A bone repair polymer material and its preparation method

Abstract

This application belongs to the field of medical device technology, and particularly relates to a bone repair polymer material and its preparation method. The bone repair polymer material with multi-level and multi-sized micro-nanoporous structure provided by this application is prepared by sequentially performing micro-feature transfer, laser-induced surface micro-nano structure processing, and reactive ion etching micro-nanopore treatment. This preparation method is simple to operate, low in cost, highly reproducible, and structurally stable, and has the potential for large-scale industrial production. At the same time, the multi-level and multi-sized micro-nanoporous structure of the prepared bone repair polymer material not only has good dimensional stability and high mechanical strength, but also facilitates the adhesion of proteins and osteocytes, promotes osteocyte growth and proliferation differentiation, thereby solving the technical problem of low performance of existing bone repair polymer materials, which is not conducive to the repair of the skeletal system.

Description

Technical Field

[0001] This application belongs to the field of medical device technology, and in particular relates to a bone repair polymer material and its preparation method. Background Technology

[0002] Skeleton is an important component of the human and animal body. For example, in the human body, it protects various organs and is the main carrier for human activities. However, bone defects caused by factors such as aging, car accidents, tumors, trauma, developmental malformations, and osteoporosis severely damage the skeletal system. Therefore, skeletal system repair in humans and animals is of utmost importance.

[0003] Currently, bone repair is mainly achieved through autologous bone grafting, allogeneic bone grafting, and allogeneic material transplantation. However, the source of autologous bone grafts is limited, leading to a shortage of donors when the damaged area of ​​the bone system is large. Although allogeneic bone grafting has a wider range of sources, it is prone to immune rejection and carries the risk of disease transmission and infection. By selecting allogeneic materials with good biocompatibility, the body's immune response can be reduced, and the risk of postoperative infection is lower, making it an important means of bone repair. The bone repair materials used in allogeneic material transplantation include metal materials and polymer materials. Although metal materials for bone repair have excellent machinability and fatigue resistance, the difference between metal materials and human bone modulus is large, resulting in a stress shielding effect. Furthermore, metal materials have poor corrosion resistance and wear resistance, and metal ion precipitation can occur, which has adverse effects on the body.

[0004] Compared with metal materials for bone repair, polyetheretherketone (PEEK) and other bone repair polymers have a smaller difference in modulus with human bone and good biocompatibility, making them important bone repair polymers. To improve the performance of PEEK and other bone repair polymers, researchers have modified them by coating them with hyaluronic acid and other substances to create composite bone repair materials. However, these composite bone repair materials are prone to detachment. Therefore, it is necessary to adopt other approaches to improve the performance of PEEK and other bone repair polymers. Summary of the Invention

[0005] In view of this, this application provides a bone repair polymer material and a preparation method to solve the technical problem that the existing bone repair polymer materials have low performance and are not conducive to the repair of the skeletal system.

[0006] The first aspect of this application provides a bone repair polymer material, including a biocompatible polymer matrix and a multi-level micro-nanoporous structure distributed on its surface.

[0007] Preferably, the multi-level micro / nanopore structure includes hexagonal micro / nano structures and micro / nanopore structures;

[0008] The hexagonal micro / nano structures and the micro / nano pore structures are distributed alternately on the surface of the biocompatible polymer matrix;

[0009] The surface of the hexagonal micro / nano structure is distributed with rhombic micro / nano structures.

[0010] Preferably, the side length of the hexagonal micro / nano structure is 50 μm to 300 μm.

[0011] The side length of the rhombic micro / nano structure is 30 μm to 100 μm;

[0012] The pore size of the micro-nano pore structure is 1μm to 10μm.

[0013] Preferably, the biocompatible polymer matrix is ​​selected from polyetheretherketone, polylactic acid, polycaprolactone, polypropylene, or polyimide.

[0014] A second aspect of this application provides a method for preparing a bone repair polymer material with a multi-layered micro-nanoporous surface structure, the method comprising the following steps:

[0015] Step A1: Transfer the micro-features of the micro-feature template to the surface of the biocompatible polymer matrix by hot pressing, and demold to obtain a biocompatible polymer material with surface micro-features;

[0016] Step A2: Laser-induced surface micro-nano structure processing is performed on biocompatible polymer materials with surface micro-features to obtain biocompatible polymer materials with multi-level micro-nano structures;

[0017] Step A3: Perform reactive ion etching on the multi-layered micro-nano structured biocompatible polymer material to obtain a bone repair polymer material with a multi-layered micro-nano structure on the surface.

