Novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants

Abstract

The invention provides a novel biodegradable magnesium-hydroxyapatite-graphene biological material system for an advanced orthopedic implant, and relates to the technical field of implants, and the novel biodegradable magnesium-hydroxyapatite-graphene biological material system for the advanced orthopedic implant comprises magnesium, hydroxyapatite and a graphene nanosheet. Hydroxyapatite and graphene nanosheets are uniformly distributed in a magnesium matrix, and the mechanical property is very close to that of a human skeleton; the mechanical adaptation of magnesium is combined with the osseointegration performance of hydroxyapatite and the strengthening and corrosion resistance of the graphene nanosheets, the orthopedic implant is naturally integrated in vivo and can be gradually decomposed and completely degraded in vivo, the problem that traditional non-degradable materials (such as titanium or stainless steel) need to be taken out through a secondary operation is solved, the graphene nanosheets inhibit pitting corrosion, and the mechanical property of the orthopedic implant is improved. The corrosion rate is reduced by about 50%, the orthopedic implant has corrosion resistance, the service life of the implant is prolonged, and hydroxyapatite promotes bone growth and accelerates bone healing.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of implants, in particular to a novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants. BACKGROUND

[0002] With the global population aging, the acceleration of life pace and the deterioration of urban environment, millions of people suffer from bone defects due to diseases or trauma, and bone repair has become a clinical focus. About 2.8 million bone repair surgeries are performed globally each year. The global orthopedic implant market size reached 50.03 billion US dollars in 2022 and is expected to reach 72.1 billion US dollars by 2030.

[0003] Artificial bone implants made of biomaterials have become a research hotspot for bone defect treatment due to their advantages such as abundant raw material resources, immune compatibility, and no risk of disease transmission. Such implants need to have sufficient mechanical strength to provide stable support and good biocompatibility (tissue compatibility and blood compatibility). Currently, biomaterials used for bone repair include biopolymers, bioceramics, and biomaterials.

[0004] Magnesium and its alloys are considered revolutionary biomaterials due to their high specific strength, natural degradation, good biocompatibility, and bone formation promoting properties. The elastic modulus of magnesium (about 45 GPa) is close to that of human bone (15-30 GPa), which can reduce the stress shielding effect in the load transfer of the bone-implant interface. Its density (1.79 g / cm 3 ) is also very close to that of human bone (1.75 g / cm 3 ).

[0005] However, pure magnesium as a bone implant material has the problem of rapid degradation rate, rapid corrosion after contacting body fluids in the body, and resulting in a sharp decline in mechanical properties. SUMMARY

[0006] The problem solved by the present application is how to solve the problem of pure magnesium as a bone implant material, which has the problem of rapid degradation rate, rapid corrosion after contacting body fluids in the body, and resulting in a sharp decline in mechanical properties.

[0007] To solve the above problems, the present application provides a novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants.

[0008] In a first aspect, the present application provides a novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants, comprising magnesium, hydroxyapatite, and graphene nanosheets.

[0009] Optionally, it comprises 70 to 90 parts by weight of magnesium, 5 to 20 parts by weight of hydroxyapatite, and 0.5 to 5 parts by weight of graphene nanosheets.

[0010] Optionally, polyvinylpyrrolidone is further included.

[0011] Optionally, it is prepared by the following steps:

[0012] S1: magnesium, hydroxyapatite and graphene nanosheet are homogeneously dispersed by mechanical ball milling to obtain a mixed powder;

[0013] S2: the mixed powder is unidirectionally pressed to obtain a green body;

[0014] S3: the green body is sintered to obtain a degradable magnesium-based mixed nanocomposite orthopedic implant.

[0015] Optionally, in step S1, zinc stearate is added during mechanical ball milling.

[0016] Optionally, in step S1, the ball-to-material ratio during mechanical ball milling is 10:1, the rotation speed is 200-300 rpm, and the ball milling time is 3-5 h.

