3D printing composite magnesium and nano-silver antibacterial degradable alveolar bone repair material and preparation method thereof

Abstract

The invention discloses a 3D printing composite magnesium and nano-silver antibacterial degradable alveolar bone repair material and a preparation method thereof.The bone repair material is prepared from, by mass, 45%-65% of biodegradable polymer, 5%-25% of biodegradable inorganic matter, 5%-20% of nano-silver and 2%-10% of magnesium powder, and the total amount of all the components is 100%; the biodegradable inorganic matter is powdery, and the particle size of the biodegradable inorganic matter is 100-400 meshes; and the particle size of the magnesium powder is 100-400 meshes. The biodegradable polymer / biodegradable inorganic matter / nano-silver / magnesium powder is compounded into the same bone repair material, the material ratio of the inorganic matter to the magnesium powder is remarkably reduced due to the addition of the nano-silver, and better physical and chemical properties, a better bone tissue regeneration guiding / inducing effect and a better antibacterial effect are generated; the material can be degraded and absorbed in vivo, has good biocompatibility, is beneficial to alveolar bone reconstruction, and can also improve inflammation.

Description

Technical Field

[0001] This invention relates to the field of alveolar bone repair technology, specifically a 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material and its preparation method. Background Technology

[0002] Clinically, autologous and allogeneic bone are mainly used for bone defect repair. However, the supply of autologous bone is limited, and artificial bone repair materials play an irreplaceable role in modern bone grafting surgery. Finding bone repair materials with good biological properties has always been a hot topic in orthopedic research. Although there are various bone repair materials available internationally, none can perfectly replace human bone to date. Significant progress has been made in the research of various materials and tissue-engineered bone, with different materials demonstrating strong bone defect repair capabilities. Composite metal bone repair materials are also widely used, but their complex preparation process and high cost limit their production. In dental surgery patients, alveolar bone and gingival wounds are easily infected due to improper care. Mediating bacterial adhesion to the oral environment and periodontal tissue surfaces allows these bacteria to colonize and produce pathogenic dental plaque biofilms, inducing host cells to express inflammatory cytokines, especially osteoclasts related to bone resorption, further increasing the risk of wound infection. Therefore, in order to reduce patient pain and improve the treatment effect, a new approach to treating alveolar bone defects has been developed, namely, to develop substitutes that can repair or improve the function of tissues or organs. The preparation of ideal tissue-engineered bone remains the goal of scholars.

[0003] Modern bone defect repair materials primarily achieve osteoconduction, osteoinduction, and osteogenic effects, along with good biocompatibility, degradability, and porous three-dimensional structure. With the development of tissue engineering in oral medicine, the preparation of scaffold materials to guide alveolar bone regeneration holds promise as a new technological approach for repairing alveolar bone defects. Bone repair materials are mainly classified into three categories: metal-based bone repair materials, non-metal-based bone repair materials, and polymer materials. Clinically, metal-based bone repair materials are commonly used for the repair of bone defects and missing teeth. Currently, clinical practice often involves combining polymers and inorganic materials with phosphate-based inorganic substances such as hydroxyapatite or calcium triphosphate to create composite bioceramic porous scaffolds. This enhances the polymer's mechanical strength, maintains local pH stability, addresses scaffold degradation, and meets the needs of seed cell adhesion, growth, and calcification. Currently, bone repair materials made from metals, ceramics, polymers, and composite materials are widely used in bone repair. Magnesium ions can promote calcium salt deposition, thereby promoting new bone tissue growth, increasing osteogenic mediation, and exhibiting good osteoinduction effects. Clinically, large-segment bone defects often involve open injuries and alveolar bone damage, posing a significant risk of bacterial contamination and infection. Nanosilver is a commonly used antibacterial agent, effective in treating various bacterial infections, such as acne caused by Propionibacterium acnes, tinea caused by tinea fungi, and mite dermatitis caused by mites. The addition of metallic nanosilver also enhances the material's density and hardness, facilitating alveolar bone reconstruction. While there is considerable research on the application of biodegradable active elements magnesium and silver in bone repair materials, mostly in the form of nanoparticles, dense bulk materials, or as active coatings for biomedical metallic materials, research on combining magnesium and silver with polymers and inorganic substances to prepare porous bone repair materials with a bone-like structure has not yet been reported. The incorporation of metal ions into bone tissue engineering materials faces many challenges. Numerous in vivo experiments have confirmed that metal ions can be released locally from the scaffold without causing systemic toxicity. The preparation of complex bone repair material structures is cumbersome and extremely costly. Ceramic materials have high melting points, making it difficult to directly 3D print them through melting / smelting. However, the adhesive properties of polymers can be used to assist in the molding of ceramic powders, enabling the preparation of metal-incorporated materials and the processing of thin-layer stacking. This makes the preparation of polymer / inorganic / metal composites in the same bone repair material no longer a distant dream.

