3D printing polylactic acid composite scaffold for bone repair and preparation method of 3D printing polylactic acid composite scaffold

Abstract

The invention belongs to the technical field of biological materials, and particularly relates to a 3D printing polylactic acid composite scaffold for bone repair and a preparation method of the 3D printing polylactic acid composite scaffold. The 3D printing polylactic acid composite scaffold for bone repair is prepared from the following raw materials: PLA / Mg-ZrO2 and BP / STAC, pLA / Mg-ZrO2 is adopted as a 3D printing stent, a BP / STAC composite coating is formed on the surface of the PLA / Mg-ZrO2 stent, the 3D printing polylactic acid composite stent for bone repair is prepared, the PLA / Mg-ZrO2 stent has graded porosity simulating natural bones, PLA has good biocompatibility, the mechanical strength and toughness of the PLA stent are enhanced due to addition of Mg-ZrO2, and the 3D printing polylactic acid composite stent for bone repair can be applied to bone repair. The BP / STAC composite coating further enhances the mechanical properties of the composite scaffold, facilitates cell attachment and growth, accelerates proliferation and differentiation of bone cells, and promotes formation of new bones.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomaterials, and particularly relates to a 3D printed polylactic acid composite scaffold for bone repair and a preparation method thereof. Background Art

[0002] Bone plays a key supporting role in human life activities. However, traumatic fractures, osteoporosis and other reasons can cause varying degrees of bone damage or loss. Although highly vascularized bone tissue has a certain regenerative ability, for bone defects exceeding the critical threshold (>2 cm), clinical intervention is usually required to achieve complete healing and functional recovery. Among many methods for treating large-area bone defects, autologous bone transplantation is the "gold standard". However, autologous bone transplantation is often difficult to be promoted clinically because it brings secondary harm to patients. Allogeneic bone transplantation has risks such as rejection reaction or disease transmission.

[0003] At present, although artificial bone substitute materials have solved some problems, their biocompatibility, mechanical properties and degradation rate still need to be improved. Although 3D printing technology and PLA materials have been applied in the field of bone repair, the current technology still has the following deficiencies: the mechanical properties of existing 3D printed bone scaffolds are not sufficient to support rapid bone regeneration; the bioactivity of the scaffolds is insufficient and cannot effectively promote the attachment and growth of bone cells; the degradation rate of the scaffolds does not match the formation speed of new bone tissue, affecting the bone repair effect. Therefore, it is necessary to develop a 3D printed polylactic acid composite scaffold for bone repair. This composite scaffold not only has good mechanical properties and bioactivity, but also its degradation rate matches the bone regeneration process, thereby improving the bone repair effect. Summary of the Invention

[0004] Aiming at the defects of the existing technology, the purpose of the present invention is to provide a 3D printed polylactic acid composite scaffold for bone repair and a preparation method thereof. The present invention uses PLA / Mg-ZrO 2 as a 3D printed scaffold, and forms a BP / STAC composite coating on the surface of the PLA / Mg-ZrO 2 scaffold to prepare a 3D printed polylactic acid composite scaffold for bone repair. The 3D printed PLA / Mg-ZrO 2 scaffold has a hierarchical porosity that mimics natural bone, can effectively fill bone defects and provide the required mechanical support, while promoting bone ingrowth. The addition of Mg-ZrO 2 enhances the mechanical strength and toughness of the PLA scaffold, enabling it to better withstand the mechanical load in the physiological environment. The composite coating BP / STAC further enhances the surface hardness of the scaffold and improves its mechanical properties. Mg and ZrO 2The addition improves the biocompatibility of the 3D printed polylactic acid composite scaffold for bone repair. The composite coating of BP / STAC also contributes to cell attachment and growth, and Mg-ZrO 2 has good osteoinductivity and can promote the proliferation and differentiation of osteocytes.

[0005] To achieve the above technical objectives, the technical solutions adopted by the present invention are as follows:

[0006] The present invention provides a 3D printed polylactic acid composite scaffold for bone repair, and the 3D printed polylactic acid composite scaffold for bone repair is prepared from the following raw materials in parts by weight: PLA (polylactic acid) / Mg-ZrO 2 50 - 80 parts, BP (black phosphorus) / STAC (stearyl trimethyl ammonium chloride) 8 - 20 parts;

[0007] The preparation raw materials of the PLA / Mg-ZrO 2 are PLA, magnesium powder and ZrO 2 , and the mass ratio of the PLA, magnesium powder and ZrO 2 is 1:0.2 - 0.5:0.08 - 0.3;