[0017] Optionally, in step S2, the pressing pressure is 200-300 MPa.

[0018] Optionally, in step S3, the green body is sintered under an inert atmosphere.

[0019] Optionally, in step S3, the step of sintering the green body comprises:

[0020] S31: pre-sintering the green body at 280-320℃;

[0021] S32: high-temperature sintering the green body at 880-920℃.

[0022] Optionally, the green body is pre-sintered for 3.5-4.5 h, and the green body is high-temperature sintered for 1.5-2.5 h.

[0023] The new biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants has the following beneficial effects: magnesium has a hexagonal close-packed (HCP) crystal structure, providing lightweight strength and ductility, strong atomic bonds ensuring durability, an elastic modulus of 45 GPa, matching the modulus of human bone, avoiding the stress shielding effect in bone-implant interface load transfer, and the density of magnesium (1.79 g / cm 3 ) is also very close to that of human bone (1.75 g / cm 3 ); hydroxyapatite has a bone-like mineral structure, and the calcium-phosphorus ion bond gives it a high compressive strength of more than 100 MPa, which can support bone integration; at the sintering interface, the Ca 2+ of hydroxyapatite exchanges with Mg 2+ ions to form a CaMgPO4 transition layer, and the hydroxyl groups of hydroxyapatite form O-H-O bonds with the magnesium surface oxide layer (MgO); Mg2+ The carbon grid is injected with graphene nanosheets, forming Mg-C dipoles, the graphene nanosheets are embedded in the magnesium grain boundaries, and the strength is improved by dislocation pinning, so that the hydroxyapatite and graphene nanosheets are uniformly distributed in the magnesium matrix, and the mechanical properties are very close to the human bone; the mechanical adaptation of magnesium, the bone integration performance of hydroxyapatite, and the strengthening and corrosion resistance of graphene nanosheets are combined, the orthopedic implant is naturally integrated in the body, and the degradation rate is 0.2-0.5mm / year, the degradation rate is reduced, and the orthopedic implant can be completely degraded, avoiding the problem that the traditional non-degradable material (such as titanium or stainless steel) needs secondary surgery to remove, in addition, the graphene nanosheets can inhibit pitting, so that the corrosion rate is reduced by about 50%, so that the orthopedic implant has corrosion resistance, prolonging the service life of the implant, and the hydroxyapatite can promote bone growth, and the bone integration cycle is 6-12 months, accelerating bone healing. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 A scanning electron microscope schematic diagram of the new biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants of Example 1;

[0025] Figure 2 Another scanning electron microscope schematic diagram of the new biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants of Example 1;

[0026] Figure 3 Still another scanning electron microscope schematic diagram of the new biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants of Example 1;

[0027] Figure 4 An energy dispersive spectrometer component analysis schematic diagram of the new biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants of Example 1;

[0028] Figure 5 An energy dispersive spectrometer component distribution schematic diagram of the new biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants of Example 1. DETAILED DESCRIPTION

[0029] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application will be described in detail below with reference to the drawings. Although some embodiments of the present application are shown in the drawings, it should be understood that the present application can be implemented in various forms, and should not be interpreted as being limited to the embodiments described herein, on the contrary, these embodiments are provided to make the present application more thorough and complete. It should be understood that the drawings and embodiments of the present application are only for exemplary purposes, and are not intended to limit the scope of protection of the present application.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application;

[0031] As used herein, the term "includes" and its variants are open-ended, meaning that "includes but is not limited to"; the term "based on" means "based, at least in part, on"; the term "one embodiment" means "at least one embodiment"; the term "another embodiment" means "at least one additional embodiment"; the term "some embodiments" means "at least some embodiments"; the term "optionally" means "optional embodiments." Related terms shall be construed accordingly.

[0032] Embodiments of the present application provide a new biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants.

[0033] Embodiments of the present application provide a new biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants, comprising magnesium, hydroxyapatite and graphene nanosheets.