[0004] In the current field of oral medicine, repairing damaged alveolar bone remains a key and challenging problem for researchers. Different types of bone defects have always been a major clinical challenge, leading to a persistently high demand for bone repair materials. Highly effective delivery carriers and material preparation and processing methods remain key research areas, while safety issues continue to be a major obstacle. Although current synthetic bone repair materials possess satisfactory mechanical properties, biocompatibility, and other excellent properties, they still have some inherent defects compared to autologous / allogeneic bone grafts. Therefore, exploring new bone repair materials, optimizing material functions, improving material preparation methods, and optimizing material structures to enhance the biocompatibility, activity, mechanical properties, and degradation performance of bone repair materials is the future direction of bone repair material development. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material and its preparation method. Using 3D printing technology, polymers, inorganic materials, nano-silver, and magnesium powder are combined into a single bone repair material. This material is effectively used for repairing non-weight-bearing bone defects in the limbs and treating alveolar bone defects, replacing diseased or damaged bones, accelerating fracture healing, or treating nonunion and bone defects. The addition of nano-silver improves the ion release of the metal material, significantly reducing the ratio of inorganic materials and magnesium powder. This not only lowers costs but also produces better physicochemical properties, guides / induces bone tissue regeneration, and provides antibacterial effects. It improves the material's density and hardness, is biodegradable and absorbable in vivo, possesses good biocompatibility, is non-cytotoxic, promotes new bone formation, and is beneficial for alveolar bone reconstruction. Furthermore, it improves the adhesion of alveolar bone microbiota to the oral cavity and periodontal tissue surface environment, inhibits microbiota adhesion to the oral cavity and periodontal tissue surface, and inhibits the expression of inflammatory cytokines by host cells, thereby improving inflammation.

[0006] To achieve the above objectives, the present invention employs the following technical solution: A 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material comprises, by weight percentage: 45%–65% biodegradable polymer, 5%–25% biodegradable inorganic matter, 5%–20% nano-silver, and 2%–10% magnesium powder, with the total amount of all components being 100%. For example, the biodegradable polymer in the bone repair material has a weight percentage of 45%, 50%, 55%, 60%, and 65%; the biodegradable inorganic matter has a weight percentage of 5%, 10%, 15%, 18%, 20%, and 25%; the nano-silver has a weight percentage of 5%, 8%, 10%, 12%, 15%, 17%, and 20%; and the magnesium powder has a weight percentage of 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10%.

[0007] The biodegradable inorganic material is in powder form with a particle size of 100-400 mesh; The magnesium powder has a particle size of 100-400 mesh.

[0008] The biodegradable polymer includes one or more of polyglycolic acid-lactic acid copolymer (PLGA), polylactic acid, polyglycolic acid, polycaprolactone, polyorthoester, polyanhydride, polyphosphazene, and polyamino acids, mixed in any proportion.

[0009] The biodegradable inorganic materials include one or more of α-tricalcium phosphate, β-tricalcium phosphate (β-TCP), hydroxyapatite, calcium phosphate, and calcium silicate, mixed in any proportion.

[0010] The nano-silver is prepared by reducing silver nitrate solution with a reducing agent, wherein the reducing agent is one or more of tin dichloride, glucose, ascorbic acid, and formaldehyde mixed in any proportion.

[0011] The bone repair material is prepared by mixing the components and 3D printing them at a low temperature of -100℃ to 0℃, then freezing them at -100℃ to 0℃ for 8 to 40 hours, and then freeze-drying them in a vacuum for 6 to 20 days.

