CN110935069B

CN110935069B - Composite material, raw material composition, bone restoration body, preparation method and application

Info

Publication number: CN110935069B
Application number: CN201811121415.9A
Authority: CN
Inventors: 魏杰; 汤亭亭; 胡兴龙; 梅师奇; 杨立利; 赵君; 黄孝敏
Original assignee: East China University of Science and Technology
Current assignee: Shanghai Hemai Medical Technology Co.,Ltd.
Priority date: 2018-09-25
Filing date: 2018-09-25
Publication date: 2021-03-05
Anticipated expiration: 2038-09-25
Also published as: CN110935069A

Abstract

The invention discloses a composite material, a raw material composition, a bone restoration body, a preparation method and application. The raw material composition of the composite material comprises the following components: the tantalum powder and the polyaryletherketone powder are in a volume ratio of (1:4) - (1:1), and the particle size of the tantalum powder is 100 nm-5 microns. The composite material prepared by the composition has good bioactivity and compatibility, and excellent mechanical property, can promote adhesion, proliferation and differentiation of cells, can stimulate bone growth, accelerates bone healing, and reduces healing time after the bone implant material is implanted. The bone repair body prepared by the composition can not cause inflammatory reaction after being implanted, and the mechanical properties such as elastic modulus, toughness, fracture strength and the like of the bone repair body are matched with human bones, so that the negative effects such as bone repair material loosening, bone absorption and the like caused by stress shielding can not be caused, and the clinical requirements on bone repair can be met.

Description

Composite material, raw material composition, bone restoration body, preparation method and application

Technical Field

The invention relates to the field of medical biomaterials, in particular to a composite material, a raw material composition, a bone restoration body, a preparation method and application.

Background

With the accelerated aging of the population in China and the increasing number of patients with bone defects, osteomyelitis and nonunion caused by various wounds, tumors or bone diseases, the demand of bone repair materials is increased year by year, thereby greatly promoting the development of the materials. The materials clinically used for repairing bone defects include medical metals, medical polymers, bioglass, bioceramics, composite materials thereof and the like. After the bone repair material is implanted into a living body, osteoblasts in the body can adhere to the surface of the material and grow to be induced into bone, and finally the material and new bone tissues generate good bonding, namely osseointegration, so that the bone repair is realized.

However, the single bone repair material has some disadvantages, such as that most metal materials have the defects of too high elastic modulus, mismatch with bone tissues, and the like, are easy to generate stress shielding and cause bone resorption, and the metal materials have structural properties which are very different from those of bones, lack biological activity, and are difficult to form osseointegration with autologous bones. In addition, the metal ions are easy to dissolve out to cause phenomena such as effusion, inflammation, necrosis and the like, and the ceramic bone implant material has the defects of difficult molding processing, poor toughness and the like. The traditional medical high-molecular material cannot be integrated with surrounding tissues and has poor osteogenic performance due to insufficient bioactivity. Therefore, the composite bone repair material with excellent mechanical properties and bioactivity becomes a hot point for research.

The mechanical properties and biological activity of biomaterials depend on the chemical composition. Polyaryletherketones (PAEKs) are an FDA approved family of thermoplastic biomaterials, which primarily include Polyetheretherketones (PEEK) and Polyetherketoneketones (PEKK). Among them, PEEK has been widely used as a bone implant material in surgical operations for the treatment of various fractures/fixations, spinal fusion/fixation, vertebroplasty, cranio/maxillofacial defects, dentistry, etc.; PEKK and PEEK have very similar structure and physicochemical properties, however, PEKK is currently under relatively little research in the field of biomaterials. Both PEKK and PEEK have the following advantages as bone implant materials: excellent mechanical property, chemical stability, density, hardness and modulus similar to those of bones, no bone absorption, good biocompatibility and biological safety. The artificial bone made of PEEK has an elastic modulus matching that of bone tissue, and is high in strength, hard and wear-resistant, and free from deterioration in mechanical strength after repeated sterilization. PEEK has been designated as the "best long-term bone graft material" and is certified by the FDA (Food and Drug Administration), and long-term implanted bone joints, elbow joints, etc. have been developed in the united states. However, the two methods have the greatest disadvantages of no biological activity and no osseointegration, i.e. the osseointegration cannot be formed with host bones after the implantation, fibrous boundary membranes are easily formed between the implantation materials and bone tissues, and the implant can loosen or even fall off with the time, which finally leads to the failure of bone implantation.

Tantalum (Ta) is currently used mainly as a surgical suture on the market, and has the advantages of good corrosion resistance and biocompatibility, and the disadvantages of excessive elastic modulus, mismatch with bone tissue, and easy bone resorption. The existing tantalum material applied to clinic is porous tantalum, namely a product named as trabecular bone metal, and the preparation process is complex: firstly, a polyurethane foam material precursor is pyrolyzed to obtain a vitreous pyrolytic carbon skeleton with a spongy porous structure, and then commercially pure tantalum is used as a raw material to react with Cl by using a chemical vapor deposition method₂Reaction is carried out to generate gaseous TaCl₅Reuse of H₂Adding TaCl₅Reducing the Ta in the porous tantalum and depositing the Ta on a carbon skeleton to obtain the porous tantalum. The preparation process is complicated, so the cost is high, and great economic burden is caused to patients.

Tantalum oxide (Ta)₂O₅) The tantalum oxide is an inorganic material, and although a large number of biocompatibility experiments prove that the tantalum oxide is non-toxic, non-irritant, non-allergic, non-mutagenic and non-destructive to biological tissues, the tantalum oxide has certain brittleness and lower strength, and the mechanical properties of the tantalum oxide are limited.

Therefore, how to obtain a bone repair material with good bioactivity, satisfactory mechanical properties and simple preparation process is an urgent problem to be solved in the field.

Disclosure of Invention

The invention aims to solve the technical problems that in the prior art, a bone repair material is not enough in biological activity and poor in osteogenesis performance, so that the bone repair material is easy to loosen after being implanted into a human body, or the mechanical property of the bone repair material is not matched with bone tissues, so that bone absorption is easy to cause, and the like, and provides a composite material, a raw material composition, a bone repair body, a preparation method and application. The composite material has good biological activity and biocompatibility and excellent mechanical property, can promote the adhesion, proliferation and differentiation of cells, can stimulate the growth of bones, accelerate the healing of the bones and reduce the healing time of the implanted bone implant material, has simple and easy process, and can adjust the preparation process to prepare the bone repair bodies with different shapes and specifications so as to adapt to the clinical use requirement. The bone restoration body can not cause inflammatory reaction after being implanted, the elastic modulus of the bone restoration body is matched with human bones, negative effects of bone restoration material loosening, bone absorption and the like caused by stress shielding can not be caused, and the clinical requirements on bone restoration are met.

In view of the problems in the background art, through continuous research and experiments of the inventor, the inventor finds that the tantalum material powder and the polyaryletherketone powder are compounded, so that the defects of the tantalum material in the aspects of mismatching of mechanical property and bone tissue, easiness in causing bone absorption and the like can be effectively overcome, and the defects of the polyaryletherketone in the aspects of insufficient bioactivity, poor osteogenesis performance, easiness in loosening after being implanted into a human body and the like can be overcome. The inventor overcomes a plurality of technical obstacles when compounding tantalum material powder and polyaryletherketone powder, and mainly comprises the following steps:

when tantalum material powder is directly used as a raw material to be compounded with polyaryletherketone, if the particle size of the powder is too large, the powder cannot be uniformly dispersed in the polyaryletherketone material, and if the particle size of the powder is too small, the powder is easy to agglomerate in a processing and forming process, so that how to obtain the particle size of the tantalum material powder with better osteogenesis is one of the technical obstacles overcome by the invention;

the performance of the final composite material is greatly influenced by the amount and the proportion of the raw materials in the composite material, if the volume fraction of the tantalum material in the composite material is too small, on one hand, a good mechanical enhancement effect cannot be achieved, and on the other hand, the surface of the composite material is poor in bone-promoting effect; if the volume fraction of the tantalum material in the composite material is too large, the tantalum material in the composite material cannot be uniformly dispersed, the mechanical property of the composite material is poor, and the standard of the mechanical strength of human bones cannot be met, so that how to obtain the composite material which has the advantages of two raw materials is the second technical obstacle overcome by the invention;

the preparation process of the porous tantalum bone restoration body used clinically at present is complex, and how to realize organic unification of the composite material with excellent performance and the simple and feasible preparation process and reduce the production cost is the third technical obstacle to be overcome by the invention.

In contrast, the inventors paid creative work and found that under the conditions that the volume ratio of the tantalum material powder to the polyaryletherketone powder is 1: 4-1: 1, and the particle size of the tantalum material powder is 100 nm-5 μm, the composite material has good bioactivity and biocompatibility and excellent mechanical properties.

The invention relates to a composite bone repair material which has excellent mechanical property and obviously improved bone formation activity, is obtained by compounding tantalum material in polyaryletherketone material to promote bone formation active material, and modifying the surface of the tantalum material by surface sulfonation and surface coating methods. Meanwhile, the invention provides an important experimental basis for the preparation of bioactive bone repair or substitute materials.

In order to achieve the purpose, the invention adopts the following technical scheme.

The invention provides a raw material composition of a composite material, which comprises the following components: the tantalum powder and the polyaryletherketone powder are in a volume ratio of (1:4) - (1:1), and the particle size of the tantalum powder is 100 nm-5 microns.

In the present invention, the tantalum material may be a compound containing tantalum element or elementary tantalum, which is conventional in the art, and is preferably tantalum and/or tantalum oxide.

In the present invention, the particle size of the tantalum material powder is preferably 500nm to5 μm or 100nm to 3 μm, for example 500nm to 1 μm or 1 to 3 μm.

When the tantalum material powder is tantalum powder, the particle size of the tantalum powder is preferably 500 nm-5 μm, and more preferably 1-3 μm or 500 nm-1 μm.

When the tantalum material powder is tantalum oxide powder, the particle size of the tantalum oxide powder is preferably 100 nm-3 μm, and more preferably 1-3 μm or 500 nm-1 μm.

In the present invention, the polyaryletherketone may be a polyaryletherketone conventional in the art, and generally refers to a crystalline polymer in which phenylene rings are connected to carbonyl groups (ketones) through oxygen bridges (ether bonds), and is preferably polyetherketoneketone (hereinafter abbreviated as PEKK) and/or polyetheretherketone (hereinafter abbreviated as PEEK).

The PEKK generally refers to a polymer composed of repeating units having one ether bond and two ketone bonds in the main chain structure.

Preferably, the PEKK has a melting point of 350-360 ℃, a glass transition temperature of 150-160 ℃ and a density of 1.0-1.5 g/cm³The polymerization degree is 150-250, and the molecular weight is 40000-60000; more preferably, the PEKK has a melting point of 355 ℃, a glass transition temperature of 156 ℃ and a density of 1.30g/cm³200 and 50000 molecular weight, for example PEKK of type OXPEKK-C (available from Oxford Performance Materials, USA).

Preferably, after injection molding, the compressive strength of the PEKK powder is 90-110 MPa, such as 100 MPa; the modulus of elasticity is 3 to 5GPa, for example 4.5GPa (test method: ISO 527). The injection molding is generally carried out in an injection molding machine; the injection molding temperature is preferably 350-380 ℃, such as 370-380 ℃ or 350-360 ℃, and further such as 375 ℃, 376 ℃, 378 ℃, 379 ℃, 350 ℃ or 360 ℃; the pressure for injection molding is preferably 100 to 120MPa, for example 100MPa, 105MPa, 110MPa, 113MPa, 115MPa or 120 MPa.