[0008] The preparation method of the PLA / Mg-ZrO 2 specifically includes the following steps:

[0009] (1) Dissolve PLA in an organic solvent, stir with a magnetic stirrer in an oil bath at 90 °C for 2 - 5 h until completely dissolved to obtain a PLA solution. Add magnesium powder to the PLA solution and perform ultrasonic treatment to make it uniformly dispersed to obtain a mixed solution A;

[0010] (2) Add ZrO 2 to the mixed solution A obtained in step (1), and stir magnetically to make it uniformly dispersed to obtain a mixed solution B;

[0011] (3) Pour the mixed solution B obtained in step (2) into a 24-well plate, add 1.5 mL to each well, then put it in the refrigerator and freeze for 20 h, and then take it out and place it at room temperature to thaw to obtain PLA / Mg-ZrO 2 .

[0012] Furthermore, the organic solvent is at least one of tetrahydrofuran, chloroform and N,N-dimethylformamide.

[0013] Furthermore, the dosage ratio of the PLA and the organic solvent is 1 g:60 - 100 mL.

[0014] The preparation raw materials of the BP / STAC are black phosphorus crystal powder and STAC, and the mass ratio of the black phosphorus crystal powder and STAC is 1:2 - 10;

[0015] The preparation method of the BP / STAC specifically includes the following steps:

[0016] (a) Take black phosphorus crystal powder, add NMP (N-methylpyrrolidone), stir and mix evenly to form a dispersion. Place the dispersion in an ice bath and ultrasonicate for 10 h, then put it into a low-temperature centrifuge and centrifuge at 3000 rpm for 10 min. Collect the supernatant, put the supernatant into a low-temperature centrifuge, centrifuge at 10000 rpm for 20 min to remove the solvent NMP, collect the precipitate, centrifuge at 10000 rpm at low temperature for 20 min again, collect the precipitate, and freeze-dry for 2 - 5 d to obtain BPNS powder;

[0017] (b) Take BPNS powder and disperse it in ultrapure water to form dispersion B. Dissolve STAC in absolute ethanol, stir and mix evenly to form solution D. Pour dispersion B into solution D, mix in a water bath to form mixture A, and dry mixture A to obtain BP / STAC.

[0018] Furthermore, the dosage ratio of the black phosphorus crystal powder to NMP is 1 g:50 mL.

[0019] Furthermore, the dosage ratio of BPNS to ultrapure water is 1 g:80 mL, and the dosage ratio of STAC to absolute ethanol is 1 g:50 mL.

[0020] The present invention also provides a preparation method of a 3D-printed polylactic acid composite scaffold for bone repair, which specifically includes the following steps:

[0021] S1, Take PLA / Mg-ZrO by weight parts 2 , add glycerol, stir and mix evenly, extrude through a twin-screw extruder, and perform 3D printing using a scaffold model designed by Solidworks 2023 software to obtain a PLA / Mg-ZrO 2 scaffold;

[0022] S2, Take BP / STAC by weight parts and put it into DMSO (dimethyl sulfoxide) to form a uniform mixture B. Immerse the PLA / Mg-ZrO 2 scaffold obtained in step S1 into mixture B, and form a coating on the surface of the PLA / Mg-ZrO 2 scaffold. Immerse it multiple times until a uniform BP / STAC composite coating is formed on the surface to obtain a composite coating scaffold;

[0023] S3, Wash the composite coating scaffold obtained in step S2 with absolute ethanol, and then vacuum dry for 6 - 12 h to obtain a 3D-printed polylactic acid composite scaffold for bone repair.

[0024] Furthermore, the PLA / Mg-ZrO 2The dosage ratio with glycerol is 1 g: 20 - 40 mL.

[0025] Furthermore, the dosage ratio of the BP / STAC and DMSO is 1 g: 30 - 60 mL.

[0026] Furthermore, the printing speed is 5 - 15 mm / s, the single-layer printing thickness is 0.2 - 0.5 mm, the room temperature is 20 °C, the nozzle temperature is 80 °C, and the hot bed temperature is 45 °C.

[0027] Furthermore, the model of the twin-screw extruder is HAAKE PloyLAb Os.

[0028] Furthermore, the 3D printing adopts FDM (Fused Deposition Modeling) printing, and the model of the 3D printer used is Snapermake2.0A350.

