Bionic bone material as well as preparation method and application thereof

Abstract

The invention provides a bionic bone material as well as a preparation method and application thereof. The bionic bone material comprises a photocuring polymer monomer, protein molecules, modified polysaccharide molecules and piezoelectric nanoparticles, the protein molecules and the modified polysaccharide molecules can be crosslinked. Therefore, the bionic bone material disclosed by the invention combines a rigid-soft dual-network structure and the piezoelectric nanoparticles, can simulate mechanical properties, a porous structure and electrophysiological activity of natural bones, and has the characteristics of rapid curing, low thermal damage, high biocompatibility and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular, to a bionic bone material and a preparation method and application thereof, and more particularly, to a bionic bone material for load-bearing bone repair and a preparation method and application thereof. Background Art

[0002] Bone defect repair is a challenging problem in orthopedics, especially for large defects in weight-bearing areas such as the tibia and femur. Repair materials must achieve a precise balance between mechanical support, bioactivity, and long-term functional reconstruction. However, several commonly used clinical approaches currently have limitations.

[0003] Although metal internal fixation can stabilize bone structure in the short term, its rigid mechanical properties block the transfer of physiological loads, leading to imbalanced bone metabolism and long-term implant failure. Although autologous bone transplantation is considered the "gold standard", donor site trauma, limited sources, and the risk of secondary surgery limit its widespread application. Although traditional artificial bone materials (such as hydroxyapatite ceramics and polymer scaffolds) have certain bone conductivity, they generally have problems such as insufficient bioactivity and mismatch between degradation rate and bone regeneration, making it difficult to meet dynamic repair needs. In addition, the above methods are unable to simulate the complex functional characteristics of natural bone, such as the ability to regulate the electrophysiological microenvironment, which can lead to delayed bone healing or even non-healing.

[0004] Therefore, there is an urgent need to develop a material that can simulate the natural bone structure and its properties to overcome the shortcomings of existing methods and achieve efficient repair of bone defects. Summary of the Invention

[0005] The present invention aims to solve at least one of the technical problems existing in the prior art to at least a certain extent.

[0006] The present invention is accomplished based on the following findings of the inventors:

[0007] Bionic strategies provide a new approach for bone repair materials. By simulating the multi-level structure (inorganic-organic composite, porous network) and functional properties (cellular directional migration, metabolic microenvironment response) of natural bone, bionic bone materials can break through the biological inertness limitations of traditional materials. For example, bionic mineralized hydrogels promote cell adhesion by simulating bone matrix components; 3D printed porous scaffolds regulate vascular ingrowth through topological structures; and smart responsive materials release growth factors through pH or enzyme triggering. However, existing bionic systems still face three core challenges:

[0008] 1) High strength and biodegradability are difficult to achieve simultaneously: high modulus materials (such as ceramics) are hard but brittle and non-degradable, while degradable polymers have good biocompatibility but insufficient mechanical strength;

[0009] 2) Single functional dimension: lack of biomimetic electrophysiological properties of bone tissue, unable to reproduce the endogenous electrical signals generated by natural bone under mechanical load and its regulatory effect on osteogenic differentiation;

[0010] 3) Insufficient clinical adaptability: Traditional bionic materials have complex molding processes and long curing times, which make it difficult to meet the needs of immediate shaping during surgery, limiting their application in complex and irregular defects.

[0011] Based on this, in order to address the core defects of existing bionic bone materials, which cannot take into account high-strength support, dynamic degradation adaptation, electrophysiological activity and clinical operability, the inventors have constructed a multifunctional bionic bone material with synergistic mechanical adaptation, biological activity and clinical operability. This material is prepared through multi-component collaboration, cross-scale structural regulation and modular integration of bionic functions, and has the following multi-dimensional functions: 1) It can dynamically adjust mechanical properties according to the bone regeneration process, provide high-strength support in the early stage, and gradually degrade in the later stage to create conditions for new tissue replacement; 2) It has electrophysiological activity, can simulate the piezoelectric effect of natural bone, activate the osteogenic signal pathway, and promote bone tissue regeneration; 3) It has both rapid prototyping capabilities and fine structural plasticity, can adapt to complex anatomical morphologies, and meet the needs of immediate shaping during surgery.

[0012] Therefore, in a first aspect, the present invention provides a biomimetic bone material. According to an embodiment of the present invention, the biomimetic bone material comprises: a photocurable polymer monomer, a protein molecule, a modified polysaccharide molecule, and piezoelectric nanoparticles; the protein molecule and the modified polysaccharide molecule are capable of cross-linking.

[0013] The bionic bone material of the present invention combines a rigid-soft dual network structure with piezoelectric nanoparticles, which can simulate the mechanical properties, porous structure and electrophysiological activity of natural bone, and has the characteristics of rapid curing, low thermal damage and high biocompatibility. Specifically, the rigid network is formed by free radical polymerization of photocurable polymer monomers, providing a rigid support that is compatible with the mechanical properties of natural bone, effectively avoiding the stress shielding effect of traditional metal implants. The soft network is constructed based on the synergistic effect of protein molecules and modified polysaccharide molecules. The modified polysaccharide molecules can dynamically cross-link with proteins under mild conditions to form a soft phase network with a gradient pore structure. The piezoelectric functional module is realized by introducing piezoelectric nanoparticles. Under external load, these nanoparticles can generate endogenous electrical signals that complement the electrophysiological microenvironment of natural bone, activate cell membrane voltage-gated ion channels, and regulate osteogenic differentiation-related signal pathways. Therefore, the bionic bone material of the present invention breaks through the multiple contradictions between mechanics, biology and processing technology of traditional materials, and can achieve efficient regeneration of load-bearing bone defects.

[0014] According to an embodiment of the present invention, the bionic bone material further includes: a photoinitiator.

[0015] According to an embodiment of the present invention, the photocurable polymer monomer includes acrylates.

[0016] According to an embodiment of the present invention, the protein molecule is an engineered protein containing elastin-like protein and growth factors, and the elastin-like protein contains lysine.

[0017] According to an embodiment of the present invention, the modified polysaccharide molecules include modified natural polysaccharides.