[0034] In this embodiment, magnesium has a hexagonal close-packed (HCP) crystal structure, providing lightweight strength and ductility, strong interatomic bonds ensuring durability, an elastic modulus of 45 GPa, matching the modulus of human bone, avoiding stress shielding effects in bone-implant interface load transfer, and the density of magnesium (1.79 g / cm 3 ) is also very close to that of human bone (1.75 g / cm 3 ); hydroxyapatite has a bone-like mineral structure, and the calcium-phosphorus ion bond gives it a high compressive strength of more than 100 MPa, enabling it to support bone integration, and at the sintering interface, the Ca 2+ of hydroxyapatite exchanges with Mg 2+ ions to form a CaMgPO4 transition layer, and the hydroxyl groups of hydroxyapatite form O-H-O bonds with the magnesium surface oxide layer (MgO); Mg 2+The carbon grid is injected with graphene nanosheets to form Mg-C dipole bonds, the graphene nanosheets are embedded into the magnesium grain boundaries, and the strength is improved by dislocation pinning, so that the hydroxyapatite and the graphene nanosheets are uniformly distributed in the magnesium matrix, the mechanical properties are very close to the human bone, the mechanical adaptation of magnesium is combined with the osteointegration performance of hydroxyapatite and the strengthening and corrosion resistance of graphene nanosheets, the orthopedic implant is naturally integrated in the body, can be gradually decomposed in the body, the degradation rate is 0.2-0.5mm / year, and the orthopedic implant is completely degraded, avoiding the problem that the traditional non-degradable material (such as titanium or stainless steel) needs secondary surgery to remove, the graphene nanosheets inhibit pitting corrosion, so that the corrosion rate is reduced by about 50%, the orthopedic implant has corrosion resistance, prolongs the service life of the implant, the hydroxyapatite promotes bone growth, and the osteointegration cycle is 6-12 months, and the bone healing is accelerated.

[0035] 1. Specifically, the two-dimensional carbon lattice (sp 2 Hybrid) provides ultra-high tensile strength (about 130 GPa), the two-dimensional honeycomb carbon network (C-C bond energy ≈ 348 kJ / mol) provides crack deflection and bridging effect, and the toughness is improved by more than 30%, and the stress distribution is improved. The Ca 10 (PO4)6(OH)2 crystal structure of hydroxyapatite (HA) is similar to bone mineral, and the Ca 2+ / PO4 3- Ion bond promotes bone cell adhesion, gives high compressive strength of more than 100 MPa, and promotes osteointegration.

[0036] Optionally, 70 to 90 parts by weight of magnesium, 5 to 20 parts by weight of hydroxyapatite, and 0.5 to 5 parts by weight of graphene nanosheets are included.

[0037] Specifically, 80 parts by weight of magnesium, 15 parts by weight of hydroxyapatite, and 5 parts by weight of graphene nanosheets are included, which have mechanical adaptation (close to human bone), biological activity (HA), and corrosion resistance (GNP).

[0038] Optionally, polyvinylpyrrolidone is further included.

[0039] In this optional embodiment, polyvinylpyrrolidone is used as a binder to bond magnesium, hydroxyapatite and graphene nanosheets together.

[0040] Optionally, it is prepared by the following steps:

[0041] S1: magnesium, hydroxyapatite and graphene nanosheets are uniformly dispersed by mechanical ball milling to obtain a mixed powder;

[0042] S2: The mixed powder is uniaxially pressed to obtain a green body;

[0043] S3: Sintering the green body to obtain a degradable magnesium-based mixed nanocomposite orthopedic implant.

[0044] In this embodiment, the hydroxyapatite and graphene nanosheet are uniformly distributed in the magnesium matrix, and the agglomeration is minimal. The degradable magnesium-based mixed nanocomposite orthopedic implant shows significant improvement in the porosity level of cell migration and biodegradability.

[0045] Optionally, in step S1, zinc stearate is added during the mechanical ball milling process.