[0029] Compared with the prior art, the beneficial effects achieved by the present invention are as follows:

[0030] The present invention uses PLA / Mg-ZrO 2 as a 3D printing scaffold, and forms a BP / STAC composite coating on the surface of the PLA / Mg-ZrO 2 scaffold to obtain a 3D printed polylactic acid composite scaffold for bone repair. The initial mechanical properties of PLA are insufficient, and the products during the degradation process can lead to an acidic environment, which is likely to cause inflammation and bone resorption at the implantation site. However, the addition of Mg-ZrO 2 enhances the mechanical strength and toughness of the PLA scaffold, enabling it to better withstand the mechanical load in the physiological environment, and can neutralize the acidic environment caused by the degradation of PLA, making the pH value tend to be stable. A stable pH microenvironment is beneficial to the growth and proliferation of cells and prolongs the degradation time of the 3D printed polylactic acid composite scaffold for bone repair; the composite coating BP / STAC further enhances the surface hardness of the scaffold and improves the mechanical properties due to the presence of BP; the 3D printed PLA / Mg-ZrO 2 scaffold has a hierarchical porosity that mimics natural bone, can effectively fill bone defects and provide the required mechanical support, and at the same time promotes bone ingrowth. By adding Mg and ZrO 2 to PLA, the biocompatibility of the composite scaffold is improved. The composite coating of BP / STAC also helps cell attachment and growth. Mg-ZrO 2 has good osteoinductivity and can promote the proliferation and differentiation of osteocytes. The two-dimensional structure and biological activity of BP further promote the regeneration and repair of bone tissue. The degradation rate of PLA can be adjusted by compounding with Mg-ZrO 2Adjusted to match the bone regeneration rate to avoid a decrease in mechanical properties caused by premature degradation. SATC in the composite coating can effectively protect BP from rapid degradation, contributing to achieving a controllable degradation rate. Moreover, after oxidation, BP can be degraded into non-toxic phosphates, continuously releasing PO 4 3- , forming calcium deposits, thus accelerating bone regeneration. The BP / STAC composite coating can be used to load and release bioactive molecules such as growth factors or antibiotics to promote the healing process or prevent infection. The presence of the coating can provide the function of sustained release or targeted drug release, enhancing the therapeutic effect. The composite coating prepared from BP / STAC has excellent antibacterial properties, reducing the inflammatory response caused by the implant, which is beneficial for rapid healing. Additionally, the bioactive molecules in the BP / STAC composite coating can promote the growth of vascular endothelial cells and accelerate the vascularization process inside the scaffold. The PLA / Mg-ZrO 2 scaffold prepared by 3D printing allows precise control of the pore structure and size of the scaffold, facilitating the ingrowth of blood vessels and bone tissue. Moreover, the BP / STAC composite coating does not significantly affect the pore structure of the scaffold, maintaining its property of promoting bone ingrowth. The 3D printed polylactic acid composite scaffold for bone repair prepared in the present invention has excellent biocompatibility, enhanced mechanical properties, the ability to promote bone regeneration, and a controllable degradation rate, providing an effective solution for bone repair and significantly improving the therapeutic effect and the patient's recovery speed. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 SEM image of the 3D printed polylactic acid composite scaffold for bone repair prepared in the present invention;

[0032] Figure 2 Water contact angle images of the 3D printed polylactic acid composite scaffolds for bone repair prepared in Example 1 of the present invention and Comparative Examples 1-3;

[0033] Figure 3 Bone volume fraction images of the 3D printed polylactic acid composite scaffolds for bone repair prepared in Example 1 of the present invention and Comparative Examples 1-3;

[0034] Figure 4 Calcium deposition content images of the 3D printed polylactic acid composite scaffolds for bone repair prepared in Example 1 of the present invention and Comparative Examples 1-3. DETAILED DESCRIPTION OF THE INVENTION

[0035] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without making creative efforts belong to the scope of protection of the present invention.

[0036] Example 1: This example provides a 3D printed polylactic acid composite scaffold for bone repair. The 3D printed polylactic acid composite scaffold for bone repair is prepared from the following raw materials in parts by weight: PLA / Mg-ZrO 2 50 parts, BP / STAC 8 parts;

[0037] The preparation raw materials of the PLA / Mg-ZrO 2 are PLA, magnesium powder and ZrO 2 , and the mass ratio of the PLA, magnesium powder and ZrO 2 is 1:0.2:0.08;

[0038] The preparation method of the PLA / Mg-ZrO 2 specifically includes the following steps:

[0039] (1) Take 65 parts of PLA and dissolve it in tetrahydrofuran. The dosage ratio of PLA to tetrahydrofuran is 1 g:60 mL. Stir it in an oil bath at 90 °C with a magnetic stirrer at a speed of 800 rpm for 2 h until it is completely dissolved to obtain a PLA solution. Add magnesium powder to the PLA solution and place it in an ultrasonic cleaner for ultrasonic treatment at 240 W for 1 h to make it evenly dispersed, obtaining a mixed solution A;

[0040] (2) Add ZrO 2 to the mixed solution A obtained in step (1), and stir it with a 40 °C constant temperature magnetic stirrer for 2 h to make it evenly dispersed, obtaining a mixed solution B;

[0041] (3) Pour the mixed solution B obtained in step (2) into a 24-well plate, add 1.5 mL to each well, then place it in a refrigerator and freeze it for 20 h, and then take it out and let it thaw at room temperature to obtain PLA / Mg-ZrO 2 .