[0018] According to an embodiment of the present invention, the piezoelectric nanoparticles include at least one of potassium sodium niobate nanoparticles, barium carbonate nanoparticles, and zinc oxide nanoparticles.

[0019] According to an embodiment of the present invention, the acrylic acid esters include at least one of methyl methacrylate, ethyl methacrylate, ethyl acrylate, and butyl acrylate.

[0020] According to an embodiment of the present invention, the protein molecule has an amino acid sequence as shown in SEQ ID NO: 1.

[0021] According to an embodiment of the present invention, the modified natural polysaccharide includes a modified sodium alginate derivative.

[0022] According to an embodiment of the present invention, the modified sodium alginate derivative is prepared by coupling oxidized sodium alginate with a photoresponsive molecule.

[0023] According to an embodiment of the present invention, the particle size of the piezoelectric nanoparticles is 1 nm-1 μm.

[0024] According to an embodiment of the present invention, the particle size of the piezoelectric nanoparticles is 50 nm-200 nm.

[0025] In the second aspect of the present invention, the present invention proposes a method for preparing the bionic bone material described in the first aspect. According to an embodiment of the present invention, the method comprises: subjecting a photocurable polymer monomer, a protein molecule, a modified polysaccharide molecule and piezoelectric nanoparticles to a first mixing treatment to obtain the bionic bone material. Thus, the preparation method and operation process of the present invention are simple and efficient, and can produce high-quality bionic bone materials on a large scale. At the same time, the bionic bone material prepared by the present invention has the following advantages: high compressive strength (≥130MPa), which can provide strong mechanical support for the load-bearing bone defect site and ensure stability in a complex stress environment; multi-level pore structure (pore size 200-250μm), which provides an ideal microenvironment for the growth and angiogenesis of bone tissue, and accelerates the repair process of bone defects; endogenous electrical signal generation capability (80-90mV), which can simulate the electrophysiological microenvironment of natural bone, activate the osteogenic signal pathway through the piezoelectric effect, and promote bone tissue regeneration and angiogenesis.

[0026] According to an embodiment of the present invention, after the first mixing process, the method further includes: curing the first mixed liquid to obtain the bionic bone material.

[0027] According to an embodiment of the present invention, the first mixed liquid further includes a photoinitiator.

[0028] According to an embodiment of the present invention, the first mixed liquid is prepared by the following method: the protein molecules, the modified polysaccharide molecules and water are subjected to a second mixing treatment to obtain a second mixed liquid; the second mixed liquid, the photocurable polymer monomer, the photoinitiator and the piezoelectric nanoparticles are mixed to obtain the first mixed liquid.

[0029] According to an embodiment of the present invention, based on the total mass of the first mixed liquid, the mass of the photocurable polymer monomer accounts for 50%-95%.

[0030] According to an embodiment of the present invention, based on the total mass of the first mixed liquid, the mass of the photocurable polymer monomer accounts for 60%-90%.

[0031] According to an embodiment of the present invention, based on the total mass of the first mixed solution, the mass of the protein molecules accounts for 1%-20%.

[0032] According to an embodiment of the present invention, based on the total mass of the first mixed solution, the mass of the protein molecules accounts for 5%-15%.

[0033] According to an embodiment of the present invention, based on the total mass of the first mixed liquid, the mass proportion of the modified polysaccharide molecules is 1%-20%.

[0034] According to an embodiment of the present invention, based on the total mass of the first mixed liquid, the mass proportion of the modified polysaccharide molecules is 5%-15%.

[0035] According to an embodiment of the present invention, based on the total mass of the first mixed liquid, the mass proportion of the piezoelectric nanoparticles is 0.1%-20%.

[0036] According to an embodiment of the present invention, based on the total mass of the first mixed liquid, the mass proportion of the piezoelectric nanoparticles is 0.1%-10%.

[0037] According to an embodiment of the present invention, based on the total mass of the first mixed liquid, the mass proportion of the photoinitiator is 0.1-2%.

[0038] According to an embodiment of the present invention, based on the total mass of the first mixed liquid, the mass proportion of the photoinitiator is 0.5-1%.

[0039] In the third aspect of the present invention, the present invention proposes a bionic bone material. According to an embodiment of the present invention, the bionic bone material is prepared by the method described in the second aspect. Thus, the compressive strength of the bionic bone material prepared by the method of the present invention is not less than 100MPa, the elastic modulus is not less than 3GPa, the porosity is not less than 50%, and the pore size is 150-250μm. Therefore, the bionic bone material of the present invention can provide strong mechanical support for the load-bearing bone defect site, ensuring stability in a complex stress environment; at the same time, it provides an ideal microenvironment for the ingrowth and angiogenesis of bone tissue, accelerating the repair process of bone defects; it can also simulate the electrophysiological microenvironment of natural bone, activate the osteogenic signal pathway through the piezoelectric effect, and promote bone tissue regeneration and angiogenesis.

[0040] According to an embodiment of the present invention, the compressive strength of the bionic bone material is not less than 100 MPa.

[0041] According to an embodiment of the present invention, the compressive strength of the bionic bone material is not less than 130 MPa.

[0042] According to an embodiment of the present invention, the elastic modulus of the bionic bone material is not less than 3 GPa.

[0043] According to an embodiment of the present invention, the elastic modulus of the bionic bone material is not less than 3.6 GPa.

[0044] According to an embodiment of the present invention, the porosity of the bionic bone material is not less than 50%.

[0045] According to an embodiment of the present invention, the porosity of the bionic bone material is not less than 54%.

[0046] According to an embodiment of the present invention, the pore size of the bionic bone material is 150-250 μm.

[0047] According to an embodiment of the present invention, the pore size of the bionic bone material is 200-250 μm.

[0048] In the fourth aspect of the present invention, the present invention proposes the use of the bionic bone material described in the first or third aspect or the bionic bone material prepared by the method described in the second aspect in preparing bone repair materials or as a surface functional coating for orthopedic implants.

