Preparation method of porous polyether-ether-ketone as guided bone regeneration barrier membrane

Abstract

The invention is applicable to the technical field of biological materials, and provides a preparation method of porous polyether-ether-ketone as a guided bone regeneration barrier membrane, which comprises the following steps: placing a special polyether-ether-ketone wire for 3D printing in a high-temperature oven, drying for 5 hours for later use, establishing an STL file, setting printing parameters, and printing; and the printed polyether-ether-ketone sheet is put into a hot press preheated to 280 DEG C for hot pressing treatment, and finally a sample is obtained. The porous polyether-ether-ketone barrier membrane which is adjustable in thickness and high in supporting performance and does not occupy bone regeneration space is prepared by combining 3D printing and a hot pressing technology, and the pore size of the porous polyether-ether-ketone barrier membrane is suitable for guiding bone regeneration. The barrier membrane material is soft and can be cut according to needs, clinical diversified requirements are met, the application range of the PEEK composite material in oral medicine is widened, the preparation method of the novel barrier membrane with mechanical performance and biological activity is provided, and a new choice is provided for clinic.

Description

Technical Field

[0001] The 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] In view of the fact that inflammation, trauma, tumors and other reasons can cause progressive atrophy of the alveolar ridge, when the remaining alveolar ridge cannot meet the needs of implant restoration, corresponding bone augmentation technology should be used to increase the height and width of the alveolar ridge to achieve the initial stability of implant restoration. Among them, guided bone regeneration (GBR) has become the most widely used and longest-lasting bone augmentation technology in clinical practice due to its simple operation and good osteogenesis effect. GBR uses surgical technology to place a barrier membrane between soft tissue and bone defect to prevent fibroblasts and epithelial cells from growing into the bone defect area, providing space for bone regeneration to ensure that the osteogenesis process in the bone defect area is not interfered with by 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 biological activity, are absorbable, and are easy to operate, they have poor mechanical properties and unclear degradation rates, which affect 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 supporting capacity is limited. When used for vertical bone absorption, titanium mesh needs to be used for reinforcement, and 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, but 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 biological activity.

[0004] Polyetheretherketone (PEEK) is a material that has been widely used in medicine in recent years. Since its elastic modulus is similar to that of bone and its biosafety is good, after passing FDA certification in the 1990s, PEEK and its composites have been used clinically in intervertebral fusion, artificial joint replacement, and trauma implantation, etc., and it has been experimentally used as a material for fixed or removable partial dentures in oral medicine. PEEK has a variety of processing methods and can be customized according to clinical needs to meet the 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 object 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, comprising the following steps:

[0009] The polyetheretherketone 3D printing special filament is placed in a high-temperature oven at 150°C and dried for 5 hours for use. An STL file is created, and printing parameters are set and printing is performed to obtain a polyetheretherketone sheet. The printed polyetheretherketone sheet is 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; print nozzle temperature of 460°C; print platform temperature of 250°C; print layer height of 0.2mm; filling rate of 35%, 40% or 45%; and print 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 is 280° C., pressure is 50 MPa, and holding time is 30 min.

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

[0014] The present invention combines 3D printing with hot pressing technology to prepare a porous polyetheretherketone (PEEK) barrier membrane with adjustable thickness, strong support and no bone regeneration space, and its pore size is suitable for guiding bone regeneration. The barrier membrane material is soft and can be cut as needed to meet the diverse clinical needs. It not only expands the application scope of PEEK composite materials in stomatology, but also provides a preparation method for a new barrier membrane with both mechanical properties and biological activity, providing a new choice for clinical practice. 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 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 osteogenic-related genes after co-culture of PEEK films (P-500, P-400 and P-300) and rBMSCs for 14 days.

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

[0020] In order to have a clearer understanding of the technical features, purposes and beneficial effects of the present invention, the technical solution of the present invention is now described in detail below, but it should not be understood 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 can be obtained from commercial sources unless otherwise specified.

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

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

[0023] Example 1: A method for preparing 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 for 5 hours for later use, create an STL file, and set its printing parameters as follows:

[0025] Table 1 Printing parameters of Example 1

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

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

[0028] Put the printed polyetheretherketone sheet into a hot press at 280°C, and heat it to 340°C for 3 minutes at a pressure of 50MPa 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 for 5 hours for later use, create an STL file, and set its printing parameters as follows:

[0031] Table 2 Example 2 Printing parameters

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

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

[0034] Put the printed polyetheretherketone sheet into a hot press at 280°C, and heat it to 340°C for 3 minutes at a pressure of 50MPa 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 for 5 hours for later use, create an STL file, and set its printing parameters as follows:

