Medical-grade polyether-ether-ketone / hydroxyapatite compound powder for selective laser sintering (SLS) and preparation method of medical-grade polyether-ether-ketone / hydroxyapatite compound powder

Abstract

The invention relates to medical-grade polyether-ether-ketone / hydroxyapatite compound powder for selective laser sintering (SLS) and a preparation method of the medical-grade polyether-ether-ketone / hydroxyapatite compound powder, and belongs to the field of biological medicine. Specifically, the invention provides medical grade polyether-ether-ketone / hydroxyapatite compound powder, and the medical grade polyether-ether-ketone / hydroxyapatite compound powder comprises polyether-ether-ketone particles and hydroxyapatite distributed on the surfaces of the polyether-ether-ketone particles, wherein the volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite compound powder is in a range of 30 microns to 60 microns, and the particle size distribution span Span of the polyetheretherketone / hydroxyapatite compound powder is less than 2.0, where Span = (Dv90-Dv10) / Dv50. The medical-grade polyether-ether-ketone / hydroxyapatite compound powder can be used for preparing bone implants or bone repair scaffolds with excellent mechanical properties and biocompatibility.

Description

Technical Field

[0001] This application relates to the field of medical biomaterials. Specifically, this application relates to a medical-grade polyetheretherketone / hydroxyapatite composite powder for SLS technology and a method for preparing the same. The resulting composite powder has a uniform morphology and excellent flowability, meeting the application requirements of SLS technology. Background Technology

[0002] Polyetheretherketone (PEEK), as a polymer material, exhibits excellent biocompatibility, chemical stability, and superior mechanical properties. Furthermore, PEEK is X-ray permeable and maintains its physicochemical properties unchanged over long periods under conditions such as high-temperature steam, gamma rays, and ethylene oxide. Therefore, PEEK materials have been widely used in clinical medicine. PEEK is non-toxic, corrosion-resistant, lightweight, and high-strength, with an elastic modulus (3-4 GPa) similar to that of human bone (14 GPa for compact bone and 1 GPa for trabecular bone), making it an ideal material to replace metals in the manufacture of human bones. However, PEEK lacks bioactivity, which limits its application in the medical field to some extent. Hydroxyapatite (HA), as the main matrix component of natural bone, has the chemical formula Ca5(PO4)3(OH), more commonly represented as Ca10(PO4)6(OH)2, indicating a crystal structure composed of two molecules. As a major inorganic mineral in bone tissue, hydroxyapatite does not trigger inflammatory responses or cause cell mutations in the body. Under the influence of bodily fluids, calcium and phosphate ions from hydroxyapatite are released, exchange substances with the body, participate in metabolic processes, and are absorbed by body tissues. They then form chemical bonds with human bone tissue, promoting the growth of new tissue. Therefore, developing polyetheretherketone (PEEK) / hydroxyapatite composite materials is an ideal approach that combines mechanical properties with bioactivity.

[0003] Selective laser sintering (SLS) 3D printing technology falls under the category of rapid prototyping. Based on digital modeling, it utilizes powdered metals or plastics to build objects layer by layer. The SLS process requires a melting and crystallization temperature difference (sintering window) greater than 20°C. Preheating begins at the crystallization temperature during powder preparation, followed by holding at near the melting point to optimize sintering quality. This technology can fabricate complex three-dimensional structures, making it particularly suitable for personalized, porous bone implants. However, SLS technology places extremely high demands on the processing properties of the powder materials, requiring not only uniform powder morphology but also excellent powder flowability.

[0004] Current methods for preparing polyetheretherketone / hydroxyapatite composite powders, such as mechanical mixing and solvent mixing, have significant drawbacks: the hydroxyapatite in the resulting powder is unevenly dispersed and prone to agglomeration, resulting in weak interfacial bonding with the polyetheretherketone matrix; the powder morphology is irregular and the flowability is poor, leading to uneven SLS powder spreading and unstable sintering quality; and the solvent method may introduce harmful residues, affecting biocompatibility.

[0005] Therefore, there is an urgent need to develop a novel polyetheretherketone / hydroxyapatite composite powder that achieves uniform dispersion and strong interfacial bonding of hydroxyapatite on the surface of polyetheretherketone particles in its microstructure, and meets the stringent requirements of the SLS process for powder flowability in terms of macroscopic properties. Summary of the Invention

[0006] This application provides a medical-grade polyetheretherketone / hydroxyapatite composite powder for SLS technology and a method for preparing the same. The composite powder not only has a uniform powder morphology, but also has excellent powder flowability, bulk density and mechanical properties.

[0007] In a first aspect, this application provides a polyetheretherketone / hydroxyapatite composite powder, the polyetheretherketone / hydroxyapatite composite powder comprising polyetheretherketone particles and hydroxyapatite distributed on the surface of the polyetheretherketone particles, wherein the volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder is in the range of 30 micrometers to 60 micrometers, and the particle size distribution span Span of the polyetheretherketone / hydroxyapatite composite powder is less than 2.0, wherein Span = (Dv90 - Dv10) / Dv50.

[0008] By controlling the volume distribution particle size Dv50 and particle size distribution span Span of the polyetheretherketone / hydroxyapatite composite powder within the aforementioned ranges, the powder not only possesses excellent flowability and high packing density, but also enables rapid and uniform powder spreading, a dense and flat powder layer, and consistent and controllable sintering behavior in the SLS process. Therefore, the polyetheretherketone / hydroxyapatite composite powder of the embodiments of this application is particularly suitable for selective laser sintering (SLS) technology.

[0009] In some embodiments, the particle size distribution span of the polyetheretherketone / hydroxyapatite composite powder is less than 1.8 but not less than 1.2.

[0010] In some embodiments, the particle size distribution span of the polyetheretherketone / hydroxyapatite composite powder is between 1.2 and 1.6.

[0011] In some embodiments, the particle size distribution span of the polyetheretherketone / hydroxyapatite composite powder is between 1.3 and 1.6.

[0012] In some embodiments, the volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder is in the range of 40 micrometers to 55 micrometers.

[0013] In some embodiments, the polyetheretherketone / hydroxyapatite composite powder satisfies one or more of the following properties, preferably both: an angle of repose not greater than 48°, preferably between 42° and 48°; and / or not less than 35 g / cm³. 3 The bulk density is preferably between 38 g / cm³. 3 Up to 45 g / cm 3 The packing density.

[0014] In some embodiments, the hydroxyapatite in the polyetheretherketone / hydroxyapatite composite powder is grown in situ on the surface of polyetheretherketone particles at the nanoscale.

[0015] In some embodiments, the hydroxyapatite is present in the polyetheretherketone / hydroxyapatite composite powder in an amount of 10% to 30% by weight relative to the total weight of the polyetheretherketone / hydroxyapatite composite powder.

[0016] In some embodiments, the polyetheretherketone / hydroxyapatite composite powder is in the form of spherical or near-spherical particles. In some embodiments, the polyetheretherketone / hydroxyapatite composite powder is substantially free of agglomerated hydroxyapatite.

[0017] Secondly, this application provides a method for preparing the polyetheretherketone / hydroxyapatite composite powder according to the first aspect of this application, the method comprising the following steps: S1. Provide polyetheretherketone (PEEK) granules; S2. The polyether ether ketone particles are surface modified, and an aqueous solution of the raw material used to form hydroxyapatite is used to conduct a biomimetic mineralization reaction on the surface of the polyether ether ketone particles to obtain a primary composite powder. S3. The primary composite powder is spheroidized to obtain the composite powder.