[0049] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the following description of the embodiments with reference to the accompanying drawings, in which:

[0051] Figure 1 This is an experimental flow chart for preparing a bionic bone material according to an embodiment of the present invention;

[0052] Figure 2 is a recorded stress-strain curve diagram of the bionic bone material prepared according to Examples 1-3 of the present invention;

[0053] Figure 3 is a scanning electron microscope image of the biomimetic bone material prepared according to Example 3 of the present invention;

[0054] Figure 4 is a thermal image of the bionic bone material prepared according to Example 3 of the present invention;

[0055] Figure 5 is a graph showing the in vitro degradation rate of the bionic bone material prepared according to Example 3 of the present invention;

[0056] Figure 6 is a water contact angle image of the surface of the bionic bone material prepared according to Example 3 of the present invention;

[0057] Figure 7 This is a diagram showing the results of promoting angiogenesis of the bionic bone material prepared according to Example 3 of the present invention;

[0058] Figure 8 This is a diagram showing the results of using the bionic bone material prepared according to Example 3 of the present invention for rat bone repair. DETAILED DESCRIPTION

[0059] The embodiments of the present application are described in detail below, which are intended to explain the present application and should not be construed as limiting the present application.

[0060] References herein to "embodiments" mean that a particular feature, structure, or characteristic described in connection with the embodiments may be included in at least one embodiment of the present application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0061] For the sake of clarity, only some numerical ranges are specifically disclosed herein. However, any lower limit may be combined with any upper limit to form an unspecified range; and any lower limit may be combined with other lower limits to form an unspecified range, and similarly, any upper limit may be combined with any other upper limit to form an unspecified range. In addition, each individually disclosed point or single value may itself serve as a lower limit or upper limit and be combined with any other point or single value, or with other lower limits or upper limits, to form an unspecified range.

[0062] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this application belongs; the terms used herein are only for the purpose of describing specific embodiments and are not intended to limit this application; the terms "including" and "having" and any variations thereof in the specification and claims of this application and the above-mentioned figure descriptions are intended to cover non-exclusive inclusions.

[0063] In this document, the terms "include" or "comprising" are open expressions, that is, including the contents specified in this application, but not excluding other contents.

[0064] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be understood to indicate or imply relative importance or implicitly specify the number of the technical features indicated. Therefore, features defined as "first" or "second" may explicitly or implicitly include one or more of such features. Furthermore, in the description of this application, unless otherwise specified, "plurality" means two or more.

[0065] The present invention provides a bionic bone material, a method for making the bionic bone material and uses thereof, which will be described in detail below.

[0066] Bionic bone materials

[0067] In a first aspect, the present invention provides a biomimetic bone material. According to an embodiment of the present invention, the biomimetic bone material comprises: a photocurable polymer monomer, a protein molecule, a modified polysaccharide molecule, and piezoelectric nanoparticles; the protein molecule and the modified polysaccharide molecule are capable of cross-linking.

[0068] The bionic bone material of the present invention combines a rigid-soft dual network structure with piezoelectric nanoparticles, which can simulate the mechanical properties, porous structure and electrophysiological activity of natural bone, and has the characteristics of rapid curing, low thermal damage and high biocompatibility. Specifically, the rigid network is formed by free radical polymerization of photocurable polymer monomers, providing a rigid support that is compatible with the mechanical properties of natural bone, effectively avoiding the stress shielding effect of traditional metal implants. The soft network is constructed based on the synergistic effect of protein molecules and modified polysaccharide molecules. The modified polysaccharide molecules can dynamically cross-link with proteins under mild conditions to form a soft phase network with a gradient pore structure. The piezoelectric functional module is realized by introducing piezoelectric nanoparticles. Under external load, these nanoparticles can generate endogenous electrical signals that complement the electrophysiological microenvironment of natural bone, activate cell membrane voltage-gated ion channels, and regulate osteogenic differentiation-related signal pathways. Therefore, the bionic bone material of the present invention breaks through the multiple contradictions between mechanics, biology and processing technology of traditional materials, can achieve efficient regeneration of load-bearing bone defects, and adapt to the needs of repairing irregular bone defects.

[0069] In this article, the term "weight-bearing bones" refers to the bones in the human skeletal system that support body weight and withstand mechanical loads. They play a key role in the body's mechanical structure, especially during upright walking and weight-bearing activities. The main weight-bearing bones include the spine, hip, femur, tibia, and fibula.

[0070] In some embodiments of the present invention, the bionic bone material further comprises a photoinitiator. Thus, the addition of the photoinitiator can promote the polymerization reaction of the photocurable polymer monomer, so that the monomer is quickly cured under light conditions to form a high molecular polymer.

[0071] In some embodiments of the present invention, the photocurable polymer monomers include acrylates. In some embodiments of the present invention, the acrylates include at least one of methyl methacrylate, ethyl methacrylate, ethyl acrylate, and butyl acrylate. Acrylate monomers are highly reactive and can rapidly form a highly cross-linked polymer network during the photocuring process, imparting high mechanical strength and hardness to the material, making it more similar to the mechanical properties of natural bone and ensuring that the material can withstand greater mechanical loads in weight-bearing areas.

[0072] In some embodiments of the present invention, the protein molecule is an engineered protein containing elastin-like proteins and growth factors, and the elastin-like proteins contain lysine. In some embodiments of the present invention, the growth factor includes epidermal growth factor. Among them, epidermal growth factor (EGF) can stimulate the proliferation and differentiation of various cells (including osteoblasts and endothelial cells). In bone defect repair, EGF can accelerate cell growth and differentiation and promote the regeneration of bone tissue. Elastin-like proteins (ELPs) contain multiple lysines, which can provide rich reaction sites for subsequent chemical modification and construct a dynamic covalent cross-linking network, thereby giving hydrogel materials good injectability, self-healing properties and adaptability, and are suitable for promoting osteogenesis in bone repair. In addition, ELPs have good biocompatibility and cell adhesion, and can promote cell adhesion and proliferation. In bone defect repair, the three-dimensional structure of the hydrogel prepared by ELPs polypeptides can provide cells with a microenvironment that is closer to natural bone, promoting the regeneration of bone tissue. Thus, the protein molecules of the present invention can give the material better biological activity, promote cell adhesion and proliferation, regulate cell behavior, and simulate the mechanical properties and dynamic repair function of natural bone.