[0037] Table 3 Example 3 Printing parameters

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

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

[0040] Put the printed polyetheretherketone sheet into a hot press at 280°C, and heat it to 340°C for 3 minutes at a pressure of 50MPa 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 for 5 hours for later use, create an STL file, and set its printing parameters as follows:

[0043] Table 4 Example 4 Printing parameters

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

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

[0046] Put the printed polyetheretherketone sheet into a hot press at 280°C, and heat it to 340°C for 3 minutes at a pressure of 50MPa 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 for 5 hours for later use, create an STL file, and set its printing parameters as follows:

[0049] Table 5 Example 5 Printing parameters

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

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

[0052] Put the printed polyetheretherketone sheet into a hot press at 280°C, and heat it until the temperature rises to 320°C and keeps it for 10 minutes, and then perform hot pressing at a pressure of 50MPa.

[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 for 5 hours for later use, create an STL file, and set its printing parameters as follows:

[0055] Table 6 Printing parameters of Example 6

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

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

[0058] Put the printed polyetheretherketone sheet into a hot press at 280°C, and heat it until the temperature rises to 300°C and keeps it for 10 minutes, with a pressure of 50MPa 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 for 5 hours for later use, create an STL file, and set its printing parameters as follows:

[0061] Table 7 Example 7 Printing parameters

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

[0063] Printing was performed according to the above printing parameters, with the filling rate set to 35% and the printing thickness set 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 for hot pressing. The resulting PEEK film was named P-500 according to 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 for 5 hours for later use, create an STL file, and set its printing parameters as follows:

[0067] Table 8 Printing parameters of Example 8

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

[0069] Printing was performed according to the above printing parameters, with the filling rate set to 40% and the printing thickness set 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 for hot pressing. The resulting PEEK film was named P-400 according to 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 for 5 hours for later use, create an STL file, and set its printing parameters as follows:

[0073] Table 9 Printing parameters of Example 9

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

[0075] Printing was performed according to the above printing parameters, with the filling rate set to 45% and the printing thickness set 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 for hot pressing. The resulting PEEK film was named P-300 according to 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 show that the higher the filling rate of 3D printing, the smaller the pore size. After hot pressing, the overall thickness can be reduced and the corresponding pore size can be reduced. In this process, corresponding adjustments can be made according to the required pore size and thickness.

[0081] Table 11 shows the mechanical properties of the PEEK films obtained by the preferred processing method (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 the tensile strength and tensile modulus increase with the decrease of pore size. In particular, the P-300 sample with the smallest pore size exhibits the highest tensile strength and tensile modulus, and its elongation at break is also the largest. In terms of roughness and contact angle, there is no obvious difference between the three samples of P-500, P-400 and P-300.

[0085] Figure 1 The ALP results (i.e. alkaline phosphatase results) of PEEK films (P-500, P-400 and P-300) co-cultured with rBMSCs for 7 days 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 gradually becomes darker, indicating that PEEK films with different pore sizes have different abilities to promote early osteogenic differentiation of stem cells in vitro.

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

[0087] Figure 3 The PCR results of osteogenic genes in PEEK films (P-500, P-400 and P-300) co-cultured with rBMSCs for 14 days. After rBMSCs were co-cultured with PEEK films for 14 days, the expression of osteogenic genes (OCN, COL1, RUNX2) was detected, and it was still found that the expression of osteogenic genes in PEEK films with smaller pore sizes was higher.

[0088] Figure 4Western Blot results of osteogenic genes in PEEK films (P-500, P-400 and P-300) co-cultured with rBMSCs for 14 days. The Western Blot results are 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 difference in osteogenesis of PEEK films with different pore sizes after 4 weeks, and the titanium mesh (Ti) was set as the control group. It can be seen from the figure that there is bone regeneration guided by the porous structure in the center of the defect, and the pore size of the new bone is also matched with the particle size of the PEEK film (P-500, P-400 and P-300). In addition, it can be clearly observed that the imaging development caused by the metal properties of the titanium mesh 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 modifications and improvements can be made without departing from the concept of the present invention. These should also be regarded as the protection scope 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: The polyetheretherketone 3D printing special filament is placed in a high-temperature oven at 150°C and dried for 5 hours for use. An STL file is created, and printing parameters are set and printing is performed to obtain a polyetheretherketone sheet. The printed polyetheretherketone sheet is placed in a hot press preheated to 280°C for hot pressing treatment to finally obtain a porous polyetheretherketone guided bone regeneration barrier membrane.

2. The method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration according to claim 1, characterized in that: 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 of 35%, 40% or 45%; and printing thickness of 0.5mm.

3. The method for preparing porous polyetheretherketone as a barrier membrane for guided bone regeneration according to claim 2, characterized in that: The filling rate is selected to be 40%.

4. 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 is 280° C., pressure is 50 MPa, and holding time is 30 min.

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