Preparation method of hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold of PLA nano CuS composite coating with photo-thermal therapy function

Abstract

The invention discloses a preparation method of a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold of a PLA nano CuS composite coating with a photo-thermal therapy function. The method comprises the following steps: (1) preparing ceramic slurry from hydroxyapatite, 58S bioactive glass powder and photosensitive resin according to a preset proportion, forming by adopting a photocuring technology, and degreasing and sintering to obtain a porous ceramic bracket; and (2) uniformly dispersing the nano copper sulphide in a PLA / organic solvent system through ultrasonic dispersion and magnetic stirring methods, and constructing a nano composite coating on the surface of a ceramic matrix by adopting a dip-coating method to obtain the composite bone scaffold with the PLA loaded with the nano copper sulphide. The 58S bioactive glass can induce nucleation and growth of bone-like apatite and improve the biological activity of the stent; the PLA nano CuS composite coating permeates into micropores and cracks of the ceramic stent, has a hole sealing effect, forms mechanical interlocking, and can effectively improve the mechanical property. The PLA nano CuS composite coating generates a photothermal effect under near-infrared light illumination, so that controllable slow release and photothermal conversion of Cu are realized, and the PLA nano CuS composite coating has long-acting antibacterial and photothermal tumor suppression functions. The scaffold has important application value in the fields of bone defect repair and postoperative tumor prevention and treatment.

Description

Technical Field

[0001] The present invention relates to a preparation method of a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with a PLA nano-CuS composite coating having a photothermal therapy function. Background Art

[0002] Hydroxyapatite (HA) is the main inorganic component of natural bone tissue and is widely used in the field of bone repair due to its excellent biocompatibility and mechanical properties. However, there are still some limitations in the practical application of HA, such as insufficient mechanical properties, slow degradation rate, limited biomineralization ability, and poor cell response, which affect its further promotion and application in bone tissue engineering.

[0003] Silicon-based bioactive glass (such as 58S) has more advantages compared with traditional bioceramics due to its excellent degradation characteristics. During the degradation process of 58S, Si 4 ⁺ can be rapidly released, and this process can not only effectively promote the deposition of Ca²⁺ and PO 4 ³⁻, improve the biomineralization ability, but also enhance the bone regeneration effect by regulating the adhesion, proliferation, and osteogenic differentiation of osteoblasts. In addition, a certain chemical reaction can occur between bioactive glass and calcium phosphate ceramics. Therefore, doping 58S into HA is expected to optimize its degradation performance and improve its biological properties.

[0004] Polylactic acid (PLA) has become a research hotspot in the field of biomaterials due to its wide source, mature process, and low cost. Its degradation products are carbon dioxide and water, without cytotoxicity, and have good biosafety. In addition, the weak acidic environment generated during the degradation of PLA can partially neutralize the alkaline substances released during the degradation of the calcium phosphate ceramic scaffold, thereby regulating the local pH value and helping to maintain the stability of the tissue microenvironment. By coating the ceramic scaffold with PLA, it can penetrate into micropores and cracks, playing a role in sealing the pores. Due to the mechanical interlocking structure formed by the micropores and cracks on the outer layer of the ceramic scaffold and the PLA coating, the interface is firmly bonded, significantly reducing the brittleness of the ceramic scaffold and improving its compressive performance.

[0005] In bone tissue engineering applications, bioceramic scaffolds may face the risk of postoperative bacterial infection. Traditional methods usually prevent implant-related infections by loading antibiotics (such as vancomycin) onto the scaffolds. However, high concentrations of antibiotics may lead to increased cytotoxicity and accelerate the development of bacterial drug resistance. In addition, for bone defects caused by bone tumor resection, residual tumor cells after surgery may trigger cancer recurrence. Existing treatment methods mainly rely on chemotherapy and targeted drugs, but these methods are often accompanied by side effects such as normal cell damage and immune system suppression. Therefore, integrating antibacterial and antitumor functions into bioceramic scaffolds to reduce the risk of postoperative infection and recurrence is an important direction in current bone tissue engineering research.

[0006] Copper sulfide (CuS) exhibits good biological effects in promoting wound healing. It can produce a photothermal effect under near-infrared light (NIR) irradiation, enabling the controllable release of Cu²⁺, and at the same time possessing long-term antibacterial and photothermal antitumor functions. Therefore, introducing CuS into HA-based scaffolds is expected to endow the scaffolds with dual antibacterial and antitumor functions, providing a more promising solution for bone defect repair. Summary of the Invention