[0042] The preparation raw materials of the BP / STAC are black phosphorus crystal powder and STAC, and the mass ratio of the black phosphorus crystal powder to STAC is 1:2;

[0043] The preparation method of the BP / STAC specifically includes the following steps:

[0044] (a) Take 10 parts of black phosphorus crystal powder, add NMP, and the dosage ratio of black phosphorus crystal powder to NMP is 1 g:50 mL. Stir and mix evenly at a speed of 1000 rpm to form dispersion A. Place dispersion A in an ice bath and ultrasonicate for 10 h, then put it into a low-temperature centrifuge and centrifuge at 3000 rpm for 10 min. Collect the supernatant, put the supernatant into a low-temperature centrifuge, and centrifuge at 10000 rpm for 20 min to remove the solvent NMP. Collect the precipitate, centrifuge at 10000 rpm at low temperature for 20 min again, collect the precipitate, and freeze-dry at -50 °C for 2 d to obtain BPNS powder;

[0045] (b) Take BPNS powder and disperse it in ultrapure water. The dosage ratio of BPNS to ultrapure water is 1 g:80 mL to form dispersion B. Dissolve STAC in absolute ethanol, and the dosage ratio of STAC to absolute ethanol is 1 g:50 mL. Stir and mix evenly to form solution D. Pour dispersion B into solution D, and stir and mix at 70 °C in a water bath at a speed of 500 rpm to form mixture A. Dry mixture A at 40 °C for 6 h to obtain BP / STAC.

[0046] This embodiment also provides a preparation method of a 3D printed polylactic acid composite scaffold for bone repair, which specifically includes the following steps:

[0047] S1, Take 50 parts of PLA / Mg-ZrO 2 , and the dosage ratio of PLA / Mg-ZrO 2 to glycerol is 1 g:20 mL. Add glycerol, stir and mix evenly at a speed of 600 rpm, extrude through a twin-screw extruder, use the scaffold model designed by Solidworks 2023 software, and perform 3D printing by the FDM printing method. The printing speed is 5 mm / s, the printing height is 0.2 mm, the room temperature is 20 °C, the nozzle temperature is 80 °C, and the hot bed temperature is 45 °C to obtain the PLA / Mg-ZrO 2 scaffold;

[0048] S2, Take 8 parts of BP / STAC and put it into DMSO. The dosage ratio of BP / STAC to DMSO is 1 g:30 mL to form a uniform mixture B. Immerse the PLA / Mg-ZrO 2 scaffold obtained in step S1 into mixture B to form a coating on the surface of the PLA / Mg-ZrO 2 scaffold. Immerse it repeatedly 5 times until a uniform composite coating is formed on the surface of the PLA / Mg-ZrO 2 scaffold to obtain a composite coating scaffold;

[0049] S3, Wash the composite coating scaffold obtained in step S2 with absolute ethanol, and then dry it in vacuum for 6 h to obtain a 3D printed polylactic acid composite scaffold for bone repair.

[0050] Example 2: This example provides a 3D printed polylactic acid composite scaffold for bone repair. The 3D printed polylactic acid composite scaffold for bone repair is prepared from the following raw materials in parts by weight: PLA / Mg-ZrO 2 60 parts, BP / STAC 12 parts;

[0051] The preparation raw materials of the PLA / Mg-ZrO 2 are PLA, magnesium powder and ZrO 2 , and the mass ratio of the PLA, magnesium powder and ZrO 2 is 1:0.25:0.15;

[0052] The preparation method of the PLA / Mg-ZrO2 specifically includes the following steps:

[0053] (1) Take 65 parts of PLA and dissolve it in chloroform. The dosage ratio of PLA to chloroform is 1 g:80 mL. Stir it with a magnetic stirrer at a speed of 800 rpm in an oil bath at 90 °C for 3 h until it is completely dissolved to obtain a PLA solution. Add magnesium powder to the PLA solution, and place it in an ultrasonic cleaner for ultrasonic treatment at 240 W for 1 h to make it evenly dispersed, obtaining a mixed solution A;

[0054] (2) Add ZrO 2 to the mixed solution A obtained in step (1), and stir it with a 40 °C constant temperature magnetic stirrer for 2 h to make it evenly dispersed, obtaining a mixed solution B;

[0055] (3) Pour the mixed solution B obtained in step (2) into a 24-well plate, add 1.5 mL to each well, then place it in a refrigerator and freeze it for 20 h, and then take it out and thaw it at room temperature to obtain PLA / Mg-ZrO 2 .