The polyether ether ketone (PEEK) generally refers to a polymer having a repeating unit containing one ketone bond and two ether bonds in a main chain structure.

Preferably, the PEEK has a melting point of 340-350 ℃, a glass transition temperature of 140-150 ℃ and a density1.0 to 1.5g/cm³The polymerization degree is 150-250, and the molecular weight is 40000-60000; more preferably, the PEEK has a melting point of 343 ℃, a glass transition temperature of 143 ℃ and a density of 1.30g/cm³200 and 50000 molecular weight, for example type 450PF PEEK (available from VICTREX, wight, uk).

Preferably, after injection molding, the PEEK powder has a compressive strength of 90-110 MPa, such as 98 MPa; the modulus of elasticity is 3 to 5GPa, for example 4.0GPa (test method: ISO 527). The injection molding is generally carried out in an injection molding machine; the injection molding temperature is preferably 350-380 ℃, such as 370-380 ℃ or 350-360 ℃, and further such as 375 ℃, 376 ℃, 378 ℃, 379 ℃, 350 ℃ or 360 ℃; the pressure for injection molding is preferably 100 to 120MPa, for example 100MPa, 105MPa, 110MPa, 113MPa, 115MPa or 120 MPa.

In the present invention, the particle size of the polyaryletherketone powder may be a particle size conventional in the art, and preferably, the particle size of the polyaryletherketone powder is 5 μm to 40 μm, such as 5 μm to 15 μm or 20 μm to 40 μm, and further such as 5 μm to 10 μm, 10 μm to 15 μm, 20 μm to 30 μm or 30 μm to 40 μm.

When the polyaryletherketone powder is PEKK powder, the particle size of the PEKK powder is preferably 20-40 μm, such as 20-30 μm or 30-40 μm.

When the polyaryletherketone powder is PEEK powder, the particle size of the PEEK powder is preferably 5-15 μm, such as 5-10 μm or 10-15 μm.

In the present invention, the volume ratio of the tantalum-containing compound powder to the polyaryletherketone powder is preferably 1:3 to 1:1, for example, 1:3, 3:7, 2:3, or 1: 1.

When the tantalum material powder is tantalum powder and the polyaryletherketone powder is PEKK powder, the volume ratio of the tantalum powder to the PEKK powder is preferably (1:3) to (1:1), for example, 1:3, 3: 7: 2:3 or 1: 1; preferably, in the raw material composition of the composite material, the volume fraction of the tantalum powder is 20-50%, such as 20%, 25%, 30%, 40% or 50%, and the volume fraction of the PEKK powder is 50-80%, such as 50%, 60%, 70%, 75% or 80%.

When the tantalum material powder is tantalum powder and the polyaryletherketone powder is PEKK powder, the particle size of the tantalum powder is preferably 500 nm-5 μm (such as 1-3 μm or 500 nm-1 μm), and the particle size of the PEKK powder is preferably 20-40 μm (such as 20-30 μm or 30-40 μm).

When the tantalum material powder is a tantalum oxide powder and the polyaryletherketone powder is a PEEK powder, the volume ratio of the tantalum oxide powder to the PEEK powder is preferably (1:3) to (1:1), for example, 1:3, 3:7, 2:3, or 1: 1; preferably, in the raw material composition of the composite material, the volume fraction of the tantalum oxide powder is 25-50%, such as 25%, 30%, 35%, 40%, 45% or 50%; the volume fraction of the PEEK powder is 50-75%, such as 50%, 55%, 60%, 65%, 70% or 75%.

When the tantalum material powder is tantalum oxide powder and the polyaryletherketone powder is PEEK powder, the particle size of the tantalum oxide powder is preferably 100 nm-3 μm (such as 1-3 μm or 500 nm-1 μm), and the particle size of the PEEK powder is preferably 5-15 μm (such as 5-10 μm or 10-15 μm).

The invention also provides an application of the raw material composition of the composite material as a raw material for preparing a bone repair body.

Wherein, the bone repair body is preferably a spine bone repair body, a dental implant or an artificial joint. The spine bone prosthesis is also called an interbody fusion cage and comprises a cervical interbody fusion cage and a thoracic/lumbar interbody fusion cage.

The invention also provides a preparation method of the composite material, which comprises the following steps: the raw material composition of the composite material is processed and molded.

In the present invention, the processing method may be a method and conditions conventional in the art, and is preferably extrusion molding, injection molding, compression sintering molding or hot pressing molding.

The extrusion molding process may be a conventional extrusion molding process in the art, and is generally performed in a twin-screw extruder. The extrusion molding temperature is preferably 340-380 ℃, such as 370-380 ℃ or 340-360 ℃, and further such as 340 ℃; the pressure for the extrusion molding is preferably 80 to 100MPa, for example 80MPa, 84MPa, 85MPa, 90MPa, 95MPa or 98 MPa.

The injection molding process may be a conventional injection molding process in the art, and is generally performed in an injection molding machine. The injection molding temperature is preferably 350-380 ℃, such as 370-380 ℃ or 350-360 ℃, and further such as 375 ℃, 376 ℃, 378 ℃, 379 ℃, 350 ℃ or 360 ℃. The pressure for injection molding is preferably 80 to 120MPa, more preferably 100 to 120MPa, for example 100MPa, 105MPa, 110MPa, 113MPa, 115MPa or 120 MPa. As is known to those skilled in the art, when the raw material composition of the composite material is processed and formed by injection molding, the raw material composition of the composite material may be prepared into a master batch, and then the master batch is injection molded. The master batch can be prepared by adopting an extrusion granulation method. The particle size of the master batch is preferably 2-5 mm, for example 3 mm.

The molding process may be a molding process, which is conventional in the art, and generally includes the following steps: and mixing the raw material compositions of the composite material, pressing and forming, then heating, and sintering and forming. The sintering molding is generally carried out in a sintering furnace, and the temperature rise speed of the sintering furnace is preferably 0.5-2 ℃/min, such as 1-2 ℃/min, and further such as 0.6 ℃/min, 0.8 ℃/min, 1 ℃/min, 1.5 ℃/min or 2 ℃/min. The temperature of the sintering molding is preferably 340-380 ℃, such as 365-380 ℃ or 340-360 ℃, and further such as 368 ℃, 370 ℃, 375 ℃, 378 ℃, 345 ℃, 350 ℃, 352 ℃ or 355 ℃. The heat preservation time of the sintering furnace is preferably 2h to 5h, such as 2h to 3h, and further such as 2.5h, 3h, 3.5h, 4h, 4.5h or 5 h.

The hot-press forming process may be a hot-press forming process conventional in the art, and is generally a hot-press forming process under heating. The pressing temperature is preferably 360-380 ℃, such as 365 ℃, 370 ℃ or 375 ℃. The pressing pressure is preferably 2 to 5MPa, for example 3MPa, 3.5MPa or 4 MPa. The holding time of the pressing is preferably 0.5-1 h, such as 1 h.

The invention also provides a composite material prepared by the preparation method.

The invention also provides an application of the composite material in bone repair.

The invention also provides a preparation method of the bone prosthesis, which comprises the following steps: and (3) processing and forming the raw material composition of the composite material in a mould of a bone repair product.

Wherein, the extrusion molding process, the injection molding process, the die pressing sintering molding process and the hot pressing compression molding process are as described above.

In the preparation method of the bone repair body, the mould of the bone repair body product is preferably a mould of a spine bone repair body, a dental implant or a mould of an artificial joint. The spine bone prosthesis preferably comprises a cervical interbody fusion cage and a thoracic/lumbar interbody fusion cage.

In the preparation method of the bone restoration, after the processing and forming, the surface of the bone restoration prepared after the processing and forming is preferably subjected to sand blasting, photoetching, sulfonation or coating.

Wherein, the sand blasting process can be a sand blasting process which is conventional in the field, and the bone restoration is generally subjected to surface sand blasting to form a porous structure on the surface of the bone restoration. The pore diameter of the porous structure is preferably 50-100 mu m. As is known to those skilled in the art, the surface blasting is generally performed by spraying sand through a surface blasting machine. The grain size of the sand material is preferably 20-50 mu m.

The surface of the bone restoration body can form a porous rough structure through sand blasting treatment, so that bone cells/bone tissues and blood vessels can easily grow into porous pores, and the bone tissues and the implant body form firm combination.

The photoetching process can be a conventional photoetching process in the field, and generally, the surface of the bone repair body is subjected to femtosecond laser surface photoetching to form a groove structure on the surface of the bone repair body. The process parameters of the femtosecond laser can be set according to the conventional operation in the field, wherein: the output wavelength of the femtosecond laser is preferably 800nm, the pulse width is preferably 300fs, the frequency is preferably 1000Hz, the optical power is preferably 20mW, and the scanning speed is preferably 600 μm/s; the width of the groove structure is preferably 20-60 mu m (more preferably 40 mu m), the depth is preferably 10 mu m, and the distance is preferably 40 mu m.

The surface of the bone restoration is processed by photoetching to form a groove structure on the surface of the bone restoration. Specifically, the inventors found that when the groove width was 40 μm, the groove depth was 10 μm, and the groove pitch was 40 μm, the resulting groove structure had the best effect of promoting adhesion, proliferation, and differentiation of cells.

The sulfonation treatment process can be a sulfonation treatment process which is conventional in the field, and generally the composite bone restoration is soaked in concentrated sulfuric acid until a porous structure is formed on the surface of the bone restoration. The concentrated sulfuric acid may be a sulfuric acid solution with a mass fraction of sulfuric acid greater than or equal to 70% as is conventional in the art, and is preferably a sulfuric acid solution with a mass fraction of sulfuric acid of 90-100%, such as 95-98%, and more such as 98%. The soaking time is preferably 10-25 min, such as 15min, 18min, 20min or 23 min. The pore diameter of the porous structure is preferably 1-5 μm. As is known to those skilled in the art, the sulfonation treatment is followed by a hydrothermal treatment to remove residual sulfur from the bone repair. The temperature of the hydrothermal treatment is preferably 120 ℃. The time of the hydrothermal treatment is preferably 4 hours.

The surface of the bone restoration body is sulfonated, so that uniform and ordered micropores can be formed on the surface of the bone restoration body, and the adhesion, proliferation and differentiation of cells are promoted.

Wherein the coating treatment process may be a coating treatment process conventional in the art, preferably: the method comprises the following steps: soaking the bone prosthesis in a suspension of tantalum material powder, and drying and sintering the bone prosthesis;

the second method comprises the following steps: and sintering the bone prosthesis in tantalum material powder to obtain the bone prosthesis.

In the first method, the solvent of the suspension is preferably ethanol.

In the first method, the mass percentage of the tantalum material powder in the suspension is preferably 5 to 10%, and more preferably 10%. The bone prosthesis is coated with a suspension of tantalum powder with the concentration of 10% (wt), and the obtained coating is uniform and flat.

In the first method, the soaking time is preferably 24 hours.

In the first method or the second method, the tantalum material powder is preferably tantalum powder and/or tantalum oxide powder. The particle size of the tantalum powder is preferably 1-3 mu m. The particle size of the tantalum oxide powder is preferably 500nm to 1 μm.

In the first method or the second method, the temperature rise speed of the sintering is preferably 0.5-2 ℃/min; the sintering temperature is preferably 365-380 ℃; the heat preservation time after sintering is preferably 2-5 h.

The bone repair body is treated by a substance coating with bone activity promoting performance, so that the bone activity promoting performance and the bone integration performance of the material can be improved.