[0007] Aiming at the problems of insufficient mechanical properties, slow degradation rate, limited bio-mineralization ability, poor cell response, and lack of antibacterial and antitumor functions in existing hydroxyapatite (HA) bone scaffolds, the present invention provides a preparation method of a PLA / nano-CuS composite coating hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with photothermal therapy function. The present invention uses a photocuring 3D printing technology to form hydroxyapatite and 58S bioactive glass powder, and prepares a composite ceramic scaffold through a debinding and sintering process. During this process, 58S reacts with HA to generate second-phase tricalcium phosphate (TCP) and other components with better degradation performance, while optimizing the microstructure of the scaffold to improve its degradation behavior, bioactivity, and cell response. Further, the present invention uses the dip-coating method to construct a PLA / nano-CuS composite coating on the surface of the ceramic matrix. The coating penetrates into the micropores and cracks of the scaffold, forming a pore-sealing effect and establishing a mechanical interlocking structure, thereby significantly enhancing the mechanical properties of the scaffold. At the same time, this coating can produce a photothermal effect under near-infrared light (NIR) irradiation, realizing the controllable slow release and photothermal conversion of Cu²⁺, endowing the scaffold with dual long-term antibacterial and photothermal antitumor functions, and thus enhancing its application potential in bone repair and bone tumor treatment.

[0008] To achieve the above technical objectives, the present invention adopts the following technical solutions

[0009] A preparation method of a PLA / nano-CuS composite coating hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with photothermal therapy function, comprising the following steps:

[0010] 1) Mix the hydroxyapatite powder and 58S bioactive glass powder evenly in proportion using a single-arm V-type blender;

[0011] 2) Gradually add the evenly mixed ceramic powder to the photosensitive resin material, and use a magnetic stirrer to stir at normal pressure each time after adding until the mass fraction of the hydroxyapatite / 58S bioactive glass composite powder reaches 55 wt%;

[0012] 3) Ball-mill the prepared ceramic slurry in a ball mill to obtain a composite ceramic slurry that can be used for photocuring forming;

[0013] 4) Import the sliced STL format model of the Schwarz-P structure in the TPMS structure into the printer;

[0014] 5) Photocure and print the Schwarz-P structure to produce a green body of the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold, and perform secondary curing;

[0015] 6) Debind and sinter the green body of the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold to remove the organic matter in the green body and sinter it into shape to make the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold;

[0016] 7) Synthesize nano copper sulfide particles using the hydrothermal method;

[0017] 8) Disperse the nano copper sulfide particles in absolute ethanol using ultrasound, disperse the PLA particles in dichloromethane using magnetic stirring, mix the two evenly and then stir evenly using magnetic force, and construct a nano composite coating on the surface of the ceramic matrix by the dip-coating method.

[0018] Preferably, the particle size of the hydroxyapatite powder is 2 - 30 μm, and the purity is not less than 97%.

[0019] Preferably, the particle size of the 58S bioactive glass powder is 2 - 30 μm, and the purity is not less than 97%.

[0020] Preferably, the mass ratio of the hydroxyapatite powder to the 58S bioactive glass powder is 5:95 - 20:80. The inventor found that when the content of 58S is too low, the degradation rate, bio-mineralization ability and cell response of the HA bone scaffold are not obvious; while when the content of 58S is too high, the mechanical properties of the bone scaffold will be reduced.

[0021] Preferably, in the method of the present invention, the following parameters are used for the process of using the single-arm V-type blender in step 1): stirring time: 0.5 - 2 h, stirring speed 100 - 300 r / min.

[0022] In a preferred embodiment, in the method of the present invention, the photosensitive resin described in step 2) includes: 1) Resin monomers: two or more of 1,6 - hexanediol diacrylate (HDDA), tripropylene glycol diacrylate (TPGDA), trimethylolpropane triacrylate (TMPTA), and ditrimethylolpropane tetraacrylate (DI - TMPTA); 2) Photoinitiators: one or more of 2,4,6 - (trimethylbenzoyl) diphenylphosphine oxide (TPO), ethyl 2,4,6 - trimethylbenzoylphosphinate (TPO - L), 2 - methyl - 1 - [4 - (methylthio)phenyl] - 2 - morpholinopropan - 1 - one (907), 2 - isopropylthioxanthone (mixture of 2,4 - isomers) (ITX), ethyl 4 - dimethylaminobenzoate (EDB), 1 - hydroxy - cyclohexyl - phenyl - methanone (184), 2 - hydroxy - 2 - methyl - 1 - phenyl - 1 - propanone (1173), methyl o - benzoylbenzoate (OMBB), 4 - chlorobenzophenone (CBP), benzoin dimethyl ether (BDK); 3) Photoinhibitor: 4 - methoxyphenol (MEHQ); 4) Dispersants: one or more of BYK - 111, BYK - 154, BYK - 161, BYK - 9076, BYK - P104S, Solsperse 24000, Solsperse 27000, Solsperse 41000, Solsperse 45000.

[0023] In a preferred embodiment, in the method of the present invention, when gradually adding the uniformly mixed ceramic powder to the photosensitive resin material in step 2): the number of times is 3 - 10 times; the magnetic stirring process uses the following parameters: stirring time: 0.5 - 1 h, stirring speed: 100 - 500 r / min.

