Modified polyether ketone ketone composite material and preparation method and application thereof

Abstract

The application discloses a modified polyether ketone ketone composite material and a preparation method and application thereof, and relates to the technical field of composite materials, in particular to a modified polyether ketone ketone composite material, which comprises a sulfonated porous composite support, a chemotactic factor and a methacrylamide crystal glue; the preparation raw material of the sulfonated porous composite support comprises polyether ketone ketone and strontium-cerium doped bioactive glass; the chemotactic factor and the methacrylamide crystal glue are loaded in the pores of the sulfonated porous composite support. The three-dimensional porous composite support prepared by adopting PEKK and BG is used as the main body of the composite material, the chemotactic factor and the GelMA crystal glue are loaded in the pores, so that the immune regulation characteristics and the bone induction property of the PEKK-based support are enhanced; the prepared modified polyether ketone ketone composite material can significantly promote the proliferation and osteogenic differentiation of mesenchymal stem cells, is beneficial to the recruitment and polarization of macrophages, has a good bone formation effect in the immune-bone cascade reaction, and can accelerate the osteogenic differentiation process of the mesenchymal stem cells after being co-cultured with the macrophages.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, and particularly relates to a modified polyether ketone ketone composite material and a preparation method and application thereof. BACKGROUND

[0002] Bone defects caused by trauma, infection or surgical resection usually require bone implants to accelerate the recovery of the corresponding tissue at the injury site. Polyether ketone ketone (PEKK) is a thermoplastic polymer material, which has a similar elastic modulus to natural bone, good biocompatibility and radiolucent properties, and is widely used in the biomedical field. However, the inherent biological inertia of PEKK leads to a lack of interaction between it and the tissue, which severely limits its clinical application as an implant.

[0003] In order to make PEKK material have better immunomodulatory effect, many modification methods have been proposed at present, including chemical treatment, surface coating and doping of bioactive materials. Among them, bioactive glass (BG) is a bioactive material widely used in bone transplantation. There are studies on using bioactive glass to improve the surface bioactivity of PEKK, but the osteogenic performance of most modified materials is general. In addition, gelatin methacrylamide (GelMA) crystal gel has good biocompatibility and can be used in combination with cells, cytokines, drugs, exosomes and the like to enhance the repair ability of bone defects.

[0004] In addition, bone regeneration after implantation of a scaffold is a dynamic process. In the early stage of inflammatory response, the recruitment of macrophages to the damaged site helps the body to resist the invasion of pathogenic microorganisms, remove cell debris, secrete signal factors and initiate tissue regeneration. Chemokines appear in the early stage of tissue injury, and are a class of polypeptide proteins that can induce the recruitment and activation of a variety of cells in the inflammatory response. They can interact with homologous G protein-coupled receptors, activate downstream signals and provide clues for the directional migration of cells. However, there is no report on the application of chemokines to PEKK composite materials at present.

[0005] Therefore, there is an urgent need to develop a modified polyether ketone ketone composite material that can induce the recruitment of a variety of cells and promote osteogenic differentiation. SUMMARY

[0006] In order to overcome the problems existing in the prior art, one of the purposes of the present application is to provide a modified polyether ketone ketone composite material. The second purpose of the present application is to provide a preparation method of the modified polyether ketone ketone composite material. The third purpose of the present application is to provide an application of the modified polyether ketone ketone composite material. The present application designs a polyether ketone ketone-based composite scaffold by dynamically adjusting the immune behavior of macrophages in the host. PEKK and BG are obtained by a fused deposition molding technology to obtain a three-dimensional porous composite scaffold. The chemotactic factor MCP-1 and the GelMA crystal gel are loaded in the holes to enhance the immune regulation characteristics and bone induction of the PEKK-based scaffold under physiological conditions.