[0046] In this optional embodiment, zinc stearate is added as a process control agent during the mechanical ball milling process to avoid powder agglomeration and to uniformly distribute the hydroxyapatite and graphene nanosheet in the magnesium matrix.

[0047] Optionally, in step S1, the ball-to-material ratio during the mechanical ball milling process is 10:1, the rotation speed is 200-300 rpm, and the ball milling time is 3-5 h.

[0048] Optionally, in step S2, the pressing pressure is 200-300 MPa.

[0049] Optionally, in step S3, the green body is sintered under an inert atmosphere.

[0050] Specifically, the green body is sintered under an argon atmosphere.

[0051] Optionally, in step S3, the step of sintering the green body includes:

[0052] S31: pre-sintering the green body at 280-320°C;

[0053] S32: high-temperature sintering the green body at 880-920°C.

[0054] In this optional embodiment, the green body is pre-sintered at 280-320°C to preliminarily bond the particles and remove volatile substances, and the green body is high-temperature sintered at 880-920°C to completely densify and reduce magnesium oxidation. Through two-stage temperature control, the porosity is <5%, the compressive strength is improved to 200-250 MPa (close to human bone cortex: 150-230 MPa), and the bending strength is improved to 180 MPa (pure magnesium: about 80 MPa) due to the directional arrangement of graphene nanosheets (GNP).

[0055] Optionally, the green body is pre-sintered for 3.5-4.5 h, and the green body is high-temperature sintered for 1.5-2.5 h.

[0056] The application is further described below in conjunction with specific embodiments.

[0057] Embodiment 1, a preparation method of a novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants, includes the following steps:

[0058] S1: Take 80 parts by weight of magnesium, 15 parts by weight of hydroxyapatite and 5 parts by weight of graphene nanosheets, add zinc stearate, and disperse them by mechanical ball milling at a ball-to-material ratio of 10:1, a speed of 250 rpm and a ball milling time of 4 h to obtain a mixed powder.

[0059] S2: Unidirectional pressing of mixed powder, pressing pressure of 250MPa, to obtain green embryo;

[0060] S3: The green embryo was sintered in an inert atmosphere, pre-sintered at 300℃ for 4 hours, and then sintered at 900℃ for 2 hours to obtain a biodegradable magnesium-based mixed nanocomposite orthopedic implant.

[0061] The morphology of the biodegradable magnesium-based hybrid nanocomposite orthopedic implant prepared in Example 1 was observed using scanning electron microscopy (SEM), such as... Figures 1 to 3 As shown. By Figures 1 to 3 It can be seen that significant improvements were observed in porosity levels and biodegradability for cell migration.

[0062] The biodegradable magnesium-based hybrid nanocomposite orthopedic implants prepared in Example 1 were analyzed by energy dispersive spectroscopy (EDS), such as... Figures 4 to 5 As shown, the content ratio of each element is shown in Table 1. Figures 4 to 5 It can be seen that the magnesium matrix exhibits remarkable uniformity and distribution of all components.

[0063] Table 1. Elemental Content Ratio of Biodegradable Magnesium-Based Hybrid Nanocomposite Orthopedic Implants

[0064] Element wt. % fraction Content proportion of atomic element C 13.98 21.49 O 38.43 44.36 Mg 40.53 30.78 P 0.82 0.49 Ca 6.24 2.88 Sum 100.00 100.00

[0065] Comparative Example 1: A method for preparing orthopedic implants, comprising the following steps:

[0066] S1: Take 100 parts of pure magnesium by weight, and disperse it by mechanical ball milling at a ball-to-material ratio of 10:1, a speed of 250 rpm, and a milling time of 4 hours to obtain a mixed powder;

[0067] S2: Unidirectional pressing of mixed powder, pressing pressure of 250MPa, to obtain green embryo;

[0068] S3: The green embryo is sintered in an inert atmosphere, pre-sintered at 300℃ for 4 hours, and then sintered at 900℃ for 2 hours to obtain the orthopedic implant.

