hot bed temperature of 40-50℃, and a printing speed of 20-30 mm / s, to print the target porous scaffold according to the preset three-dimensional model.

7. The method according to claim 6, characterized in that, In step (2), Fe3O4 is dispersed by ultrasonic treatment for 10-30 minutes to ensure uniform particle distribution; in step (3), the printing path is filled with 0 / 90° orthogonal filling and the layer thickness is 0.1–0.2 mm to ensure interconnected pores and mechanical properties.

8. The use of the fused deposition modeling printed iron(III) oxide functionalized biodegradable polymer nanocomposite bone scaffold with near-infrared light / magnetic field activated shape memory and thermotherapy functions as described in claim 1 in the preparation of implantable materials for treating complex irregular bone defects, especially bone defects after tumor resection. It is implanted through minimally invasive compression and unfolds to fill the defect under in vivo light / magnetic stimulation, while exerting multiple functions such as thermotherapy to inhibit tumors, promote bone regeneration, and degradability and absorption.

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