[0012] A method for preparing a 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material includes the following steps: Raw material pretreatment: After crushing the biodegradable inorganic material, pass it through a 100-400 mesh sieve to obtain biodegradable inorganic powder; pass the magnesium powder through a 100-400 mesh sieve to obtain magnesium powder with a particle size of 100-400 mesh. Preparation of nano-silver solution: A reducing agent is added to a silver nitrate solution and ultrasonically treated for 2 to 48 hours to obtain a nano-silver solution. The reducing agent is one or more of tin dichloride, glucose, ascorbic acid, and formaldehyde, mixed in any proportion. Preparation of homogeneous solution: The biodegradable inorganic powder is dispersed in a 1,4-dioxane solution and stirred until there are no large particles. Then, the biodegradable polymer, the nano silver solution, and the magnesium powder with a particle size of 100-400 mesh are added. Stirring is continued at room temperature for 5-30 hours to form a homogeneous solution. 3D printing molding: 3D printing molding is carried out using a low-temperature rapid prototyping equipment. First, the molding working chamber of the equipment is precooled to ≤-100℃~0℃. Then, a homogeneous solution is added to the equipment and 3D printing is carried out in the working chamber at a temperature of ≤-100℃~0℃ to form a bracket. Post-processing: The 3D-printed scaffold is frozen at -100℃ to 0℃ for 8 to 40 hours, then vacuum freeze-dried for 6 to 20 days, and finally cut and sterilized to obtain the bone repair material.

[0013] Compared with existing technologies, the beneficial effects of this invention are as follows: This invention combines a biodegradable polymer / biodegradable inorganic material / nano silver / magnesium powder into the same bone repair material. The addition of nano silver significantly reduces the material ratio of inorganic material and magnesium powder, which not only reduces costs but also produces better physicochemical properties, guides / induces bone tissue regeneration, and has antibacterial effects. It improves the density and hardness of the material itself, is biodegradable and absorbable in vivo, has good biocompatibility, and is non-cytotoxic, which is beneficial to alveolar bone reconstruction. Furthermore, it improves the adhesion of alveolar bone flora to the oral cavity and periodontal tissue surface environment, inhibits the adhesion of flora to the oral cavity and periodontal tissue surface, inhibits the expression of inflammatory cytokines by host cells, thereby improving inflammation. It is non-cytotoxic, biodegradable and absorbable in vivo, and promotes new bone formation. Attached Figure Description

[0014] Figure 1 Micro-CT 3D image and scanning electron microscope image of the bone repair material prepared in Example 1.

[0015] Figure 2 The diagram shows the antibacterial activity mechanism of the bone repair material prepared in Example 1 at different pH values.

[0016] Figure 3 The diagram shows the antibacterial activity mechanism of the bone repair material prepared in Example 1 at different metal ion concentrations.

[0017] Figure 4 The diagram shows the antibacterial activity mechanism of the bone repair material prepared in Example 1 at different osmotic pressure concentrations.

[0018] Figure 5 The image shows a SEM image of the bone repair material prepared in Example 1. Detailed Implementation

[0019] The present invention will be further described in conjunction with specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined in this application.

[0020] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those skilled in the art. Test methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or according to the conditions recommended by the respective manufacturers. In addition to the specific methods, equipment, and materials used in the embodiments, based on the knowledge of the prior art by those skilled in the art and the description of the present invention, any prior art methods, equipment, and materials similar to or equivalent to those described, used, and materials in the embodiments of the present invention can be used to implement the present invention.

[0021] A 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material comprises, by weight percentage, the following components: 45%–65% biodegradable polymer, 5%–25% biodegradable inorganic matter, 5%–20% nano-silver solution, and 2%–10% magnesium powder, wherein the total amount of the above components is 100%. The biodegradable inorganic material is in powder form with a particle size of 100-400 mesh; The magnesium powder has a particle size of 100-400 mesh.

[0022] The biodegradable polymer includes one or more of the following: polyglycolic acid-lactic acid copolymer, polylactic acid, polyglycolic acid, polycaprolactone, polyorthoester, polyanhydride, polyphosphazene, and polyamino acid, mixed in any proportion.

[0023] The biodegradable inorganic material includes one or more of α-tricalcium phosphate, β-tricalcium phosphate, hydroxyapatite, calcium phosphate, and calcium silicate, mixed in any proportion.

[0024] The nano-silver is prepared by reducing silver nitrate solution with a reducing agent, wherein the reducing agent is one or more of tin dichloride, glucose, ascorbic acid, and formaldehyde mixed in any proportion.

[0025] The bone repair material is prepared by mixing the components and 3D printing them at a low temperature of -100℃ to 0℃, then freezing them at -100℃ to 0℃ for 8 to 40 hours, and then freeze-drying them in a vacuum for 6 to 20 days.