[0073] It should be noted that, in the protein molecule design of the present invention, elastin-like protein and growth factor are integrated into the same protein segment through fusion expression technology, and the two are co-expressed in the form of a fusion protein to achieve functional synergy.

[0074] In some embodiments of the present invention, the protein molecule has an amino acid sequence as shown in SEQ ID NO: 1.

[0075] MNSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR MGAGPGVG(VPGVG(VPGKG)9)8VPGWPHHHHH(SEQ ID NO:1)

[0076] In some embodiments of the present invention, the modified polysaccharide molecules include modified natural polysaccharides. In some embodiments of the present invention, the modified natural polysaccharides include modified sodium alginate derivatives. In some embodiments of the present invention, the modified sodium alginate derivatives are prepared by coupling oxidized sodium alginate with photoresponsive molecules. Thus, after oxidized sodium alginate is modified with photoresponsive groups, it can be dynamically cross-linked with protein molecules under mild conditions to form a soft phase network with a gradient void structure. The flexible soft phase network formed by the hydrogel constructs a three-dimensional porous structure with a gradient distribution through dynamic cross-linking, providing cells with pore environments of different scales. This multi-level pore structure not only significantly improves the adhesion efficiency of cells on the surface of the material, but also provides a physical channel for deep infiltration, spatial expansion and orderly migration of cells, thereby supporting the uniform proliferation and organized arrangement of cells in three-dimensional space. This structure can effectively simulate the complex microenvironmental characteristics of natural bone tissue, including microscopic spatial distribution, biomechanical buffering and cell-matrix interaction, thereby promoting the regulation of cell behavior and reconstruction of tissue structure during bone regeneration.

[0077] It should be noted that the photoresponsive molecule involved in the present invention is a compound containing an o-nitrobenzene alcohol structure. The key characteristic of this type of compound is that it can be coupled with oxidized sodium alginate, thereby promoting a cross-linking reaction between oxidized sodium alginate and protein molecules. Exemplarily, the photoresponsive molecule can be N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butanamide. However, the present invention is not limited to this particular compound, and any compound having an o-nitrobenzene alcohol structure and capable of achieving the above-mentioned functions can be used as the photoresponsive molecule described in the present invention.

[0078] In some embodiments of the present invention, the piezoelectric nanoparticles include at least one of potassium sodium niobate nanoparticles, barium carbonate nanoparticles, and zinc oxide nanoparticles. As such, the piezoelectric nanoparticles of the present invention can mimic the electrophysiological properties of natural bone. The endogenous electrical signals generated by external forces can activate voltage-gated ion channels on the cell membrane, regulate osteogenic differentiation-related signaling pathways, promote bone tissue regeneration, and thus play an important role in bone defect repair.

[0079] In some embodiments of the present invention, the particle size of the piezoelectric nanoparticles is 1 nm-1 μm. For example, it can be 1 nm, 10 nm, 50 nm, 100 nm, 200 nm, 400 nm, 600 nm, 800 nm, 1 μm, etc., or it can be a range consisting of any of the above numerical values. In some embodiments of the present invention, the particle size of the piezoelectric nanoparticles is 50 nm-200 nm. Thus, by making the particle size within the above range, it is possible to ensure uniform dispersion of the nanoparticles in the matrix, avoid uneven mechanical properties caused by particle aggregation, thereby enhancing the mechanical properties of the material and making it closer to the mechanical properties of natural bone.

[0080] In some embodiments of the present invention, the piezoelectric nanoparticles have a perovskite crystallinity of no less than 90% and are capable of generating an output voltage of 80-90 mV under a compressive load of 10 N. This enhances the material's piezoelectric effect and electrophysiological activity, improving its mechanical properties and biocompatibility, thereby increasing the efficiency of bone tissue regeneration and the quality of newly formed bone.

[0081] Method for preparing bionic bone material and bionic bone material

[0082] In the second aspect of the present invention, the present invention provides a method for preparing the bionic bone material of the first aspect. Figure 1 As shown, the method includes:

[0083] S100: First mixing process

[0084] In this process, the photocurable polymer monomers, protein molecules, modified polysaccharide molecules and piezoelectric nanoparticles are subjected to a first mixing treatment to obtain a first mixed solution.

[0085] In some embodiments of the present invention, the first mixed solution further includes a photoinitiator.

[0086] In some embodiments of the present invention, the first mixed liquid is prepared by the following method: subjecting the protein molecules, the modified polysaccharide molecules and water to a second mixing treatment to obtain a second mixed liquid; and mixing the second mixed liquid, the photocurable polymer monomer, the photoinitiator and the piezoelectric nanoparticles to obtain the first mixed liquid.

[0087] In some embodiments of the present invention, the mass percentage of the photocurable polymer monomer is 50%-95% based on the total mass of the first mixed liquid. For example, it can be 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, etc., or any range consisting of the above values. Therefore, by controlling the mass percentage of the photocurable polymer monomer within the above range, the crosslinking density of the polymer network can be adjusted, thereby optimizing the mechanical properties of the material.

[0088] In some embodiments of the present invention, the photocurable polymer monomer includes acrylates. In some embodiments of the present invention, the acrylates include at least one of methyl methacrylate, ethyl methacrylate, ethyl acrylate, and butyl acrylate.

[0089] In some embodiments of the present invention, the mass percentage of the photoinitiator is 0.1-2% based on the total mass of the first mixed liquid. For example, it can be 0.1%, 0.5%, 0.7%, 1%, 1.2%, 1.5%, 1.7%, 2%, etc., or any range consisting of the above values. Thus, by controlling the mass percentage of the photoinitiator within the above range, it is possible to ensure efficient initiation of the polymerization reaction under light conditions, so that the material cures in a short time.

[0090] In some embodiments of the present invention, the mass proportion of the protein molecules is 1%-20% based on the total mass of the first mixed solution. For example, it can be 1%, 2%, 5%, 7%, 10%, 12%, 15%, 17%, 20%, etc., or it can be a range composed of any of the above values. As a result, the protein molecules can provide cell adhesion sites and promote cell adhesion and proliferation. By controlling the mass proportion of protein molecules, the surface properties of the material can be optimized to make it more conducive to cell growth and metabolism.