[0024] In a preferred embodiment, in the method of the present invention, the ball - milling process described in step 3) uses the following ball - milling parameters: Preferably, the ball - to - material ratio is 1:3 - 5, Preferably, the ball - milling material is zirconia or natural agate Preferably, the diameter of the grinding balls is 2 - 10 mm, Preferably, the ball - milling speed is 500 - 1000 r / min, Preferably, the ball - milling time is 5 - 10 min.

[0025] In a preferred embodiment, in the method of the present invention, the porosity of the Schwarz - P structure in the TPMS structure described in step 4) is 40% - 80%, and the average pore diameter is 100 - 1500 μm.

[0026] Preferably, in the method of the present invention, the photocuring 3D printing process in step 5) includes the following steps: slicing the model to be formed and then importing it into a DLP or LCD or SLA photocuring printer for layer-by-layer printing, putting the cleaned sample into a secondary curing machine for secondary curing, setting the printing parameters as layer thickness 50 - 200 μm, exposure time 4 - 8 s, bottom layer exposure time 20 - 60 s, bottom layer number 5 - 10 layers, and secondary curing time 3 - 5 minutes.

[0027] Preferably, in the method of the present invention, the debinding and sintering in step 6) includes the following steps: putting the green body of the scaffold into a muffle furnace or a tube furnace for debinding and sintering, setting the sintering temperature at 1100 - 1400 °C, and the holding time at 0 - 4 h.

[0028] Preferably, in the method of the present invention, for the synthesis of nano - copper sulfide particles using the hydrothermal method in step 7), Cu(Ac) 2 ·H 2 O (0.02 mol), CH 3 CSNH 2 (0.04 mol) and PEG400 (5 mL) are used as raw materials, ground and reacted in an agate mortar for 1 - 2 hours until it completely turns black. It is placed in an 80 °C constant temperature water bath and heated for 8 - 12 hours, then naturally cooled, washed alternately with distilled water and absolute ethanol 3 times, and dried in vacuum to obtain a black product.

[0029] Preferably, in the method of the present invention, the construction of the PLA - nano CuS composite coating in step 8) includes: ultrasonically dispersing the nano - CuS particles in absolute ethanol for 0.5 - 1 h, dissolving the PLA particles in dichloromethane using a magnetic stirrer, with the stirring time: 0.5 - 1 h and the stirring speed 100 - 500 r / min. The nano - copper sulfide particles and the PLA particles are mixed in a mass ratio of 0.02:100 to 1:100 and then magnetically stirred for 1 hour, and a film is formed on the surface of the ceramic matrix by the dip - coating method.

[0030] Compared with the prior art, the positive effects brought by the technical solution of the present invention are as follows:

[0031] 1) The present invention uses photocuring 3D printing technology to form hydroxyapatite and 58S bioactive glass powder, and prepares a composite ceramic scaffold through a debinding and sintering process. During this process, 58S reacts with HA to generate components such as the second - phase tricalcium phosphate (TCP) with better degradation performance, and at the same time optimizes the microstructure of the scaffold to improve its degradation behavior, bioactivity, and cell response.

[0032] 2) The present invention uses the dip - coating method to construct a PLA / nano - CuS composite coating on the surface of the ceramic matrix. The coating penetrates into the micropores and cracks of the scaffold, forming a pore - sealing effect and establishing a mechanical interlocking structure, thereby significantly enhancing the mechanical properties of the scaffold.

[0033] 3) The present invention utilizes a PLA coating to load nano - copper sulfide. This coating can generate a photothermal effect under near - infrared light (NIR) irradiation, realizing the controllable slow release of Cu²⁺ and photothermal conversion, endowing the scaffold with dual functions of long - term antibacterial and photothermal tumor inhibition, and thus enhancing its application potential in bone repair and bone tumor treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 is the flow chart for scaffold preparation;

[0035] Figure 2 is the morphology of the scaffolds in Examples 1 - 3 and Comparative Examples 1 - 3;

[0036] Figure 3 is the compressive strength of the scaffolds in Examples 1 - 3 and Comparative Examples 1 - 3;

[0037] Figure 4 is the mass loss of the bone scaffolds prepared in Examples 1 - 3 and Comparative Examples 1 - 3 after 28 days of degradation.

[0038] Figure 5 is the staining condition of the bone scaffolds prepared in Examples 1 - 3 and Comparative Examples 1 - 3 after inoculating cells for 7 days.

[0039] Figure 6 is the photothermal effect of the bone scaffolds prepared in Examples 1 - 3 and Comparative Examples 1 - 3. DETAILED DESCRIPTION OF THE INVENTION

[0040] The following further describes the specific embodiments of the present invention in conjunction with specific examples, but the content of the present invention is not limited thereto.