[0018] In the method according to this application, by modifying the surface of polyetheretherketone (PEEK) particles, the precursor material of hydroxyapatite can be grown in situ on the surface of the PEEK particles, thereby forming good interfacial bonding. Furthermore, by spheroidizing the formed primary composite powder, the sphericity, flowability, bulk density, and / or sintering stability of the obtained composite powder are synergistically improved. This results in a PEEK / hydroxyapatite composite powder with a volume distribution particle size Dv50 in the range of 30 to 60 micrometers and a particle size distribution span of less than 2.0, which is particularly suitable for selective laser sintering (SLS) technology.

[0019] In some embodiments, in step S2 of the method, the surface modification includes impregnating the polyetheretherketone particles with an aqueous solution of a bio-based surfactant, wherein the bio-based surfactant is selected from one or more of gelatin, collagen, and silk fibroin, preferably present at a concentration of 0.3 mg / mL to 0.8 mg / mL.

[0020] In some embodiments, in step S2 of the method, the raw material used to form hydroxyapatite is in the form of an aqueous solution. Optionally, the raw material includes an aqueous solution of a calcium source and an aqueous solution of a phosphate, wherein the calcium source includes calcium chloride, and the phosphate includes an alkali metal hydrogen phosphate, preferably disodium hydrogen phosphate. Preferably, the concentration of the aqueous solution of the raw material used to form hydroxyapatite is in the range of 20 mg / mL to 80 mg / mL.

[0021] In some embodiments, in step S3 of the method, the spheroidizing treatment is achieved by subjecting the primary composite powder to hydrothermal treatment in a sealed container at a high temperature of 150°C to 250°C and a high pressure of 5 MPa to 12 MPa in the presence of an aqueous solvent. Preferably, the aqueous solvent includes water, C1-C4 alkyl alcohols, or combinations thereof.

[0022] The third aspect of this application provides the application of polyetheretherketone / hydroxyapatite composite powder prepared according to the method of the first aspect of this application or according to the method of the second aspect of this application in selective laser sintering 3D printing technology.

[0023] The fourth aspect of this application provides a method for manufacturing a bone implant or bone repair scaffold, the method comprising: using polyetheretherketone / hydroxyapatite composite powder according to the first aspect of this application or polyetheretherketone / hydroxyapatite composite powder prepared according to the method of the second aspect of this application as raw material, and then shaping the raw material by selective laser sintering 3D printing technology.

[0024] The fifth aspect of this application provides a bone implant or bone repair scaffold made from polyetheretherketone / hydroxyapatite composite powder prepared according to the first aspect of this application or polyetheretherketone / hydroxyapatite composite powder prepared according to the method of the second aspect of this application by selective laser sintering 3D printing technology.

[0025] The bone implants or bone repairs of this application contain the polyetheretherketone / hydroxyapatite provided in this application, and thus have at least the same advantages as the polyetheretherketone / hydroxyapatite.

[0026] Compared with the prior art, the method of the present invention has at least the following advantages and beneficial effects: 1. The preparation of hydroxyapatite / PEEK composites typically involves physical blending or dispersion in a specific solvent. By adding bio-based surfactants, in-situ growth sites are provided for hydroxyapatite, thereby forming good interfacial bonding. This increases the steric hindrance potential energy between particles and effectively reduces the aggregation of hydroxyapatite.

[0027] 2. The in-situ growth process of hydroxyapatite uses water as the reaction medium, which is not only environmentally and human-friendly, but also does not affect the biocompatibility of the hydroxyapatite / polyetheretherketone / composite powder material. The surfactant transforms the PEEK surface from hydrophobic to hydrophilic, and the abundant negatively charged groups can attract Ca... 2+ Cations provide initial sites for HA growth, enabling HA to grow in situ on the PEEK surface through a biomimetic mineralization process.

[0028] 3. After high-temperature treatment, sufficient heat energy and medium are provided to the powder, enabling the particles to recombine and tend towards a spherical shape with lower surface energy. This makes the powder morphology increasingly regular. As the pressure inside the reactor increases, the agglomeration of PEEK powder decreases, and the sharp edges of the powder surface gradually disappear. In addition, the sintering window of the powder is significantly improved, and the bulk density reaches 35 g / cm³. 3 The above results show that the high-temperature powder spreading effect is significantly improved. Attached Figure Description

[0029] To more clearly illustrate the technical solutions of the embodiments of this application, the drawings used in the embodiments of this application will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on the drawings without creative effort.

[0030] Figure 1 This is a particle size distribution diagram of the polyetheretherketone / hydroxyapatite composite powder prepared in Example 2 of this application.

[0031] Figure 2This is a particle size distribution diagram of the polyetheretherketone / hydroxyapatite composite powder prepared in Comparative Example 2 of this application.

[0032] Figure 3 The image shows a low-magnification SEM (scanning electron microscope) image of the polyether ether ketone / hydroxyapatite composite powder prepared in Example 2 of this application.

[0033] Figure 4 This is a high-magnification SEM (scanning electron microscope) image of the polyether ether ketone / hydroxyapatite composite powder prepared in Example 2 of this application. Detailed Implementation

[0034] The following detailed description, with appropriate reference to the accompanying drawings, discloses embodiments of the porous polyetheretherketone (PEEK) material, its preparation method, and related applications of this application. However, unnecessary details may be omitted. For example, detailed descriptions of well-known matters and repetitive descriptions of essentially the same structures may be omitted. This is to avoid unnecessarily lengthy descriptions and to facilitate understanding by those skilled in the art. Furthermore, the accompanying drawings and the following description are provided to enable those skilled in the art to fully understand this application and are not intended to limit the subject matter described herein.

[0035] The "range" disclosed in this application is defined by a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, which define the boundaries of a particular range. Ranges defined in this way can include or exclude endpoints and can be arbitrarily combined; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for a specific parameter, it is expected that ranges of 60-110 and 80-120 are also included. Furthermore, if minimum range values ​​of 1 and 2 are listed, and if maximum range values ​​of 3, 4, and 5 are listed, then the following ranges are all expected: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5. In this application, unless otherwise stated, the numerical range "ab" represents a shortened representation of any combination of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0-5" indicates that all real numbers between "0-5" have been listed in this article; "0-5" is simply a shortened representation of these numerical combinations. Furthermore, when a parameter is stated as an integer ≥2, it is equivalent to disclosing that the parameter is, for example, an integer such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0036] Unless otherwise specified, all embodiments and optional embodiments of this application may be combined with each other to form new technical solutions, and such technical solutions should be considered to be included in the disclosure of this application.

[0037] Unless otherwise specified, all technical features and optional technical features of this application may be combined to form new technical solutions, and such technical solutions shall be deemed to be included in the disclosure of this application.

[0038] Unless otherwise specified, all steps of this application may be performed sequentially or randomly, preferably sequentially. For example, the method includes steps (a) and (b), indicating that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, the method may also include step (c), indicating that step (c) may be added to the method in any order. For example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc.

[0039] Unless otherwise specified, the terms "comprising" and "including" as used in this application can be open-ended or closed-ended. For example, "comprising" and "including" can mean that other components not listed may also be included, or that only the listed components may be included.

[0040] Unless otherwise specified, the term "or" is inclusive in this application. For example, the phrase "A or B" means "A, B, or both A and B". More specifically, the condition "A or B" is satisfied by any of the following conditions: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0041] Unless otherwise specified, in this application, the terms "first," "second," "third," etc., are used to distinguish different objects, rather than to describe a specific order or primary / secondary relationship.

[0042] In this application, the terms "multiple", "various", etc., refer to two or more kinds.

[0043] Unless otherwise stated, the terms used in this application have the common meanings as commonly understood by those skilled in the art.

[0044] Unless otherwise stated, the values ​​of the parameters mentioned in this application can be determined using various testing methods commonly used in the art, for example, according to the testing methods given in the embodiments of this application. Unless otherwise stated, the test temperature is 25°C.