[0007] In order to achieve the above-mentioned purposes, the technical scheme adopted by the present application is:

[0008] The first aspect of the present application provides a modified polyether ketone ketone composite material, which comprises a sulfonated porous composite scaffold, a chemotactic factor and a methacrylamide crystal gel. The preparation raw material of the sulfonated porous composite scaffold comprises polyether ketone ketone and strontium-cerium doped bioactive glass. The chemotactic factor and the methacrylamide crystal gel are loaded in the holes of the sulfonated porous composite scaffold.

[0009] Preferably, the mass ratio of the polyether ketone ketone to the strontium-cerium doped bioactive glass is 97:(1-5).

[0010] Preferably, the mass ratio of the sulfonated porous composite scaffold to the methacrylamide crystal gel is (10-15):1.

[0011] Preferably, the chemotactic factor is monocyte chemoattractant factor 1 (MCP-1).

[0012] Preferably, the mass of the sulfonated porous composite scaffold is 100-150 mg.

[0013] Preferably, the preparation raw material of the sulfonated porous composite scaffold is a blend of polyether ketone ketone and strontium-cerium doped bioactive glass.

[0014] The second aspect of the present application provides a preparation method of the modified polyether ketone ketone composite material of the first aspect, which comprises the following steps:

[0015] S1, mixing polyether ketone ketone and strontium-cerium doped bioactive glass to obtain a composite scaffold by fused deposition molding;

[0016] S2, sulfonating the composite scaffold with acid liquid, and obtaining a sulfonated porous composite scaffold through hydrothermal treatment;

[0017] S3, loading methacrylated crystal glue into the pores of the sulfonated porous composite scaffold by a UV grafting method, and then immersing the sulfonated porous composite scaffold in a culture medium containing a chemotactic factor to load the chemotactic factor into the pores of the sulfonated porous composite scaffold, to obtain a modified polyether ketone ketone composite material.

[0018] Preferably, the strontium-cerium doped bioactive glass is prepared by a preparation method comprising the following steps: mixing tetraethyl orthosilicate, a calcium salt and a strontium salt in an alcohol solution to obtain a sol, drying to obtain a bioactive glass gel precursor, and performing heat treatment to obtain a bioactive glass powder containing strontium ions; immersing the bioactive glass powder containing strontium ions in a solution containing cerium ions, and then performing heat treatment to obtain a strontium-cerium doped bioactive glass mixture.

[0019] Preferably, in step S1, the fused deposition modeling is specifically: heating and melting the filament-shaped hot melt material, and extruding and forming through a nozzle of a spray head with micro nozzles; wherein the process parameters are: the feeding cylinder heating temperature is 300-500℃, the nozzle temperature is 300-500℃, the printing speed is 10-32mm / s, the needle thickness is 0.2-0.4mm, the micro wire width is 0.3-0.5mm, and the micro wire spacing is 1-2mm.

[0020] Preferably, in step S2, the acid liquid treatment is specifically: immersing and suspending the composite scaffold in concentrated sulfuric acid, and the immersion time is 0.5-3min.

[0021] More preferably, the concentration of the concentrated sulfuric acid is 95%-98%.

[0022] More preferably, in step S2, the acid liquid treatment is specifically: immersing the composite scaffold in concentrated sulfuric acid, and stirring at a constant rate to keep the composite scaffold in a suspended state in the concentrated sulfuric acid, and the immersion time is 0.5-3min.

[0023] Preferably, in step S2, the hydrothermal treatment time is 3-5h, and the hydrothermal treatment temperature is 80-130℃.

[0024] Preferably, in step S3, the UV grafting method is specifically: first immersing the sulfonated porous composite scaffold in a methacrylate solution, and performing grafting under ultraviolet light irradiation; then refilling the methacrylate solution into the scaffold pores, freezing, and performing secondary ultraviolet light irradiation to obtain a sulfonated porous composite scaffold loaded with methacrylated crystal glue.

[0025] More preferably, the concentration of the methacrylate solution GelMA solution is 5-20%(w / v), and the degree of substitution is 70%-90%.

[0026] More preferably, the methacrylate solution GelMA solution further comprises a photoinitiator (Lap) at a concentration of 0.05-0.5% (w / v).