[0041] Example 1

[0042] 1) Mix 49.5 g of hydroxyapatite powder (4.5 microns) and 5.5 g of 58S bioactive glass powder (10 microns) evenly by using a single - arm V - type mixer according to the ratio. Stirring time: 0.5 hour, stirring speed: 300 r / min;

[0043] 2) 28.28 g of HDDA and 12.12 g of TPGDA photosensitive resin monomers were formulated with 4 g of dispersant BYK-111, 0.5 g of photoinitiator, and 0.1 g of light inhibitor MEHQ to form a photosensitive resin. The uniformly mixed ceramic powder was added to the photosensitive resin material in 5 portions. After each addition, it was stirred at normal pressure using a magnetic stirrer for 0.5 hours at a stirring speed of 500 r / min until the mass fraction of hydroxyapatite / 58S bioactive glass composite powder reached 55 wt%;

[0044] 3) The prepared ceramic slurry was ball-milled in a ball mill using zirconia grinding balls with a ball-to-material ratio of 1:3, a grinding ball diameter of 5 mm, a ball-milling speed of 800 r / min, and a ball-milling time of 5 minutes to obtain a composite ceramic slurry that can be used for photocuring forming;

[0045] 4) The STL format model of the Schwarz-P structure in the TPMS structure was sliced and then imported into the printer. The porosity of the Schwarz-P structure model was 50%, the average pore diameter was 1200 μm, and the size was 15×15×15 mm;

[0046] 5) The Schwarz-P structure was photocured and printed to produce a green body of hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold, and secondary curing was carried out. The printing parameters were set as a layer thickness of 50 μm, an exposure time of 5 seconds, a bottom layer exposure time of 60 seconds, a bottom layer number of 5 layers, and a secondary curing time of 3 minutes;

[0047] 6) The green body of the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold was degreased and sintered to remove the organic matter in the green body and sinter it into a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold. The sintering temperature was set at 1300 °C and the holding time was 2 hours;

[0048] 7) Nanoscale copper sulfide particles were synthesized using the hydrothermal method with Cu(Ac) 2 ·H 2 O (3.993 g), CH 3 CSNH 2 (3.0052 g) and PEG400 (5 mL) as raw materials. After grinding and reacting in an agate mortar for 1 hour, it completely turned black. It was placed in an 80 °C constant temperature water bath and heated for 12 hours, then naturally cooled, washed 3 times alternately with distilled water and absolute ethanol, and dried under vacuum to obtain a black product;

[0049] 8) Ultrasonically disperse 0.002 g of nano-CuS particles in 100 ml of absolute ethanol for 0.5 hours. Dissolve 9.998 g of PLA particles in 500 ml of dichloromethane using a magnetic stirrer, with a stirring time of 0.5 hours and a stirring speed of 100 - 500 r / min. Form a film on the surface of the ceramic substrate by the dip-coating method.

[0050] Through mechanical property testing, it was found that the compressive strength of the HA-10wt%58S-PLA-0.02%CuS composite scaffold was 55.89 MPa.

[0051] Through degradation property testing, it was found that the mass loss of the HA-10wt%58S-PLA-0.02%CuS composite scaffold after 28 days of degradation was 6.9%.

[0052] Through biomineralization testing, it was found that after soaking the HA-10wt%58S-PLA-0.02%CuS composite scaffold in SBF solution for 7 days, a large amount of cauliflower-like calcium phosphate deposits formed on the surface.

[0053] Through cell compatibility testing, it was found that the cells on the HA-10wt%58S-PLA-0.02%CuS composite scaffold had good adhesion morphology, proliferation rate, and differentiation ability after 7 days of culture.

[0054] Through photothermal testing, it was found that the HA-10wt%58S-PLA-0.02%CuS composite scaffold had good photothermal effects. In PBS solution, it could be heated to 50 °C within 30 seconds under the irradiation of infrared light (808 nm) with an intensity of 2 w / cm², showing strong photothermal antibacterial and antitumor effects.

[0055] Example 2

[0056] 1) Mix 49.5 g of hydroxyapatite powder (4.5 microns) and 5.5 g of 58S bioactive glass powder (10 microns) evenly using a single-arm V-type mixer, with a stirring time of 0.5 hours and a stirring speed of 300 r / min.

[0057] 2) Prepare a photosensitive resin by mixing 28.28 g of HDDA and 12.12 g of TPGDA photosensitive resin monomers with 4 g of dispersant BYK-111, 0.5 g of photoinitiator, and 0.1 g of photo inhibitor MEHQ. Add the evenly mixed ceramic powder to the photosensitive resin material in 5 portions. After each addition, stir at normal pressure using a magnetic stirrer, with a stirring time of 0.5 hours and a stirring speed of 500 r / min, until the mass fraction of the hydroxyapatite / 58S bioactive glass composite powder reaches 55 wt%.

[0058] 3) The prepared ceramic slurry is ball-milled in a ball mill using zirconia grinding balls. The ball-to-material ratio is 1:3, the diameter of the grinding balls is 5 mm, the ball-milling speed is 800 r / min, and the ball-milling time is 5 minutes to obtain a composite ceramic slurry that can be used for photocuring forming.

[0059] 4) After slicing the STL format model of the Schwarz-P structure in the TPMS structure, it is imported into the printer. The porosity of the Schwarz-P structure model is 50%, the average pore diameter is 1200 μm, and the size is 15×15×15 mm.