[0045] In this application, the term "polyetheretherketone" refers to a linear aromatic polymer compound whose molecular chain contains -O-aryl-O-aryl-CO-aryl linkages, wherein the aryl group includes, but is not limited to, phenyl, substituted phenyl, biphenyl, or other aromatic groups known to those skilled in the art. Therefore, polyetheretherketone can also be collectively referred to as polyaryletherketone.

[0046] In this application, “D-values”—D10, D50, D90, D95, and D99—are the particle sizes that divide a sample volume into a specified percentage when particles are arranged based on increasing particle size. For example, for a particle size distribution, the median is referred to as D50 (or x50 when following certain ISO guidelines). D50 is the particle size in micrometers that divides the distribution into the upper and lower halves of that diameter. Dv50 (or Dv0.5) is the median of the volume distribution. D10 describes a distribution in which 10 percent has smaller particle sizes and 90 percent has larger particle sizes. D90 describes a distribution in which 90 percent has smaller particle sizes and 10 percent has larger particle sizes. D95 describes a distribution in which 95 percent has smaller particle sizes and 5 percent has larger particle sizes. D99 describes a distribution in which 99 percent has smaller particle sizes and 1 percent has larger particle sizes. Unless otherwise stated herein, D10, D50, D90, D95, and D99 refer to D10, D50, D90, D95, and D99 respectively. v 50. D v 90. D v 95 and D v 99. The D value specified in this paper can be determined by laser diffraction particle size analysis.

[0047] In this application, the Span value refers to the degree of concentration of the powder particle size distribution, which is calculated by the formula (Dv90-Dv10) / Dv50. The smaller the value, the more uniform the particle size.

[0048] In the context of this application, the term "tensile strength of a material" refers to the maximum engineering stress that the material can withstand during tension. The tensile strength described above can be understood as the maximum ability of a material to resist tensile failure. In this application, the tensile strength of the material can be measured using methods known in the art. For example, it can be determined using ISO 527: Plastics—Determination of tensile properties.

[0049] In the context of this application, the term "flexural modulus / strength of a material" refers to the ratio of stress to strain within the elastic range when the material is subjected to bending deformation. The aforementioned flexural modulus can be understood as a measure of a material's ability to resist elastic bending deformation as a structural member, representing the bending stiffness of the structure. In this application, the flexural modulus of the material can be measured using methods known in the art. For example, it can be determined using ISO 178: "Plastics—Determination of flexural properties".

[0050] Polyetheretherketone / hydroxyapatite composite powder Selective laser sintering (SLS) 3D printing technology is a rapid prototyping technology based on digital modeling, utilizing powdered metals or plastics to build objects layer by layer. The SLS process requires a melting and crystallization temperature difference (sintering window) greater than 20°C. Preheating begins at the crystallization temperature during powder spreading, and the temperature is maintained near the melting point to optimize sintering quality. This technology can manufacture complex three-dimensional structures, and is particularly suitable for the fabrication of personalized, porous bone implants. SLS technology places extremely high demands on the processing properties of the powder materials, requiring not only uniform powder morphology but also good powder flowability. As described in the background section, currently known methods for preparing polyetheretherketone / hydroxyapatite composite powders have significant drawbacks: the resulting powder exhibits uneven dispersion and agglomeration of hydroxyapatite, resulting in weak interfacial bonding with the polyetheretherketone matrix; irregular powder morphology and poor flowability lead to uneven SLS powder spreading and unstable sintering quality; and solvent methods may introduce harmful residues, affecting biocompatibility.

[0051] To this end, through extensive experimental research, by controlling the volume distribution particle size Dv50 and particle size distribution span Span of the polyetheretherketone / hydroxyapatite composite powder within a specific range, not only is the powder exhibiting excellent flowability and high packing density, but it also enables rapid and uniform powder spreading, a dense and flat powder layer, and consistent and controllable sintering behavior in the SLS process. Therefore, a polyetheretherketone / hydroxyapatite composite powder particularly suitable for selective laser sintering (SLS) technology has been obtained.

[0052] According to embodiments of this application, a polyetheretherketone (PEEK) / hydroxyapatite composite powder is provided. The PEEK / hydroxyapatite composite powder comprises PEEK particles and hydroxyapatite distributed on the surface of the PEEK particles. The volume distribution particle size (Dv50) of the PEEK / hydroxyapatite composite powder is in the range of 30 to 60 micrometers, and the particle size distribution span (Span) of the PEEK / hydroxyapatite composite powder is less than 2.0, where Span = (Dv90 - Dv10) / Dv50. As described above, by controlling the volume distribution particle size (Dv50) and particle size distribution span (Span) of the PEEK / hydroxyapatite composite powder within specific ranges, not only is the powder exhibiting excellent flowability and high packing density, but it also enables rapid and uniform powder spreading, a dense and flat powder layer, and consistent and controllable sintering behavior in the SLS process. Therefore, a PEEK / hydroxyapatite composite powder particularly suitable for selective laser sintering (SLS) technology is obtained.

[0053] In embodiments of this application, the volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder is in the range of 30 micrometers to 60 micrometers. As an example, the volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder can be 30 micrometers, 31 micrometers, 32 micrometers, 33 micrometers, 34 micrometers, 35 micrometers, 36 micrometers, 37 micrometers, 38 micrometers, 39 micrometers, 40 micrometers, 41 micrometers, 42 micrometers, 43 micrometers, 44 micrometers, 45 micrometers, 46 micrometers, 47 micrometers, 48 ​​micrometers, 49 micrometers, 50 micrometers, 51 micrometers, 52 micrometers, 53 micrometers, 54 micrometers, 55 micrometers, 56 micrometers, 57 micrometers, 58 micrometers, 59 micrometers, or 60 micrometers, or fall within any range consisting of any two of the above values. In some embodiments of the present invention, the volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder is in the range of 40 micrometers to 55 micrometers. According to the present invention, by setting the volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder within the above-mentioned range, the composite powder can be made more suitable for the SLS process.

[0054] The Span value refers to the concentration of the particle size distribution in a powder, calculated using the formula (Dv90-Dv10) / Dv50. A smaller value indicates more uniform particle size. In the embodiments of this application, controlling the Span value of the polyetheretherketone / hydroxyapatite composite powder within a certain range not only gives the powder excellent flowability and high packing density but also enables rapid and uniform powder spreading, a dense and flat powder layer, and consistent and controllable sintering behavior in the SLS process. Therefore, the polyetheretherketone / hydroxyapatite composite powder of this application is particularly suitable for selective laser sintering (SLS) technology. As an example, the Span value of the polyetheretherketone / hydroxyapatite composite powder can be 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, or fall within any range consisting of any two of the above values. In some embodiments, the particle size distribution span (Span) of the polyetheretherketone / hydroxyapatite composite powder is less than 1.8 but not less than 1.2, preferably in the range of 1.2-1.6, and more preferably in the range of 1.3-1.6. According to the present invention, controlling the particle size distribution span (Span) of the polyetheretherketone / hydroxyapatite composite powder within the above-mentioned range results in a powder with excellent flowability and high packing density, making it particularly suitable for selective laser sintering (SLS) technology.

[0055] In some embodiments of this application, the polyetheretherketone / hydroxyapatite composite powder satisfies one or more of the following properties, preferably both: an angle of repose not greater than 48°, preferably between 42° and 48°; and / or not less than 35 g / cm³. 3 The bulk density is preferably between 38 g / cm³. 3 Up to 45 g / cm 3 The packing density.