The invention also provides a bone repair body prepared by the method.

In the invention, the shape and the specification of the bone repair body can be changed by selecting different moulds according to actual needs.

In the invention, the mechanical performance indexes of the tantalum/PEKK composite material or the bone restoration body are approximately as follows: the elastic modulus is 4-5 GPa, the compressive strength is 120-160 MPa, the tensile strength is 80-95 MPa, and the bending strength is 70-80 MPa.

In the invention, the mechanical performance indexes of the tantalum oxide/PEEK composite material or the bone repair body are approximately as follows: the elastic modulus is 4.6-6.2 GPa, the compressive strength is 120-160 MPa, the tensile strength is 70-95 MPa, and the bending strength is 70-80 MPa.

In the invention, the shape of the composite material obtained after the processing and forming, such as tantalum/PEKK and tantalum oxide/PEEK composite material, is not limited. If the mould used in the processing and forming is a mould of a bone repair body (such as an orthopedic internal fixing instrument and the like) product, the composite material can be directly used as the bone repair body (such as the orthopedic internal fixing instrument and the like). If the mold used in the machining is not a mold for a bone repair product, a bone repair of a desired shape may be prepared by a subsequent machining operation, such as machining or the like.

In the invention, the tantalum/PEKK composite bone repair material, the Ta/PEKK composite biological material and the tantalum/PEKK composite material are synonymous, and refer to the tantalum/PEKK composite bone repair material in the invention. Wherein the tantalum/PEKK composite material is a composite material which uses tantalum to strengthen PEKK.

In the invention, tantalum oxide/PEEK composite bone repair material and Ta₂O₅PEEK composite Material, Ta₂O₅the/PEEK composite biological material and the tantalum oxide/PEEK composite material are synonymous and refer to the tantalum oxide/PEEK composite bone repair material in the invention. Wherein, the tantalum oxide/PEEK composite material is a composite material for reinforcing PEEK by using tantalum oxide.

In the present invention, the master batch means a raw material composition of the composite material prepared in a volume fraction ratio, such as tantalum powder and PEKK powder, or tantalum powder and PEKK powder.

In the invention, the shape and specification of the bone repair body (such as an orthopedic internal fixation instrument and an intervertebral fusion device) can be changed by selecting different moulds according to actual needs. Wherein, the mould of the bone repair body (such as an orthopedic internal fixation instrument and an intervertebral fusion device) product is a mould which is used conventionally when preparing the bone repair body product.

As known to those skilled in the art, the particle size ranges of the tantalum-containing compound powder and the polyaryletherketone powder in the present invention mean that the mass percentage of the powder having the particle size distribution between the upper limit and the lower limit of the range is > 90%, for example, the particle size of the tantalum powder is 1-3 μm, which means that the mass percentage of the tantalum powder having the particle size distribution of 1 μm or more and 3 μm or less is > 90%.

On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.

The reagents and starting materials used in the present invention are commercially available.

The positive progress effects of the invention are as follows:

(1) the composite material has good biological activity and biocompatibility, particularly the tantalum/PEKK and tantalum oxide/PEEK composite materials have good biological activity and biocompatibility, have good mechanical compatibility with bone tissues, can promote adhesion, proliferation and differentiation of cells, can stimulate bone growth, accelerate bone healing and reduce healing time after the bone implant material is implanted.

(2) The composite material of the invention has excellent mechanical property, especially Ta/PEKK and Ta₂O₅The elastic modulus of the PEEK composite bone repair material is similar to that of natural bone, and the PEEK composite bone repair material has good osteogenic bioactivity. Ta/PEKK and Ta prepared on this basis₂O₅The PEEK bone restoration body has excellent mechanical compatibility, and can not cause bone absorption due to stress shielding. The implanted bone prosthesis (such as an orthopedic internal fixation instrument and an intervertebral fusion device) can promote the regeneration of peripheral bone tissues and the fusion with natural bone tissues, and can meet the requirements of immediate fixation and long-term stability of postoperative orthopedic instruments.

(3) The preparation method of the composite material is simple and easy to implement, and the bone repair bodies (such as orthopedic internal fixation instruments, intervertebral fusion devices and the like) with different shapes, specifications and mechanical properties can be prepared by correspondingly adjusting the preparation process according to clinical requirements.

(4) The surface of the bone repair body is treated by adopting a surface sand blasting technology, a porous rough structure is formed on the surface of the composite material, and bone cells/bone tissues and blood vessels are easy to grow into porous pores, so that the bone tissues and the implant form firm combination.

(5) The surface sulfonation technology is adopted to process the bone repair body, a porous structure is formed on the surface of the obtained bone repair body, bone cells/bone tissues and blood vessels are easy to grow into porous pores, and the bone tissues and the implant body are firmly combined. In addition, the surface of the composite bone restoration body is provided with sulfonic acid groups, so that the surface of the implant body has certain antibacterial property.

(6) The composite bone repair body (such as an orthopedic internal fixation instrument and an intervertebral fusion device) has good biocompatibility, bioactivity and osseointegration compatibility, and can shorten the bone healing time. The elastic modulus of the bone repair body is matched with human bones, so that negative effects of bone repair material loosening, bone absorption and the like caused by stress shielding can not be caused, and the clinical requirements on bone repair can be met.

Drawings

FIG. 1 is a Scanning Electron Microscope (SEM) surface and cross-section image of PT25 and PT50 materials of example 2, and a PEKK material of comparative example 1; the surface appearance of the PEKK material is shown in a diagram a and a diagram b, the section appearance of the PEKK material is shown in a diagram c, the surface appearance of the PT25 material is shown in a diagram d and a diagram e, the surface appearance of the PT 3578 material is shown in a diagram f, the section appearance of the PT25 material is shown in a diagram g and a diagram h, the surface appearance of the PT50 material is shown in a diagram i, and the section appearance of the PT50 material is shown in a diagram i;

FIG. 2 is SEM photographs of the sulfonated PT25, PT50 material and PEKK material of example 7; wherein, a graph and d graph show the surface appearance of the PEKK material after sulfonation treatment under different magnifications, b graph and e graph show the surface appearance of the PT25 material after sulfonation treatment under different magnifications, c graph and f graph show the surface appearance of the PT50 material after sulfonation treatment under different magnifications;

FIG. 3 is an SEM photograph of the PT25 material of example 8 after the surface is treated with a coating; wherein, the a picture, the b picture and the c picture are respectively surface topography pictures of the PT25 material after coating treatment under different magnifications;

FIG. 4 is an SEM photograph of the surface topography of the PT50 composite bone restoration body of example 9 after the surface is processed by femtosecond laser photoetching;

fig. 5 shows absorbance data measured in cytotoxicity experiments performed on PT25 material of example 1 and PEKK material of comparative example 1 in effect example 2;

FIG. 6 shows the absorbance data of the cell adhesion proliferation test performed on the PT25 and PT50 materials of example 1 and the PEKK material of comparative example 1 in Effect example 3;

FIG. 7 is a photograph of cell adhesion taken by a confocal laser microscope after 12h, 24h and 48h of cells were seeded with PT25 and PT50 materials of example 1 and PEKK material of comparative example 1 respectively in effect example 3; wherein, panels a, b and c respectively represent the cell adhesion condition after the PEKK group is inoculated with cells for 12h, 24h and 48 h; panels d, e and f show cell adhesion after 12h, 24h and 48h respectively for the PT25 group; g, h and i show the cell adhesion of PT50 group after seeding cells for 12h, 24h and 48h respectively;

FIG. 8 shows the results of alkaline phosphatase (ALP) activity data measured on cells seeded with PT25 and PT50 materials of example 1 and PEKK material of comparative example 1 in example 4;

FIG. 9 shows the water contact angle and the methylene iodide contact angle of the surface of the material measured by the hydrophilicity test of the PT25 and PT50 materials of example 1 and the PEKK material of comparative example 1 in example 5;

fig. 10 is an appearance photograph (a to c) of the PEEK material of comparative example 2, the PTO25 material of example 10, and the PTO50 material of example 11, an appearance photograph (d to f) after sandblasting, wherein a to f refer to appearance photographs of PEEK, PTO25, PTO50, sandblasted PEEK, sandblasted PTO25, and sandblasted PTO50, respectively;

fig. 11 is a scanning electron micrograph of the PEEK material of comparative example 2, the PTO25 material of example 10, and the PTO50 material of example 11, wherein: the picture a, the picture d show SEM pictures of PEKK material under the magnification of 2000 times and 5000 times respectively, the picture b, the picture e show SEM pictures of PTO25 material under the magnification of 2000 times and 5000 times respectively, the picture c, the picture f show SEM pictures of PTO50 material under the magnification of 2000 times and 5000 times respectively;

FIG. 12 is an SEM photograph of samples of the PEEK, PTO25, PTO50 bone restoration of example 17 after sand blasting; wherein, the a picture and the d picture are surface appearance pictures of PEEK bone repair body surface after sand blasting under different magnification; b, e are surface topography maps of PTO25 bone prosthesis after surface sand blasting under different magnifications; c, f, surface topography after surface sand blasting of PTO50 bone repair body under different magnifications;

FIG. 13 is a photograph of scans of samples of the bone prosthesis of example 18 after sulfonation treatment of PEEK, PTO25 and PTO 50; wherein, the picture a and the picture d are surface appearance pictures after the surface sulfonation treatment of the PEEK bone repair body under different magnification; b, e, surface topography after surface sulfonation treatment of PTO25 bone repair body under different magnification; the c picture and the f picture are surface topography pictures of the PTO50 bone restoration body surface after sulfonation treatment under different magnifications;

fig. 14 is a photograph of a scan of PTO50 bone restoration sample after coating treatment in example 19; wherein, a picture, b picture and c picture respectively show the scanning pictures of PTO50 bone repair body surface coating after being processed under different magnifications;

fig. 15 is measured absorbance data of the cytotoxicity experiments performed on the PTO25 material of example 10, the PTO50 material of example 13, and the TCP control group in effect example 7;

fig. 16 is absorbance data measured by a cell adhesion proliferation experiment performed on the PTO50 material of example 11 and the PEEK material of comparative example 2 in effect example 8;

fig. 17 is a photograph showing cell adhesion obtained by using a laser confocal microscope to photograph the cell adhesion images of the PTO25 material of example 10, the PTO50 material of example 11, and the PEEK material of comparative example 2, which were seeded on the surfaces of the cells 12h and 24h, respectively, after fixing the cells on the above materials using a fixing solution, in example 8; wherein, the picture a and the picture d are respectively cell adhesion pictures after the PEEK group is inoculated with cells for 12h and 24 h; panels b and e are photographs of cell adhesion 12h and 24h after the PTO25 group is inoculated with the cells respectively; panels c and f are photographs of cell adhesion 12h and 24h after the PTO50 group is inoculated with the cells respectively;

fig. 18 shows ALP activity data measured on cells after the PTO50 material of example 11 and the PEEK material of comparative example 2 were seeded in the cells in example 9.

Detailed Description

The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.

The technical solution adopted by the present invention will be further described with reference to the following examples.

In the following examples:

the polyether ketone (30-40 μm) and the polyether ketone (20-30 μm) are all OXPEKK-C (available from Oxford Performance Materials, USA);

the types of polyetheretherketone (10-15 μm) and polyetheretherketone (5-10 μm) are both 450PF (purchased from VICTREX of Wedges, UK);

tantalum powder (1-3 μm) and tantalum powder (500 nm-1 μm) were purchased from Allantin Biotechnology Ltd (Shanghai) with a specification of 99.99% metals basis;

tantalum oxide (500 nm-1 μm) and tantalum oxide (1-3 μm) were purchased from Mobe Biotechnology Ltd (Shanghai) with a specification of 99.99% metals basis.