[0060] 5) Photocure and print the Schwarz-P structure to produce a green body of a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold, and perform secondary curing. The printing parameters are set as layer thickness 50 μm, exposure time 5 seconds, bottom layer exposure time 60 seconds, number of bottom layers 5, and secondary curing time 3 minutes.

[0061] 6) Debind and sinter the green body of the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold to remove the organic matter in the green body and sinter it into shape to produce a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold. The sintering temperature is set at 1300 °C and the holding time is 2 hours.

[0062] 7) Synthesize nano copper sulfide particles using the hydrothermal method, using Cu(Ac) 2 ·H 2 O (3.993 g), CH 3 CSNH 2 (3.0052 g) and PEG400 (5 mL) as raw materials. Grind and react in an agate mortar for 1 hour until it completely turns black. Place it in an 80 °C constant temperature water bath and heat for 12 hours, then cool naturally. Wash it 3 times alternately with distilled water and absolute ethanol, and dry it in vacuum to obtain a black product.

[0063] 8) Ultrasonically disperse 0.01 g of nano CuS particles in 100 ml of absolute ethanol for 0.5 hours. Use a magnetic stirrer to dissolve 9.99 g of PLA particles in 500 ml of dichloromethane. The stirring time is 0.5 hours and the stirring speed is 100 - 500 r / min. Form a film on the surface of the ceramic matrix by the dip-coating method.

[0064] Through mechanical property tests, it is found that the compressive strength of the HA-10wt%58S-PLA-0.1%CuS composite scaffold is 53.01 MPa.

[0065] Through degradation property tests, it is found that the mass loss of the HA-10wt%58S-PLA-0.1%CuS composite scaffold after 28 days of degradation is 7.15%.

[0066] Through biomineralization tests, it was found that after the HA-10wt% 58S-PLA-0.1% CuS composite scaffold was immersed in SBF solution for 7 days, a large amount of cauliflower-like calcium phosphate deposits appeared on the surface;

[0067] Through cell compatibility tests, it was found that the cells on the HA-10wt% 58S-PLA-0.1% CuS composite scaffold had good adhesion morphology, proliferation rate and differentiation ability after 7 days of culture;

[0068] Through photothermal tests, it was found that the HA-10wt% 58S-PLA-0.1% CuS composite scaffold had good photothermal effect. In PBS solution, it could be heated to 55 °C within 60 seconds under the irradiation of infrared light (808 nm) with an intensity of 2 W / cm², showing strong photothermal antibacterial and anti-tumor effects.

[0069] Example 3

[0070] 1) Mix 49.5 g of hydroxyapatite powder (4.5 microns) and 5.5 g of 58S bioactive glass powder (10 microns) evenly using a single-arm V-type mixer. Mixing time: 0.5 hour, mixing speed: 300 r / min;

[0071] 2) Prepare a photosensitive resin by mixing 28.28 g of HDDA and 12.12 g of TPGDA photosensitive resin monomers with 4 g of dispersant BYK-111, 0.5 g of photoinitiator, and 0.1 g of light inhibitor MEHQ. Add the evenly mixed ceramic powder to the photosensitive resin material in 5 portions. After each addition, stir at normal pressure using a magnetic stirrer. Stirring time: 0.5 hour, stirring speed: 500 r / min until the mass fraction of the hydroxyapatite / 58S bioactive glass composite powder reaches 55 wt%;

[0072] 3) Ball-mill the prepared ceramic slurry in a ball mill using zirconia grinding balls. Ball-to-material ratio: 1:3, grinding ball diameter: 5 mm, ball-mill speed: 800 r / min, ball-mill time: 5 minutes to obtain a composite ceramic slurry that can be used for photocuring forming;

[0073] 4) After slicing the STL format model of the Schwarz-P structure in the TPMS structure, import it into the printer. The porosity of the Schwarz-P structure model is 50%, the average pore diameter is 1200 μm, and the size is 15×15×15 mm;

[0074] 5) Photocure and print the Schwarz-P structure to produce a green body of the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold, and perform secondary curing. The printing parameters are set as layer thickness 50 μm, exposure time 5 seconds, bottom layer exposure time 60 seconds, bottom layer number 5 layers, and secondary curing time 3 minutes;

[0075] 6) Degreasing and sintering the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold green body, removing organic matter in the green body and sintering to form a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold, the sintering temperature is set to 1300°C, and the holding time is 2 hours;

[0076] 7) Nano-copper sulfide particles were synthesized by hydrothermal method using Cu(Ac) 2 ·H 2 O (3.993 g), CH 3 CSNH 2 (3.0052 g) and PEG400 (5 mL) were used as raw materials, and the mixture was ground in an agate mortar and reacted for 1 hour until it turned completely black. It was placed in a constant temperature water bath at 80°C and heated for 12 hours, cooled naturally, and washed alternately with distilled water and anhydrous ethanol for 3 times, and dried in vacuum to obtain a black product;