[0056] In this application, the angle of repose refers to the angle between the inclined surface of the cone formed by the natural accumulation of powder through a specific funnel and the horizontal plane. It is a core indicator characterizing powder flowability and is usually measured according to the standard ASTM C1444-00. The smaller the angle of repose, the better the flowability. In some embodiments of this application, the angle of repose of the polyetheretherketone / hydroxyapatite composite powder is ≤48°, indicating that the composite powder has excellent flowability. As an example, the angle of repose of the polyetheretherketone / hydroxyapatite composite powder can be 48°, 47.5°, 47°, 46.5°, 46°, 45.5°, 45°, 44.5°, 44°, 43.5°, 43°, 42.5°, 42°, 41.5°, 41°, 40.5°, 40°, or fall within any range of any two of the above values. In some embodiments, the angle of repose of the polyetheretherketone / hydroxyapatite composite powder is between 42° and 48°. The angle of repose of the polyetheretherketone / hydroxyapatite composite powder is controlled within the above range, ensuring that the composite powder can spread quickly and evenly like a fluid during the SLS powder spreading process, forming a flat and dense powder layer, fundamentally avoiding printing defects caused by uneven powder spreading.

[0057] In this application, bulk density refers to the mass per unit volume of powder in its naturally loose state, reflecting the compactness of the powder particles themselves and the tightness of their natural packing. It is typically measured according to standard GB / T16913-2008. In some embodiments of this application, the bulk density of the polyetheretherketone / hydroxyapatite composite powder is ≥35 g / cm³. 3 This indicates that the composite powder particles are regular in shape and have a concentrated particle size, enabling close packing. As an example, the packing density of the polyetheretherketone / hydroxyapatite composite powder can be 35 g / cm³. 3 35.5 g / cm 3 36 g / cm 3 36.5 g / cm 3 37 g / cm 3 37.5 g / cm 3 38 g / cm 3 38.5 g / cm 3 39 g / cm3 39.5 g / cm 3 40 g / cm 3 40.5 g / cm 3 41 g / cm 3 41.5 g / cm 3 42 g / cm 3 42.5 g / cm 3 43 g / cm 3 43.5 g / cm 3 44 g / cm 3 44.5 g / cm 3 45 g / cm 3 45.5 g / cm 3 46 g / cm 3 46.5 g / cm 3 47 g / cm 3 47.5 g / cm 3 48 g / cm 3 48.5 g / cm 3 49 g / cm 3 49.5 g / cm 3 50 g / cm 3 Or, it falls within any range consisting of any two of the above values. In some embodiments, the bulk density of the polyetheretherketone / hydroxyapatite composite powder is 38 g / cm³. 3 Up to 45 g / cm 3 Within the specified range, the bulk density of the polyetheretherketone / hydroxyapatite composite powder is controlled within the above range, resulting in a high initial density of the powder bed after spreading. This facilitates efficient and uniform heat conduction and full particle fusion during sintering, thereby significantly improving the density, mechanical strength, and dimensional stability of the final product.

[0058] In some embodiments, the hydroxyapatite in the polyetheretherketone (PEEK) / hydroxyapatite composite powder is grown in situ at the nanoscale on the surface of PEEK particles. In this document, "in-situ growth" refers to the direct nucleation and growth of hydroxyapatite (HA) on the surface of PEEK particles through a chemical biomimetic mineralization reaction, forming nanoscale hydroxyapatite. This "in-situ growth" method establishes a strong chemical bond interface between the hydroxyapatite and the PEEK matrix, fundamentally solving the common problems of weak interfacial bonding and easy component separation in physical mixing. Nanoscale hydroxyapatite not only significantly increases its specific surface area and bioactivity but also allows for more uniform dispersion due to its size effect, avoiding significant damage to the original morphology and thermal properties of the PEEK particles.

[0059] In some embodiments, the hydroxyapatite in the polyetheretherketone / hydroxyapatite composite powder is present in an amount of 10% to 30% by weight relative to the total weight of the polyetheretherketone / hydroxyapatite composite powder. As an example, the content of hydroxyapatite in the polyetheretherketone / hydroxyapatite composite powder can be 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, or fall within any range of any two of the above values. The proportion of hydroxyapatite (HA) in the total mass of the composite powder is controlled within the above-mentioned specific range to better balance bioactivity and basic material properties. A content of not less than 10% ensures that the composite material possesses significant and effective bioactivity. At the same time, a content of no more than 30% avoids substantial damage to the inherent excellent properties of the polyether ether ketone (PEEK) matrix caused by the introduction of excessive hydroxyapatite, thereby maximizing the preservation of the core mechanical and processing advantages of PEEK as an SLS molding material and load-bearing implant while endowing the material with bioactivity.

[0060] In some embodiments, the polyetheretherketone / hydroxyapatite composite powder is in the form of spherical or near-spherical particles. Spherical particles have the smallest specific surface area and optimal rolling properties, which endow the powder with excellent flowability (low angle of repose) and high packing density. During SLS powder spreading, the spherical or near-spherical powder can spread evenly like miniature bearings, forming a dense and flat powder bed.

[0061] In some embodiments, the polyetheretherketone / hydroxyapatite composite powder is substantially free of agglomerated hydroxyapatite. In this document, "substantially free of agglomerated hydroxyapatite" means that in the polyetheretherketone / hydroxyapatite composite powder, hydroxyapatite exists primarily as nanoparticles grown in situ on the surface of polyetheretherketone particles, with very few secondary agglomerates independent of polyetheretherketone formed by the disordered aggregation of multiple hydroxyapatite nanoparticles. This ensures a uniform distribution of hydroxyapatite in the matrix, eliminates defects such as localized stress concentration points and uneven sintering caused by hydroxyapatite agglomeration, ensures the reliability and consistency of the material's mechanical properties, and simultaneously makes the distribution of bioactive sites more uniform.

[0062] Preparation method of polyetheretherketone / hydroxyapatite composite powder Another aspect of the present invention provides a method for preparing polyetheretherketone / hydroxyapatite composite powder, the method comprising the following steps: S1. Provide polyetheretherketone (PEEK) granules; S2. The polyether ether ketone particles are surface modified, and an aqueous solution of the raw material used to form hydroxyapatite is used to conduct a biomimetic mineralization reaction on the surface of the polyether ether ketone particles to obtain a primary composite powder. S3. The primary composite powder is spheroidized to obtain the composite powder.

[0063] In the method according to this application, the surface of polyetheretherketone (PEEK) particles is modified so that the precursor material for forming hydroxyapatite can be grown in situ on the surface of the PEEK particles, thereby forming good interfacial bonding. Furthermore, by spheroidizing the formed primary composite powder, the sphericity, flowability, bulk density, and / or sintering stability of the resulting composite powder are synergistically improved. This results in a PEEK / hydroxyapatite composite powder with a volume distribution particle size Dv50 in the range of 30 to 60 micrometers and a particle size distribution span of less than 2.0, which is particularly suitable for selective laser sintering (SLS) technology.

[0064] In embodiments according to this application, the polyetheretherketone (PEEK) particles can be any powdered form of PEEK known in the art. For example, PEEK powder with a volumetric particle size distribution (Dv50) in the range of 10 to 80 micrometers, preferably in the range of 20 to 80 micrometers, more preferably in the range of 30 to 70 micrometers, and even more preferably in the range of 30 to 60 micrometers can be used. The powdered PEEK particles can be commercially available or synthetic. In one embodiment of this application, the powdered PEEK particles are prepared as follows: A certain amount of diphenyl sulfone is added to a reactor equipped with a reflux condenser, and then the pressure is reduced to vacuum, and an inert gas is introduced to atmospheric pressure. Under inert gas protection, the temperature is raised to 180°C while stirring. After the diphenyl sulfone melts, an alkali metal carbonate, difluorobenzophenone, and hydroquinone are added to the reactor, and the temperature is gradually raised to 320°C, and the reaction is carried out for 2.5 h. When the target molecular weight is reached, the material is cooled and the reaction product is removed. The sample was pulverized using a pulverizer, and then washed five times with acetone and pure water, filtered, and dried under vacuum.