[0091] In some embodiments of the present invention, the protein molecule is an engineered protein comprising elastin-like protein and a growth factor, wherein the elastin-like protein comprises lysine. In some embodiments of the present invention, the growth factor comprises epidermal growth factor. In some embodiments of the present invention, the protein molecule has the amino acid sequence set forth in SEQ ID NO: 1.

[0092] In some embodiments of the present invention, the protein molecule contains epidermal growth factor and elastin-like protein, and the protein molecule is constructed through genetic engineering technology.

[0093] In some embodiments of the present invention, based on the total mass of the first mixed solution, the mass proportion of the modified polysaccharide molecules is 1%-20%. For example, it can be 1%, 2%, 5%, 7%, 10%, 12%, 15%, 17%, 20%, etc., or it can be a range composed of any of the above numerical values. Thus, the modified polysaccharide molecules can be cross-linked with protein molecules to form a soft phase network with a gradient void structure. By controlling the mass proportion of the modified polysaccharide molecules, the proportion of the hydrogel and the porosity of the material can be regulated, so that the material is conducive to the adhesion of osteoblasts and the generation of blood vessels, thereby improving the regeneration efficiency of bone tissue.

[0094] In some embodiments of the present invention, the modified polysaccharide molecule comprises a modified natural polysaccharide. In some embodiments of the present invention, the modified natural polysaccharide comprises a modified sodium alginate derivative. In some embodiments of the present invention, the modified sodium alginate derivative is prepared by coupling oxidized sodium alginate with a photoresponsive molecule.

[0095] In some embodiments of the present invention, the mass proportion of the piezoelectric nanoparticles is 0.1%-20%. For example, it can be 0.1%, 0.5%, 1%, 2%, 5%, 7%, 10%, 12%, 15%, 17%, 20%, etc., or it can be a range composed of any of the above values. The mass proportion of piezoelectric nanoparticles directly affects the piezoelectric effect of the material. By controlling the mass proportion of piezoelectric nanoparticles, it can generate sufficient charge under the action of external force, simulate the piezoelectric effect of natural bone, activate the osteogenic signal pathway, and promote the regeneration of bone tissue.

[0096] In some embodiments of the present invention, the piezoelectric nanoparticles include at least one of potassium sodium niobate nanoparticles, barium carbonate nanoparticles, and zinc oxide nanoparticles.

[0097] S200: Curing treatment

[0098] During this process, the first mixed liquid is solidified to obtain the bionic bone material.

[0099] In some embodiments of the present invention, the curing process is performed by ultraviolet light irradiation. In some embodiments of the present invention, the intensity of the ultraviolet light is 5-15 mW / cm 2 . For example, it can be 5mW / cm 2 , 7mW / cm 2 、10mW / cm 2 , 12mW / cm 2 , 15mW / cm 2 In some embodiments of the present invention, the curing time is 5-10 min. For example, it can be 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, etc., or it can be within the range of any of the above values.

[0100] In some embodiments of the present invention, the biomimetic bone material exhibited an in vitro degradation rate of 30-35% mass loss over 21 days. This demonstrates that the biomimetic bone material prepared using the present invention exhibits good biodegradability and is capable of sustained degradation in a physiological environment. This degradation behavior aligns with the tissue repair process, meeting the basic clinical requirements for degradable bone repair materials.

[0101] In some embodiments of the present invention, the water contact angle of the biomimetic bone material is 45°-55°. In some embodiments of the present invention, the water contact angle of the biomimetic bone material is 48.2°. Thus, the biomimetic bone material prepared using the method of the present invention has good hydrophilicity, can reduce the interfacial tension between cells and the material, and makes it easier for cells to spread and grow on the surface of the material.

[0102] In the third aspect of the present invention, the present invention proposes a bionic bone material. According to an embodiment of the present invention, the bionic bone material is prepared by the method described in the second aspect. Thus, the compressive strength of the bionic bone material prepared by the method of the present invention is not less than 100MPa, the elastic modulus is not less than 3GPa, the porosity is not less than 50%, and the pore size is 150-250μm. Therefore, the bionic bone material of the present invention can provide strong mechanical support for the load-bearing bone defect site, ensuring stability in a complex stress environment; at the same time, it provides an ideal microenvironment for the ingrowth and angiogenesis of bone tissue, accelerating the repair process of bone defects; it can also simulate the electrophysiological microenvironment of natural bone, activate the osteogenic signal pathway through the piezoelectric effect, and promote bone tissue regeneration and angiogenesis.

[0103] In some embodiments of the present invention, the compressive strength of the bionic bone material is not less than 100 MPa. In some embodiments of the present invention, the compressive strength of the bionic bone material is not less than 130 MPa.

[0104] In some embodiments of the present invention, the elastic modulus of the bionic bone material is not less than 3 GPa. In some embodiments of the present invention, the elastic modulus of the bionic bone material is not less than 3.6 GPa.

[0105] In some embodiments of the present invention, the porosity of the bionic bone material is not less than 50%. In some embodiments of the present invention, the porosity of the bionic bone material is not less than 54%.

[0106] In some embodiments of the present invention, the pore size of the bionic bone material is 150-250 μm. In some embodiments of the present invention, the pore size of the bionic bone material is 200-250 μm.

[0107] Uses and methods

[0108] In a fourth aspect of the present invention, the present invention provides a use of the bionic bone material described in the first or third aspect or the bionic bone material prepared by the method described in the second aspect, wherein the use has at least one of the following characteristics:

[0109] Use in preparing bone repair materials;

[0110] Used for bone defect repair;

[0111] Used to treat bone nonunion;

[0112] As a surface functional coating for orthopedic implants.

[0113] In some embodiments of the present invention, the bones include but are not limited to weight-bearing bones, skull, spine, or fracture filling. In some embodiments of the present invention, the weight-bearing bones include but are not limited to spine, hip bone, femur, tibia, fibula, etc.

[0114] As used herein, the term "orthopedic implant" refers to a medical device used to treat injuries, diseases, or deformities of the skeletal system. These implants are surgically implanted into the bones or joints of the human body to provide structural support, promote healing, restore function, or improve the patient's quality of life. The present invention does not limit the specific types of orthopedic implants. For example, orthopedic implants may include metal implants (such as titanium and titanium alloys, stainless steel), ceramic implants, polymer implants, and the like.