In the following examples: the detection standard of the elastic modulus is ISO 527; the building material standard of the compressive strength is ISO 527; the detection standard of the tensile strength is GB/T228.1-2010; the detection standard of the bending strength is GB/T6569-86.

In the mechanical property detection method in the following examples:

for the elastic modulus, preparing the composite material/bone prosthesis into a cylindrical sample with the diameter of 12mm and the height of 25mm, testing by using a universal tensile testing machine, and calculating according to a stress-strain curve to obtain the elastic modulus;

for the compressive strength, the composite material/bone prosthesis is prepared into a cylindrical sample with the diameter of 12mm and the height of 10mm, and a universal tensile testing machine is used for testing;

for tensile strength, the composite material/bone restoration is prepared into a dumbbell-shaped sample (with the length of 150mm, the width of 10mm and the thickness of 3mm), and a universal tensile testing machine is used for testing;

for flexural strength, the composite/bone restoration was prepared as a dumbbell specimen (length 80mm, width 10mm, thickness 4mm) and tested with a universal tensile tester.

Wherein, above-mentioned universal tensile testing machine all purchases in Shenzhen new mitus materials detection Limited company, model: 2T/CMT 4204.

In the following examples, the density of the tantalum powder was 16.65g/cm³The density of the polyetherketoneketone powder was 1.30g/cm³The density of the tantalum oxide powder was 8.20g/cm³The density of the polyether-ether-ketone powder is 1.30g/cm³The density of the silicon nitride powder was 3.2g/cm³。

In the following examples:

PT25 refers to the raw materials of the composite material, namely tantalum powder and polyether ketone powder, wherein the volume percentage of the tantalum powder is 25%;

PT50 refers to the raw materials of the composite material, namely tantalum powder and polyether ketone powder, wherein the volume percentage of the tantalum powder is 50%;

PEKK means that the raw material of the material only contains polyether ketone powder;

PTO25 refers to the raw materials of the composite material, namely tantalum oxide powder and polyether-ether-ketone powder, wherein the volume percentage of the tantalum oxide powder is 25%;

PTO50 refers to the raw materials of the composite material, namely tantalum oxide powder and polyether-ether-ketone powder, wherein the volume percentage of the tantalum oxide powder is 50%;

PEEK means that the material raw material of the material contains only polyetheretherketone powder.

Example 1

The preparation method of the PT25 material comprises the following steps: mixing 8.10kg of tantalum powder with the volume fraction of 25% and the particle size of 1-3 mu m with 1.90kg of polyether ketone powder with the volume fraction of 75% and the particle size of 30-40 mu m by using a high-speed mixer to obtain mixed powder; then extruding and granulating the mixed powder by using a double-screw extruder, wherein the extrusion temperature of the extruder is 370-380 ℃; the extrusion pressure is 80MPa to 100 MPa; the particle size of the extruded master batch is 2-5 mm; then, injection molding the master batch by using an injection molding machine, wherein the injection molding temperature is 370-380 ℃; the pressure of the injection molding machine is 80-120 MPa.

The preparation method of the PT50 material comprises the following steps: mixing 18.56kg of tantalum powder with the volume fraction of 50% and the particle size of 1-3 mu m and 1.44kg of PEKK powder with the volume fraction of 50% and the particle size of 30-40 mu m by using a high-speed mixer to obtain mixed powder; the rest steps are the same as the preparation method of the PT25 material in the embodiment.

Example 2

The preparation method of the PT25 material comprises the following steps: mixing 8.10kg of tantalum powder with the volume fraction of 25% and the particle size of 1-3 mu m with 1.90kg of polyether ketone powder with the volume fraction of 75% and the particle size of 30-40 mu m by using a high-speed mixer to obtain mixed powder; then extruding and molding the mixed powder by using a double-screw extruder, wherein the extrusion temperature of the extruder is 370-380 ℃; the extrusion pressure is 80 MPa-100 MPa. SEM photographs of the surface and the section appearance of the prepared PT25 material are shown as a d picture, an e picture and a f picture in figure 1.

The preparation method of the PT50 material comprises the following steps: mixing 18.56kg of tantalum powder with the volume fraction of 50% and the particle size of 1-3 mu m and 1.44kg of polyether ketone powder with the volume fraction of 50% and the particle size of 30-40 mu m by using a high-speed mixer to obtain mixed powder; the rest steps are the same as the preparation method of the PT25 material in the embodiment. SEM photographs of the surface and the section appearance of the prepared PT50 material are shown as a g picture, an h picture and an i picture in figure 1.

Comparative example 1

The preparation method of the PEKK material comprises the following steps: 10kg of polyetherketoneketone powder having a particle size of 30 to 40 μm was uniformly stirred by a high-speed mixer, and the rest of the procedure was the same as in example 2. SEM photographs of the surface and section appearance of the prepared PEKK material are shown in a figure a, a figure b and a figure c in figure 1.

The preparation method of the PEKK bone restoration is the same as that of the PEKK material (a mold for the bone restoration is used).

Example 3

The preparation method of the PT50 bone restoration comprises the following steps: mixing 18.56kg of tantalum powder with the volume fraction of 50% and the particle size of 1-3 mu m and 1.44kg of polyether ketone powder with the volume fraction of 50% and the particle size of 30-40 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1 (mold for artificial joint). The mechanical properties of the obtained PT50 bone prosthesis are shown in table 1.

Example 4

The preparation method of the PT50 bone restoration comprises the following steps: mixing 18.56kg of tantalum powder with the volume fraction of 50% and the particle size of 1-3 mu m with 1.44kg of polyether ketone powder with the volume fraction of 50% and the particle size of 30-40 mu m by using a high-speed mixer to obtain mixed powder, then performing compression molding by using a mold (using a mold of a spinal prosthesis), and performing sintering molding in a sintering furnace to obtain the product; the temperature rising speed of the sintering furnace is 1 ℃/min; the sintering temperature is 370 ℃; the incubation time was 5 hours. The mechanical properties of the PT50 bone prosthesis prepared in this example are shown in table 1.

The preparation method of the PT25 bone restoration comprises the following steps: the raw materials were replaced with the mixed powder of PT25 material prepared in example 1, and the remaining steps were the same as the method for preparing the PT50 bone prosthesis in this example.

Example 5

The preparation method of the PT50 bone restoration comprises the following steps: the procedure was as in example 4 (using a mold for dental implants). The mechanical properties of the PT50 bone prosthesis prepared in this example are shown in table 1.

Example 6

The preparation method of the PT50 bone restoration comprises the following steps: the mixed powder of the PT50 material prepared in the example 1 is subjected to hot pressing and forming by a heating mould (an artificial joint mould is used), and the hot pressing temperature is 370 ℃; the pressure is 4 MPa; the hot-pressing heat preservation time is 1 hour. The mechanical properties of the PT50 bone prosthesis prepared in this example are shown in table 1.

Example 7

The preparation method of the PEKK bone restoration comprises the following steps: the surface sulfonation treatment is carried out on the PEKK bone restoration prepared in the comparative example 1, and the specific steps are as follows: and (3) soaking the PEKK bone restoration body obtained by extrusion molding in 95-98% concentrated sulfuric acid, sulfonating, stirring for 15 minutes, and carrying out hydrothermal treatment for 4 hours at 120 ℃ to remove residual sulfur in the bone restoration body, thereby obtaining the sulfonated modified bone restoration body with porous surface.

The preparation method of the PT25 bone restoration comprises the following steps: the PT25 bone restoration prepared in example 5 was surface-sulfonated according to the method for preparing a PEEK sulfonation modified bone restoration of this example.

The preparation method of the PT50 bone restoration comprises the following steps: the PT50 bone restoration prepared in example 5 was surface-sulfonated according to the method for preparing a PEEK sulfonation modified bone restoration of this example.

The SEM photograph of the above bone prosthesis is shown in fig. 2, wherein: a, a diagram and a diagram d show surface topography diagrams of the PEKK bone restoration body after sulfonation treatment under different magnifications, and the average aperture is 2 mu m; b, e, a surface topography of the sulfonated PT25 bone prosthesis under different magnifications, wherein the average pore diameter is 2 mu m, and tantalum particles are distributed on the surface; and the graph c and the graph f show surface topography graphs of the sulfonated PT50 bone restoration under different magnifications, and compared with the sulfonated PT25 bone restoration, the surface distribution of particles is increased.

As will be appreciated by those skilled in the art, the procedure of sulfonation after hot press forming and press sintering is similar to the above-described process. Among them, the sulfonation treatment process may be applied to the PT50 material.

Example 8

The preparation method of the PT25 bone restoration comprises the following steps: the PT25 bone restoration prepared in example 5 was surface coated as follows: soaking the bone prosthesis obtained by injection molding in ethanol suspension of tantalum powder with the mass concentration of 10% and the particle size of 1-3 microns, stirring for 24 hours, taking out and drying the bone prosthesis, and sintering in a sintering furnace at the temperature rising speed of 0.5-2 ℃/min; the sintering temperature is 365-380 ℃; and keeping the temperature for 2-5 hours to obtain the tantalum-coated bone restoration, wherein SEM pictures of the bone restoration are shown in figure 3, wherein a picture, b picture and c picture are respectively surface topography pictures of the PT25 bone restoration treated by the coating under different magnifications.

Further, it is known to those skilled in the art that the coating process is performed after injection molding, hot press molding and extrusion molding, similar to the above-described process. In addition, the tantalum coating process can also be applied to PT50, and the process flow thereof is the same as that in PT25, which is specifically referred to the above description and is not repeated herein.

Example 9

The photoetching treatment method of the PT50 bone restoration comprises the following steps: the surface of the PT50 bone restoration prepared in example 7 was photo-etched in the same direction using a femtosecond laser. The parameters of the femtosecond laser are as follows: the output wavelength is 800nm, the pulse width is 300fs, the frequency is 1000Hz, the optical power is 20mW, and the scanning speed is 600 μm/s. The scanning times were adjusted so that the etched grooves were arranged in parallel, the width of the grooves was 40 μm, the depth was 10 μm, and the pitch of the grooves was 40 μm, and the SEM photograph of the surface topography of the PT50 bone prosthesis prepared in this example is shown in fig. 4.

In order to verify the beneficial effects of the embodiments, the invention further provides corresponding experimental bases, which comprise a mechanical property experiment, a cytotoxicity experiment, a cell adhesion proliferation experiment, a cell differentiation experiment, a hydrophilicity test and an antibacterial experiment, and specifically comprise the following steps:

effect example 1 mechanical Property experiment

Respectively measuring the elastic modulus (GPa), the compressive strength (MPa), the tensile strength (MPa) and the bending strength (MPa) of the PT50 bone restoration prepared in the embodiment 3-6 and the human bone (human femur), wherein the detection standard of the elastic modulus is ISO 527; the building material standard of the compressive strength is ISO 527; the detection standard of the tensile strength is GB/T228.1-2010; the detection standard of the bending strength is GB/T6569-86. Specific data can be seen in table 1 below.

TABLE 1 mechanical Properties of PT50 composite bone prosthesis of examples 3-6

As can be seen from Table 1, the bone repair performances of the bone prostheses prepared in examples 3, 4, 5 and 6 are equivalent to those of human bone; wherein, the performance of the composite bone prosthesis prepared in the example 3 is better than that of the composite bone prosthesis prepared in the examples 4, 5 and 6. In addition, the mechanical properties of the composite bone prosthesis prepared by different preparation methods are different, and the comprehensive properties of the composite bone prosthesis are evaluated according to the following sequence: injection molding (example 3) > hot press molding (example 6) > press sintering molding (examples 4, 5).