[0056] The preparation raw materials of the BP / STAC are black phosphorus crystal powder BP and STAC, and the mass ratio of the black phosphorus crystal powder BP to STAC is 1:5;

[0057] The preparation method of the BP / STAC specifically includes the following steps:

[0058] (a) Take 15 parts of black phosphorus crystal powder, add NMP. The dosage ratio of black phosphorus crystal powder to NMP is 1 g:50 mL. Stir and mix evenly at a speed of 1000 rpm to form dispersion A. Place dispersion A in an ice bath and ultrasonicate for 10 h, then put it into a low-temperature centrifuge and centrifuge at 3000 rpm for 10 min. Collect the supernatant. Put the supernatant into a low-temperature centrifuge and centrifuge at 10000 rpm for 20 min to remove the solvent NMP. Collect the precipitate. Centrifuge at 10000 rpm at low temperature for 20 min again and collect the precipitate. Freeze-dry at -50 °C for 3 d to obtain BPNS powder;

[0059] (b) Take BPNS powder and disperse it in ultrapure water. The dosage ratio of BPNS to ultrapure water is 1 g:80 mL to form dispersion B. Dissolve STAC in absolute ethanol. The dosage ratio of STAC to absolute ethanol is 1 g:50 mL. Stir and mix evenly to form solution D. Pour dispersion B into solution D and stir and mix at 70 °C in a water bath at a speed of 500 rpm to form mixture A. Dry mixture A at 40 °C for 6 h to obtain BP / STAC.

[0060] This example also provides a preparation method of a 3D-printed polylactic acid composite scaffold for bone repair, which specifically includes the following steps:

[0061] S1, Take 60 parts of PLA / Mg-ZrO 2 , The dosage ratio of PLA / Mg-ZrO 2 to glycerol is 1 g:30 mL. Add glycerol and stir and mix evenly at a speed of 600 rpm. Extrude through a twin-screw extruder. Use the scaffold model designed by Solidworks 2023 software and adopt the FDM printing method for 3D printing. The printing speed is 10 mm / s, the printing height is 0.28 mm, the room temperature is 20 °C, the nozzle temperature is 80 °C, and the hot bed temperature is 45 °C to obtain the PLA / Mg-ZrO 2 scaffold;

[0062] S2, Take 12 parts of BP / STAC and put it into DMSO. The dosage ratio of BP / STAC to DMSO is 1 g:45 mL to form a uniform mixture B. Immerse the PLA / Mg-ZrO 2 scaffold obtained in step S1 into mixture B to form a coating on the surface of the PLA / Mg-ZrO 2 scaffold. Immerse it 5 times repeatedly until a uniform composite coating is formed on the surface of the PLA / Mg-ZrO 2 scaffold to obtain a composite coating scaffold;

[0063] S3, Wash the composite coating scaffold obtained in step S2 with absolute ethanol, and then dry it in vacuum for 10 h to obtain a 3D-printed polylactic acid composite scaffold for bone repair.

[0064] Example 3: This example provides a 3D printed polylactic acid composite scaffold for bone repair. The 3D printed polylactic acid composite scaffold for bone repair is prepared from the following raw materials in parts by weight: PLA / Mg-ZrO 2 80 parts, BP / STAC 20 parts;

[0065] The preparation raw materials of the PLA / Mg-ZrO 2 are PLA, magnesium powder and ZrO 2 , and the mass ratio of the PLA, magnesium powder and ZrO 2 is 1:0.5:0.3;

[0066] The preparation method of the PLA / Mg-ZrO2 specifically includes the following steps:

[0067] (1) Take 90 parts of PLA and dissolve it in N,N-dimethylformamide. The dosage ratio of PLA to N,N-dimethylformamide is 1 g:100 mL. Stir it in an oil bath at 90 °C with a magnetic stirrer at a speed of 800 rpm for 5 h until it is completely dissolved to obtain a PLA solution. Add magnesium powder to the PLA solution and place it in an ultrasonic cleaner for ultrasonic treatment at 240 W for 1 h to make it evenly dispersed, obtaining a mixed solution A;

[0068] (2) Add ZrO 2 to the mixed solution A obtained in step (1), and stir it with a 40 °C constant temperature magnetic stirrer for 2 h to make it evenly dispersed, obtaining a mixed solution B;

[0069] (3) Pour the mixed solution B obtained in step (2) into a 24-well plate, add 1.5 mL to each well, then place it in a refrigerator and freeze it for 20 h, and then take it out and let it thaw at room temperature to obtain PLA / Mg-ZrO 2 .

