A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration

Abstract

The present invention is applicable to the field of biomaterial technology, and provides a method for preparing a porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps: placing a special filament for polyetheretherketone 3D printing in a high-temperature oven, drying it for 5 hours for standby use, creating an STL file, setting printing parameters and printing; placing the printed polyetheretherketone sheet in a hot press preheated to 280°C for hot pressing treatment, and finally obtaining a sample. The present invention combines 3D printing with hot pressing technology to prepare a porous polyetheretherketone barrier membrane with adjustable thickness, strong support, and no bone regeneration space. The pore size is suitable for guiding bone regeneration. The barrier membrane material is soft and can be cut as needed to meet diverse clinical needs. It not only expands the application range of PEEK composite materials in oral medicine, but also provides a method for preparing a new barrier membrane with both mechanical properties and biological activity, providing a new choice for clinical practice.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomaterials, and in particular relates to a method for preparing porous polyetheretherketone as a barrier membrane for guiding bone regeneration. Background Art

[0002] Given that inflammation, trauma, tumors, and other factors can cause progressive atrophy of the alveolar ridge, when the remaining alveolar ridge cannot meet the needs of implant restoration, appropriate bone augmentation techniques must be performed to increase the height and width of the alveolar ridge to achieve initial stability for implant restoration. Among them, guided bone regeneration (GBR) has become the most widely used and longest-standing bone augmentation technique in clinical practice due to its simple operation and good osteogenesis effect. GBR uses surgical techniques to place a barrier membrane between the soft tissue and the bone defect, preventing fibroblasts and epithelial cells from growing into the bone defect area, providing space for bone regeneration, and ensuring that the osteogenesis process in the bone defect area is not interfered with by the epithelial tissue.

[0003] At present, the barrier membranes used in clinical practice are mainly divided into two types: absorbable and non-absorbable membranes. Although absorbable membranes represented by collagen membranes have good bioactivity, are absorbable, and are easy to operate, they have poor mechanical properties and an unclear degradation rate, which affects the effect of bone regeneration. Polytetrafluoroethylene and titanium are commonly used non-absorbable membranes. Polytetrafluoroethylene was the material originally used for barrier membranes, but its support capacity is limited. When used for vertical bone resorption, it needs to be reinforced with titanium mesh. In addition, problems such as bacterial infection and poor support have occurred in the later stages of application. Titanium is a material with good biosafety and excellent mechanical properties. Its use as a barrier membrane increases the success rate of vertical bone augmentation. However, the mechanical properties of titanium are far different from those of bone tissue, and stress shielding is prone to occur. In addition, sharp titanium can easily damage soft tissue and affect healing. Therefore, it is very necessary to develop a barrier membrane that can take into account both mechanical properties and bioactivity.

[0004] Polyetheretherketone (PEEK) is a material that has been widely used in medicine in recent years. Due to its elastic modulus similar to that of bone and its excellent biosafety, PEEK and its composites have been clinically used in interbody fusion cages, artificial joint replacements, and trauma implants since receiving FDA approval in the 1990s. It has also been experimentally used in dentistry as a material for fixed and removable partial dentures. PEEK can be processed in a variety of ways and can be customized to meet diverse clinical needs.

[0005] Based on the above background, the present invention proposes a method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration. Summary of the Invention

[0006] The purpose of the present invention is to provide a method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, aiming to solve the problems raised in the above background technology.

[0007] The purpose of the present invention is achieved through the following technical solutions:

[0008] A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration comprises the following steps:

[0009] The polyetheretherketone 3D printing special filament was placed in a high-temperature oven at 150°C and dried for 5 hours. An STL file was created, the printing parameters were set, and printing was performed to obtain a polyetheretherketone sheet. The printed polyetheretherketone sheet was placed in a hot press preheated to 280°C for hot pressing treatment to finally obtain a porous polyetheretherketone guided bone regeneration barrier membrane.

[0010] Furthermore, the printing parameters include: nozzle diameter of 0.4mm; nozzle temperature of 460°C; printing platform temperature of 250°C; printing layer height of 0.2mm; filling rate selection of 35%, 40% or 45%; and printing thickness of 0.5mm.

[0011] Furthermore, the filling rate is selected to be 40%.

[0012] Furthermore, the conditions of the hot pressing treatment are: hot pressing temperature of 280° C., pressure of 50 MPa, and holding time of 30 min.