[0027] More preferably, the time of the ultraviolet light irradiation is 50-150 min.

[0028] More preferably, the time of the secondary ultraviolet light irradiation is 0.5-2 min.

[0029] More preferably, the ultraviolet radiation intensity is 0.01-0.05 w / cm 2 . Further preferably, the ultraviolet radiation intensity is 0.01-0.03 w / cm 2 .

[0030] More preferably, the freezing temperature is -40~-10℃. Further preferably, the freezing temperature is -30~-20℃.

[0031] Preferably, the nutrition system of the chemotactic factor-containing medium is: 88-90% DMEM high-sugar medium, 8-12% serum, 1% penicillin-streptomycin.

[0032] Preferably, the concentration of the chemotactic factor in the chemotactic factor-containing medium is 1-5 mg / L. More preferably, the concentration of the chemotactic factor is 2-3 mg / L.

[0033] The third aspect of the present application provides an application of the modified polyether ketone ketone composite material in the preparation of a bone implant material.

[0034] The beneficial effects of the present application are:

[0035] 1) The present application provides a modified polyether ketone ketone composite material, wherein a three-dimensional porous composite scaffold is prepared by fusing and depositing polyether ketone ketone and strontium-cerium doped bioactive glass and then sulfonating, a chemotactic factor and a GelMA crystal glue are loaded in the pores, and a microporous reticular structure is formed on the surface. The material can significantly promote the proliferation and osteogenic differentiation of mesenchymal stem cells, and is conducive to promoting the recruitment and polarization of macrophages, and has good osteogenic effect in the immune-osteogenic cascade reaction.

[0036] 2) The bioactive glass of the modified polyether ketone ketone composite material of the application is doped with strontium and cerium, wherein strontium ions can stimulate the proliferation of osteoblasts and inhibit the activity of osteoclasts, and cerium ions can protect cells from oxidative stress, thereby inhibiting inflammatory response to a certain extent and promoting osteogenesis. The GelMA crystal gel has good biocompatibility, and the application loads the GelMA crystal gel in the pores of the sulfonated porous composite scaffold by ultraviolet grafting, further improves the biocompatibility of the composite material, and enhances the repair ability of bone defects. Monocyte chemoattractant protein 1 (MCP-1) is one of the key chemotactic factors for regulating macrophage migration, and the application loads the chemotactic factor in the PEKK composite material, which plays a key role in the immune-osteogenesis cascade reaction, and can accelerate the osteogenic differentiation process of mesenchymal stem cells after co-culture with macrophages. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 SEM and elemental analysis graphs of P, PCM and PBCM; wherein, (a) and (d) are SEM graphs of P at different magnifications; (b) and (e) are SEM graphs of PCM at different magnifications; (c) and (f) are SEM graphs of PBCM at different magnifications; (g) is an elemental analysis graph of P, PCM and PBCM.

[0038] Figure 2 Combination analysis of PEKK and GelMA crystal gel under ultraviolet irradiation; wherein, (a) is a reaction schematic diagram of PEKK and GelMA; (b) is an electron paramagnetic resonance spectrum; (c) is an infrared analysis graph;

[0039] Figure 3 Recruitment and polarization results of macrophages by P, PCM and PBCM; wherein, (a)-(c) are the effects of P, PCM and PBCM on macrophage migration, respectively; (d) is the number of cells induced by P, PCM and PBCM; (e) is a flow cytometry analysis graph; scale = 100 μm;

[0040] Figure 4 Proliferation results of mesenchymal stem cells by P, PCM and PBCM; wherein, (a) is a live / dead cell double staining graph of the composite scaffold, scale = 500 μm; (b) is a CCK-8 analysis graph;

[0041] Figure 5 In vitro osteogenesis of P, PCM and PBCM; wherein, (a) is an ALP and ARS staining graph of the composite scaffold; (b) is an ALP quantitative analysis graph; (c) is an ARS quantitative analysis graph; scale = 200 μm;