[0065] In some embodiments, in step S2 of the method, the surface modification includes impregnating the polyetheretherketone (PEEK) particles with an aqueous solution of a bio-based surfactant. The bio-based surfactant is selected from one or more of gelatin, collagen, and silk fibroin, preferably present at a concentration of 0.3 mg / mL to 0.8 mg / mL, more preferably at a concentration of 0.4 mg / mL to 0.6 mg / mL. This surface modification with the bio-based surfactant introduces abundant hydrophilic functional groups and negatively charged sites onto the hydrophobic surface of PEEK, transforming it from hydrophobic to hydrophilic, and enabling the subsequent absorption of calcium ions (Ca). 2+This provides specific adsorption sites, thus laying a crucial interfacial foundation for the in-situ, uniform nucleation and growth of hydroxyapatite (HA). In one specific embodiment of this application, the surface modification is achieved by placing polyetheretherketone particles with a selected volumetric particle size distribution in an aqueous solution of a bio-based surfactant at a concentration between 0.3 mg / mL and 0.8 mg / mL, and immersing them at 35°C for a period of time, for example, 10-30 minutes.

[0066] In some embodiments, in step S2 of the method, the raw material used to form hydroxyapatite is in the form of an aqueous solution. Optionally, the raw material includes an aqueous solution of a calcium source and an aqueous solution of a phosphate, wherein the calcium source includes calcium chloride, and the phosphate includes an alkali metal hydrogen phosphate, preferably disodium hydrogen phosphate. Preferably, the concentration of the aqueous solution of the raw material used to form hydroxyapatite is in the range of 5 mg / mL to 80 mg / mL. As an example, the concentration of the aqueous solution of the raw material used to form hydroxyapatite can be 5 mg / mL, 10 mg / mL, 15 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 mg / mL, 80 mg / mL, or any range consisting of any two of the above values. In a preferred embodiment, the concentration of the aqueous solution of the raw material used to form hydroxyapatite can be in the range of 10 mg / mL to 30 mg / mL. Controlling the concentration of the aqueous solution of the raw materials used to form hydroxyapatite within the aforementioned range is crucial for achieving controllable and uniform biomimetic mineralization. Too low a concentration leads to slow hydroxyapatite growth and incomplete coating; too high a concentration easily triggers homogeneous nucleation in the solution, producing free hydroxyapatite particles instead of growth only on the polyetheretherketone (PEEK) surface, resulting in uneven coating or even hydroxyapatite agglomeration. In other words, controlling the concentration of the aqueous solution of the raw materials used to form hydroxyapatite within the aforementioned range ensures a moderate supersaturation of reactant ions on the PEEK surface, driving the preferential and directional growth of hydroxyapatite at the modification sites. During the aforementioned biomimetic mineralization reaction, controlling the concentration of the aqueous solutions of the calcium source and phosphate raw materials and their treatment time on the PEEK particles within a specific range (e.g., the concentration of the raw material aqueous solution is in the range of 10 mg / mL to 30 mg / mL, and the treatment time is in the range of 20-30 minutes) can further improve the mechanical properties of the resulting composite powder, including the combination of tensile strength, flexural strength, and flexural modulus. In one specific embodiment, the biomimetic mineralization reaction of the raw material for forming hydroxyapatite on the surface of the polyetheretherketone (PEEK) particles is achieved as follows: the surface-modified PEEK particles are placed in a calcium source aqueous solution of a specific concentration with a neutral pH (e.g., pH between 7.0 and 8.0) and kept at 30 °C for a period of time, for example, 10-30 minutes (preferably 20-30 minutes); then the particles are rinsed with deionized water and placed in a phosphate aqueous solution of a specific concentration with an alkaline pH (e.g., pH between 8.0 and 9.0) and kept at 30 °C for a period of time, for example, 10-30 minutes (preferably 20-30 minutes); finally, the sample is rinsed with deionized water, filtered, and dried.

[0067] In some embodiments, in step S3 of the method, the spheroidization treatment is achieved by subjecting the primary composite powder to hydrothermal treatment in a sealed container at a high temperature of 150°C to 250°C and a high pressure of 5 MPa to 12 MPa in the presence of a solvent. Preferably, the aqueous solvent includes water, C1-C4 alkyl alcohols, or combinations thereof. The spheroidization treatment provides the primary composite powder with sufficient thermal energy and a suitable medium environment, causing surface reconstruction under high temperature, high pressure, and solvent action, driving its morphology to evolve towards a regular spherical shape with lower surface energy. Simultaneously, this spheroidization treatment can further strengthen the interfacial bonding between hydroxyapatite and polyetheretherketone (PEEK) and may eliminate microscopic defects, ultimately synergistically improving the sphericity, flowability (reducing the angle of repose), bulk density, and sintering stability of the composite powder, resulting in a qualitative leap in its adaptability to the SLS process. During the above spheroidization treatment, controlling the treatment time within a specific range (e.g., 1-4 hours) can further improve the mechanical properties of the resulting composite powder, including a combination of tensile strength, flexural strength, and flexural modulus. In one specific embodiment, the spheroidization treatment is achieved as follows: the dried primary composite powder is placed in a reaction vessel containing solvent, wherein the amount of solvent used is 10-50 mL per gram of powder; the temperature is raised to 150-200°C; stirring is started at a rate of 400-1000 rpm; the pressure is 9.8 MPa; the temperature is maintained at the set temperature for 1-10 hours (preferably 1-4 hours); the treated powder is then washed with deionized water, filtered, and dried.

[0068] Optionally, the spheroidizing temperature can be 150℃, 160℃, 170℃, 180℃, 190℃, 200℃, 210℃, 220℃, 230℃, 240℃, 250℃, or any range consisting of any two of the above values. Optionally, the spheroidizing pressure can be 5 MPa, 5.5 MPa, 6 MPa, 6.5 MPa, 7 MPa, 7.5 MPa, 8 MPa, 8.5 MPa, 9 MPa, 9.5 MPa, 10 MPa, 10.5 MPa, 11 MPa, 11.5 MPa, 12 MPa, or any range consisting of any two of the above values. Optionally, the spheroidizing time can be 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, or any range consisting of any two of the above values.

[0069] Optionally, the aqueous solvent includes water, methanol, ethanol, propanol, or a mixture thereof, preferably water, ethanol, or a mixture of water and ethanol.

[0070] The polyetheretherketone / hydroxyapatite composite powder obtained by the above method can, in addition to having the aforementioned volume distribution particle size Dv50 and particle size distribution span, also have an angle of repose of not more than 48°, preferably between 42° and 48°; and / or not less than 35 g / cm³. 3 The bulk density is preferably between 38 g / cm³. 3 Up to 45 g / cm 3 The packing density and acceptable mechanical properties.

[0071] In some embodiments of the invention, the polyetheretherketone / hydroxyapatite composite powder has a tensile strength of 77 MPa to 94 MPa, preferably 87 MPa to 94 MPa, and more preferably 90-94 MPa.

[0072] In some embodiments of the invention, the polyetheretherketone / hydroxyapatite composite powder has a flexural strength of 142 MPa to 171 MPa, preferably 158 MPa to 171 MPa.

[0073] In some embodiments of the invention, the polyetheretherketone / hydroxyapatite composite powder has a flexural modulus of 3950 MPa to 4550 MPa, preferably 4200 MPa to 4550 MPa.

[0074] Therefore, the polyetheretherketone / hydroxyapatite composite powder according to this application is particularly suitable for selective laser sintering (SLS) technology.

[0075] The third aspect of this application provides the application of polyetheretherketone / hydroxyapatite composite powder prepared according to the method of the first aspect of this application or according to the method of the second aspect of this application in selective laser sintering 3D printing technology.

[0076] The fourth aspect of this application provides a method for manufacturing a bone implant or bone repair scaffold, the method comprising: using polyetheretherketone / hydroxyapatite composite powder according to the first aspect of this application or polyetheretherketone / hydroxyapatite composite powder prepared according to the method of the second aspect of this application as raw material, and then shaping the raw material by selective laser sintering 3D printing technology.