Effect example 2 cytotoxicity test of tantalum/PEKK composite Material

The PT25 material prepared in example 1 and the PEKK material prepared in comparative example 1 were used as samples to be tested for cytotoxicity, and the samples were all round pieces (12 mm in diameter and 2mm in thickness) of the same specification prepared in a die with a diameter of 12mm and a thickness of 2 mm.

The specific method of cytotoxicity test is as follows:

the biosafety of the composites was tested according to ISO10993-5 cytotoxicity standards. The PT25 material prepared in example 1 and the PEKK material prepared in comparative example 1 are respectively soaked in serum-free cell culture medium (200mg/mL) for 24 hours at 37 ℃, and then filtered to obtain leaching liquor. At 3X 10²The fibroblast cells are inoculated to a 96-hole cell culture plate according to the concentration of each hole, the culture medium is removed after the continuous culture for 1 day, and PBS is washed for 3 times; adding 10% FBS-containing leaching solution, and continuously culturing for 1 day; the material extract (tissue culture plate TCP) containing 10% FBS was not added as an experimental blank control. After 24h of incubation, 30. mu.L of MTT solution was added to each well, incubation was continued for 4 hours, the culture medium was discarded, PBS was washed 3 times, 100. mu.L of DMSO was added to each well, and after standing at room temperature for 10 minutes, the absorbance of the solution was measured at 490nm using an enzyme reader, as shown in FIG. 5. As can be seen from fig. 5, there is no significant difference in absorbance values of the experimental group (sample of example 1) compared to the control group (PEKK material prepared in comparative example 1), indicating that the composite material prepared in example 1 of the present application has no negative effect on the growth of fibroblasts. The calculation shows that the cell survival rates of the cells in the material leaching solution and the blank control group are both over 95%, which indicates that the composite material prepared in the embodiment 1 of the present application has no toxicity to the fibroblasts, and the specific data can be seen in table 2.

TABLE 2

Group of	Control group	Example 1
			Cell survival rate (%)	95.43±1.24	97.64±0.86

Effect example 3 cell adhesion proliferation experiment

(1) Cell adhesion proliferation experiments were performed on the PT25 material obtained in example 1, the PT50 material obtained in example 1, and the PEKK material obtained in comparative example 1, which were samples of the same size (12 mm diameter and 2mm thickness) prepared in a mold having a diameter of 12mm and a thickness of 2 mm.

The specific method of cell adhesion proliferation assay is as follows:

cell proliferation experiments were performed using the CCK8 method. Before the cell inoculation is started, the above-mentioned groups of samples are sterilized by ethylene oxide, placed in 24-well plate, and then inoculated with 1X 10⁴Individual cells/mL rat bone marrow mesenchymal stem cells. Changing the cell culture solution every two days during the culture process, respectively taking out the samples of the groups at corresponding time points after the cells are cultured for 1, 3 and 7 days, putting the samples into a new 24-well plate, adding 500 mu L of CCK8 reagent, putting the samples back into an incubator for culture for 4 hours, sucking 100 mu L of the culture solution into a 96-well plate, and measuring the corresponding Optical Density (OD) value at the position of 450nm by using a microplate reader

The PEKK material prepared in comparative example 1 was used as a control. The results are shown in Table 3 and FIG. 6.

TABLE 3

Group of	PEKK	PT25	PT50
				Absorbance (D1)	0.23±0.02	0.49±0.03*	0.52±0.06**
Absorbance (D3)	0.26±0.02	0.55±0.03*	0.83±0.03**
				Absorbance (D7)	0.27±0.03	0.70±0.05*	0.93±0.06**

Note: d1, D3 and D7 represent the absorbance measured after the cells were cultured for 1, 3 and 7 days, respectively; compared to the PEKK group,: p <0.05, x: p < 0.01.

As can be seen from table 3 and fig. 6, the proliferation capacities of the cells in the respective groups were ranked from high to low: PT50 material prepared in example 1 > PT25 material prepared in example 1 > PEKK material prepared in comparative example 1.

(2) Rat bone marrow mesenchymal stem cells were cultured at 1 × 10 per well⁴Density inoculation ofThe PT25 material obtained in 1, the PT50 material obtained in example 1 and the PEKK material surface obtained in comparative example 1 (all of the above samples are discs of the same size (diameter 12mm, thickness 2mm) prepared in a mold having a diameter 12mm and a thickness 2mm), after 12h, 24h and 48h, respectively, cell nuclei and cytoplasm were stained with DAPI and FITC, respectively, and cell adhesion was observed under a 3D laser confocal microscope, as shown in fig. 7, wherein: panel a, b and c are cell adhesion after PEKK group inoculation of cells for 12h, 24h and 48h respectively; panels d, e and f are cell adhesion after 12h, 24h and 48h respectively for PT25 group inoculated cells; and g, h and i are cell adhesion after 12h, 24h and 48h respectively for PT50 group of seed cells. The cell adhesion rate data is shown in Table 4.

The calculation formula of the cell adhesion rate is as follows:

cell adhesion rate (OD value of cells on the test material at this time t-initial time t)₀Cell OD of (1)/(cell OD of blank well at this time point t-initial time point t)₀Cell OD value of (a).

TABLE 4

Group of	PEKK	PT25	PT50
				Cell adhesion Rate/% (12h)	21.2±1.5	34.5±2.7*	42.3±2.4**
Cell adhesion Rate/% (24h)	38.8±4.7	45.8±4.9*	55.9±5.3**
				Cell adhesion Rate/% (48h)	41.7±5.2	57.8±6.1*	80.3±7.6**

Note: compared to the PEKK group,: p <0.05, x: p < 0.01.

As can be seen from fig. 7 and table 4, the PT25 material and the PT50 material prepared in example 1 both have higher cell adhesion and proliferation rate on the surface, and the PT50 material group has more adhered cells (the cell adhesion rate can reach 80.3% after 48h), more extended cytoskeleton, more obvious filopodia, and more filopodia, and has better adhesion morphology, which indicates that the PT50 material has better cell compatibility.

Effect example 4 cell differentiation experiment

Cell differentiation experiments were performed on the PT25 material obtained in example 1, the PT50 material obtained in example 1, and the PEKK material obtained in comparative example 1, which were samples of the same size (12 mm in diameter and 2mm in thickness) prepared in a mold having a diameter of 12mm and a thickness of 2 mm.

The specific method of cell differentiation experiments is as follows:

cells were studied for differentiation on each of the above-mentioned groups using an alkaline phosphatase (ALP) kit (purchased from Shanghai Ciki Biotech, Inc., alkaline phosphatase detection kit). Sterilizing the sample with ethylene oxide, placing in 24-well plate, inoculating 2.5 × 10⁴Individual cells/mL rat bone marrow mesenchymal stem cells. Observing the differentiation condition of cells after 7, 10 and 14 days of culture on the material surface by ALP staining, and changing the cells again every two days for fine cells in the process of cell cultureCell culture fluid. At the corresponding time, the medium in the well plate was aspirated, and the wells were then washed three times with PBS buffer.

To the wells containing the material, 500. mu.L of a 1% ethyl phenyl polyethylene glycol solution was added to obtain a cell lysate. After completion of the cleavage, 50. mu.L of a 1mg/mL solution of P-nitrophenylphosphate was added to each well and after 15min at room temperature, the reaction was terminated by adding 100. mu.L of a 0.1M NaOH solution. Finally, OD value in the well was measured at a wavelength of 405nm with a microplate reader, and ALP activity of the cells was calculated from the OD value. A sample of the PEKK material prepared in comparative example 1 was used as a control. The results are shown in FIG. 8 and Table 5.

TABLE 5

Group of	PEKK	PT25	PT50
				ALP Activity (D7)	0.066±0.0008	0.186±0.0055*	0.236±0.0041**
ALP Activity (D10)	0.069±0.0012	0.289±0.0039*	0.299±0.0024**
				ALP Activity (D14)	0.087±0.0009	0.357±0.0021*	0.397±0.0035**

Note: d7, D10 and D14 represent ALP activity measured after 7, 10 and 14 days of cell culture, respectively; compared to the PEKK group,: p <0.05, x: p < 0.01.

As can be seen from table 5, the PT25 material prepared in example 1, the PT50 material prepared in example 1, and the PEKK material prepared in comparative example 1 all inoculated cells and then the ALP activity of the cells was gradually increased as the cell culture time was prolonged. Overall, PT50 material was the highest in cell differentiation activity, and PT25 material was the second lowest. The cell differentiation activity of PEKK material was the lowest. It is understood that the composite material prepared in example 1 of the present application has a good effect of promoting cell differentiation.

Effect example 5 hydrophilicity test

The PT25 material prepared in example 1, the PT50 material prepared in example 1 and the PEKK material prepared in comparative example 1 were subjected to a hydrophilicity test (contact angle measurement standard: GB/T30693-.

TABLE 6

Note: compared to the PEKK group,: p <0.05, x: p < 0.01; compared to PT25 group, #: p < 0.05.

As can be seen from fig. 9 and table 6, the water contact angles of the PEKK material were 82.0 °, and the water contact angles of the PT25 material and the PT50 material were 77.0 ° and 57.0 °, respectively. Therefore, the hydrophilicity of the composite material prepared by the embodiment of the application is obviously improved, the surface energy of the composite material is improved, the adhesion of protein and cells to the surface of the composite material is facilitated, and the surface energy of the PT50 material is obviously higher than that of the PT25 material.

Example 10

Preparation method of PTO25 material: mixing 6.78kg of tantalum oxide powder with the volume fraction of 25% and the particle size of 500 nm-1 mu m with 3.22kg of PEEK powder with the volume fraction of 75% and the particle size of 10-15 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the PTO25 material prepared in this example are shown in table 7; the sample photograph is shown in the b picture in FIG. 10; the photograph of the sample after grit blasting is shown in fig. 10, panel e; the sample specification is phi 12 multiplied by 2mm (i.e. diameter is 12mm, thickness is 2 mm); the surface SEM photographs are shown in fig. 11 as b and e (wherein b and e represent SEM photographs at 2000 x and 5000 x magnification, respectively).

Example 11

Preparation method of PTO50 material: mixing 8.63kg of tantalum oxide powder with the volume fraction of 50% and the particle size of 500 nm-1 mu m with 1.37kg of polyether-ether-ketone powder with the volume fraction of 50% and the particle size of 10-15 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the PTO50 material prepared in this example are shown in table 7; the sample photograph is shown in fig. 10, panel c; the photograph of the sample after sandblasting is shown in fig. 10 as f; the sample specification phi 12 multiplied by 2 mm; the surface SEM photographs are shown in FIG. 11 as c and f (wherein c and f represent SEM photographs at 2000 and 5000 magnifications, respectively).

Example 12

Preparation method of PTO25 material: mixing 6.78kg of tantalum oxide powder with the volume fraction of 25% and the particle size of 500 nm-1 mu m with 3.22kg of polyether-ether-ketone powder with the volume fraction of 75% and the particle size of 10-15 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 2. The mechanical properties of the PTO25 material prepared in this example are shown in table 7.

Example 13

Preparation method of PTO50 material: mixing 8.63kg of tantalum oxide powder with the volume fraction of 50% and the particle size of 500 nm-1 mu m with 1.37kg of polyether-ether-ketone powder with the volume fraction of 50% and the particle size of 10-15 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 4. The mechanical properties of the PTO50 material prepared in this example are shown in table 7.