[0042] Figure 6Results of co-culture experiments of P, PCM and PBCM; (a)-(c) are the effects of P, PCM and PBCM on the migration of mesenchymal stem cells in growth medium, respectively; (d)-(f) are the effects of P, PCM and PBCM on the migration of mesenchymal stem cells in conditioned medium, respectively; (g)-(i) are the calcium deposition in the conditioned medium of P, PCM and PBCM, respectively; scale = 200 μm. DETAILED DESCRIPTION

[0043] The present application will be further described in details by specific examples. In the following examples, the raw materials used, unless specifically stated, can be obtained from conventional commercial sources or prepared by simple synthesis and isolation; the processes used, unless specifically stated, are conventional processes in the art.

[0044] Example 1

[0045] (1) Preparation of strontium-cerium doped bioactive glass

[0046] Strontium-cerium doped bioactive glass (BG) was prepared by sol-gel method and post-dipping method. Specifically, first, A solution (25 mL anhydrous ethanol, 3 mL TEOS) was added to B solution (8.2 mL ethanol, 12.4 mL water, 4.5 mL ammonia water) and stirred at 900 rpm for 20 min, then the stirring speed was adjusted to 300 rpm for 10 min, and then 0.64 g Ca(NO3)2·4H2O and 0.57 g Sr(NO3)2 were added and stirred for 1.5 h. The stirred solution was centrifuged to obtain a white precipitate, which was washed with ethanol and deionized water twice and then dried in an oven at 60 °C overnight. Then the precipitate was sintered at 600 °C for 2 h with a heating rate of 3 °C / min. After sintering, strontium-containing bioactive glass (SrBG) was obtained. Then 1 g of SrBG was soaked in a 0.2 mol / L Ce(NO3)3·6H2O ethanol solution for 24 h, and the washing and drying processes were the same as above. Finally, the strontium-cerium doped bioactive glass was sintered at 600 °C for 2 h.

[0047] (2) Preparation of sulfonated porous composite scaffold

[0048] The PEKK and 3% strontium-cerium doped bioactive glass were mixed by mass percentage, and then drawn by a micro twin-screw extruder. The PEKK / BG 3D printing composite scaffold was prepared by a fused deposition modeling technology, the feeding cylinder heating temperature was 400℃, the nozzle temperature was 400℃, the printing speed was 21mm / s, the needle thickness was 0.2mm, the micro-wire width was 0.3mm, and the micro-wire spacing was 1mm. The scaffold was sequentially cleaned by alcohol and ultrapure water for 30min each time, and then dried in a 60℃ vacuum drying oven. The dried PEKK / BG 3D printing composite scaffold sample was placed in a glass bottle containing concentrated sulfuric acid (95%-98%) at room temperature, and stirred at a constant speed of 400rpm to keep the sample in suspension in the concentrated sulfuric acid. After 1min, the sample was taken out and immersed in deionized water for 5min. Then the sample treated by concentrated sulfuric acid was immersed in 50mL of deionized water and hydrothermally treated in a high-pressure reaction kettle at 100℃ for 4h. Finally, the product was washed with deionized water for 3 times and naturally air-dried to obtain a sulfonated porous composite scaffold, denoted as PB, and the average mass of the product was 114mg.

[0049] (3) Preparation of modified polyether ketone ketone composite material

[0050] A 0.25% LAP-containing aqueous solution was used to prepare a 5% and 10% methacrylamide (GelMA) solution with a degree of substitution of 90%. First, the sulfonated porous composite scaffold was immersed in a 10% GelMA solution and irradiated with a UV lamp for 90min. Then, 200μL of 5% GelMA solution was refilled into the scaffold pores, which was frozen at -20℃ for 2h and then transferred to ice for 1min of 405nm UV irradiation. The UV irradiation intensity was 0.02w / cm 2 After the sample melted at room temperature, it was immersed in 75% alcohol for 24h, and then washed with PBS for 10min each time for 3 times. After air-drying, the sample was immersed in a culture medium containing MCP-1 (89% DMEM high-sugar culture medium + 10% serum + 1% double-antibiotic (penicillin, streptomycin)) for 12h, and then naturally air-dried to obtain a modified polyether ketone ketone composite material, denoted as PBCM.