[0070] The preparation raw materials of the BP / STAC are black phosphorus crystal powder BP and STAC, and the mass ratio of the black phosphorus crystal powder to STAC is 1:10;

[0071] The preparation method of the BP / STAC specifically includes the following steps:

[0072] (a) Take 30 parts of black phosphorus crystal powder, add NMP, and the dosage ratio of black phosphorus crystal powder to NMP is 1 g:50 mL. Stir and mix evenly at a speed of 1000 rpm to form dispersion A. Place dispersion A in an ice bath and ultrasonicate for 10 h, then put it into a low-temperature centrifuge and centrifuge at 3000 rpm for 10 min. Collect the supernatant, put the supernatant into a low-temperature centrifuge, and centrifuge at 10000 rpm for 20 min to remove the solvent NMP. Collect the precipitate, centrifuge at 10000 rpm at low temperature for 20 min again, collect the precipitate, and freeze-dry at -50 °C for 5 d to obtain BPNS powder;

[0073] (b) Take BPNS powder and disperse it in ultrapure water. The dosage ratio of BPNS to ultrapure water is 1 g:80 mL to form dispersion B. Dissolve STAC in absolute ethanol, and the dosage ratio of STAC to absolute ethanol is 1 g:50 mL. Stir and mix evenly to form solution D. Pour dispersion B into solution D, and stir and mix at 70 °C in a water bath at a speed of 500 rpm to form mixture A. Dry mixture A at 40 °C for 6 h to obtain BP / STAC.

[0074] This example also provides a preparation method of a 3D printed polylactic acid composite scaffold for bone repair, which specifically includes the following steps:

[0075] S1, Take 80 parts of PLA / Mg-ZrO 2 , The dosage ratio of PLA / Mg-ZrO 2 to glycerol is 1 g:40 mL. Add glycerol and stir and mix evenly at a speed of 600 rpm. Extrude through a twin-screw extruder, use the scaffold model designed by Solidworks 2023 software, and perform 3D printing by the FDM printing method. The printing speed is 15 mm / s, the printing height is 0.5 mm, the room temperature is 20 °C, the nozzle temperature is 80 °C, and the hot bed temperature is 45 °C to obtain the PLA / Mg-ZrO 2 scaffold;

[0076] S2, Take 20 parts of BP / STAC and put it into DMSO. The dosage ratio of BP / STAC to DMSO is 1 g:60 mL to form a uniform mixture B. Immerse the PLA / Mg-ZrO 2 scaffold obtained in step S1 into mixture B to form a coating on the surface of the PLA / Mg-ZrO 2 scaffold. Immerse it 5 times repeatedly until a uniform composite coating is formed on the surface of the PLA / Mg-ZrO 2 scaffold to obtain a composite coating scaffold;

[0077] S3, Wash the composite coating scaffold obtained in step S2 with absolute ethanol, and then dry it in vacuum for 12 h to obtain a 3D printed polylactic acid composite scaffold for bone repair.

[0078] The difference between Comparative Example 1 and Example 1 is that the addition of magnesium powder is cancelled, and the rest is the same as Example 1.

[0079] The difference between Comparative Example 2 and Example 1 is that the addition of BP is cancelled, and the rest is the same as Example 1.

[0080] The difference between Comparative Example 3 and Example 1 is that the addition of the BP / STAC composite coating is cancelled, and the rest is the same as Example 1.

[0081] Experimental Example 1: Using the 3D printed polylactic acid composite scaffolds for bone repair prepared in Examples 1-3 and Comparative Examples 1-3 of the present invention as specimens, a compression experiment test was carried out on the specimens using an electronic universal testing machine (AGS-X5KN) to determine their compressive strength and whether it meets the mechanical requirements for bone repair. The specimens were placed on the loading platform, the loading speed of the indenter was set at 0.5 mm / min, and the preloading pressure was 0.1 N. Four specimens of each type were taken, and the average value was taken. The load-displacement data of each sample was recorded and the stress-strain curve was plotted, and the compressive strength of the scaffold was calculated and the results were recorded in Table 1.