Example 14

The preparation method of the PTO25 bone restoration comprises the following steps: mixing 6.78kg of tantalum oxide powder with the volume fraction of 25% and the particle size of 500 nm-1 mu m with 3.22kg of polyether-ether-ketone powder with the volume fraction of 75% and the particle size of 10-15 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1 (using a mold for spinal bone prosthesis). The mechanical properties of the PTO25 bone prosthesis prepared in this example are shown in table 7.

Example 15

The preparation method of the PTO50 bone restoration comprises the following steps: mixing 8.63kg of tantalum oxide powder with the volume fraction of 50% and the particle size of 500 nm-1 mu m with 1.37kg of polyether-ether-ketone powder with the volume fraction of 50% and the particle size of 10-15 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 4 (using a mold for dental implants). The mechanical properties of the PTO50 bone prosthesis prepared in this example are shown in table 7.

Example 16

The preparation method of the PTO50 bone restoration comprises the following steps: mixing 8.63kg of tantalum oxide powder with the volume fraction of 50% and the particle size of 500 nm-1 mu m with 1.37kg of polyether-ether-ketone powder with the volume fraction of 50% and the particle size of 10-15 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 2 (mold for artificial joint).

Comparative example 2

The preparation method of the PEEK material comprises the following steps: 10kg of polyetheretherketone powder having a particle size of 10 to 15 μm was uniformly stirred by a high-speed mixer, and the rest of the procedure was the same as in example 1. The sample photograph of the PEEK material prepared in this example is shown in a in fig. 10, the sample photograph after sand blasting is shown in d in fig. 10, and the surface SEM photograph is shown in a and d in fig. 11 (wherein a and d represent scanning electron micrographs at 2000 and 5000 magnifications, respectively).

The preparation method of the PEEK bone repair body is the same as that of a PEEK material (a bone repair body mould is used).

Example 17

The present example illustrates the sandblasting surface treatment, specifically:

the PEEK bone prosthesis prepared in comparative example 2, the PTO25 bone prosthesis prepared in example 15, and the PTO50 bone prosthesis prepared in example 16 were subjected to surface blasting, specifically as follows: and (3) performing surface sand blasting on the bone restoration formed in the comparative example 2 and the examples 15 and 16 by using a surface sand blasting machine and using a sand material with the particle size of 20-50 microns until a porous surface with the pore diameter of 50-100 microns is formed on the surface of the bone restoration, thus obtaining the bone restoration after sand blasting. After the surface sand blasting treatment is carried out, SEM pictures of the surface appearance of the PEEK, PT25 and PT50 bone repair bodies are shown in figure 12, wherein, a picture and d picture are the surface appearance pictures of the PEEK bone repair bodies after the surface sand blasting under different magnifications; b, e are surface topography maps of PTO25 bone prosthesis after surface sand blasting under different magnifications; and the c picture and the f picture are surface topography pictures of PTO50 bone repair body surface after sand blasting treatment under different magnifications. As can be seen, the amount of tantalum oxide particles on the surface of the composite material increased after the sandblasting treatment.

Example 18

This example illustrates a sulfonated surface treatment, specifically:

the PEEK bone prosthesis prepared in comparative example 2, the PTO25 bone prosthesis prepared in example 15, and the PTO50 bone prosthesis prepared in example 16 were subjected to surface sulfonation, specifically as follows: the bone restoration obtained by processing and forming is soaked by using 98 percent concentrated sulfuric acid, and then is subjected to hydrothermal treatment at 120 ℃. Wherein the soaking time is 15min, and the hydrothermal treatment time is 4 h. After the surface sulfonation treatment, surface morphology SEM pictures of the bone repair bodies of PTO25 and PTO50 are shown in figure 13, wherein, a picture and a picture d are surface morphology pictures of the PEEK bone repair bodies after the surface sulfonation treatment under different magnifications, and the average pore diameter is 3 mu m; b, e, surface topography after surface sulfonation treatment of PTO25 bone prosthesis under different magnifications, wherein the average pore diameter is 1 μm; and the c picture and the f picture are surface topography pictures of the PTO50 bone repair body surface after sulfonation treatment under different magnifications, and the average pore diameter is 500 nm.

Example 19

The present example illustrates the surface treatment of the coating, specifically:

the PTO50 bone prosthesis prepared in example 16 was subjected to a surface coating treatment as follows: and (3) placing the block obtained by processing and forming in tantalum oxide powder by using a muffle furnace for sintering treatment until a uniform tantalum oxide coating is formed on the surface of the block. Wherein the particle size of the tantalum oxide powder is 500 nm-1 μm. After surface coating treatment, the surface topography SEM photograph of the PTO50 bone prosthesis is shown in fig. 14, wherein, a, b and c respectively show the PTO50 bone prosthesis after surface coating treatment at different magnifications.

Comparative example 3

Raw materials: 1kg of tantalum oxide powder with the grain size of 500 nm-1 mu m and 9kg of PEEK powder with the grain size of 10-15 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the composite are shown in Table 7.

Comparative example 4

Raw materials: 2kg (4vt percent), tantalum oxide powder with the grain diameter of 500 nm-1 mu m and 8kg (96vt percent), polyetheretherketone powder with the grain diameter of 10-15 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the composite are shown in Table 7.

Comparative example 5

Raw materials: 5kg (14vt percent), tantalum oxide powder with the grain diameter of 500 nm-1 mu m and 5kg (86vt percent), polyetheretherketone powder with the grain diameter of 10-15 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the composite are shown in Table 7.

Effect example 6 mechanical Property test

The bone repair materials prepared in examples 10-13, the bone prostheses prepared in examples 14-15, and the bone repair materials prepared in comparative examples 1-3 were used as samples to be tested to perform mechanical property tests, and the samples were prepared into mechanical test sample strips according to the detection standard in effect example 1.

TABLE 7 mechanical Properties of bone repair materials/bone prostheses of examples 10 to 15

As can be seen from Table 7:

(1) compared with the composite materials prepared in the comparative examples 3-5, the elastic modulus of the tantalum oxide/PEEK composite material is closer to that of human bones, and each parameter index in the mechanical property is better, so that the composite material is very suitable for being used as a substitute material (bones and teeth) of human hard tissues;

(2) the bone repair materials/bone prostheses prepared in examples 11, 13 and 15 are superior in mechanical properties to those prepared in examples 10, 12 and 14.

Effect example 7 cytotoxicity test of tantalum oxide/PEEK composite Material

The PTO25 material obtained in example 10 and the PTO50 material obtained in example 13 were used as samples for cytotoxicity tests, which were all wafers of the same specification (12 mm diameter and 2mm thickness) produced in a mold having a diameter of 12mm and a thickness of 2 mm.

The specific procedure of the cytotoxicity test was the same as in example 2. The absorbance of each group of culture was shown in FIG. 15, and the cell viability was shown in Table 8.

TABLE 8

Group of	Example 10	Example 13	TCP control group
				Cell survival rate (%)	96.10±1.03	97.81±0.67	95.13±0.94

Effect example 8 cell adhesion proliferation test

(1) The PEEK material obtained in comparative example 2 and the PTO50 material obtained in example 11 were used as samples for cell adhesion proliferation test, which were all wafers (12 mm in diameter and 2mm in thickness) of the same size prepared in a mold having a diameter of 12mm and a thickness of 2 mm.

The specific method of the cell adhesion proliferation test was the same as that of example 3.

TABLE 9

Group of	PEEK	PTO50
			Absorbance (D1)	0.191±0.018	0.262±0.010
Absorbance (D3)	0.394±0.009	0.543±0.006*
			Absorbance (D7)	0.796±0.012	0.914±0.008*

Note: d1, D3 and D7 represent the absorbance measured after the cells were cultured for 1, 3 and 7 days, respectively; compared to the PEEK group,: p < 0.05.

As can be seen from table 9 and fig. 16, the cell adhesion proliferation capacity of the composite material-treated group was significantly higher than that of the PEEK material group.

(2) BMSCs cells (rat bone marrow mesenchymal stem cells) were plated at 1X 10 per well⁴The cell adhesion conditions of the samples were respectively observed under a scanning electron microscope after cells were fixed by using a fixing solution 12h and 24h after inoculation, and then the samples were respectively inoculated on the surface of the PTO25 composite material prepared in example 10, the PTO50 composite material prepared in example 11, and the surface of the polyetheretherketone material prepared in comparative example 2 (all the samples are round pieces (diameter is 12mm and thickness is 2mm) with the same specification prepared in a mold with diameter of 12mm and thickness of 2mm), and the cell adhesion conditions are respectively observed after the cells are respectively inoculated on the polyetheretherketone group for 12h and 24h, as shown in fig. 17, wherein, a diagram and d diagram are respectively the cell adhesion conditions after the cells are inoculated on the polyetheretherketone group; panel b and panel e show the cell adhesion condition after the PTO25 composite material group is inoculated with cells for 12h and 24h respectively; and the c picture and the f picture respectively show the cell adhesion condition after the PTO50 composite material group is inoculated with the cells for 12h and 24 h. The cell adhesion rate data is shown in Table 10.

The cell adhesion rate was calculated in the same manner as in example 3.

Watch 10

Group of	PEEK	PTO25	PTO50
				Cell adhesion Rate/% (12h)	10.2±1.1	32.3±1.6*	45.1±3.1**
Cell adhesion Rate/% (24h)	39.2±5.2	50.1±7.7*	69.7±7.5**

Note: compared to the PEEK group,: p <0.05, x: p < 0.01.

As can be seen from fig. 17 and table 10, the PTO25 material prepared in example 10 and the PTO50 material prepared in example 11 all have cell adhesion and proliferation on the surface, and the PTO50 material group has a larger number of adhered cells, a more extended cytoskeleton, more obvious filopodia, and a larger number of filopodia, and has a better adhesion morphology, indicating that the PTO50 material has better cell compatibility.

Effect example 9 cell differentiation experiment

The cell differentiation test was carried out using the PTO50 material obtained in example 11 and the PEEK material obtained in comparative example 2 as samples, which were all wafers of the same size (12 mm in diameter and 2mm in thickness) prepared in a mold having a diameter of 12mm and a thickness of 2 mm.

The specific method of the cell differentiation experiment was the same as that of example 4:

TABLE 11

Group of	PEEK	PTO50
			ALP Activity (D1)	0.050±0.0032	0.064±0.0020*
ALP Activity (D7)	0.106±0.0028	0.174±0.0030*
			ALP Activity (D14)	0.175±0.0046	0.273±0.0016*

Note: d1, D7 and D14 represent ALP activity measured after 1, 7 and 14 days of cell culture, respectively; compared to the PEEK group,: p < 0.05.

As can be seen from table 11 and fig. 18, the ALP activity of the cells was gradually increased in both the PT50 material prepared in example 11 and the PEEK material prepared in comparative example 2 as the cell culture time was prolonged. Overall, the cell differentiation activity of the composite material group was higher compared to the PEEK material group. It was found that the PT50 material obtained in example 11 of the present application has a good effect of promoting cell differentiation.

The composite bone repair material/bone prosthesis may also be prepared according to the following formulation shown in table 12, wherein vt% refers to the volume percentage in the raw material composition.

TABLE 12

Example 20

Raw materials: mixing 7.62kg of tantalum powder with the volume fraction of 20% and the particle size of 1-3 mu m with 2.38kg of polyether ketone powder with the volume fraction of 80% and the particle size of 30-40 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1 (using a mold for dental implants). The mechanical properties of the composite bone prosthesis are shown in table 13.