[0051] Comparative Example 1

[0052] The preparation process of Comparative Example 1 was similar to that of Example 1, except that the PEKK of Comparative Example 1 was not mixed with strontium-cerium doped bioactive glass. The PEKK was sequentially sulfonated, loaded with methacrylamide crystal glue by UV grafting, and loaded with a chemotactic factor to obtain a product, denoted as PCM.

[0053] Comparative Example 2

[0054] PEKK was sulfonated, the sulfonation process was similar to Example 1(2), and the product prepared was denoted as P.

[0055] Experimental analysis

[0056] 1. Physicochemical properties of the scaffolds

[0057] The surface morphology of the scaffolds was observed by scanning electron microscopy (SEM) (Fig. 2). Figure 1 Fig. 2 shows SEM images and elemental analysis maps of P, PCM and PBCM; (a) and (d) are SEM images of P at different magnifications; (b) and (e) are SEM images of PCM at different magnifications; (c) and (f) are SEM images of PBCM at different magnifications). Figure 1 It can be seen that the pores of the three samples are connected, and a microporous network structure is formed on the surface, which is mainly due to the sulfonation effect of concentrated sulfuric acid. GelMA crystals fill the pores of PCM and PBCM. Figure 1 Fig. 2g shows that C, O and S elements are uniformly distributed on all scaffolds, but only Si, Ca, Sr and Ce elements appear on PBCM, indicating that BG is successfully loaded into the PEKK scaffold.

[0058] The combination principle of PEKK with GelMA crystals under ultraviolet irradiation is shown in Fig. 3(a). Figure 2 The benzophenone segment on the PEKK backbone can produce active radicals and form C-C covalent bonds with the alkenyl double bonds of GelMA, similar to the photoinitiator benzophenone. Further electron paramagnetic resonance (EPR) tests were carried out, and the results are shown in Fig. 3(b). Figure 2 The results show that the TEMPO peak intensity of PEKK decreased by 20.25% after 90 min of ultraviolet irradiation, indicating that PEKK can produce active radicals under ultraviolet irradiation. FTIR results are shown in Fig. 3(c). Figure 2 Fig. 3(c) shows that the four peaks at 1653, 1586, 1237 and 1161 cm -1 are the C=O stretching vibration peak of diphenyl, the C=C characteristic peak of benzene ring and the C-O-C stretching vibration peak of diaryl in PEKK, respectively. The O=S=O symmetric stretching vibration peak appears at 1013 cm -1 , which may be the result of concentrated sulfuric acid sulfonation. The peak value of PCM and PBCM increases at 1616 cm -1 , and a new peak value appears at 1571 cm -1 , indicating that GelMA has been grafted onto the scaffold.

[0059] 2. Macrophage recruitment and polarization experiment

[0060] To evaluate the ability of the scaffolds prepared in Example 1, Comparative Examples 1 and 2 to recruit macrophages, the migration of M2 macrophages was investigated by cell migration experiment Figure 3 a-c). The specific results are shown in Figure 3 d. The number of cells induced by PCM and PBCM was 10.28 and 11.28 times that of P, respectively, indicating that the migration of macrophages was significantly affected by PCM and PBCM.

[0061] After culturing macrophages on the scaffold surface for 3 days, the effect of different scaffolds on macrophage polarization was analyzed by flow cytometry Figure 3 e). The results showed that the polarization ratio of M2 macrophages on the surface of P, PCM and PBCM was 31.2%, 34.4% and 87.2%, respectively. This indicates that PBCM can promote the polarization of macrophages to an anti-inflammatory phenotype.

