Manufacturing method and application of PCL / nHA composite wire suitable for fused deposition 3D printing

Abstract

The invention relates to the field of medical bone defect repair, in particular to a manufacturing method and application of a PCL / nHA composite wire suitable for fused deposition 3D printing. The method mainly comprises the following steps: preparing PCL / nHA mixture homogenate; adding the homogenate into a 3DPANY wire machine to extrude a PCL / nHA composite wire with a uniform diameter; the bionic bone scaffold manufactured by applying the material to fused deposition 3D printing is stable in forming and high in precision. The method is simple, no chemical solvent is needed in the whole process, the method is safe and efficient, nHA can be evenly mixed in the PCL material, and it is believed that a wide application prospect is provided for application of PCL and nHA materials to the field of bone defect repair through wire manufacturing and 3D printing.

Description

Technical Field

[0001] The present invention relates to the field of medical bone defect repair, and in particular to a method for manufacturing a polycaprolactone / nanohydroxyapatite (PCL / nHA) composite wire suitable for fused deposition 3D printing and an application thereof.

[0002] The method mainly includes: preparing a PCL / nHA mixture homogenate; adding the homogenate to a 3DPANY wire machine to extrude a PCL / nHA composite wire with uniform diameter and applying it to a 3D printed bionic bone scaffold. The method of the present invention is simple, does not require the use of any chemical solvents in the entire process, is safe and efficient, and can evenly mix nHA in the PCL / nHA composite wire. The internal pores of the bionic bone scaffold printed by fused deposition 3D printing are connected, the molding is stable, and the precision is high. It is believed that this method can provide broad application prospects for the application of PCL and nHA materials in bone defect repair through wire manufacturing and 3D printed bionic bone scaffolds. Background Art

[0003] Tumors, trauma, infection and osteonecrosis can lead to bone defects of varying degrees. Among them, the repair of larger bone defects (>2 cm) that cannot heal by themselves is a problem that needs to be solved urgently. Autologous and allogeneic bone transplantation has problems such as limited donors, high bone resorption rate, disease transmission and immune rejection. In order to solve the problem of bone defect repair, substitutes based on metals, bone cement, polymers and ceramics have appeared one after another. At present, titanium alloys are widely used due to their good mechanical strength, biosafety and corrosion resistance. However, the Young's modulus of titanium alloys is much larger than that of natural bones, which is prone to stress concentration. In addition, its surface inertness cannot reshape with the host bone tissue, resulting in bone absorption and aseptic loosening. Bone cement hinders the formation of new bone due to its biological inertness, low degradability, potential cytotoxicity and lack of porous structure. In recent years, polymer and ceramic composites have great application prospects in the field of bone tissue engineering due to their low price, wide source and good biocompatibility.

[0004] Among biocompatible materials, polycaprolactone (PCL) has been widely used in bone tissue engineering and is widely used in 3D printing, making it possible to manufacture complex patient-specific and biomimetic structures. PCL is a resorbable polymer with low production cost, which can be combined with osteoinductive materials such as nano-hydroxyapatite (nHA) to improve its mechanical properties and bioactivity. 3D printed PCL / nHA biomimetic bone scaffolds are expected to become an adjunct or substitute for bone transplantation.

[0005] The most commonly used 3D printing technologies currently include fused deposition 3D printing, stereolithography, and selective laser melting. Among them, stereolithography printers use photosensitive resin as raw material for printing, which is non-degradable and requires chemical solvents for post-processing of printed samples, and is prone to cytotoxicity. Selective laser melting printers are expensive, use biocompatible metals as raw materials, have high post-processing costs and a large difference in elastic modulus from natural bone, resulting in stress concentration. In contrast, fused deposition printing has become one of the most widely used technologies due to its wide range of selectable materials, low cost, good printing accuracy, and biocompatibility.

[0006] Manufacturing PCL / nHA composite wire is the first step in applying PCL and HA to fused deposition 3D printing. Currently, the main methods for manufacturing composite wire are the solvent method and the extrusion method. The solvent method is to use chemical solvents to achieve uniform mixing of the two materials, but it has the following disadvantages: solvents are prone to residue and have cytotoxicity; the operation process is relatively complex and the volatilization of chemical solvents is harmful to the body. The extrusion method is to directly melt the two materials in a wire machine and manufacture composite wire. Its disadvantage is that it cannot ensure the uniform mixing of the two materials in the manufactured composite wire, and it is easy to have the accumulation of auxiliary material agglomerates (especially obvious when adding nano-level auxiliary materials), resulting in forming defects in 3D printed parts. Therefore, a new technical solution is needed to solve the above problems. Summary of the Invention

[0007] The purpose of the present invention is to provide a method for manufacturing PCL / nHA composite wire suitable for fused deposition 3D printing to solve the problems raised in the above background technology.

[0008] The method for manufacturing the PCL / nHA composite wire described in the present invention includes the following steps:

[0009] 1. Prepare the PCL / nHA mixture homogenate: First, put PCL into a glass cup, place the glass cup in a water bath at 100 °C, and after the PCL melts, add nHA powder to prepare the PCL / nHA mixture homogenate.