[0077] 8) Ultrasonic dispersion of 0.05 g of nano CuS particles in 100 ml of anhydrous ethanol for 0.5 h, dissolving 9.95 g of PLA particles in 500 ml of dichloromethane using a magnetic stirrer for 0.5 h at a stirring speed of 100-500 r / min, and forming a film on the surface of the ceramic substrate by an immersion-coating method;

[0078] The mechanical properties test showed that the compressive strength of the HA-10wt%58S-PLA-0.5%CuS composite scaffold was 46.5MPa;

[0079] The degradation performance test found that the mass loss of the HA-10wt%58S-PLA-0.5%CuS composite scaffold after 28 days of degradation was 7.8%;

[0080] The biomineralization test found that after the HA-10wt%58S-PLA-0.5%CuS composite scaffold was immersed in SBF solution for 7 days, a large amount of cauliflower-like calcium phosphate was deposited on the surface;

[0081] The cell compatibility test found that the cells on the HA-10wt%58S-PLA-0.5%CuS composite scaffolds had average adhesion morphology, proliferation rate, and differentiation ability after 7 days of culture, which may be due to the high content of copper sulfide, which is more toxic to cells;

[0082] Photothermal testing found that the HA-10wt%58S-PLA-0.5%CuS composite scaffold has a good photothermal effect. In PBS solution, it can be heated to 55°C in 30 seconds under irradiation with 1w / cm² infrared light (808nm), showing strong photothermal antibacterial and anti-tumor effects.

[0083] Comparative Example 1

[0084] 1) 28.28 g of HDDA and 12.12 g of TPGDA photosensitive resin monomers were mixed with 4 g of dispersant BYK-111, 0.5 g of photoinitiator and 0.1 g of photo inhibitor MEHQ to prepare a photosensitive resin, and 55 g of hydroxyapatite powder (particle size 4.5 microns) was added to the photosensitive resin in 5 portions. After each addition, it was stirred using a magnetic stirrer under normal pressure for 0.5 hours at a stirring speed of 500 r / min until the mass fraction of the hydroxyapatite powder reached 55 wt%;

[0085] 2) The prepared ceramic slurry was ball-milled in a ball mill using zirconia grinding balls with a ball-to-material ratio of 1:3, a grinding ball diameter of 5 mm, a ball milling speed of 800 r / min, and a ball milling time of 5 minutes to obtain a ceramic slurry that can be used for photocuring forming;

[0086] 3) The Schwarz-P structure STL format model in the TPMS structure was sliced and then imported into the printer. The porosity of the Schwarz-P structure was 50%, the average pore diameter was 1200 μm, and the size was 15×15×15 mm.

[0087] 4) The Schwarz-P structure was printed using a photocuring printer. After obtaining the green body of the hydroxyapatite ceramic bone scaffold, secondary curing was carried out. The printing parameters were set as follows: layer thickness 50 μm, exposure time 5 s, bottom layer exposure time 60 s, number of bottom layers 5 layers, and secondary curing time 3 minutes;

[0088] 5) The green body of the hydroxyapatite ceramic bone scaffold was degreased and sintered to remove the organic matter in the green body and complete the sintering to obtain the final hydroxyapatite ceramic bone scaffold. The sintering temperature was 1300 °C, and the holding time was 2 hours, named HA;

[0089] After mechanical property testing, the compressive strength of the HA scaffold was 33.57 MPa;

[0090] After degradation property testing, the mass loss of the HA scaffold within 28 days was 2.79%;

[0091] After biomineralization testing, after the HA scaffold was immersed in SBF solution for 7 days, only a small amount of apatite microspheres were deposited on the surface;

[0092] After cell compatibility testing, the cells on the HA scaffold showed weak adhesion morphology, proliferation rate, and differentiation ability after 7 days of culture;

[0093] After photothermal testing, the HA scaffold had no photothermal antibacterial and antitumor effects.

[0094] Comparative Example 2

[0095] 1) Mix 49.5 g of hydroxyapatite powder (particle size 4.5 microns) and 5.5 g of 58S bioactive glass powder (particle size 10 microns) evenly in proportion using a single-arm V-type mixer. The stirring time is 0.5 hours, and the stirring speed is 300 r / min;

[0096] 2) Mix 28.28 g of HDDA and 12.12 g of TPGDA photosensitive resin monomers with 4 g of dispersant BYK-111, 0.5 g of photoinitiator, and 0.1 g of photo-inhibitor MEHQ to prepare a photosensitive resin. Add the evenly mixed ceramic powder to the photosensitive resin material in 5 portions. After each addition, stir using a magnetic stirrer under normal pressure. The stirring time is 0.5 hours, and the stirring speed is 500 r / min until the mass fraction of the hydroxyapatite / 58S bioactive glass composite powder reaches 55 wt%;