[0082] Experimental Example 2: Using the 3D printed polylactic acid composite scaffolds for bone repair prepared in Examples 1-3 and Comparative Examples 1-3 of the present invention as specimens, the elastic modulus of the specimens was tested. After the specimens were melted respectively, they were poured into a mold according to the standard GBT1041 to make cuboid samples. Each sample was slowly compressed using a multi-functional tester, and the stress and strain data were recorded to measure the elastic modulus of the composite material. During the experiment, it was ensured that the compression rate was consistent and the environmental temperature was constant. The elastic modulus of each group of samples was recorded and analyzed, and the elastic modulus of each specimen was recorded in Table 1.

[0083] Experimental Example 3: Using the 3D printed polylactic acid composite scaffolds for bone repair prepared in Examples 1-3 and Comparative Examples 1-3 of the present invention as specimens, an antibacterial test was carried out on them. The antibacterial properties were tested using Gram-negative Escherichia coli (ATCC25922) and Gram-positive Staphylococcus aureus (ATCC25923). A 10-fold dilution method was used to quantitatively measure the antibacterial rate. The bacterial strains were incubated in the culture medium for 24 h, and the second-generation subculture was used as the prefabricated bacterial solution. The prefabricated bacterial solution (100 μL) was dropped on the sample and incubated for 2 h, then 2 mL of normal saline was added. Subsequently, the mixture of the bacterial solution and normal saline extracted from each sample was diluted 10 4 times. Finally, 100 μL of each diluted liquid sample was inoculated onto a nutrient Luria-Bertani agar plate, and the number of bacterial colonies was counted to reach 30-300 colony-forming units. Using the formula: BR(%) = [(n 0 -n) / n 0 ×100%, to calculate the antibacterial rate, where, n0 is the number of colonies on the control plate, n is the number of colonies on the experimental group plate, and the results of the antibacterial rate are recorded in Table 1.

[0084] Table 1

[0085]

[0086] The data results in Table 1 show that Examples 1-3 exhibit higher compressive strength, all higher than those of the comparative examples, indicating that the addition of Mg-ZrO in the composite scaffold 2 significantly enhances the mechanical properties of the composite scaffold; the elastic modulus of the examples is higher than that of the comparative examples, indicating that the prepared 3D printed polylactic acid composite scaffold for bone repair has high stiffness and toughness; the antibacterial properties of all examples reach more than 99%, showing excellent antibacterial properties.

[0087] Figure 1 This is the SEM image of the surface of the 3D printed polylactic acid composite scaffold for bone repair prepared by the present invention. It can be seen that the pore sizes on the surface of the composite scaffold are uniform, about 800 μm, indicating that the printing process is highly precise and the printing is very neat; Figure 2 This is the water contact angle image of the 3D printed polylactic acid composite scaffold for bone repair prepared in Example 1 and Comparative Examples 1-3 of the present invention. By coating a composite coating on the surface of the scaffold, the hydrophilicity of the scaffold is significantly improved, the biocompatibility of the composite scaffold is enhanced, which is beneficial to cell attachment and bone tissue integration; Figure 3 This is the bone volume fraction image of the 3D printed polylactic acid composite scaffold for bone repair prepared in Example 1 and Comparative Examples 1-3 of the present invention, showing excellent ability to promote bone tissue formation; Figure 4 This is the calcium deposition content image of the 3D printed polylactic acid composite scaffold for bone repair prepared in Example 1 and Comparative Examples 1-3 of the present invention. The release of magnesium ions from the polylactic acid scaffold and the phosphate ions of the composite coating promote calcium deposition and bone growth.

[0088] In summary, the present invention uses PLA / Mg-ZrO 2 scaffold and BP / STAC coating to prepare a 3D printed polylactic acid composite scaffold for bone repair. Through precise printing process, improved hydrophilicity, enhanced biocompatibility and promoted calcium deposition ability, it provides an efficient solution for bone repair and significantly promotes the bone regeneration and repair process. PLA / Mg-ZrO 2 scaffold has a hierarchical porosity that mimics natural bone, can effectively fill bone defects and provide the required mechanical support, while promoting bone in-growth. The addition of Mg and ZrO 2 improves the mechanical properties of the scaffold, and the composite coating of BP / STAC helps cell attachment and growth. Mg-ZrO 2It has good osteoinductivity and can promote the proliferation and differentiation of bone cells. The two-dimensional structure and biological activity of BP further promote the regeneration and repair of bone tissue. The degradation rate of PLA can be regulated by compounding with Mg-ZrO 2 to match the bone regeneration rate and avoid the decline of mechanical properties caused by premature degradation.