[0010] 2. Start the preheating of the 3DPANY wire machine, set the "mid-section temperature", "extrusion temperature", "extrusion motor speed", "cooling motor speed", and "traction motor speed". After reaching the set parameters, add the PCL / nHA homogenate prepared in the previous step to the feeding bin of the wire machine to achieve continuous feeding of the homogenate into the wire machine.

[0011] 3. The wire machine extrudes the un-solidified PCL / nHA composite wire, and after passing through the water cooling tank, it is cooled and solidified into shape. During this period, the wire diameter is monitored in real time by a laser diameter gauge.

[0012] Compared with the existing methods, the preparation method described in the present invention has the following beneficial effects:

[0013] 1. The entire manufacturing process does not use any chemical solvents, is non-toxic, harmless, and has good biocompatibility.

[0014] 2. Prepare PCL / nHA composite wires with uniform material mixing and stable diameter, achieving a perfect combination of the two materials, making the forming stable and with high precision during the subsequent 3D printing process. Description of the Drawings

[0015] Figure 1 It is a schematic diagram of the preparation of PCL / nHA composite wires and their application in 3D printing mode;

[0016] Figure 2 It is the manufacturing parameters of PCL / nHA composite wires;

[0017] Figure 3 It is the specific implementation flow chart of the manufacturing of PCL / nHA composite wires;

[0018] Figure 4 It is the SEM scan and EDX elemental analysis of the cross-section of PCL and PCL / nHA composite wires. A) SEM scan of the cross-section of PCL wire B) EDX elemental analysis of the cross-section of PCL wire C) SEM scan of the cross-section of PCL / nHA composite wire D) EDX elemental analysis of the cross-section of PCL / nHA composite wire;

[0019] Figure 5 It is the fused deposition 3D printing of PCL / nHA bionic bone scaffolds and SEM scan. A) General view B) SEM scan: front view C) SEM scan: longitudinal section;

[0020] Figure 6 It is the test result diagram of Raman spectroscopy and X-ray diffraction test (Raman spectroscopy analysis and XRD analysis)

[0021] Figure 7 It is the test result diagram of thermogravimetric analysis (thermogravimetric analysis A) Thermogravimetric curve B) Thermogravimetric differential curve) Detailed Implementation Manner

[0022] I. Preparation of PCL / nHA composite wires and detection: Taking PCL and nHA (weight ratio 4:1) as an example

[0023] 1. After melting 80 g of PCL in a water bath, add 20 g of nHA and stir to prepare a homogeneous slurry of PCL / nHA mixture.

[0024] 2. Add the above PCL / nHA homogenate into the feeding bin of the 3D PANY wire machine, and adjust the parameters of the wire machine as follows: middle section temperature 160 °C, extrusion temperature 130 °C, extrusion speed 70, cooling motor speed 10, traction motor speed 2. When the composite wire is extruded from the extrusion port, it is cooled and solidified through a water-cooling tank. The diameter of the wire is monitored in real time by a laser diameter gauge, and the wire diameter is stable at 1.75 ± 0.05 mm. The detailed manufacturing parameters are shown in Table 1.

[0025] II. 3D printing of bionic bone scaffolds using PCL / nHA composite wires Design bionic bone scaffolds using Tinkercad and Prusaslicer software. Design parameters: filling pattern: Gyroid; layer height: 200 μm; filling angle: 0 / 120°. Print the designed bone scaffolds using a Prusa i3 MK3S printer, and set the control board parameters as follows: extrusion temperature: 198 °C; extrusion speed: 80; extrusion amount: 100%; printing platform temperature: 30 °C; cooling fan speed: 255.

[0026] III. Detection results

[0027] 1. Scanning electron microscopy (SEM) observation of the cross-section of PCL and PCL / nHA composite wires and energy-dispersive X-ray spectroscopy (EDX) elemental analysis: SEM scanning and EDX elemental analysis of the cross-section of pure PCL wires showed the presence of C and O elements, and no particulate components were seen on the surface. SEM scanning and EDX elemental analysis of the cross-section of PCL / nHA composite wires showed that nHA was uniformly distributed in PCL, and the presence of Ca, P, C, and O elements was detected ( Figure 3 ).

[0028] 2. Gross observation and SEM results of 3D printed PCL / nHA bionic bone scaffolds showed that the bionic scaffolds had an interconnected pore structure, stable forming, and high precision ( Figure 4 ).

[0029] 3. Raman spectroscopy analysis: Raman spectroscopy was used to analyze the functional groups in nHA powder, PCL particles, PCL bionic scaffolds, and PCL / nHA bionic scaffolds ( Figure 5 A). Among them, nHA powder showed an obvious peak only at 960.41 cm -1 , corresponding to the peak of the PCL / nHA bionic scaffold group, which was the characteristic peak of the PO 4 3- functional group. PCL particles, PCL bionic scaffolds, and PCL / nHA bionic scaffolds all showed peaks at 1108.73 cm -1 , 1303.87 cm -1 and 1722.67 cm -1Characteristic peaks of C-O and C=O functional groups appear at [the specified position]. The above results confirm that the main body of PCL is a carbon skeleton; nHA has been successfully added to the PCL / nHA composite wire and the bionic scaffolds printed with it.