[0026] A method for preparing a 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material includes the following steps: Raw material pretreatment: After crushing the biodegradable inorganic material, pass it through a 100-400 mesh sieve to obtain biodegradable inorganic powder; pass the magnesium powder through a 100-400 mesh sieve to obtain magnesium powder with a particle size of 100-400 mesh. Preparation of nano-silver solution: A reducing agent is added to a silver nitrate solution and ultrasonically treated for 2 to 48 hours to obtain a nano-silver solution. The reducing agent is one or more of tin dichloride, glucose, ascorbic acid, and formaldehyde, mixed in any proportion. Preparation of homogeneous solution: The biodegradable inorganic powder is dispersed in a 1,4-dioxane solution and stirred until there are no large particles. Then, the biodegradable polymer, the nano silver solution, and the magnesium powder with a particle size of 100-400 mesh are added. Stirring is continued at room temperature for 5-30 hours to form a homogeneous solution. 3D printing molding: 3D printing molding is carried out using a low-temperature rapid prototyping equipment. First, the molding working chamber of the equipment is precooled to ≤-100℃~0℃. Then, a homogeneous solution is added to the equipment and 3D printing is carried out in the working chamber at a temperature of ≤-100℃~0℃ to form a bracket. Post-processing: The 3D-printed scaffold is frozen at -100℃ to 0℃ for 8 to 40 hours, then vacuum freeze-dried for 6 to 20 days, and finally cut and sterilized to obtain the bone repair material. Example

[0027] A method for preparing a 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material is provided, comprising the following steps: Raw material pretreatment: After pulverizing the β-TCP material, pass it through a 100-400 mesh sieve to obtain β-TCP powder; pass the magnesium powder through a 100-400 mesh sieve to obtain magnesium powder with a particle size of 100-400 mesh. Preparation of nano-silver solution: A reducing agent is added to a silver nitrate solution and ultrasonically treated for 2 to 48 hours to obtain a nano-silver solution. The reducing agent is one or more of tin dichloride, glucose, ascorbic acid, and formaldehyde, mixed in any proportion. Preparation of homogeneous solution: β-TCP powder is dispersed in a 1,4-dioxane solution and stirred until no large particles are present. Then, PLGA glycolide-lactide copolymer, the nano-silver solution, and the magnesium powder with a particle size of 100-400 mesh are added. The mixture is stirred at room temperature for 5-30 hours to form a homogeneous solution. The mass percentages of each component are 45%-65% PLGA, 5%-25% β-TCP, 5%-20% nano-silver, and 2%-10% of the magnesium powder with a particle size of 100-400 mesh, and the total amount of all components is 100%. For example, the mass percentages of each component are 45% PLGA, 25% β-TCP, 20% nano-silver solution, and 10% of the magnesium powder with a particle size of 100-400 mesh.

[0028] 3D printing molding: 3D printing molding is carried out using a low-temperature rapid prototyping equipment. First, the molding working chamber of the equipment is precooled to ≤-100℃~0℃. Then, a homogeneous solution is added to the equipment and 3D printing is carried out in the working chamber at a temperature of ≤-100℃~0℃ to form a bracket. Post-processing: The 3D-printed scaffold is frozen at -100℃ to 0℃ for 8 to 40 hours, then vacuum freeze-dried for 6 to 20 days, and finally cut and sterilized to obtain the bone repair material.

[0029] The bone repair material prepared in Example 1 was tested.

[0030] Figure 1 -A is a macroscopic image of the bone repair material prepared in Example 1, showing a morphology with regular pores; Figure 1 - B, C, and D are scanning electron microscope (SEM) images, which clearly show the regularly arranged large pore structure on the material surface. These pores are relatively uniformly distributed, and the size of the large pores is in the micrometer range, which reflects the macroscopic porosity and regular pore arrangement of the material. Figure 1 - C shows the microstructure of parts such as pore walls, revealing finer textures and structures, allowing us to understand the scale of these fine structures and reflecting the morphological characteristics of the material at the micro level. Figure 1 - D reveals a porous structure with interconnected pores of varying sizes, indicating a microscopic structure. This demonstrates that the material not only has macroscopic, regular pores but also abundant micropores or mesopores. This hierarchical porous structure may have a significant impact on the material's performance.

[0031] Figure 2This diagram illustrates the antibacterial activity mechanism of the bone repair material prepared in Example 1 at different pH values, showing the microbial colony formation at 360 and 480 minutes under different pH conditions. The results show that at these two time points, the number of microbial colonies at pH=7.4 and pH=8.0 was significantly higher than that at pH=8.5, pH=9.0, and pH=9.5, indicating that a neutral to slightly alkaline environment is more conducive to microbial growth, while excessive alkalinity inhibits its growth, and this trend remains largely consistent over time.