[0018] Preferably, in step A1, the hot pressing process includes: fixing the micro-feature template in a mold, heating to cause the biocompatible polymer matrix to be hot-pressed on the micro-feature template, and demolding to obtain a biocompatible polymer material with surface micro-features.

[0019] Preferably, in step A1, the hot pressing time is 10 min to 30 min, and the temperature is the temperature at which the macromolecular chains in the biocompatible polymer matrix have not undergone chemical decomposition, but the chain motion is sufficient to achieve significant relative displacement between molecules. At this temperature, the biocompatible polymer matrix melts to a flowable state.

[0020] Preferably, in step A1, the biocompatible polymer matrix is ​​polyetheretherketone, and the molding temperature is 350℃~420℃.

[0021] Preferably, the biocompatible polymer matrix is ​​polyetheretherketone, and the molding temperature is 390℃~410℃.

[0022] Preferably, in step A1, the biocompatible polymer matrix is ​​polypropylene, and the molding temperature is 160℃~230℃.

[0023] Preferably, the biocompatible polymer matrix is ​​polypropylene, and the molding temperature is 180℃~200℃.

[0024] In step A1, the pressure during the hot pressing pre-pressing stage is 3MPa to 8MPa, and the pressure during the pressurization stage is 10MPa to 13MPa.

[0025] Preferably, in step A1, the micro-feature template is a sieve.

[0026] Preferably, in step A2, the laser-induced surface micro / nano structure processing process includes: placing a biocompatible polymer material with surface micro-features in a laser, adjusting the laser processing parameters, and performing laser-induced surface micro / nano structure processing on the biocompatible polymer material with surface micro-features to obtain a biocompatible polymer material with a multi-level micro / nano structure.

[0027] Preferably, in step A2, the laser processing parameters are: laser power of 5W to 100W, scanning speed of 50mm / s to 2000mm / s, laser wavelength of 200nm to 1070nm, spot diameter of 30μm to 100μm, and scanning speed of 20mm / s to 3000mm / s.

[0028] Preferably, in step A3, the reactive ion etching micro-nanopore treatment process includes: placing a multi-layered micro-nano structured biocompatible polymer material into the vacuum chamber of a reactive ion etching instrument, turning on the gas pipeline and water circulation cooling system, closing the chamber door, and performing reactive ion etching micro-nanopore treatment to obtain a bone repair polymer material with a multi-layered micro-nanopore structure on the surface.

[0029] Preferably, in step A3, the power of the reactive ion etching micro-nano hole treatment is 200W to 500W, and the reactive ion treatment time is 600s to 3000s.

[0030] Preferably, in step A3, the gas in the gas pipeline is: air, oxygen, hydrogen, carbon dioxide, argon, or nitrogen.

[0031] Preferably, the gas flow rate in the gas pipeline is 30 Nl / min to 100 Nl / min.

[0032] In summary, this application provides a bone repair polymer material and its preparation method. The bone repair polymer material provided by this application is prepared by sequentially performing micro-feature transfer, laser-induced surface micro / nano-structure processing, and reactive ion etching micro / nano-pore treatment on the surface of a biocompatible matrix material such as polyetheretherketone. This preparation method is simple to operate, low in cost, highly reproducible, and structurally stable, and has the potential for large-scale industrial production. Furthermore, the prepared bone repair polymer material includes a multi-layered micro / nano-porous structure composed of spaced-distributed rhombic micro / nano-structures and micro / nano-pore structures. The surface of the multi-layered micro / nano-porous structure has higher roughness and specific surface area, good hydrophilicity, which is conducive to the adhesion of proteins and osteocytes, promotes osteocyte growth and proliferation differentiation, significantly improves the stability of newly formed bone tissue, and is beneficial to the repair of the skeletal system. This solves the technical problem that the existing bone repair polymer materials have low performance and are not conducive to the repair of the skeletal system. Attached Figure Description

[0033] To more clearly illustrate the technical solutions in the specific embodiments of this application or the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0034] Figure 1 This is a schematic diagram of the preparation process of a bone repair polymer material provided in Embodiment 2 of this application;

[0035] Figure 2 The images shown are scanning electron microscope (SEM) images of surface micro-features in a bone repair polymer material provided in Embodiment 2 of this application. Image a is a global SEM image of the surface micro-features, and image b is a partial SEM image of the rhomboid surface micro-features.