[0077] The fifth aspect of this application provides a bone implant or bone repair scaffold made from polyetheretherketone / hydroxyapatite composite powder prepared according to the first aspect of this application or polyetheretherketone / hydroxyapatite composite powder prepared according to the method of the second aspect of this application by selective laser sintering 3D printing technology.

[0078] In some embodiments, the bone implant or bone repair scaffold has a porous structure with a porosity of 30% to 80% and an average pore size of 100 to 600 micrometers.

[0079] In some embodiments, the bone implant or bone repair scaffold has a compressive modulus of 0.5 GPa to 3 GPa; and / or its surface is capable of inducing apatite deposition after immersion in simulated body fluid for 7 days.

[0080] Example The following embodiments describe the disclosure of this application in more detail. These embodiments are merely illustrative, as various modifications and variations will be apparent to those skilled in the art within the scope of the disclosure of this application. Unless otherwise stated, all parts, percentages, and ratios reported in the following embodiments are based on mass, and all reagents used in the embodiments are commercially available or synthesized by conventional methods and can be used directly without further processing, and the instruments used in the embodiments are commercially available.

[0081] Test method: 1) Volume distribution particle size Dv50 and particle size distribution span: The volume distribution particle size Dv50 and particle size distribution span of the polyether ether ketone / hydroxyapatite composite powder prepared according to the embodiments and comparative examples of the present invention were determined by laser diffraction particle size analyzer.

[0082] 2) Angle of repose: The angle of repose of the polyetheretherketone / hydroxyapatite composite powder prepared according to the embodiments and comparative examples of the present invention was measured in accordance with standard ASTM C1444-00.

[0083] 3) Bulk density: The bulk density of the polyetheretherketone / hydroxyapatite composite powder prepared according to the embodiments and comparative examples of the present invention was determined in accordance with standard GB / T 16913-2008.

[0084] 4) Flexural modulus and flexural strength: The flexural modulus and flexural strength of the polyetheretherketone / hydroxyapatite composite powder prepared according to the embodiments and comparative examples of the present invention can be determined by ISO 178: Plastics—Determination of flexural properties.

[0085] 5) Tensile strength: The tensile strength of the polyetheretherketone / hydroxyapatite composite powder prepared according to the embodiments and comparative examples of the present invention can be determined by ISO 527: Plastics—Determination of tensile properties.

[0086] Example 1: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0087] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in a 1 g (w / mL) gelatin aqueous solution with a concentration of 0.5 mg / mL and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a 15.71 g (w / mL) CaCl2 buffer solution (pH=7.5) and kept at 30°C for 20 min. After soaking, it was rinsed with deionized water. Next, it was placed in a 7.37 g (w / mL) Na2HPO4 buffer solution (pH=8.5) and kept at 30°C for 20 min. After rinsing with deionized water, it was filtered and vacuum dried at 150°C for 6 h.

[0088] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol), with a powder-to-solvent ratio of 1:30 g / mL. The temperature is raised to 180 ℃, the pressure is 9.8 MPa, the stirring is started at a speed of 400 rpm, and the temperature is maintained for 4 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 ℃ for 6 h.

[0089] Example 2: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0090] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in a 1 g (0.5 mg / mL) aqueous solution of silk fibroin and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a 35.35 g (10 mg / mL) CaCl2 buffer solution (pH=7.5) and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water. Next, it was placed in a 16.58 g (10 mg / mL) Na2HPO4 buffer solution (pH=8.5) and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water, filtered, and vacuum dried at 150°C for 6 h.

[0091] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol), with a powder-to-solvent ratio of 1:30 g / mL. The temperature is raised to 180 ℃, the pressure is 9.8 MPa, the stirring is started at a speed of 400 rpm, and the temperature is maintained for 4 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 ℃ for 6 h.

[0092] Example 3: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0093] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in an aqueous solution containing 1 g of collagen at a concentration of 0.5 mg / mL and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a buffer solution of 60.60 g of CaCl2 at a concentration of 30 mg / mL (pH=7.5) and kept at 30°C for 20 min. After soaking, it was rinsed with deionized water. Then, it was placed in a buffer solution of 28.31 g of Na2HPO4 at a concentration of 30 mg / mL (pH=8.5) and kept at 30°C for 20 min. After soaking, it was rinsed with deionized water, filtered, and vacuum dried at 150°C for 6 h.

[0094] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol), with a powder-to-solvent ratio of 1:30 g / mL. The temperature is raised to 180 ℃, the pressure is 9.8 MPa, the stirring is started at a speed of 400 rpm, and the temperature is maintained for 4 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 ℃ for 6 h.

[0095] Example 4: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0096] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in a 1 g (w / mL) collagen aqueous solution with a concentration of 0.5 mg / mL and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a 94.27 g (w / mL) CaCl2 buffer solution (pH=7.5) with a concentration of 50 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water. Next, it was placed in a 44.22 g (w / mL) Na2HPO4 buffer solution (pH=8.5) with a concentration of 50 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water, filtered, and vacuum dried at 150°C for 6 h.

[0097] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol), with a powder-to-solvent ratio of 1:30 g / mL. The temperature is raised to 180 ℃, the pressure is 9.8 MPa, the stirring is started at a speed of 400 rpm, and the temperature is maintained for 4 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 ℃ for 6 h.

[0098] Example 5: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0099] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in a 1 g (w / mL) collagen aqueous solution with a concentration of 0.5 mg / mL and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a 35.35 g (w / mL) CaCl2 buffer solution (pH=7.5) with a concentration of 10 mg / mL and kept at 30°C for 10 min. Afterward, it was rinsed with deionized water. Next, it was placed in a 16.58 g (w / mL) Na2HPO4 buffer solution (pH=8.5) with a concentration of 10 mg / mL and kept at 30°C for 10 min. Afterward, it was rinsed with deionized water, filtered, and vacuum dried at 150°C for 6 h.

[0100] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol), with a powder-to-solvent ratio of 1:30 g / mL. The temperature is raised to 250 °C, the pressure is 9.8 MPa, the stirring is started at a speed of 400 rpm, and the temperature is maintained for 4 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 °C for 6 h.

[0101] Example 6: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0102] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in a 1 g (w / mL) collagen aqueous solution with a concentration of 0.5 mg / mL and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a 35.35 g (w / mL) CaCl2 buffer solution (pH=7.5) with a concentration of 10 mg / mL and kept at 30°C for 30 min. Afterward, it was rinsed with deionized water. Next, it was placed in a 16.58 g (w / mL) Na2HPO4 buffer solution (pH=8.5) with a concentration of 10 mg / mL and kept at 30°C for 30 min. Afterward, it was rinsed with deionized water, filtered, and vacuum dried at 150°C for 6 h.

[0103] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol), with a powder-to-solvent ratio of 1:30 g / mL. The temperature is raised to 180 ℃, the pressure is 9.8 MPa, the stirring is started at a speed of 400 rpm, and the temperature is maintained for 4 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 ℃ for 6 h.

[0104] Example 7: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0105] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in a 1 g (w / mL) collagen aqueous solution with a concentration of 0.5 mg / mL and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a 35.35 g (w / mL) CaCl2 buffer solution (pH=7.5) with a concentration of 10 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water. Next, it was placed in a 16.58 g (w / mL) Na2HPO4 buffer solution (pH=8.5) with a concentration of 10 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water, filtered, and vacuum dried at 150°C for 6 h.

[0106] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol), with a powder-to-solvent ratio of 1:30 g / mL. The temperature is raised to 150 °C, the pressure is 9.8 MPa, the stirring is started at a speed of 400 rpm, and the temperature is maintained for 4 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 °C for 6 h.