[0013] Compared with the prior art, the present invention has the following beneficial effects:

[0014] This study combines 3D printing with hot pressing to create a porous polyetheretherketone (PEEK) barrier membrane with adjustable thickness, strong support, and minimal space occupation for bone regeneration. The membrane's pore size is ideal for guiding bone regeneration. This flexible and customizable barrier membrane meets diverse clinical needs, expanding the application of PEEK composites in stomatology. It also provides a method for preparing a novel barrier membrane with both mechanical properties and biological activity, offering a novel clinical option. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The ALP results of PEEK films (P-500, P-400 and P-300) co-cultured with rBMSCs for 7 days and 14 days.

[0016] Figure 2 The ARS results of PEEK films (P-500, P-400 and P-300) co-cultured with rBMSCs for 21 and 28 days.

[0017] Figure 3PCR results of osteogenesis-related genes after co-culture of PEEK films (P-500, P-400 and P-300) with rBMSCs for 14 days.

[0018] Figure 4 Western Blot results of osteoblast-related genes after co-culture of PEEK films (P-500, P-400 and P-300) with rBMSCs for 14 days.

[0019] Figure 5 To establish the in vivo osteogenesis results of rat skull defect model. DETAILED DESCRIPTION

[0020] To provide a clearer understanding of the technical features, objectives, and beneficial effects of the present invention, the following detailed description of the technical solution of the present invention is provided. However, this description should not be construed as limiting the scope of the present invention. The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0021] The specific implementation of the present invention is described in detail below with reference to specific embodiments.

[0022] The raw material for 3D printing is polyetheretherketone, which is provided by Jida Special Plastics Co., Ltd.

[0023] Example 1: A method for preparing a porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps:

[0024] Place the polyetheretherketone 3D printing filament in a 150℃ high-temperature oven and dry it for 5 hours. Create an STL file and set its printing parameters as follows:

[0025] Table 1 Printing parameters of Example 1

[0026] Printing parameters Numerical Nozzle diameter (mm) 0.6 Print head temperature (℃) 460 Print platform temperature (℃) 250 Floor height (mm) 0.2

[0027] Print according to the above printing parameters, set the fill rate to 35%, and the printing thickness to 1.5mm.

[0028] The printed polyetheretherketone sheet was placed in a hot press at 280°C, and the temperature was raised to 340°C and kept for 3 minutes, and the pressure was 50 MPa for hot pressing.

[0029] Example 2: A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps:

[0030] Place the polyetheretherketone 3D printing filament in a 150℃ high-temperature oven and dry it for 5 hours. Create an STL file and set its printing parameters as follows:

[0031] Table 2 Printing parameters of Example 2

[0032] Printing parameters Numerical Nozzle diameter (mm) 0.6 Print head temperature (℃) 460 Print platform temperature (℃) 250 Floor height (mm) 0.2

[0033] Print according to the above printing parameters, set the fill rate to 35%, and the printing thickness to 1.0mm.

[0034] The printed polyetheretherketone sheet was placed in a hot press at 280°C, and the temperature was raised to 340°C and kept for 3 minutes, and the pressure was 50 MPa for hot pressing.

[0035] Example 3: A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps:

[0036] Place the polyetheretherketone 3D printing filament in a 150℃ high-temperature oven and dry it for 5 hours. Create an STL file and set its printing parameters as follows:

[0037] Table 3 Printing parameters of Example 3

[0038] Printing parameters Numerical Nozzle diameter (mm) 0.6 Print head temperature (℃) 460 Print platform temperature (℃) 250 Floor height (mm) 0.2

[0039] Print according to the above printing parameters, set the fill rate to 35% and the printing thickness to 0.5mm.

[0040] The printed polyetheretherketone sheet was placed in a hot press at 280°C, and the temperature was raised to 340°C and kept for 3 minutes, and the pressure was 50 MPa for hot pressing.

[0041] Example 4: A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps:

[0042] Place the polyetheretherketone 3D printing filament in a 150℃ high-temperature oven and dry it for 5 hours. Create an STL file and set its printing parameters as follows:

[0043] Table 4 Example 4 Printing parameters

[0044] Printing parameters Numerical Nozzle diameter (mm) 0.4 Print head temperature (℃) 460 Print platform temperature (℃) 250 Floor height (mm) 0.2

[0045] Print according to the above printing parameters, set the fill rate to 35% and the printing thickness to 0.5mm.