Example 21

Raw materials: 8.46kg of tantalum powder with the volume fraction of 30% and the particle size of 1-3 mu m and 1.54kg of polyether ketone powder with the volume fraction of 70% and the particle size of 30-40 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1 (mold for artificial joint). The mechanical properties of the composite bone prosthesis are shown in table 13.

Example 22

Raw materials: 8.95kg of tantalum powder with the volume fraction of 40% and the particle size of 1-3 mu m and 1.05kg of polyether ketone powder with the volume fraction of 60% and the particle size of 30-40 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1 (using a mold for spinal bone prosthesis). The mechanical properties of the composite bone prosthesis are shown in table 13.

Example 23

Raw materials: mixing 7.30kg of tantalum oxide powder with the volume fraction of 30% and the particle size of 500 nm-1 mu m with 2.70kg of polyether-ether-ketone powder with the volume fraction of 70% and the particle size of 10-15 mu m by using a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the composite are shown in Table 13.

Example 24

Raw materials: 8.08kg of tantalum oxide powder with the volume fraction of 40% and the particle size of 500 nm-1 mu m and 1.92kg of polyether-ether-ketone powder with the volume fraction of 60% and the particle size of 10-15 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the composite are shown in Table 13.

Example 25

Raw materials: 9.28kg of tantalum powder with the volume fraction of 50% and the particle size of 500 nm-1 mu m and 1.54kg of polyether ketone powder with the volume fraction of 50% and the particle size of 20-30 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1 (using a mold for dental implants). The mechanical properties of the composite bone prosthesis are shown in table 13.

Example 26

Raw materials: 8.63kg of tantalum oxide powder with the volume fraction of 50% and the particle size of 1-3 mu m and 1.37kg of polyether-ether-ketone powder with the volume fraction of 50% and the particle size of 5-10 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the composite are shown in Table 13.

Comparative example 6

Raw materials: 9.28kg of tantalum powder with the volume fraction of 50% and the particle size of 50-100 nm and 0.72kg of polyether ketone powder with the volume fraction of 50% and the particle size of 30-40 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1 (mold for artificial joint). The mechanical properties of the composite bone prosthesis are shown in table 13.

Comparative example 7

Raw materials: 9.28kg of tantalum powder with the volume fraction of 50% and the particle size of 5-50 mu m and 0.72kg of polyether ketone powder with the volume fraction of 50% and the particle size of 30-40 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1 (using a mold for dental implants). The mechanical properties of the composite bone prosthesis are shown in table 13.

Comparative example 8

Raw materials: 8.63kg of tantalum oxide powder with the volume fraction of 50% and the particle size of 50-100 nm and 1.37kg of polyether-ether-ketone powder with the volume fraction of 50% and the particle size of 10-15 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the composite are shown in Table 13.

Comparative example 9

Raw materials: 8.63kg of tantalum oxide powder with the volume fraction of 50% and the particle size of 5-50 mu m and 1.37kg of polyether-ether-ketone powder with the volume fraction of 50% and the particle size of 10-15 mu m are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the composite are shown in Table 13.

Comparative example 10

Raw materials: 9.51kg of tantalum powder with volume fraction of 60% and particle size of 1-3 μm and 1.54kg of polyether ketone powder with volume fraction of 40% and particle size of 30-40 μm are mixed by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1 (mold for artificial joint). The mechanical properties of the composite bone prosthesis are shown in table 13.

Comparative example 11

Raw materials: mixing 9.04kg of tantalum oxide powder with volume fraction of 60% and particle size of 500 nm-1 μm and 0.96kg of polyether-ether-ketone powder with volume fraction of 40% and particle size of 10-15 μm by a high-speed mixer to obtain mixed powder; the rest of the procedure was the same as in example 1. The mechanical properties of the composite are shown in Table 13.

Effect example 10

The mechanical properties of the composite bone repair material/bone prosthesis prepared according to the formulation shown in table 12 are shown in table 13, and the test methods are the same as those of example 1.

TABLE 13 mechanical Properties of composite bone repair materials/bone prostheses of examples 20 to 26 and comparative examples 6 to 11

As can be seen from table 13:

(1) from examples 20 to 22, it can be seen that the composite bone repair material/bone prosthesis prepared from tantalum powder and polyether ketone powder at a volume ratio of 1:4, 3:7 and 4:6 has an elastic modulus of 4.0 to 4.2GPa, a compressive strength of 128 to 140MPa, a tensile strength of 84 to 91MPa, a bending strength of 73 to 78MPa, and excellent mechanical properties equivalent to human bones;

(2) from examples 23 to 24, it can be seen that the composite bone repair material/bone prosthesis prepared from tantalum oxide powder and polyether ether ketone powder at a volume ratio of 3:7 to 4:6 has an elastic modulus of 4.6 to 5.3GPa, a compressive strength of 132 to 139MPa, a tensile strength of 82 to 84MPa, a bending strength of 73 to 76MPa, and excellent mechanical properties equivalent to human bone;

(3) from examples 25 to 26, the particle size of the tantalum powder is 500nm to 1 μm, the particle size of the tantalum oxide powder is 1 to 3 μm, and the prepared composite bone repair material/bone repair body has excellent mechanical properties and is equivalent to human bones;

(4) as can be seen from comparative examples 6 to 9, when the particle size of the tantalum material (tantalum powder, tantalum oxide powder) is not in the range of 100nm to5 μm, the prepared composite bone repair material/bone prosthesis has poor mechanical properties, and the elastic modulus, compressive strength, tensile strength and bending strength can not meet the requirements of the mechanical properties of human bones;

(5) as can be seen from comparative examples 10 to 11, when the volume ratio of the tantalum material to the polyaryletherketone is not in the range of (1:4) to (1:1), the prepared composite bone repair material/bone repair body has poor mechanical properties, and the elastic modulus, the compressive strength, the tensile strength and the bending strength do not meet the requirements of the mechanical properties of human bones.

Effect example 11

The cell adhesion rates of the composite bone repair material/bone prosthesis prepared according to the formulation shown in Table 12 are shown in Table 14, and the test methods are the same as those of example 3.

TABLE 14

Group of	Cell adhesion Rate/% (12h)	Cell adhesion Rate/% (24h)
			Example 20	26.3±1.3	44.1±0.7
Example 21	34.7±2.1	53.3±1.5
			Example 22	35.4±1.7	62.6±2.2
Example 23	28.4±0.9	50.7±1.7
			Example 24	33.3±1.2	59.8±1.8
Example 25	36.4±1.4	68.6±0.9
			Example 26	36.2±0.5	66.7±1.4
Comparative example 6	27.7±2.1	40.9±0.5
			Comparative example 7	21.9±1.3	40.1±1.5
Comparative example 8	38.3±1.8	51.0±2.1
			Comparative example 9	31.2±1.5	50.3±2.4

As can be seen from table 14:

(1) from examples 20 to 22, it can be seen that the cell adhesion rate of the composite bone repair material/bone repair body prepared by the tantalum powder and the polyether ketone powder in the volume ratio of 1:4, 3:7 and 4:6 after the composite bone repair material/bone repair body is inoculated to the rat bone marrow mesenchymal stem cells for 24 hours can reach 44.1 to 62.6 percent;

(2) from examples 23 to 24, it can be seen that the cell adhesion rate of the composite bone repair material/bone repair body prepared by the tantalum oxide powder and the polyether ether ketone powder can reach 50.7 to 59.8% after rat bone marrow mesenchymal stem cells are inoculated for 24 hours at the volume ratio of 3:7 and 4: 6;

(3) from example 25, it can be seen that the cell adhesion rate of the composite bone repair material/bone prosthesis prepared with the tantalum powder having the particle size of 500nm to 1 μm is significantly improved after the rat mesenchymal stem cells are inoculated for 24 hours, compared with the composite bone repair material/bone prosthesis prepared with the tantalum powder having the particle size of 1 to 3 μm (see table 4);

(4) from example 26, it can be seen that, compared with the composite bone repair material/bone prosthesis prepared with tantalum oxide powder having a particle size of 500nm to 1 μm (see table 10), the cell adhesion rate of the composite bone repair material/bone prosthesis prepared with tantalum oxide powder having a particle size of 1 to 3 μm after being inoculated with rat mesenchymal stem cells for 24 hours has no significant change;

(5) as can be seen from comparative examples 6-9, when the particle size of the tantalum material (tantalum powder, tantalum oxide powder) is larger than 5 μm or smaller than 100nm, the cell adhesion rate of the prepared composite bone repair material/bone repair body is significantly reduced.

Effect example 12

The cell adhesion ability and the cell differentiation ability of each sample were measured using the sulfonated PEKK bone prosthesis, the sulfonated PT25 bone prosthesis, and the sulfonated PT50 bone prosthesis prepared in example 7, the coated PT25 bone prosthesis prepared in example 8, the photo-etched PT50 bone prosthesis prepared in example 9, the sand-blasted PEEK bone prosthesis, the sand-blasted PTO25 bone prosthesis, and the sand-blasted PTO50 bone prosthesis prepared in example 17, the sulfonated PEEK bone prosthesis, the sulfonated PTO25 bone prosthesis, and the sulfonated PTO50 bone prosthesis prepared in example 18, and the coated PTO50 bone prosthesis prepared in example 19, according to the test methods in effect example 3 and effect example 4. The above samples were all wafers of the same specification (12 mm diameter and 2mm thickness) made in a 12mm diameter and 2mm thickness die.

The cell adhesion data of the above samples are shown in Table 15, and the cell adhesion rate was calculated in the same manner as in example 3.

The cell differentiation data for each of the above samples are shown in Table 16.

Watch 15

Note: compared to the PEKK group,: p <0.05, x: p < 0.01; compared to PEEK group, #: p <0.05, # #: p < 0.01.

As can be seen from table 15:

(1) compared with the bone repair body without surface treatment in tables 4 and 10, after the bone repair body in the application is subjected to sulfonation treatment, the cell adhesion rate is slightly improved at 12h, the cell adhesion rate is obviously improved at 24h, and the improvement amplitudes are ordered as follows: sulfonated PT50 is more than sulfonated PT 25; sulfonated PTO50 > sulfonated PTO 25; after the PEKK and PEEK are sulfonated, the cell adhesion rate has no obvious change;

(2) compared with the bone restoration body without surface treatment in the tables 4 and 10, the cell adhesion rate is obviously improved after the bone restoration body is subjected to coating treatment for 12 hours; after photoetching treatment, the cell adhesion rate is remarkably improved in 12 h; after sand blasting treatment, the cell adhesion rate is slightly improved in 12h, the cell adhesion rate is obviously improved in 24h, and the improvement range is ordered as follows: sandblasting PTO5 > sandblasting PTO25 > sandblasting PEEK;

(3) different surface treatment modes can effectively improve the cell adhesion rate, and the surface coating and the surface photoetching treatment can more obviously improve the cell adhesion rate of the composite material/composite bone repair body.

TABLE 16

Note: d1, D7 and D14 represent ALP activity measured after 1, 7 and 14 days of cell culture, respectively; compared to the PEKK group,: p <0.05, x: p < 0.01; compared to PEEK group, #: p <0.05, # #: p < 0.01.