[0036] Figure 3 The images shown are scanning electron microscope (SEM) images of a multi-layered micro / nano structure in a bone repair polymer material provided in Example 2 of this application. Image a is an overall SEM image of the multi-layered micro / nano structure, and image b is a partial SEM image of the multi-layered micro / nano structure before reactive ion etching.

[0037] Figure 4 The images are scanning electron microscope (SEM) images of a multi-layered micro-nano porous structure in a bone repair polymer material provided in Example 2 of this application. a is an overall SEM image of the multi-layered micro-nano structure, and b is a local SEM image of the multi-layered micro-nano structure after reactive ion etching.

[0038] Figure 5 The graph shows the hydrophilicity test results of a bone repair polymer material provided in Examples 2-4 of this application. Detailed Implementation

[0039] This application provides a bone repair polymer material and its preparation method, which addresses the technical problem that existing bone repair polymer materials have low performance and are not conducive to the repair of the skeletal system.

[0040] The technical solutions of this application will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this application. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0041] Example 1

[0042] In view of the defects of bone repair materials currently used in allogeneic transplantation, Embodiment 1 of this application provides a bone repair polymer material, which includes a biocompatible polymer matrix and a multi-layered micro-nanoporous structure distributed on its surface; the multi-layered micro-nanoporous structure includes spaced-apart rhombic micro-nano structures and micro-nanoporous structures; on different structural surfaces, the growth and adhesion of cells show significant differences. Compared with a flat surface, the multi-layered micro-nanoporous structure is closer to bone tissue, exhibiting higher roughness and specific surface area, which is more conducive to protein and cell adhesion, promotes osteoblast growth and proliferation differentiation, and significantly improves the stability of newly formed bone tissue; at the same time, the multi-layered micro-nanoporous structure has high geometrical stability, high mechanical strength, and a certain supporting effect, and is not easily damaged during long-term use, thereby solving the technical problem that the existing bone repair polymer materials have low performance and are not conducive to the repair of the skeletal system.

[0043] Regarding the dimensions of hexagonal micro / nanostructures, rhombic micro / nanostructures, and micro / nanopore structures in bone repair polymer materials, the hexagonal micro / nanostructures are obtained by micro-feature transfer from a sieve, with side lengths ranging from 50 μm to 300 μm. The rhombic micro / nanostructures are regular rhombic shapes, obtained through laser processing, with dimensions matching the laser spot, and side lengths ranging from 30 μm to 100 μm. The shorter first side has a length of 20 μm to 50 μm, and the longer second side has a length of 50 μm to 100 μm. The micro / nanopores in the micro / nanopore structures are obtained by reactive ion etching, with pore sizes ranging from 1 to 10 μm.

[0044] For the biocompatible polymer matrix used in bone repair polymer materials, it can be selected from polyetheretherketone, polylactic acid, polycaprolactone, polypropylene, or polyimide.

[0045] For the screen used in the micro-feature template transfer process, a 3000-500 mesh screen can be selected, and a 2200-3000 mesh screen can be further selected. Using a screen with a corresponding aperture of this mesh number, combined with a hot pressing molding process, micro-sized micro-features can be transferred to the surface of a biocompatible polymer matrix.

[0046] Example 2

[0047] Example 2 of this application provides a preparation process for the bone repair polymer material with a multi-layered micro-nanoporous structure described in Example 1. The preparation process is as follows: Figure 1 As shown, the fabrication process includes pretreatment of micro-feature templates, transfer of micro-feature templates, laser-induced surface micro / nano structure fabrication, and reactive ion etching of micro / nano holes.

[0048] The pre-processing micro-feature template includes: ultrasonically cleaning a 3000-mesh sieve, drying it at 100°C for 10 minutes, and then fixing it onto a hot-pressing template. The sieve has regular hexagonal holes.