[0089] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions recorded in the foregoing embodiments or perform equivalent replacements for some of the technical features. However, such modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A 3D printed polylactic acid composite scaffold for bone repair, characterized in that: The 3D printed polylactic acid composite scaffold for bone repair is prepared from the following raw materials in parts by weight: 50-80 parts of PLA / Mg-ZrO2 and 8-20 parts of BP / STAC; The PLA / Mg-ZrO2 is prepared by using PLA, magnesium powder and ZrO2 in a mass ratio of 1:0.2-0.5:0.08-0.

3. The preparation method of PLA / Mg-ZrO2 specifically comprises the following steps: (1) dissolving PLA in an organic solvent and mixing to obtain a PLA solution, adding magnesium powder to the PLA solution, and ultrasonically treating the PLA solution to obtain a mixed solution A; (2) adding ZrO2 to the mixed solution A obtained in step (1), stirring to make it uniformly dispersed, to obtain a mixed solution B; (3) Freeze the mixed solution B obtained in step (2), take it out and thaw it at room temperature to obtain PLA / Mg-ZrO2.

2. A 3D printed polylactic acid composite scaffold for bone repair according to claim 1, characterized in that: In step (1), the organic solvent is at least one of tetrahydrofuran, chloroform and N,N-dimethylformamide.

3. According to claim 1, a 3D printed polylactic acid composite scaffold for bone repair, characterized in that: In step (1), the amount ratio of PLA to organic solvent is 1g:60-100mL.

4. A 3D printed polylactic acid composite scaffold for bone repair according to claim 1, characterized in that: The raw materials for preparing the BP / STAC are black phosphorus crystal powder and STAC, and the mass ratio of the black phosphorus crystal powder to STAC is 1:2-10; The preparation method of the BP / STAC specifically comprises the following steps: (a) black phosphorus crystal powder is added with NMP, stirred and mixed, and then placed in an ice bath for ultrasonication to form a dispersion A, centrifuged at low temperature, and the precipitate is collected and freeze-dried to obtain BPNS powder; (b) BPNS powder is dispersed in ultrapure water to form a uniform dispersion B, STAC is dissolved in anhydrous ethanol, stirred and mixed to form a solution D, dispersion B is poured into solution D, mixed in a water bath to form a mixture A, and mixture A is dried to obtain BP / STAC.

5. A 3D printed polylactic acid composite scaffold for bone repair according to claim 4, characterized in that: In step (a), the usage ratio of the black phosphorus crystal powder and NMP is 1 g:50 mL.

6. A 3D printed polylactic acid composite scaffold for bone repair according to claim 4, characterized in that: In step (a), the low-temperature centrifugation operation is as follows: placing dispersion A in a low-temperature centrifuge, centrifuging at 3000 rpm for 10 min, collecting the supernatant, placing the supernatant in a low-temperature centrifuge, centrifuging at 10000 rpm for 20 min, collecting the precipitate, and centrifuging again at 10000 rpm for 20 min.

7. A 3D printed polylactic acid composite scaffold for bone repair according to claim 4, characterized in that: In step (b), the usage ratio of BPNS to ultrapure water is 1 g:80 mL, and the usage ratio of STAC to anhydrous ethanol is 1 g:50 mL.

8. A method for preparing a 3D printed polylactic acid composite scaffold for bone repair according to any one of claims 1 to 7, characterized in that: The specific steps include: S1, taking PLA / Mg-ZrO2 by weight, adding glycerol, stirring and mixing evenly, extruding, designing a scaffold model, and performing 3D printing to obtain a PLA / Mg-ZrO2 scaffold; S2, taking BP / STAC by weight and putting them into DMSO to form a uniform mixture B, immersing the PLA / Mg-ZrO2 stent obtained in step S1 into the mixture B to form a coating on the surface of the PLA / Mg-ZrO2 stent, and immersing the mixture multiple times until a uniform composite coating is formed on the surface to obtain a composite coating stent; S3, washing the composite coated scaffold obtained in step S2, and vacuum drying for 6-12 hours to obtain a 3D printed polylactic acid composite scaffold for bone repair.

9. The method for preparing a 3D printed polylactic acid composite scaffold for bone repair according to claim 8, characterized in that: In step S1, the dosage ratio of PLA / Mg-ZrO2 to glycerol is 1 g:20-40 mL.

10. The method for preparing a 3D printed polylactic acid composite scaffold for bone repair according to claim 8, characterized in that: In step S2, the usage ratio of BP / STAC and DMSO is 1 g:30-60 mL.

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