[0107] Example 8: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0108] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in a 1 g (w / mL) collagen aqueous solution with a concentration of 0.5 mg / mL and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a 35.35 g (w / mL) CaCl2 buffer solution (pH=7.5) with a concentration of 10 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water. Next, it was placed in a 16.58 g (w / mL) Na2HPO4 buffer solution (pH=8.5) with a concentration of 10 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water, filtered, and vacuum dried at 150°C for 6 h.

[0109] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol) at a ratio of 1:30 g / mL. The temperature is raised to 250 °C and the pressure is 9.8 MPa. Stirring is started at a speed of 400 rpm. The temperature is maintained for 4 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 °C for 6 h.

[0110] Example 9: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0111] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in a 1 g (w / mL) collagen aqueous solution with a concentration of 0.5 mg / mL and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a 35.35 g (w / mL) CaCl2 buffer solution (pH=7.5) with a concentration of 10 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water. Next, it was placed in a 16.58 g (w / mL) Na2HPO4 buffer solution (pH=8.5) with a concentration of 10 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water, filtered, and vacuum dried at 150°C for 6 h.

[0112] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol) at a ratio of 1:30 g / mL. The temperature is raised to 180 °C, the pressure is 9.8 MPa, the stirring is started at a speed of 400 rpm, and the temperature is maintained for 1 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 °C for 6 h.

[0113] Example 10: S1: 400 g of diphenyl sulfone was added to a reaction vessel, the pressure was reduced to vacuum, and inert gas was introduced until atmospheric pressure was reached. Under inert gas protection, a reflux condenser was connected. The temperature was raised to 180 °C while heating and stirring. After the diphenyl sulfone melted, 42.40 g of sodium carbonate, 87.26 g of difluorobenzophenone, and 48.45 g of hydroquinone were added. The temperature was gradually raised to 320 °C, and the reaction was carried out for 2.5 h. After the molecular weight reached about 5000, the mixture was cooled and the powdered reaction product was taken out. The powder was pulverized using a pulverizer, and the pulverized sample was washed five times with acetone and pure water, filtered, and vacuum dried at 150 °C for 6 h.

[0114] S2: 100 g of polyetheretherketone (PEEK) powder with a particle size of 40 μm was placed in a 1 g (w / mL) collagen aqueous solution with a concentration of 0.5 mg / mL and soaked at 35°C for 10 min. Then, the PEEK powder was placed in a 35.35 g (w / mL) CaCl2 buffer solution (pH=7.5) with a concentration of 10 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water. Next, it was placed in a 16.58 g (w / mL) Na2HPO4 buffer solution (pH=8.5) with a concentration of 10 mg / mL and kept at 30°C for 20 min. Afterward, it was rinsed with deionized water, filtered, and vacuum dried at 150°C for 6 h.

[0115] S3: The dried powder is placed in a reaction vessel containing solvent (deionized water, ethanol, or a mixture of deionized water and ethanol) at a ratio of 1:30 g / mL. The temperature is raised to 180 °C, the pressure is 9.8 MPa, the stirring is started at a speed of 400 rpm, and the temperature is maintained for 8 h after reaching the set temperature. The powder is then rinsed with deionized water, filtered, and vacuum dried at 150 °C for 6 h.

[0116] Comparative Example 1: Take 80 grams of polyetheretherketone powder with a particle size of 30-50 μm and 20 grams of hydroxyapatite powder, and mix them in a mixing tank for 30 minutes to obtain polyetheretherketone / hydroxyapatite composite powder.

[0117] Comparative Example 2: Take 80 g of polyetheretherketone powder with a particle size of 30-50 μm and 20 g of hydroxyapatite powder, put them into 500 ml of water, stir for 30 min, filter and dry, and dry in a vacuum oven at 150℃ for 8 hours to obtain polyetheretherketone / hydroxyapatite composite powder.

[0118] The volume distribution particle size (Dv50), particle size distribution span (Span), angle of repose, bulk density, tensile strength, flexural strength, and flexural modulus of the polyetheretherketone / hydroxyapatite composite powders obtained in the above examples and comparative examples were determined according to the test methods given in the experimental section above. The results are summarized in Table 1 below.

[0119] Table 1: Properties of Polyetheretherketone / Hydroxyapatite Composite Powder

[0120] As can be seen from the results in Table 1, by controlling the volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder within the range of 30 micrometers to 60 micrometers, and controlling the particle size distribution span Span of the polyetheretherketone / hydroxyapatite composite powder to less than 2.0, not only can the powder have excellent flowability and high packing density, but the mechanical properties of the powder can also be improved. Figure 1 The particle size distribution diagram of the composite powder in Example 2 shows that the powder's D50 is 49.9 μm and the particle size distribution span is 1.475 (span = (Dv90 - Dv10) / Dv50). Figure 2 The particle size distribution of the composite powder obtained by solvent mixing of PEEK and HA in Comparative Example 2 is shown. The particle size D50 is 45.6 μm, and the particle size distribution span is 2.219. The hydroxyapatite-reinforced polyetheretherketone composite powder prepared in this invention has a lower angle of repose, making it more suitable for selective laser sintering printing. Furthermore, the higher mechanical properties of the composite powder demonstrate that the hydroxyapatite is more uniformly dispersed within the matrix.

[0121] To more clearly show the morphology of the polyetheretherketone / hydroxyapatite composite powder, Figure 3 and Figure 4 Electron micrographs of the hydroxyapatite-modified PEEK composite material prepared according to Example 2 of this application are shown at low and high magnification. The images show that hydroxyapatite is uniformly grown on the surface of the PEEK and exhibits good interfacial bonding. Figure 3 The results show that the powder is in the form of regular spheres, which has a better morphology and is more conducive to selective laser sintering applications.

[0122] Some exemplary implementations are described below: Embodiment 1. A medical-grade polyetheretherketone / hydroxyapatite composite powder, characterized in that the polyetheretherketone / hydroxyapatite composite powder comprises polyetheretherketone particles and hydroxyapatite distributed on the surface of the polyetheretherketone particles, wherein... The volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder is in the range of 30 micrometers to 60 micrometers, and The particle size distribution span Span of the polyetheretherketone / hydroxyapatite composite powder is less than 2.0, where Span = (Dv90 - Dv10) / Dv50.

[0123] Embodiment 2. The medical-grade polyetheretherketone / hydroxyapatite composite powder according to Embodiment 1, wherein the particle size distribution span of the polyetheretherketone / hydroxyapatite composite powder is less than 1.8 but not less than 1.2, preferably in the range of 1.2-1.6, and more preferably in the range of 1.3-1.6.

[0124] Embodiment 3. The medical-grade polyetheretherketone / hydroxyapatite composite powder according to Embodiment 1, wherein the volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder is in the range of 40 micrometers to 55 micrometers.

[0125] Embodiment 4. A medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of Embodiments 1 to 3, wherein the polyetheretherketone / hydroxyapatite composite powder satisfies one or more of the following properties, preferably both: An angle of repose not greater than 48°, preferably between 42° and 48°; Not less than 35 g / cm 3 The bulk density is preferably between 38 g / cm³. 3 Up to 45 g / cm 3 The packing density.

[0126] Embodiment 5. Medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of Embodiments 1 to 3, wherein the hydroxyapatite is grown in situ on the surface of polyetheretherketone particles at the nanoscale.

[0127] Embodiment 6. Medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of Embodiments 1 to 3, wherein the hydroxyapatite is present in an amount of 10% to 30% by weight relative to the total weight of the polyetheretherketone / hydroxyapatite composite powder.

[0128] Embodiment 7. Medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of Embodiments 1 to 3, wherein the polyetheretherketone / hydroxyapatite composite powder is in the form of spherical or near-spherical particles.