[0097] 3) Ball-mill the prepared ceramic slurry in a ball mill. Use zirconia grinding balls, with a ball-to-material ratio of 1:3, a grinding ball diameter of 5 mm, a ball-milling speed of 800 r / min, and a ball-milling time of 5 minutes to obtain a composite ceramic slurry that can be used for photocuring forming;

[0098] 4) After slicing the Schwarz-P structure STL format model in the TPMS structure, import it into the printer. The porosity of the Schwarz-P structure is 50%, the average pore diameter is 1200 μm, and the size is 15×15×15 mm;

[0099] 5) Use a photocuring printer to print the Schwarz-P structure. After obtaining the green body of the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold, perform secondary curing. The printing parameters are set as follows: layer thickness 50 μm, exposure time 5 seconds, bottom layer exposure time 60 seconds, number of bottom layers 5 layers, and secondary curing time 3 minutes;

[0100] 6) Degrease and sinter the green body of the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold to remove the organic matter in the green body and complete sintering to obtain the final hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold. The sintering temperature is 1300 °C, and the holding time is 2 hours, named HA-10wt%58S;

[0101] After mechanical property testing, the compressive strength of the HA-10wt%58S scaffold is 30.98 MPa;

[0102] After degradation property testing, the mass loss of the HA-10wt%58S scaffold within 28 days is 12.8%;

[0103] After biomineralization testing, after the HA-10wt%58S scaffold was immersed in SBF solution for 7 days, a large amount of cauliflower-like calcium phosphate deposits appeared on the surface;

[0104] After cytocompatibility testing, the cells on the HA-10wt%58S scaffold showed good adhesion morphology, proliferation rate and differentiation ability after 7 days of culture;

[0105] After photothermal testing, the HA-10wt%58S scaffold had no photothermal antibacterial and antitumor effects.

[0106] Comparative Example 3

[0107] 1) Mix 49.5 g of hydroxyapatite powder (particle size 4.5 microns) and 5.5 g of 58S bioactive glass powder (particle size 10 microns) evenly by using a single-arm V-type mixer. The stirring time is 0.5 hours and the stirring speed is 300 r / min;

[0108] 2) Mix 28.28 g of HDDA and 12.12 g of TPGDA photosensitive resin monomers with 4 g of dispersant BYK-111, 0.5 g of photoinitiator and 0.1 g of photo inhibitor MEHQ to prepare a photosensitive resin, and add the evenly mixed ceramic powder to the photosensitive resin in 5 times. After each addition, use a magnetic stirrer to stir under normal pressure. The stirring time is 0.5 hours and the stirring speed is 500 r / min until the mass fraction of the hydroxyapatite / 58S bioactive glass composite powder reaches 55 wt%;

[0109] 3) Ball-mill the prepared ceramic slurry in a ball mill. Use zirconia grinding balls, the ball-to-material ratio is 1:3, the diameter of the grinding balls is 5 mm, the ball-milling speed is 800 r / min, and the ball-milling time is 5 minutes to obtain a composite ceramic slurry that can be used for photocuring forming;

[0110] 4) After slicing the Schwarz-P structure STL format model in the TPMS structure, import it into the printer. The porosity of the Schwarz-P structure is 50%, the average pore diameter is 1200 μm, and the size is 15×15×15 mm;

[0111] 5) Use a photocuring printer to print the Schwarz-P structure, and perform secondary curing on the green body of the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold obtained. The printing parameters are set as follows: layer thickness 50 μm, exposure time 5 seconds, bottom layer exposure time 60 seconds, the number of bottom layers is 5 layers, and the secondary curing time is 3 minutes;

[0112] 6) Debind and sinter the green body of the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold to remove the organic matter in the green body and complete the sintering, obtaining the final composite ceramic bone scaffold. The sintering temperature is 1300 °C and the holding time is 2 hours;

[0113] 7) Dissolve 10 g of PLA particles in 500 ml of dichloromethane using a magnetic stirrer. The stirring time is 0.5 hours and the stirring speed is 100 - 500 r / min. Form a film on the surface of the ceramic matrix by the dip-coating method to obtain the HA-10wt%58S-PLA composite scaffold;

[0114] After mechanical property testing, the compressive strength of the HA-10wt%58S-PLA composite scaffold is 55.88 MPa;

[0115] After degradation property testing, the mass loss of the HA-10wt%58S-PLA composite scaffold within 28 days is 5.3%;

[0116] After biomineralization testing, after the HA-10wt%58S-PLA composite scaffold is immersed in SBF solution for 7 days, a large amount of cauliflower-like calcium phosphate deposits on the surface;

[0117] After cytocompatibility testing, the cells on the HA-10wt%58S-PLA composite scaffold show good adhesion morphology, proliferation rate and differentiation ability after 7 days of culture;

[0118] After photothermal testing, the HA-10wt%58S-PLA composite scaffold has no photothermal effect.