[0062] 3. Proliferation and osteogenesis of mesenchymal stem cells

[0063] The cell viability and proliferation activity of mesenchymal stem cells (rMSCs) on different scaffolds were evaluated by live / dead cell double staining and cell counting kit-8 (CCK-8) method Figure 4 a-b). Live cells are represented by green fluorescence. It was found that the number of rMSCs increased significantly as the cell culture time was prolonged, and the number of live cells on PBCM was higher than that on P and PCM. This result is consistent with the trend of CCK-8, further indicating that PBCM can promote the proliferation of rMSCs

[0064] To explore the in vitro osteogenic effect of the scaffold, rMSCs were cultured with the extract of the scaffold, and the osteogenic effect was quantified by ALP and ARS Figure 5 a-c). The color of alkaline phosphatase and calcium nodule in the extract of PBCM was darker than that in P and PCM. Quantitative analysis showed that the ALP activity and calcium deposition of rMSCs on PBCM were the highest among the three groups. Therefore, PBCM has excellent osteogenic performance in vitro.

[0065] 4. Co-culture experiment

[0066] To investigate the effects of the three scaffolds on the migration and osteogenic differentiation of rMSCs after stimulating macrophages, a co-culture system was designed, which means that the mesenchymal stem cells were cultured in the medium in which macrophages were cultured, aiming to explore whether the factors secreted by macrophages would have further effects on mesenchymal stem cells under the influence of the scaffolds. For the cell migration experiment, the conditioned medium refers to the supernatant collected after culturing macrophages in serum-free growth medium for 1 day, which is then mixed with serum-free growth medium at a ratio of 1:1. For the osteogenic differentiation experiment, the conditioned medium refers to the supernatant collected after culturing macrophages in growth medium for 3 days, which is then mixed with growth medium at a ratio of 1:1.

[0067] The results in the growth medium are shown in Figure 6 a-c, respectively. As can be seen from the cell migration experiment, PCM and PBCM can only attract a small amount of rMSCs in the growth medium, and the cells are spherical, indicating that the scaffolds containing MCP-1 have limited recruitment ability and slow speed for rMSCs. The results in the conditioned medium are shown in Figure 6 d-f, respectively. Among them, the number of recruited cells by C-P is 37.3 times that of P, the number of recruited cells by C-PCM is 5.6 times that of PCM, and the number of recruited cells by C-PBCM is 5.1 times that of PBCM. The number of cells recruited by each scaffold in the conditioned medium is much higher than that in the growth medium. In addition, the number of cells recruited by C-PCM and C-PBCM is significantly higher than that by C-P, and all the cells present a good spindle shape. This indicates that the scaffolds can further promote the recruitment of rMSCs by affecting macrophages.

[0068] The osteogenic differentiation of rMSCs is accompanied by calcium deposition. In the co-culture system, alizarin red staining was positive on the 14th day Figure 6 g-i). Compared with the growth medium, the calcium deposition of rMSCs in the conditioned medium increased significantly, indicating that the co-culture of the scaffolds with macrophages can accelerate the osteogenic differentiation process of rMSCs.

[0069] The above examples are the preferred embodiments of the present application, but the embodiments of the present application are not limited to the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application are equivalent replacement methods and are included in the protection scope of the present application.

Claims

1. A modified polyetherketoneketone composite material, characterized in that: The invention comprises a sulfonated porous composite scaffold, a chemokine and a GelMA crystal gel; the raw materials for preparing the sulfonated porous composite scaffold include polyetherketoneketone and strontium-cerium-doped bioactive glass; the chemokine and the GelMA crystal gel are loaded in the pores of the sulfonated porous composite scaffold; The preparation method of the modified polyetherketoneketone composite material comprises the following steps: S1, mixing polyetherketoneketone with strontium-cerium-doped bioactive glass, and obtaining a composite scaffold by melt deposition molding; S2, subjecting the composite scaffold to acid sulfonation treatment, and obtaining a sulfonated porous composite scaffold through hydrothermal treatment; S3, loading the GelMA crystal gel into the pores of the sulfonated porous composite scaffold by an ultraviolet grafting method, and then immersing the sulfonated porous composite scaffold in a culture medium containing a chemokine, so that the chemokine is loaded into the pores of the sulfonated porous composite scaffold, thereby preparing a modified polyetherketoneketone composite material; in step S3, the ultraviolet grafting method is specifically as follows: first immersing the sulfonated porous composite scaffold in the GelMA solution and performing grafting under ultraviolet light irradiation; then refilling the GelMA solution into the pores of the scaffold, freezing, and performing a second ultraviolet light irradiation to obtain a sulfonated porous composite scaffold loaded with the GelMA crystal gel; The chemokine is monocyte chemoattractant factor-1.