[0049] The micro-feature template transfer process includes: heating to 400℃ to melt polyether ether ketone (PEEK), constructing micro-features on the PEEK surface using hot pressing, and demolding to obtain a PEEK sample with micro-features on the surface. The pressure of the pre-pressing stage of hot pressing is 5 MPa for 5 min, and the pressure of the pressurization stage is 12 MPa for 15 min. Demolding can be performed by using a water circulation cooling system to cool the biocompatible polymer matrix to a near-room temperature of 20℃~35℃, and then sequentially removing the micro-feature template and the biocompatible polymer matrix from the mold simultaneously, and then removing the single-stage micro-feature template from the biocompatible polymer matrix to obtain a biocompatible polymer material with surface micro-features.

[0050] Laser-induced surface micro / nano structure fabrication includes: placing a polyether ether ketone (PEEK) sample with micro-features on its surface under a laser, adjusting the laser processing parameters, and performing laser-induced surface micro / nano structure fabrication on the PEEK sample with micro-features. The laser processing parameters are set as follows: power 10W, frequency 250kHz, scanning speed 300mm / s, scanning spacing 100μm, and 50 scans. A regular rhomboid structure is obtained on the PEEK sample with micro-features on its surface, resulting in a PEEK sample with a multi-layered micro / nano structure on its surface.

[0051] The reactive ion etching (RIE) micro-nanopore treatment process includes: placing a polyetheretherketone (PEEK) sample with a multi-layered micro-nano structure on its surface into the vacuum chamber of a reactive ion etching instrument, turning on the gas pipeline and water circulation cooling system, closing the chamber door, and performing reactive ion etching surface treatment. The reactive ion processing parameters are set as follows: power 300W, air flow rate 50 Nl / min, and reactive ion processing time 1200 s, resulting in a PEEK sample (PSJ1) with a multi-layered micro-nanopore structure on its surface.

[0052] Example 3

[0053] Example 3 of this application provides a method for preparing a bone repair polymer material. The difference between the preparation method and Example 2 is that the laser-induced surface micro / nano structure processing and reactive ion etching micro / nano hole treatment are not performed. Instead, a polyether ether ketone (PS) sample with micro-features on the surface is obtained by sequentially performing pretreatment of micro-feature templates and micro-feature template transfer.

[0054] Example 4

[0055] Example 4 of this application provides a method for preparing a bone repair polymer material. The difference between the preparation method and Example 2 is that the reactive ion etching micro-nano pore treatment is not performed. Instead, a polyether ether ketone (PSJ) sample with a multi-layered micro-nano structure is obtained by sequentially performing pretreatment micro-feature template, micro-feature template transfer, and laser-induced surface micro-nano structure processing.

[0056] Example 5

[0057] Example 5 of this application provides another preparation process for the bone repair polymer material with multi-level micro-nano porous structure described in Example 1. The preparation process uses anodized aluminum oxide (AAO) template instead of a sieve, and then performs micro-feature template transfer, laser-induced surface micro-nano structure processing, and reactive ion etching micro-nano pore treatment in sequence.

[0058] The micro-feature template transfer process includes: heating to 180°C to melt polypropylene (PP), and using hot pressing to construct micro-features on the surface of the polypropylene to obtain a polypropylene sample with micro-features on the surface.

[0059] Laser-induced surface micro / nanostructure fabrication involves laser processing of a polypropylene sample with micro-features on its surface. The polypropylene sample with micro-features is placed under a laser, and the laser processing parameters are adjusted to induce surface micro / nanostructure fabrication. The laser processing parameters are set as follows: power 5W, frequency 200kHz, scanning speed 200mm / s, scanning interval 100μm, and 50 scans. This process yields a regular rhomboid structure on the polypropylene sample with micro-features, resulting in a polypropylene sample with a multi-layered micro / nanostructure on its surface.

[0060] The reactive ion etching (RIE) micro-nanopore treatment involves placing a polypropylene sample with a multi-layered micro-nano structure on its surface into the vacuum chamber of a reactive ion instrument, activating the gas pipeline and water circulation cooling system, closing the chamber door, and performing reactive ion surface treatment. The reactive ion processing parameters are set as follows: power 200W, air flow rate 50 Nl / min, and processing time 1200 s, resulting in a polypropylene sample with a multi-layered micro-nano structure on its surface.