[0129] Embodiment 8. Medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of Embodiments 1 to 3, wherein the polyetheretherketone / hydroxyapatite composite powder is substantially free of agglomerated hydroxyapatite.

[0130] Embodiment 9. A method for preparing medical-grade polyetheretherketone / hydroxyapatite composite powder as described in any one of Embodiments 1 to 8, characterized in that the method comprises the following steps: S1. Provide polyetheretherketone (PEEK) granules; S2. The polyetheretherketone particles are surface modified, and the raw material used to form hydroxyapatite undergoes a biomimetic mineralization reaction on the surface of the polyetheretherketone particles to obtain a primary composite powder. S3. The primary composite powder is spheroidized to obtain the composite powder.

[0131] Implementation Method 10. According to the method of Implementation Method 9, wherein in step S2, the surface modification includes impregnating the polyether ether ketone particles with an aqueous solution of a bio-based surfactant, wherein the bio-based surfactant is selected from one or more of gelatin, collagen, and silk fibroin, preferably present at a concentration of 0.3 mg / mL to 0.8 mg / mL.

[0132] Implementation Method 11. The method according to Implementation Method 10, wherein in step S2, the raw material for forming hydroxyapatite is in the form of an aqueous solution, including an aqueous solution of a calcium source and an aqueous solution of a phosphate, wherein the calcium source includes calcium chloride and the phosphate includes an alkali metal hydrogen phosphate, preferably disodium hydrogen phosphate.

[0133] Embodiment 12. According to the method of Embodiment 10, wherein in step S2, the concentration of the aqueous solution of the raw material used to form hydroxyapatite is in the range of 20 mg / mL to 80 mg / mL.

[0134] Embodiment 13. The method according to any one of Embodiments 9 to 12, wherein in step S3, the spheroidizing treatment is achieved by subjecting the primary composite powder to hydrothermal treatment in a sealed container in the presence of an aqueous solvent at a high temperature of 150°C to 250°C and a high pressure of 5 MPa to 12 MPa, preferably, the aqueous solvent comprising water, C1-C4 alkyl alcohols or combinations thereof.

[0135] Example 14. Application of polyetheretherketone / hydroxyapatite composite powder as described in any one of Examples 1 to 8 or polyetheretherketone / hydroxyapatite composite powder prepared by any one of Examples 9 to 13 in selective laser sintering 3D printing technology.

[0136] Embodiment 15. A method for manufacturing a bone implant or bone repair scaffold, characterized in that the method comprises: using the medical-grade polyetheretherketone / hydroxyapatite composite powder described in any one of Embodiments 1 to 8 or the medical-grade polyetheretherketone / hydroxyapatite composite powder prepared by any one of Embodiments 9 to 13 as raw material, and forming it by selective laser sintering 3D printing technology.

[0137] Embodiment 16. A bone implant or bone repair scaffold made by selective laser sintering 3D printing technology from medical-grade polyetheretherketone / hydroxyapatite composite powder prepared by any one of Embodiments 1 to 8 or by any one of Embodiments 9 to 13.

[0138] Embodiment 17. The bone implant or bone repair scaffold according to Embodiment 16 has a porous structure with a porosity of 30% to 80% and an average pore size of 100 micrometers to 600 micrometers.

[0139] Implementation Method 18. The bone implant or bone repair scaffold according to Implementation Method 17 has a compressive modulus of 0.5 GPa to 3 GPa; and / or its surface can induce apatite deposition after immersion in simulated body fluid for 7 days.

[0140] Although this application has been described with reference to numerous embodiments and examples, those skilled in the art will recognize from the disclosure of this application that other embodiments can be designed without departing from the protection scope of this application.

Claims

1. A medical-grade polyetheretherketone / hydroxyapatite composite powder, characterized in that, The medical-grade polyetheretherketone / hydroxyapatite composite powder comprises polyetheretherketone particles and hydroxyapatite distributed on the surface of the polyetheretherketone particles, wherein... The volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder is in the range of 30 micrometers to 60 micrometers, and The particle size distribution span Span of the polyetheretherketone / hydroxyapatite composite powder is less than 2.0, where Span = (Dv90 - Dv10) / Dv50.

2. The medical-grade polyetheretherketone / hydroxyapatite composite powder according to claim 1, wherein, The particle size distribution span of the polyetheretherketone / hydroxyapatite composite powder is less than 1.8 but not less than 1.

2.

3. The medical-grade polyetheretherketone / hydroxyapatite composite powder according to claim 1, wherein, The volume distribution particle size Dv50 of the polyetheretherketone / hydroxyapatite composite powder is in the range of 40 micrometers to 55 micrometers.

4. The medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of claims 1 to 3, wherein, The polyetheretherketone / hydroxyapatite composite powder satisfies one or more of the following properties: Angle of repose not greater than 48°; Not less than 35 g / cm 3 The packing density.

5. The medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of claims 1 to 3, wherein, The hydroxyapatite is grown in situ on the surface of polyetheretherketone particles at the nanoscale.

6. The medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of claims 1 to 3, wherein, The hydroxyapatite is present in an amount of 10% to 30% by weight relative to the total weight of the polyetheretherketone / hydroxyapatite composite powder.

7. The medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of claims 1 to 3, wherein, The polyetheretherketone / hydroxyapatite composite powder is in the form of spherical or near-spherical particles.

8. The medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of claims 1 to 3, wherein, The polyetheretherketone / hydroxyapatite composite powder does not contain agglomerated hydroxyapatite.

9. A method for preparing medical-grade polyetheretherketone / hydroxyapatite composite powder as described in any one of claims 1 to 8, characterized in that, The method includes the following steps: S1. Provide polyetheretherketone (PEEK) granules; S2. The polyetheretherketone particles are surface modified, and the raw material used to form hydroxyapatite undergoes a biomimetic mineralization reaction on the surface of the polyetheretherketone particles to obtain a primary composite powder. S3. The primary composite powder is spheroidized to obtain the composite powder.

10. The method according to claim 9, wherein, In step S2, the surface modification includes impregnating the polyether ether ketone particles with an aqueous solution of a bio-based surfactant, wherein the bio-based surfactant is selected from one or more of gelatin, collagen, and silk fibroin.

11. The method according to claim 10, wherein, In step S2, the raw materials used to form hydroxyapatite are in the form of aqueous solutions, including aqueous solutions of calcium sources and aqueous solutions of phosphates, wherein the calcium source includes calcium chloride and the phosphates include alkali metal hydrogen phosphates.

12. The method according to claim 10, wherein, In step S2, the concentration of the aqueous solution of the raw material used to form hydroxyapatite is in the range of 5 mg / mL to 80 mg / mL.

13. The method according to any one of claims 9 to 12, wherein, In step S3, the spheroidization process is achieved by subjecting the primary composite powder to hydrothermal treatment in a sealed container in the presence of an aqueous solvent at a high temperature of 150°C to 250°C and a high pressure of 5 MPa to 12 MPa.

14. The application of the medical-grade polyetheretherketone / hydroxyapatite composite powder as described in any one of claims 1 to 8 or the medical-grade polyetheretherketone / hydroxyapatite composite powder prepared by the method of any one of claims 9 to 13 in selective laser sintering 3D printing technology.

15. A method for manufacturing a bone implant or bone repair scaffold, characterized in that, The method includes: using the medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of claims 1 to 8 or the medical-grade polyetheretherketone / hydroxyapatite composite powder prepared by any one of claims 9 to 13 as raw material, and forming it by selective laser sintering 3D printing technology.

16. A bone implant or bone repair scaffold made by selective laser sintering 3D printing technology from the medical-grade polyetheretherketone / hydroxyapatite composite powder according to any one of claims 1 to 8 or the medical-grade polyetheretherketone / hydroxyapatite composite powder prepared by any one of claims 9 to 13.

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