As can be seen from table 16:

(1) compared with the bone repair body without surface treatment in tables 5 and 11, after sulfonation treatment, the cell ALP activity is remarkably improved after 7 days of cell culture, the cell ALP activity is more remarkably improved after 14 days, and the improvement amplitudes are ordered as follows: sulfonated PT50 is more than sulfonated PT25 is more than sulfonated PEKK; sulfonated PTO50 > sulfonated PTO25 > sulfonated PEEK;

(2) compared with the bone repair body without surface treatment in the tables 5 and 11, the ALP activity of the cells of the coating PT25 bone repair body is slightly improved after 7 days of cell culture, and the ALP activity of the cells is obviously improved after 14 days; the ALP activity of cells is remarkably improved after 7 days of culture of the coated PTO50 bone repair cells, and the ALP activity of cells is remarkably improved after 14 days;

(3) compared with the bone repair body without surface treatment in the table 5, after photoetching treatment, the ALP activity of the cells is slightly improved after 7 days of cell culture, and the ALP activity of the cells is obviously improved after 14 days;

(4) compared with the bone prosthesis without surface treatment in the table 11, the PTO50 bone prosthesis after sand blasting treatment has the advantages that the cell ALP activity is obviously improved after 7 days of cell culture, the cell ALP activity is more obviously improved after 14 days, and the cell ALP activity is only slightly improved after 7 days of cell culture in the PEEK bone prosthesis after sand blasting treatment;

(5) different surface treatment modes can effectively improve the cell adhesion rate, and the cell adhesion rate of the composite material/composite bone restoration body can be improved more remarkably through sulfonation treatment, surface coating and sand blasting treatment.

In the above examples, polyetherketoneketone powder (30 to 40 μm); polyether-ether-ketone powder (10-15 mu m)); tantalum powder (1-3 μm); the particle size distribution of tantalum oxide powder (500nm to 1 μm) is shown in Table 17.

TABLE 17

The above description is only a preferred embodiment of the present invention, and does not limit the present invention in any way. It will be understood by those skilled in the art that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims

1. A bone repair material, characterized in that it comprises the following components: tantalum material powder and polyaryletherketone powder;

the tantalum material powder is tantalum powder, the polyaryletherketone powder is PEKK powder, and the volume ratio of the tantalum powder to the PEKK powder is (1:3) - (1: 1); the particle size of the tantalum powder is 500 nm-5 mu m, and the particle size of the PEKK powder is 20-40 mu m;

or the tantalum material powder is tantalum oxide powder, the polyaryletherketone powder is PEEK powder, and the volume ratio of the tantalum oxide powder to the PEEK powder is (1:3) - (1: 1); the particle size of the tantalum oxide powder is 100 nm-3 mu m, and the particle size of the PEEK powder is 5-15 mu m.

2. The bone repair material according to claim 1, wherein when the tantalum material powder is a tantalum powder, the particle size of the tantalum material powder is 500nm to 1 μm or 1 to 3 μm;

and/or when the tantalum material powder is tantalum oxide powder, the particle size of the tantalum material powder is 500 nm-1 mu m or 1-3 mu m;

and/or the PEKK is model OXPEKK-C available from Oxford Performance Materials, USA;

and/or the PEEK is VICTREX model 450PF available from Wegener, UK.

3. The bone repair material of claim 1, wherein when the polyaryletherketone powder is PEKK powder, the particle size of the PEKK powder is 20-30 μm or 30-40 μm;

and/or when the polyaryletherketone powder is PEEK powder, the particle size of the PEEK powder is 5-10 mu m or 10-15 mu m.

4. The bone repair material of claim 1, wherein when the tantalum material powder is a tantalum powder and the polyaryletherketone powder is a PEKK powder, the volume ratio of the tantalum powder to the PEKK powder is 1:3, 3:7, 2:3 or 1: 1;

and/or when the tantalum material powder is tantalum oxide powder and the polyaryletherketone powder is PEEK powder, the volume ratio of the tantalum oxide powder to the PEEK powder is 1:3, 3:7, 2:3 or 1: 1.

5. The bone repair material of claim 1, wherein when the tantalum material powder is tantalum powder and the polyaryletherketone powder is PEKK powder, the composition of the bone repair material comprises 20-50% by volume of the tantalum powder and 50-80% by volume of the PEKK powder;

and/or when the tantalum material powder is tantalum oxide powder and the polyaryletherketone powder is PEEK powder, in the components of the bone repair material, the volume fraction of the tantalum oxide powder accounts for 25-50%, and the volume fraction of the PEEK powder accounts for 50-75%.

6. Use of the bone repair material according to any one of claims 1 to5 as a raw material for producing a bone repair.

7. Use of the bone repair material according to claim 6 as a raw material for producing a bone repair, wherein the bone repair is a spinal bone repair, a dental implant or an artificial joint.

8. Use of the bone repair material as a raw material for preparing a bone repair according to claim 7, wherein the spinal bone repair comprises a cervical interbody fusion cage and a thoracic/lumbar interbody fusion cage.

9. The preparation method of the bone repair material is characterized by comprising the following steps: shaping the component of the bone repair material according to any one of claims 1 to 5.

10. The method of claim 9, wherein the forming comprises extrusion, injection molding, compression sintering, or hot pressing.

11. The method of preparing a bone repair material according to claim 10 wherein the extrusion molding comprises the steps of: the components of the bone repair material are mixed and extruded and molded in a double-screw extruder.

12. The method for preparing a bone repair material according to claim 11, wherein the temperature of the extrusion molding is 340 to 380 ℃; and/or the pressure of the extrusion molding is 80-100 MPa.

13. The method of preparing a bone repair material according to claim 10 wherein the injection molding comprises the steps of: the components of the bone repair material are mixed, extruded and granulated in a double-screw extruder to prepare bone repair material particles, and then the bone repair material particles are molded in an injection molding machine.

14. The method for preparing a bone repair material according to claim 13, wherein the temperature of the extrusion granulation is 340 to 380 ℃;

and/or the pressure of the extrusion granulation is 80-100 MPa;

and/or the injection molding temperature is 350-380 ℃;

and/or the pressure of the injection molding is 80-120 MPa.

15. The method for preparing a bone repair material according to claim 14, wherein the pressure of the injection molding is 100 to 120 MPa.

16. The method for preparing a bone repair material according to claim 10 wherein the compression sintering molding comprises the steps of: mixing the components of the bone repair material, pressing and forming, then heating, and sintering and forming.

17. The method for preparing a bone repair material according to claim 16, wherein the temperature of the sintering molding is 340-380 ℃;

and/or the sintering molding is carried out in a sintering furnace, the temperature rising speed of the sintering furnace is 0.5-2 ℃/min, and the heat preservation time of the sintering furnace is 2-5 h.

18. The method for preparing a bone repair material according to claim 10, wherein the hot press forming comprises the steps of: and (3) pressing and molding the components of the bone repair material under the heating condition.

19. The method for preparing a bone repair material according to claim 18 wherein the temperature of the pressing is 360 to 380 ℃;

and/or the pressing pressure is 2-5 MPa;

and/or the heat preservation time of the pressing is 0.5-1 h.

20. A bone repair material produced by the method of producing a bone repair material according to any one of claims 9 to 19.

21. The preparation method of the bone prosthesis is characterized by comprising the following steps: the bone repair material as set forth in any one of claims 1 to5, which is formed by molding the components in a mold for a bone repair product.

22. The method for producing a bone prosthesis according to claim 21, wherein the mold for a bone prosthesis product is a mold for a spinal bone prosthesis, a mold for a dental implant or a mold for an artificial joint;

and/or the forming operations and conditions are as defined in any one of claims 9 to 19;

and/or in the preparation method of the bone repair body, the surface of the bone repair body prepared after processing and forming is also subjected to sand blasting treatment;

and/or in the preparation method of the bone repair body, the surface of the bone repair body prepared after processing and forming is also subjected to photoetching treatment; the photoetching treatment comprises the following steps: performing femtosecond laser photoetching on the surface of the bone repair body to form a groove structure on the surface of the bone repair body;

and/or in the preparation method of the bone repair body, the surface of the bone repair body prepared after processing and forming is also sulfonated;

and/or in the preparation method of the bone restoration, the surface of the bone restoration prepared after processing and forming is further subjected to coating treatment.

23. The method of producing a bone prosthesis set forth in claim 22, wherein said spinal bone prosthesis includes a cervical interbody fusion cage and a thoracic/lumbar interbody fusion cage;

and/or when the surface of the bone restoration prepared after the processing and shaping is also subjected to sand blasting in the preparation method of the bone restoration, the sand blasting comprises the following steps: performing surface sand blasting on the bone restoration to form a porous structure on the surface of the bone restoration;

and/or when the surface of the processed and molded bone prosthesis is subjected to photoetching treatment in the preparation method of the bone prosthesis, the output wavelength of the femtosecond laser is 800nm, the pulse width is 300fs, the frequency is 1000Hz, the optical power is 20mW, and the scanning speed is 600 mu m/s; and/or the width of the groove structure is 20-60 mu m, the depth is 10 mu m, and the distance is 40 mu m;

and/or, when the surface of the bone repair body prepared after processing and shaping is further sulfonated in the preparation method of the bone repair body, the sulfonation treatment comprises the following steps: soaking the bone restoration body in concentrated sulfuric acid until the surface of the bone restoration body forms a porous structure;

and/or, when the surface of the bone repair body prepared after processing and shaping is further subjected to coating treatment in the preparation method of the bone repair body, the coating treatment comprises the following steps: the method comprises the following steps: soaking the bone prosthesis in a suspension of tantalum powder and/or tantalum oxide powder, and then drying and sintering the bone prosthesis; the second method comprises the following steps: and sintering the bone prosthesis in tantalum powder and/or tantalum oxide powder to obtain the bone prosthesis.

24. The method for manufacturing a bone prosthesis according to claim 23, wherein when the surface of the molded bone prosthesis is further subjected to sand blasting in the method for manufacturing a bone prosthesis, the pore size of the porous structure is 50 to 100 μm; and/or spraying sand materials on the surface sand blasting machine, wherein the particle size of the sand materials is 20-50 mu m;

and/or when the surface of the processed and molded bone prosthesis is further sulfonated in the preparation method of the bone prosthesis, the mass fraction of sulfuric acid in the concentrated sulfuric acid is 90-100%; and/or the soaking time is 10-25 min; and/or the pore size of the porous structure is 1-5 mu m; and/or carrying out hydrothermal treatment after the sulfonation treatment, wherein the temperature of the hydrothermal treatment is 120 ℃, and the time is 4 hours;

and/or, when the surface of the bone repair body prepared after processing and forming is further subjected to coating treatment in the preparation method of the bone repair body, in the first method, the solvent of the suspension is ethanol; and/or in the first method, the mass percent of the tantalum powder and/or the tantalum oxide powder in the suspension is 5-10%; and/or in the first method, the soaking time is 24 hours; and/or in the first method or the second method, the temperature rise speed of the sintering is 0.5-2 ℃/min, and/or the temperature of the sintering is 365-380 ℃, and/or the heat preservation time after the sintering is 2-5 h.

25. The method for producing a bone prosthesis according to claim 24, wherein when the surface of the molded bone prosthesis is further sulfonated in the method for producing a bone prosthesis, the mass fraction of sulfuric acid in the concentrated sulfuric acid is 95 to 98%;

and/or, when the surface of the bone prosthesis prepared after processing and forming is further subjected to coating treatment in the preparation method of the bone prosthesis, in the first method, the mass percent of the tantalum powder and/or the tantalum oxide powder in the suspension is 10%; and/or in the first method or the second method, the particle size of the tantalum powder is 1-3 mu m, and the particle size of the tantalum oxide powder is 500 nm-1 mu m.

26. A bone prosthesis produced by the method for producing a bone prosthesis according to any one of claims 21 to 25.