[0032] Figure 3 The diagram illustrates the antibacterial activity mechanism of the bone repair material prepared in Example 1 at different metal ion concentrations. The structure shows the microbial colony-forming units at different Mg²⁺ concentrations at 360 and 480 minutes. As can be seen from the figure, there was no significant difference in the number of microbial colonies corresponding to different Mg²⁺ concentrations at these two time points, indicating that within the Mg²⁺ concentration range involved in the experiment, the Mg²⁺ concentration did not significantly affect the number of microorganisms, and the number of microorganisms remained relatively stable under different Mg²⁺ concentrations.

[0033] Figure 4 The diagram illustrates the antibacterial activity mechanism of the bone repair material prepared in Example 1 at different osmotic pressure concentrations, showing the microbial colony-forming units at 360 minutes and 480 minutes under different osmotic pressures. As can be seen from the figure, there is no significant difference in the number of microbial colonies at these two time points corresponding to different osmotic pressures, indicating that within the osmotic pressure range involved in the experiment, osmotic pressure has no significant effect on the number of microorganisms, and the number of microorganisms is relatively stable under different osmotic pressures.

[0034] Figure 5 The SEM images of the bone repair material prepared in Example 1 show the microstructural changes of different treatment groups (PT and PTMM) at different times (6 hours, 24 hours, and 48 hours) after coating with the bone repair material. These images reflect that the microstructure of the PT and PTMM groups underwent different evolutions over time.

Claims

1. A 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material, characterized in that, By weight percentage, it comprises the following components: 45%–65% biodegradable polymer, 5%–25% biodegradable inorganic matter, 5%–20% nano-silver, and 2%–10% magnesium powder, with the total amount of the above components being 100%. The biodegradable inorganic material is in powder form with a particle size of 100-400 mesh; The magnesium powder has a particle size of 100-400 mesh.

2. The 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material according to claim 1, characterized in that, The biodegradable polymer includes one or more of the following: polyglycolic acid-lactic acid copolymer, polylactic acid, polyglycolic acid, polycaprolactone, polyorthoester, polyanhydride, polyphosphazene, and polyamino acid, mixed in any proportion.

3. The 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material according to claim 1, characterized in that, The biodegradable inorganic material includes one or more of α-tricalcium phosphate, β-tricalcium phosphate, hydroxyapatite, calcium phosphate, and calcium silicate, mixed in any proportion.

4. The 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material according to claim 1, characterized in that, The nano-silver is prepared by reducing silver nitrate solution with a reducing agent, wherein the reducing agent is one or more of tin dichloride, glucose, ascorbic acid, and formaldehyde mixed in any proportion.

5. The 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material according to claim 1, characterized in that, The bone repair material is prepared by mixing the components and 3D printing them at a low temperature of -100℃ to 0℃, then freezing them at -100℃ to 0℃ for 8 to 40 hours, and then freeze-drying them in a vacuum for 6 to 20 days.

6. A method for preparing a 3D-printed composite magnesium and nano-silver antibacterial and biodegradable alveolar bone repair material according to any one of claims 1-5, characterized in that, Includes the following steps: Raw material pretreatment: After crushing the biodegradable inorganic material, pass it through a 100-400 mesh sieve to obtain biodegradable inorganic powder; pass the magnesium powder through a 100-400 mesh sieve to obtain magnesium powder with a particle size of 100-400 mesh. Preparation of nano-silver solution: A reducing agent is added to a silver nitrate solution and ultrasonically treated for 2 to 48 hours to obtain a nano-silver solution. The reducing agent is one or more of tin dichloride, glucose, ascorbic acid, and formaldehyde, mixed in any proportion. Preparation of homogeneous solution: The biodegradable inorganic powder is dispersed in a 1,4-dioxane solution and stirred until there are no large particles. Then, the biodegradable polymer, the nano silver solution, and the magnesium powder with a particle size of 100-400 mesh are added. Stirring is continued at room temperature for 5-30 hours to form a homogeneous solution. 3D printing molding: 3D printing molding is carried out using a low-temperature rapid prototyping equipment. First, the molding working chamber of the equipment is precooled to ≤-100℃~0℃. Then, a homogeneous solution is added to the equipment and 3D printing is carried out in the working chamber at a temperature of ≤-100℃~0℃ to form a bracket. Post-processing: The 3D-printed scaffold is frozen at -100℃ to 0℃ for 8 to 40 hours, then vacuum freeze-dried for 6 to 20 days, and finally cut and sterilized to obtain the bone repair material.

Images