[0115] In the fifth aspect of the present invention, the present invention proposes a method for treating fractures or repairing bone defects. According to an embodiment of the present invention, the method is carried out by injection-in situ curing, comprising: injecting the first mixed solution prepared in the method described in the second aspect into the fracture or bone defect area, followed by photocuring treatment. Therefore, the method of the present invention is suitable for the repair of weight-bearing bones or other bone fractures or bone defects. Since the first mixed solution has good fluidity and tissue adaptability, it can accurately fill irregular bone defect sites. Subsequently, the material is induced to rapidly photocured by ultraviolet light irradiation to form a porous scaffold with a rigid-flexible dual network structure, which provides reliable mechanical support in the early stage. At the same time, the material has excellent biological activity, and its gradient pore structure and piezoelectric microenvironment can promote cell adhesion, angiogenesis and osteogenic differentiation. As the bone tissue is gradually repaired, the material can be degraded in the body and eventually completely replaced by new bone tissue, thereby achieving functional reconstruction of weight-bearing bones or other bones.

[0116] The following embodiments of the present invention are described in detail. The embodiments described below are exemplary and are only used to explain the present invention, and are not to be construed as limiting the present invention. Where specific techniques or conditions are not specified in the embodiments, the techniques or conditions described in the literature in this field or the product specifications are used. Where the manufacturer of the reagents or instruments is not specified, all are conventional products that can be obtained commercially.

[0117] Example 1: Preparation of biomimetic bone material

[0118] 1. Preparation of Protein Molecules

[0119] The protein molecules are selected from epidermal growth factor (EGF) and elastin-like polypeptide. The preparation method refers to Li M, Liu B, Xu W, et al. Engineering protein coacervates into a robust adhesive for real-time skin healing [J]. Engineering, 2023, 31: 76-85. The specific process is as follows: a plasmid encoding epidermal growth factor (EGF) and elastin-like polypeptide (elastin-like polypeptide amino acid sequence is SEQ ID NO: 1) is constructed and verified by DNA sequencing. The recombinant expression vector is transformed into Escherichia coli BLR (DE3) competent cells for protein expression. After seed culture and expansion culture, expression is induced under appropriate conditions. The collected bacteria are resuspended in buffer and ultrasonically disrupted, and then purified in multiple steps by affinity chromatography, ion exchange chromatography and desalting column. The purified protein is freeze-dried and stored at -80°C for future use.

[0120] 2. Preparation of modified polysaccharide molecules

[0121] The modified polysaccharide molecule is selected from oxidized sodium alginate derivatives. The preparation method is based on Ding W, Zhou J, Zeng Y, et al. Preparation of oxidized sodium alginate with different molecular weights and its application for crosslinking collagen fiber [J]. Carbohydrate polymers, 2017, 157: 1650-1656. The specific process is as follows:

[0122] 1) Synthesis of oxidized sodium alginate (OSA): This is accomplished by oxidizing the vicinal diol groups in sodium alginate with periodate, and selectively modifying sodium alginate using the sodium periodate oxidation method. Sodium alginate is dissolved and reacted with an oxidant in the dark. After the reaction is complete, a terminator is added to quench the reaction. The product is dialyzed to remove small molecule impurities, and then freeze-dried to obtain a white powdered OSA product. The final product is stored at -80°C for a long term. The synthesis steps are shown in the following reaction formula:

[0123]

[0124] 2) Synthesis of oxidized sodium alginate derivative (OSA-NB): First, the purified OSA was dissolved in an appropriate amount of deionized water, and then the calculated amount of the photoresponsive molecule N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butanamide (NB) and the HOBt activation reagent were added in sequence. After the pH of the reaction system was adjusted to a weak acidic state, an appropriate amount of carbodiimide condensing agent was added, and the coupling reaction was carried out for a long time at room temperature. After the reaction was completed, the product was purified by graded dialysis. First, most of the unreacted products were dialyzed with an acidic salt solution, and then the residual salt was dialyzed with deionized water. Finally, a white sponge-like OSA-NB was obtained by freeze-drying and stored at -80°C for future use. The reaction conditions were strictly controlled throughout the synthesis process to ensure that the carboxyl group on the OSA molecule formed a stable amide bond with the amino group of the NB molecule. The dialysis purification step adopted a gradient elution strategy to effectively remove reaction byproducts and small molecule reagents. The final solution was freeze-dried to obtain the OSA-NB product. The reaction formula of the synthesis step is shown below:

[0125]

[0126] 3. Preparation of Piezoelectric Nanoparticles

[0127] The piezoelectric nanoparticles are selected from potassium sodium niobate (KNN) nanoparticles. The preparation process is based on Wang S, Chen C, Wang J, et al. Synergetic chemo-piezodynamic therapy of osteosarcoma enabled by defect-driven lead-free piezoelectrics [J]. Advanced Functional Materials, 2022, 32(44): 2208128. The solid-phase reaction method is used for preparation. The specific process is as follows: high-purity (≥99.9%) K2CO3, Na2CO3 and Nb2O5 are accurately weighed according to the stoichiometric ratio, and excess K2CO3 and Na2CO3 are added to compensate for the alkali metal volatilization loss during the high-temperature sintering process. The precursor is placed in a high-temperature resistant container and calcined under controlled temperature conditions to complete the formation and transformation of the perovskite phase. The final product is ground and sieved to obtain KNN nanoparticles with a particle size range of 50-200nm.

[0128] 4. Preparation of Bionic Bone Materials

[0129] 1) The protein molecules prepared in step 1 and the OSA-NB prepared in step 2 (protein molecules to OSA-NB mass ratio of 1:1) were mixed with water to prepare a composite solution with a mass fraction of 10 wt%, and the mixture was stirred at 4°C for 5 minutes to complete dynamic pre-crosslinking;

[0130] 2) adding methyl methacrylate (MMA) monomer, photoinitiator Irgacure 2959, and KNN nanoparticles to the composite solution to obtain a mixed solution, wherein the concentration of MMA monomer in the mixed solution is 80 wt %, the concentration of photoinitiator Irgacure 2959 is 1 wt %, and the concentration of KNN is 10 wt %;

[0131] 3) After the mixture is injected into the mold, it is immediately placed under a 365nm UV light source (intensity 10mW / cm 2 ) for 6 minutes until completely cured;

[0132] 5) The solidified material was immersed in a pre-cooled PBS solution (4° C.) to quench the reaction and remove unreacted monomers.