Claims

1. A method for preparing a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with a PLA nano-CuS composite coating having a photothermal therapy function, characterized in that The following steps are involved: 1) mixing hydroxyapatite powder and 58S bioactive glass powder in batches according to a certain proportion, wherein the mass ratio of 58S bioactive glass powder to hydroxyapatite powder is 10:100 to 20:80; 2) gradually adding it to the photosensitive resin material, stirring it at normal pressure with a magnetic stirrer after each addition until the mass fraction of the hydroxyapatite / 58S bioactive glass composite powder reaches 55 wt%; 3) ball milling the prefabricated slurry in step 1) in a ball mill at a rotation speed of 500-1000 r / min for 5-10 minutes to obtain a composite ceramic slurry that can be used for photocuring molding; 4) Slice the STL format model of the Schwarz-P structure in the TPMS structure and import it into the printer; 5) Photocuring printing of Schwarz-P structure to produce hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold green body; 6) degreasing and sintering the hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold green body, removing organic matter in the green body and sintering to form a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold; 7) Synthesizing nano copper sulfide particles using a hydrothermal method; 8) using ultrasound to disperse nano copper sulfide particles in anhydrous ethanol, using magnetic stirring to disperse PLA particles in dichloromethane, mixing the two and magnetically stirring for 1 hour, and constructing a nano-composite coating on the surface of the ceramic substrate by an immersion pulling method, wherein the mass ratio of nano copper sulfide to PLA particles is 0.02:100 to 1:

100.

2. The method for preparing a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with a PLA nano-CuS composite coating having a photothermal therapy function according to claim 1, characterized in that: The photosensitive resin described in step 2) comprises: 1) Resin monomer: two or more of 1,6-hexanediol diacrylate (HDDA), tripropylene glycol diacrylate (TPGDA), trimethylolpropane triacrylate (TMPTA), and ditrimethylolpropane tetraacrylate (DI-TMPTA); 2) Photoinitiator: one or more of 2,4,6-(trimethylbenzoyl)diphenylphosphine oxide (TPO), ethyl 2,4,6-trimethylbenzoylphosphonate (TPO-L), 2-methyl-1-[4-methylthiophenyl]-2-morpholinyl-1-propanone (907), 2-isopropylthioxanthone (2,4 isomer mixture) (ITX), ethyl 4-dimethylaminobenzoate (EDB), 1-hydroxy-cyclohexyl-phenyl ketone (184), 2-hydroxy-2-methyl-1-phenyl-1-propanone (1173), methyl o-benzoylbenzoate (OMBB), 4-chlorobenzophenone (CBP), and dimethyl benzoate (BDK); 3) Photoinhibitor: 4-methoxyphenol (MEHQ); 4) Dispersant: one or more of BYK-111, BYK-154, BYK-161, BYK-9076, BYK-P104S, Solsperse 24000, Solsperse 27000, Solsperse 41000, Solsperse 45000.

3. The method for preparing a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with a PLA nano-CuS composite coating having a photothermal therapy function according to claim 1, characterized in that: The porosity of the Schwarz-P structure in the TPMS structure described in step 4) is 40%-80%, and the average pore size is 100-1500 μm.

4. The method for preparing a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with a PLA nano-CuS composite coating having a photothermal therapy function according to claim 1, characterized in that: The light-curing 3D printing process described in step 5) comprises the following steps: slicing the model to be formed and importing it into a DLP, LCD or SLA light-curing printer for printing layer by layer, placing the cleaned sample into a secondary curing machine for secondary curing, and setting the printing parameters to a layer thickness of 50-200 μm, an exposure time of 4-8 seconds, a bottom layer exposure time of 20-60 seconds, a bottom layer number of 5-10 layers, and a secondary curing time of 3-5 minutes.

5. The method for preparing a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with a PLA nano-CuS composite coating having a photothermal therapy function according to claim 1, characterized in that: The debinding and sintering in step 6) comprises the following steps: placing the bracket green body in a muffle furnace or a tube furnace for debinding and sintering, and the sintering temperature is set to 1100-1400°C.

6. The method for preparing a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with a PLA nano-CuS composite coating having a photothermal therapy function according to claim 1, characterized in that: The nano copper sulfide particles were synthesized by hydrothermal method described in step 7, using Cu(Ac)2·H2O (0.02 mol), CH3CSNH2 (0.04 mol) and PEG400 (5 mL) as raw materials, and the mixture was ground with an agate mortar for 1-2 hours and turned completely black. The mixture was heated in a constant temperature water bath at 80°C for 8-12 hours, cooled naturally, washed alternately with distilled water and anhydrous ethanol for 3 times, and dried in vacuo to obtain a black product.

7. The method for preparing a hydroxyapatite / 58S bioactive glass composite ceramic bone scaffold with a PLA nano-CuS composite coating having a photothermal therapy function according to claim 1, characterized in that: The construction of the PLA nano-CuS composite coating in step 8) includes: ultrasonically dispersing nano-CuS particles in anhydrous ethanol, dissolving PLA particles in dichloromethane, mixing the two at a mass ratio of 0.02:100 to 1:100, magnetically stirring for 1 hour, and forming a film on the surface of the ceramic substrate by an immersion pulling method.

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