[0046] The printed polyetheretherketone sheet was placed in a hot press at 280°C, and the temperature was raised to 340°C and kept for 3 minutes, and the pressure was 50 MPa for hot pressing.

[0047] Example 5: A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps:

[0048] Place the polyetheretherketone 3D printing filament in a 150℃ high-temperature oven and dry it for 5 hours. Create an STL file and set its printing parameters as follows:

[0049] Table 5 Printing parameters of Example 5

[0050] Printing parameters Numerical Nozzle diameter (mm) 0.4 Print head temperature (℃) 460 Print platform temperature (℃) 250 Floor height (mm) 0.2

[0051] Print according to the above printing parameters, set the fill rate to 35% and the printing thickness to 0.5mm.

[0052] The printed polyetheretherketone sheet was placed in a hot press at 280°C, and the temperature was raised to 320°C and kept for 10 minutes, and the pressure was 50 MPa for hot pressing.

[0053] Example 6: A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps:

[0054] Place the polyetheretherketone 3D printing filament in a 150℃ high-temperature oven and dry it for 5 hours. Create an STL file and set its printing parameters as follows:

[0055] Table 6 Printing parameters of Example 6

[0056] Printing parameters Numerical Nozzle diameter (mm) 0.4 Print head temperature (℃) 460 Print platform temperature (℃) 250 Floor height (mm) 0.2

[0057] Print according to the above printing parameters, set the fill rate to 35% and the printing thickness to 0.5mm.

[0058] The printed polyetheretherketone sheet was placed in a hot press at 280°C, and the temperature was raised to 300°C and kept for 10 minutes, and the pressure was 50 MPa for hot pressing.

[0059] Example 7: A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps:

[0060] Place the polyetheretherketone 3D printing filament in a 150℃ high-temperature oven and dry it for 5 hours. Create an STL file and set its printing parameters as follows:

[0061] Table 7 Example 7 Printing parameters

[0062] Printing parameters Numerical Nozzle diameter (mm) 0.4 Print head temperature (℃) 460 Print platform temperature (℃) 250 Floor height (mm) 0.2

[0063] Printing was performed according to the above printing parameters, with the fill rate set to 35% and the printing thickness to 0.5 mm. The pore size of the obtained polyetheretherketone sheet was 1.2 mm.

[0064] The printed polyetheretherketone sheet was placed in a hot press at 280°C for 30 minutes at a pressure of 50 MPa. The resulting PEEK film was named P-500 based on its pore size.

[0065] Example 8: A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps:

[0066] Place the polyetheretherketone 3D printing filament in a 150℃ high-temperature oven and dry it for 5 hours. Create an STL file and set its printing parameters as follows:

[0067] Table 8 Printing parameters of Example 8

[0068] Printing parameters Numerical Nozzle diameter (mm) 0.4 Print head temperature (℃) 460 Print platform temperature (℃) 250 Floor height (mm) 0.2

[0069] Printing was performed according to the above printing parameters, with the fill rate set to 40% and the printing thickness to 0.5 mm. The pore size of the obtained polyetheretherketone sheet was 1 mm.

[0070] The printed polyetheretherketone sheet was placed in a hot press at 280°C for 30 minutes at a pressure of 50 MPa. The resulting PEEK film was named P-400 based on its pore size.

[0071] Example 9: A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, comprising the following steps:

[0072] Place the polyetheretherketone 3D printing filament in a 150℃ high-temperature oven and dry it for 5 hours. Create an STL file and set its printing parameters as follows:

[0073] Table 9 Example 9 Printing parameters

[0074] Printing parameters Numerical Nozzle diameter (mm) 0.4 Print head temperature (℃) 460 Print platform temperature (℃) 250 Floor height (mm) 0.2

[0075] Printing was performed according to the above printing parameters, with the fill rate set to 45% and the printing thickness to 0.5 mm. The pore size of the obtained polyetheretherketone sheet was 0.8 mm.

[0076] The printed polyetheretherketone sheet was placed in a hot press at 280°C for 30 minutes at a pressure of 50 MPa. The resulting PEEK film was named P-300 based on its pore size.

[0077] Table 10 shows the pore size and thickness of the PEEK films obtained after hot pressing in Examples 1-9.