[0030] 4. X-Ray Diffraction (XRD): XRD tests were carried out on nHA powder, PCL particles, PCL bionic scaffolds, and PCL + 20% nHA bionic scaffolds to confirm the phase composition in the samples ( Figure 5 B). Two typical peaks appeared between 20° < 2θ < 25° for PCL particles, PCL bionic scaffolds, and PCL / nHA bionic scaffolds, which are characteristic peaks of the PCL component. The nHA powder group and the PCL / nHA bionic scaffold group showed consistent peaks at 25° < 2θ < 30°, 30° < 2θ < 40°, and 46° < 2θ < 54°, while no obvious peaks appeared in the above wavelength bands for the PCL particle and PCL bionic scaffold groups. The above results show that the PCL + 20% nHA bionic scaffold contains the crystal phases of PCL and nHA particles, and their properties have not changed during the wire manufacturing and 3D printing processes.

[0031] 5. Thermogravimetric analysis: When the temperature reaches 350 °C, the components in the PCL + 20% nHA bionic scaffold, PCL bionic scaffold, and PCL particles start to vaporize and lose weight, while the nHA powder does not show obvious weight loss due to its melting point reaching about 1000 °C ( Figure 6 A). The remaining weight ratio of the nHA powder group after high temperature is 98.9%; the remaining weight ratio of the PCL scaffold group and the PCL particle group after high temperature is about 0.3%; the remaining weight ratio of nHA in the PCL + 20% nHA group of bionic scaffolds after high temperature is 19.4%, proving that a uniformly mixed composite wire was successfully prepared by adding 20% nHA to PCL in the previous experiment and used for 3D printing bionic scaffolds ( Figure 6 A).

[0032] Figure 6 Figure B shows that the nHA powder does not show vaporization due to its melting point reaching above 1000 °C. The PCL group of bionic scaffolds shows the fastest vaporization rate of 2.19 mg / min at 406 °C; the PCL particle group shows the fastest vaporization rate of 1.1 mg / min at 405 °C; the PCL / 20% nHA group of bionic scaffolds shows the fastest vaporization rate of 0.9 mg / min at 402 °C. In summary, the PCL particles, the PCL group of bionic scaffolds, and the PCL + 20% nHA group of bionic scaffolds all show the fastest vaporization rate at about 400 °C, indicating that the properties of PCL particles and nHA powder have not changed during the wire manufacturing and 3D printing processes.

[0033] Conclusion: This method manufactures PCL + 20% nHA composite wires with uniform diameters without using any chemical reagents and successfully applies them to the fused deposition 3D printing of bionic bone scaffolds. Through scanning electron microscopy, EDX elemental analysis, Raman spectroscopy analysis, XRD analysis, and thermogravimetric analysis, it is verified that nHA powder is uniformly distributed in the PCL / nHA composite wires and the detected amount is close to the added amount (19.4% detected amount vs 20% added amount). It is believed that this method can provide broad application prospects for the manufacture of PCL and nHA materials through wires and the application of 3D printing bionic bone scaffolds in bone defect repair, and is expected to significantly reduce the cost of implants and benefit patients in the future.

Claims

1. A method for manufacturing a PCL / nHA composite wire suitable for fused deposition 3D printing and its application, characterized in that it comprises the following steps: 1.

1. Prepare PCL / nHA mixture slurry. 1.

2. Place the mixture into a 3DPANY wire machine and adjust the parameters to obtain PCL / nHA composite wires with uniform diameter. 1.

3. Design of Gyroid filling pattern bionic bone scaffold inspired by the microstructure of butterfly wings. 1.

4. PCL / nHA composite filaments were used to print bionic bone scaffolds using the fused deposition modeling 3D printer PRUSA i3 MK3S.

2. The manufacturing method and application according to claim 1, characterized in that: The preparation method of the mixture slurry in step 1.1 is: first put PCL into a glass cup, then place it in a water bath and heat it to 100°C to melt it, and finally add nHA powder and adjust the temperature to 150°C and stir it thoroughly to form a PCL / nHA mixture slurry.

3. The manufacturing method and application according to claim 1, characterized in that: In the step 1.2, the parameters of the 3DPANY wire machine for extruding the wire are set as follows: middle section temperature 160°C, extrusion temperature 130°C, extrusion speed 70, cooling motor speed 10, and traction motor speed 2.

4. The manufacturing method and application according to claim 1, characterized in that: The design parameters of the bionic scaffold in step 1.3 are: filling mode: Gyroid; Layer height: 200 μm; Fill angle: 0 / 120°.

5. The manufacturing method and application according to claim 1, characterized in that: The parameters for 3D printing bionic scaffolds using PCL / nHA composite wire in step 1.4 are: extrusion temperature: 198°C; extrusion speed: 80; extrusion volume: 100%; printing platform temperature: 30°C; cooling fan speed: 255.

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