[0133] Example 2: Preparation of biomimetic bone material

[0134] Protein molecules, modified polysaccharide molecules and piezoelectric nanoparticles were prepared according to steps 1-3 in Example 1.

[0135] 4. Preparation of Bionic Bone Materials

[0136] 1) The protein molecules prepared in step 1 and the OSA-NB prepared in step 2 (protein molecules to OSA-NB mass ratio of 1:1) were mixed with water to prepare a composite solution with a mass fraction of 20 wt%, and the mixture was stirred at 4°C for 5 minutes to complete dynamic pre-crosslinking;

[0137] 2) adding methyl methacrylate (MMA) monomer, photoinitiator Irgacure 2959, and KNN nanoparticles to the composite solution to obtain a mixed solution, wherein the concentration of MMA monomer in the mixed solution is 70 wt %, the concentration of photoinitiator Irgacure 2959 is 1 wt %, and the concentration of KNN is 10 wt %;

[0138] 3) After the mixture is injected into the mold, it is immediately placed under a 365nm UV light source (intensity 10mW / cm 2 ) for 6 minutes until completely cured;

[0139] 5) The solidified material was immersed in a pre-cooled PBS solution (4° C.) to quench the reaction and remove unreacted monomers.

[0140] Example 3: Preparation of bionic bone material

[0141] Protein molecules, modified polysaccharide molecules and piezoelectric nanoparticles were prepared according to steps 1-3 in Example 1.

[0142] 4. Preparation of Bionic Bone Materials

[0143] 1) The protein molecules prepared in step 1 and the OSA-NB prepared in step 2 (protein molecules to OSA-NB mass ratio of 1:1) were mixed with water to prepare a composite solution with a mass fraction of 30 wt%, and the mixture was stirred at 4°C for 5 minutes to complete dynamic pre-crosslinking;

[0144] 2) adding methyl methacrylate (MMA) monomer, photoinitiator Irgacure 2959, and KNN nanoparticles to the composite solution to obtain a mixed solution, wherein the concentration of MMA monomer in the mixed solution is 60 wt %, the concentration of photoinitiator Irgacure 2959 is 1 wt %, and the concentration of KNN is 10 wt %;

[0145] 3) After the mixture is injected into the mold, it is immediately placed under a 365nm UV light source (intensity 10mW / cm 2 ) for 6 minutes until completely cured;

[0146] 5) The solidified material was immersed in a pre-cooled PBS solution (4° C.) to quench the reaction and remove unreacted monomers.

[0147] Performance Testing

[0148] 1. The compressive strength and compression modulus of the bionic bone materials prepared in Examples 1-3 were tested, and the porosity and pore size distribution of the bionic bone material prepared in Example 3 were tested to evaluate its mechanical support performance and microstructural characteristics in load-bearing bone repair applications.

[0149] The compressive performance test was conducted using a universal material testing machine (Instron 5943, loading rate 1 mm / min). The specimens were made into cylinders with a diameter of 10 mm and a height of 10 mm. Vertical compression was performed in a dry state. The stress-strain curve was recorded. The maximum stress was taken as the compressive strength, and the slope of the initial linear segment was taken as the elastic modulus. The experimental results are shown in Figure 2. Figure 2 As shown, the compressive strength of the bionic bone materials prepared in Examples 1-3 are respectively in the range of 130-180 MPa, and the compression modulus is respectively in the range of 3.6-7 GPa, indicating that their mechanical properties match those of natural load-bearing bones, can provide effective support for the fracture site, and meet the application requirements of load-bearing bone repair.

[0150] The porosity was determined by liquid replacement method (ethanol as medium); the pore size distribution was statistically analyzed by scanning electron microscopy (SEM) combined with ImageJ software. Figure 3 As shown, the pore size of the biomimetic bone material prepared in Example 3 is in the range of 200-250 μm, and the porosity is 55%. The highly interconnected pore structure in this size range is conducive to cell infiltration, nutrient exchange and the formation of new blood vessels, which helps promote the regeneration and integration of bone tissue.

[0151] 2. The biomimetic bone material prepared in Example 3 was subjected to a polymerization heat test. The polymerization precursor solution (mixed solution before solidification) was injected into a standard mold. Subsequently, a FLIR E85 infrared thermal imager (FLIR Systems, USA) was used to monitor the temperature change during the solidification process in real time. The thermal imaging curves of each experimental group were recorded, and the peak exothermic temperature that occurred during the polymerization reaction was analyzed. The polymerization heat experimental results of Example 3 biomimetic bone material are shown in FIG. Figure 4 As shown, the maximum polymerization temperature is about 44.6° C. This temperature is significantly lower than the thermal threshold that may cause tissue damage, indicating that the bionic bone material of the present invention has good thermal safety during the in situ curing process and will not cause thermal damage to surrounding tissues, making it suitable for clinical injection filling and repair applications.

[0152] 3. The biomimetic bone material prepared in Example 3 was subjected to in vitro degradation rate and water contact angle tests. The biomimetic bone material sample prepared in Example 3 was immersed in PBS solution, and the ratio of solution to sample surface area was 20 mL·cm -2 , and placed at 37±0.5℃ for 21 days, and the PBS solution was replaced every 48 hours. The in vitro degradation behavior of the biomimetic bone material was evaluated by measuring the mass loss at 37℃. Figure 5 As shown, the mass degradation rate of 30%-35% within 21 days demonstrates the biomimetic bone material's excellent biodegradability and its ability to gradually degrade and be replaced by new tissue during the tissue repair process. This moderate degradation rate not only facilitates the dynamic matching of scaffold function and tissue regeneration, but also avoids mechanical instability caused by excessively rapid degradation or tissue rejection caused by excessively slow degradation, thus providing an important guarantee for the biofunctional repair of load-bearing bone defects.