[0069] Comparative Example 2, a method for preparing orthopedic implants, comprising the following steps:

[0070] S1: Take 90 parts magnesium and 10 parts hydroxyapatite by weight, add zinc stearate, and disperse them by mechanical ball milling at a ball-to-material ratio of 10:1, at a speed of 250 rpm, for 4 hours to obtain a mixed powder.

[0071] S2: The mixed powder was unidirectionally pressed at a pressure of 250 MPa to obtain a green body;

[0072] S3: The green body was sintered under an inert atmosphere, pre-sintered at 300°C for 4 h, and high-temperature sintered at 900°C for 2 h to obtain the orthopedic implant.

[0073] The orthopedic implants prepared in Example 1, Comparative Example 1 and Comparative Example 2 were subjected to corrosion testing, and the corrosion rate was determined in a simulated body fluid at 37°C (ASTM G31 standard) (formula: corrosion rate = ΔW / (A·t), wherein: ΔW is the mass loss of the sample (initial weight - final weight), A is the surface area of the particle, and t is the soaking time).

[0074] As shown in Table 2, the corrosion rate and mechanical retention rate of the orthopedic implants prepared in Example 1, Comparative Example 1 and Comparative Example 2 were determined.

[0075] Table 2 Corrosion rate and mechanical retention rate of orthopedic implants prepared in Example 1, Comparative Example 1 and Comparative Example 2

[0076] Orthopedic implant 7-day corrosion rate (mm / year) Mechanical retention rate (after 30 days) Example 1 3.2 45％ Comparative Example 1 2.1 65％ Comparative Example 2 0.9 85％

[0077] As shown in Table 2, the orthopedic implants prepared by combining magnesium, hydroxyapatite and graphene nanosheets have corrosion resistance, strong mechanical retention performance, and improved mechanical strength.

[0078] Although the present application is disclosed as above, the protection scope of the present application is not limited to this. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present application, and these changes and modifications shall fall within the protection scope of the present application.

Claims

1. A novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants, characterized in that, It includes magnesium, hydroxyapatite, and graphene nanosheets.

2. The novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants according to claim 1, characterized in that, By weight, it comprises 70 to 90 parts magnesium, 5 to 20 parts hydroxyapatite, and 0.5 to 5 parts graphene nanosheets.

3. The novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants according to claim 1, characterized in that, It also includes polyvinylpyrrolidone.

4. The novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants according to claim 1, characterized in that, It is prepared by the following steps: S1: Magnesium, hydroxyapatite, and graphene nanosheets were homogenized and dispersed by mechanical ball milling to obtain a mixed powder; S2: Unidirectionally press the mixed powder to obtain a green embryo; S3: Sinter the green embryo to obtain a biodegradable magnesium-based mixed nanocomposite orthopedic implant.

5. The novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants according to claim 4, characterized in that, In step S1, zinc stearate is added during the mechanical ball milling process.

6. The novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants according to claim 4, characterized in that, In step S1, the ball-to-material ratio during the mechanical ball milling process is 10:1, the rotation speed is 200 to 300 rpm, and the milling time is 3 to 5 hours.

7. The novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants according to claim 4, characterized in that, In step S2, the pressing pressure is 200 to 300 MPa.

8. The novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants according to claim 4, characterized in that, In step S3, the green embryo is sintered under an inert atmosphere.

9. The novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants according to claim 4, characterized in that, In step S3, the step of sintering the green embryo includes: S31: Pre-sinter the green embryo at 280 to 320°C; S32: The green embryo is sintered at a high temperature of 880 to 920°C.

10. The novel biodegradable magnesium-hydroxyapatite-graphene biomaterial system for advanced orthopedic implants according to claim 9, characterized in that, The green embryo is pre-sintered for 3.5 to 4.5 hours and then sintered at high temperature for 1.5 to 2.5 hours.

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