[0061] Experimental Example 1

[0062] Experimental Example 1 of this application tests the performance of the bone repair polymer materials prepared in Examples 2-4.

[0063] Among them, the surface micro-features obtained by micro-feature template transfer in the bone repair polymer material provided in Example 2 are as follows: Figure 2 As shown, the multi-level micro-nano structures obtained in the bone repair polymer material through sequential micro-feature template transfer and laser-induced surface micro-nano structure processing are as follows: Figure 3 As shown, the multi-level micro-nanoporous structure obtained in the bone repair polymer material through sequential micro-feature template transfer, laser-induced surface micro-nano structure processing, and reactive ion etching micro-nanopore treatment is as follows: Figure 4 As shown, from Figure 2-4 As can be seen, the multi-layered, multi-sized micro-nanoporous structure in the bone repair polymer material provided in Example 2 of this application includes interspersed rhomboid micro-nano structures and micro-nanoporous structures. The bone repair polymer material with this multi-layered, multi-sized micro-nanoporous structure is closer to bone tissue and is beneficial to promoting bone cell growth, proliferation and differentiation.

[0064] The hydrophilicity test results of the bone repair polymer materials provided in Examples 2-4 are as follows: Figure 5 As shown, from Figure 5 It can be seen that, compared with the bone repair polymer materials provided in Examples 3-4, the bone repair polymer material provided in Example 4 has the smallest water contact angle and is more easily wetted, indicating better hydrophilicity, which is beneficial to bone cell adhesion, growth and proliferation differentiation.

[0065] The above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A method for preparing a bone repair polymer material, characterized in that, Including the following steps: Step A1: Transfer the micro-features of the micro-feature template to the surface of the polyetheretherketone matrix by hot pressing, and demold to obtain the polyetheretherketone material with surface micro-features; Step A2: Laser-induced surface micro-nano structure processing is performed on the polyether ether ketone material with surface micro-features to obtain a polyether ether ketone material with multi-level micro-nano structure; Step A3: Perform reactive ion etching on the multi-layered micro-nano structured polyetheretherketone sample to obtain a bone repair polymer material with a multi-layered micro-nano porous surface. The multi-level micro-nano pore structure includes hexagonal micro-nano structures and micro-nano pore structures; The hexagonal micro / nano structures and the micro / nano porous structures are distributed alternately on the surface of the polyetheretherketone matrix; The surface of the hexagonal micro / nano structure is distributed with rhombic micro / nano structures; The side length of the hexagonal micro / nano structure is 50 μm to 300 μm; The side length of the rhombic micro / nano structure is 30 μm to 100 μm; The pore size of the micro-nano pore structure is 1 μm to 10 μm.

2. The method for preparing a bone repair polymer material according to claim 1, characterized in that, In step A1, the hot pressing process includes: fixing the micro-feature template in the mold, heating to cause the polyether ether ketone matrix to be hot pressed on the micro-feature template, and demolding to obtain the polyether ether ketone material with surface micro-features.

3. The method for preparing a bone repair polymer material according to claim 1, characterized in that, In step A2, the laser-induced surface micro / nano structure processing process includes: placing the polyether ether ketone material with surface micro-features in a laser, adjusting the laser processing parameters, and performing laser-induced surface micro / nano structure processing on the polyether ether ketone material with surface micro-features to obtain a multi-layered micro / nano structure polyether ether ketone material.

4. The method for preparing a bone repair polymer material according to claim 1, characterized in that, In step A3, the reactive ion etching micro-nanopore treatment process includes: placing the multi-layered micro-nano structured polyether ether ketone material into the vacuum chamber of the reactive ion instrument, turning on the gas pipeline and water circulation cooling system, closing the chamber door, and performing reactive ion etching micro-nanopore treatment to obtain a bone repair polymer material with a multi-layered micro-nanopore structure on the surface.

5. The method for preparing a bone repair polymer material according to claim 1, characterized in that, In step A1, the hot pressing time is 10 min to 30 min, and the temperature is 350℃ to 420℃.

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