2. The modified polyetherketoneketone composite material according to claim 1, characterized in that The mass ratio of the polyetherketoneketone to the strontium-cerium doped bioactive glass is 97:(1-5); And / or, the mass ratio of the sulfonated porous composite scaffold to the methacrylamide crystal gel is (10-15):

1.

3. The method for preparing the modified polyetherketoneketone composite material according to claim 1 or 2, characterized in that: The steps include: S1, mixing polyetherketoneketone with strontium-cerium-doped bioactive glass, and obtaining a composite scaffold by melt deposition molding; S2, subjecting the composite scaffold to acid sulfonation treatment, and obtaining a sulfonated porous composite scaffold through hydrothermal treatment; S3. The GelMA crystal gel is loaded into the pores of the sulfonated porous composite scaffold by an ultraviolet grafting method, and the sulfonated porous composite scaffold is then immersed in a culture medium containing chemokines, so that the chemokines are loaded into the pores of the sulfonated porous composite scaffold to obtain a modified polyetherketoneketone composite material; in step S3, the ultraviolet grafting method is specifically as follows: first, the sulfonated porous composite scaffold is immersed in the GelMA solution and grafted under ultraviolet light irradiation; then, the GelMA solution is refilled into the pores of the scaffold, frozen, and subjected to a second ultraviolet irradiation to obtain a sulfonated porous composite scaffold loaded with GelMA crystal gel.

4. The method for preparing the modified polyetherketoneketone composite material according to claim 3, characterized in that: The strontium-cerium doped bioactive glass is prepared by the following preparation method: 1) mixing ethyl orthosilicate, calcium salt, and strontium salt in an alcohol solution to obtain a sol, drying the sol to obtain a bioactive glass gel precursor, and heat treating the sol to obtain a bioactive glass powder containing strontium ions; 2) Immersing the bioactive glass powder containing strontium ions in a solution containing cerium ions, and then performing heat treatment to obtain a strontium-cerium doped bioactive glass mixture.

5. The method for preparing the modified polyetherketoneketone composite material according to claim 3, characterized in that: In step S1, the fused deposition modeling is specifically as follows: heating and melting the filamentous hot-melt material, and extruding and molding it through a nozzle with a fine nozzle; wherein the process parameters are: feed barrel heating temperature of 300-500°C, nozzle temperature of 300-500°C, printing speed of 10-32mm / s, needle thickness of 0.2-0.4mm, microfilament width of 0.3-0.5mm, and microfilament spacing of 1-2mm.

6. The method for preparing the modified polyetherketoneketone composite material according to claim 3, characterized in that: In step S2, the acid sulfonation is specifically as follows: the composite scaffold is immersed and suspended in concentrated sulfuric acid for 0.5-3 minutes; And / or, in step S2, the hydrothermal treatment time is 3-5 h; the hydrothermal treatment temperature is 80-130°C.

7. The method for preparing the modified polyetherketoneketone composite material according to claim 3, characterized in that: The ultraviolet irradiation time is 50-150 min; And / or, the secondary ultraviolet irradiation time is 0.5-2 min; And / or, the freezing temperature is -40 ~ -10°C.

8. The method for preparing the modified polyetherketoneketone composite material according to claim 3, characterized in that: The concentration of the chemokine in the chemokine-containing culture medium is 1-5 mg / L.

9. Use of the modified polyetherketoneketone composite material according to claim 1 or 2 in the preparation of bone implant materials.

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