[0153] The hydrophilicity was characterized by using an OCA25 video optical contact angle meter (Dataphysics, Germany). First, the biomimetic bone material sample prepared in Example 3 was gently polished to ensure that its upper and lower surfaces were parallel. Subsequently, the scaffold was washed three times with deionized water and ethanol, respectively, and thoroughly dried in an oven. During the test, deionized water was added dropwise to the sample surface, and a high-speed camera was used to capture and record the contact angle image of the sample surface. The experimental results are shown in Figure 2. Figure 6 As shown in the figure, the contact angle of a water droplet on the sample surface is 48.2°, indicating that the material surface has good hydrophilicity. Moderate hydrophilicity helps promote cell adhesion and spreading on the scaffold surface, thereby improving its biocompatibility and osteogenic properties in the bone repair environment.

[0154] 4. Cell experiment: In vitro angiogenesis experiment Matrigel was added to a 48-well plate and incubated at 37°C for 2 hours to complete gelation. Subsequently, human umbilical vein endothelial cells (HUVECs) were seeded into the wells of the culture plate and the biomimetic bone material of Example 3 was added for co-culture for 6 hours. The tube structure was imaged by randomly selecting the field of view using an inverted optical microscope (Nikon, Japan). The experimental results are shown in Figure 2. Figure 7 The results showed that compared with the blank control group, the number of tubular structures formed after adding bionic bone materials increased significantly, the tube length extended more fully, and the number of key nodes increased significantly, indicating that the material has good angiogenesis-promoting ability and helps promote the formation of new blood vessels during bone repair.

[0155] 5. Animal experiment: The right hind limb of the rat was treated aseptically, disinfected with 75% ethanol and iodine tincture three times alternately, and then shaved. Then, a 1.5 cm longitudinal incision was made along the anterior edge of the tibia, and the periosteum was bluntly separated. A standardized fracture was made in the middle part of the tibia using bone forceps. The mixed solution obtained in step 2) of Example 3 was injected into the fracture site and allowed to solidify. Then, the myofascia and skin were sutured in layers. External fixation was performed using plaster. After 12 weeks, the rats were sacrificed and the tibia was removed for Micro CT analysis. The results are shown in Figure 2. Figure 8 As shown, compared with the control group (only plaster fixation), the bionic bone group performed better in fracture healing, the fracture line basically disappeared, no obvious callus formation was observed, and the force line was well restored, indicating that the bionic bone material of the present invention has an excellent bone repair effect.

[0156] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0157] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention.

Claims

1. A bionic bone material, characterized in that: include: Photocurable polymer monomers, protein molecules, modified polysaccharide molecules and piezoelectric nanoparticles; The protein molecules and the modified polysaccharide molecules are capable of cross-linking.

2. The bionic bone material according to claim 1, characterized in that The bionic bone material further includes a photoinitiator.

3. The bionic bone material according to claim 2, characterized in that The photocurable polymer monomers include acrylates; Optionally, the protein molecule is an engineered protein containing elastin-like protein and growth factors, and the elastin-like protein contains lysine; Optionally, the modified polysaccharide molecule comprises a modified natural polysaccharide; Optionally, the piezoelectric nanoparticles include at least one of potassium sodium niobate nanoparticles, barium carbonate nanoparticles, and zinc oxide nanoparticles.

4. The bionic bone material according to claim 3, characterized in that The acrylic acid esters include at least one of methyl methacrylate, ethyl methacrylate, ethyl acrylate, and butyl acrylate; Optionally, the protein molecule has an amino acid sequence as shown in SEQ ID NO: 1; Optionally, the modified natural polysaccharide comprises a modified sodium alginate derivative; Optionally, the modified sodium alginate derivative is prepared by coupling oxidized sodium alginate with a photoresponsive molecule; Optionally, the particle size of the piezoelectric nanoparticles is 1 nm-1 μm, preferably 50 nm-200 nm.

5. A method for preparing the bionic bone material according to any one of claims 1 to 4, characterized in that: include: The photocurable polymer monomers, piezoelectric nanoparticles, protein molecules and modified polysaccharide molecules are subjected to a first mixing process to obtain the bionic bone material.

6. The method according to claim 5, further comprising, after the first mixing process: solidifying the first mixed liquid to obtain the bionic bone material; Optionally, the first mixed solution further includes a photoinitiator.

7. The method according to claim 6, characterized in that The first mixed solution is prepared by the following method: performing a second mixing process on the protein molecules, the modified polysaccharide molecules and water to obtain a second mixed solution; The second mixed liquid, the photocurable polymer monomer, the photoinitiator and the piezoelectric nanoparticles are mixed to obtain the first mixed liquid.

8. The method according to claim 7, characterized in that Based on the total mass of the first mixed liquid, the mass proportion of the photocurable polymer monomer is 50%-95%, preferably 60%-90%; Optionally, based on the total mass of the first mixed solution, the mass proportion of the protein molecules is 1%-20%, preferably 5%-15%; Optionally, based on the total mass of the first mixed solution, the mass proportion of the modified polysaccharide molecules is 1%-20%, preferably 5%-15%; Optionally, based on the total mass of the first mixed solution, the mass proportion of the piezoelectric nanoparticles is 0.1%-20%, preferably 0.1%-10%; Optionally, based on the total mass of the first mixed liquid, the mass proportion of the photoinitiator is 0.1%-2%, preferably 0.5%-1%.

9. A bionic bone material, characterized in that: It is prepared by the method according to any one of claims 5 to 8; Optionally, the compressive strength of the bionic bone material is not less than 100 MPa, preferably not less than 130 MPa; Optionally, the elastic modulus of the bionic bone material is not less than 3 GPa, preferably not less than 3.6 GPa; Optionally, the porosity of the bionic bone material is not less than 50%, preferably not less than 54%; Optionally, the pore size of the bionic bone material is 150-250 μm, preferably 200-250 μm.

10. Use of the bionic bone material according to any one of claims 1 to 4 and 9 or the bionic bone material prepared by the method according to any one of claims 5 to 8 in preparing bone repair materials or as a surface functional coating for orthopedic implants.

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