[0078] Table 10 Pore size and thickness of PEEK films obtained after hot pressing in Examples 1-9

[0079] Aperture size (mm) Thickness (mm) Example 1 1 1.3 Example 2 1 0.8 Example 3 1 0.3 Example 4 0.9 0.3 Example 5 0.9 0.25 Example 6 0.9 0.25 Example 7 0.5 0.2 Example 8 0.4 0.2 Example 9 0.3 0.2

[0080] The data in Table 10 shows that the higher the fill rate in 3D printing, the smaller the pore size. Hot pressing can reduce the overall thickness and correspondingly the pore size. During this process, adjustments can be made based on the desired pore size and thickness.

[0081] Table 11 shows the mechanical properties of the PEEK films obtained by the preferred processing methods (Examples 7-9).

[0082] Table 11 Mechanical properties of PEEK films obtained by preferred processing methods (Examples 7-9)

[0083]

[0084] The data in Table 11 show that both tensile strength and tensile modulus increase with decreasing pore size. In particular, the P-300 sample, with the smallest pore size, exhibits the highest tensile strength and modulus, as well as the greatest elongation at break. In terms of roughness and contact angle, no significant differences are observed between the P-500, P-400, and P-300 samples.

[0085] Figure 1 The following are the ALP results (i.e., alkaline phosphatase results) of PEEK films (P-500, P-400, and P-300) co-cultured with rBMSCs for 7 and 14 days. As can be seen from the figure, as the pore size of the PEEK film decreases, the number of ALP-positive cells gradually increases, and the staining becomes darker, indicating that PEEK films of different pore sizes have different abilities to promote the early osteogenic differentiation of stem cells in vitro.

[0086] Figure 2 The following are the ARS results (i.e., Alizarin Red staining) of PEEK membranes (P-500, P-400, and P-300) co-cultured with rBMSCs for 21 and 28 days. The results in the figure show that the ARS results at 21 and 28 days are consistent with the ALP staining results. They also show that as the pore size of the PEEK membrane decreases, the number of calcium nodules increases and the staining becomes darker, indicating that PEEK membranes of different pore sizes have different abilities to promote late-stage osteogenic differentiation of stem cells in vitro.

[0087] Figure 3 PCR results for osteoblast-related genes after 14-day co-culture of rBMSCs with PEEK films (P-500, P-400, and P-300). After 14 days of co-culture of rBMSCs with PEEK films, expression of osteoblast-related genes (OCN, COL1, and RUNX2) was measured. The expression of osteoblast-related genes was still higher in PEEK films with smaller pore sizes.

[0088] Figure 4The Western Blot results of osteogenesis-related genes after 14-day co-culture of PEEK films (P-500, P-400, and P-300) with rBMSCs were consistent with the PCR results.

[0089] Figure 5 To establish the results of in vivo osteogenesis in a rat skull defect model. A rat skull defect model was established to observe the differences in the osteogenesis effects of PEEK films with different pore sizes after 4 weeks, and a titanium mesh (Ti) was set as the control group. As can be seen from the figure, there is bone regeneration guided by the porous structure in the center of the defect. The pore size of the new bone also matches the particle size of the PEEK film (P-500, P-400 and P-300). In addition, the imaging development caused by the metallic properties of the titanium mesh can be clearly observed, which has a certain effect on the observation of new bone tissue. By calculating the ratio of bone volume fraction (BV / TV), it was found that the P-400 sample had the best osteogenesis effect.

[0090] The above are only preferred embodiments of the present invention. It should be pointed out that for those skilled in the art, several variations and improvements can be made without departing from the concept of the present invention. These should also be regarded as the scope of protection of the present invention. These will not affect the effect of the implementation of the present invention and the practicality of the patent.

Claims

1. A method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration, characterized in that: The following steps are involved: Place the polyetheretherketone 3D printing filament in a high-temperature oven at 150°C and dry it for 5 hours. Create an STL file, set the printing parameters, and print it to obtain a polyetheretherketone sheet with a pore size of 1 mm. The printing parameters include: nozzle diameter of 0.4mm; nozzle temperature of 460℃; printing platform temperature of 250℃; printing layer height of 0.2mm; filling rate of 40%; printing thickness of 0.5mm; The printed polyetheretherketone sheet was placed in a hot press preheated to 280°C for hot pressing treatment, and finally a porous polyetheretherketone guided bone regeneration barrier membrane with a pore size of 0.4 mm and the best osteogenesis effect was obtained.

2. The method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration according to claim 1, characterized in that: The conditions of the hot pressing treatment are: hot pressing temperature of 280° C., pressure of 50 MPa, and holding time of 30 min.

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