CN111643725A

CN111643725A - Artificial bone material for repairing bone defect and preparation method of artificial bone particles

Info

Publication number: CN111643725A
Application number: CN202010486126.XA
Authority: CN
Inventors: 杨晓; 杨龙; 朱向东; 张兴栋
Original assignee: Sichuan University
Current assignee: Sichuan University
Priority date: 2020-06-01
Filing date: 2020-06-01
Publication date: 2020-09-11
Anticipated expiration: 2040-06-01
Also published as: CN111643725B

Abstract

The present disclosure relates to an artificial bone material for repairing a bone defect, which comprises a plurality of artificial bone particles stacked on each other to form an artificial bone material having a porosity of 60% to 90%, wherein the artificial bone particles comprise a body part and a plurality of supporting pillars formed on the body part, the body part is in a long strip shape and has an upper surface and a lower surface which are oppositely arranged, and the body part has a through hole penetrating between the upper surface and the lower surface; the plurality of support columns are arranged around the main body along the longitudinal direction of the main body, and the support columns extend along the longitudinal direction and protrude from the main body. According to the present disclosure, the stability of the artificial bone material at the defect site can be improved.

Description

Artificial bone material for repairing bone defect and preparation method of artificial bone particles

Technical Field

The present disclosure generally relates to the field of clinical bone repair, and more particularly to a method for preparing an artificial bone material and an artificial bone granule for repairing bone defects.

Background

Bone defects are one of the common diseases in clinic, and bone tissue defects are caused by various factors such as trauma, inflammation, bone diseases, operation and the like. At present, various methods for treating bone defects include autologous bone grafting, allogeneic bone grafting and the like. Although autologous bone grafting is the gold standard for clinical bone defect repair, it has limited bone supply, difficult shaping and fails to meet the repair requirements of large area and specific shape. Although the allogeneic bone can solve the problem of limited bone source, the allogeneic bone is easy to absorb and deform after being implanted, has strong antigenicity and influences the treatment effect.

In order to solve the above problems, synthetic bone repair materials have been produced, and research and development and industrialization of synthetic bone repair materials are in a new stage of vigorous development driven by huge clinical demands. The active artificial bone filling and repairing material which is used in clinic at present in large quantity adopts calcium phosphate-based bioceramic, silicate-based bioglass and degradable high polymer material. The active artificial bone filling and repairing material has the characteristics of good biocompatibility, degradability and easiness in forming.

The artificial bone repair material (i.e. artificial bone material) is composed of artificial bone particles. The artificial bone particles are generally made into shapes of blocks, wedges, columns, spherical particles and the like according to different requirements of use positions and operations. However, when the existing artificial bone particles are implanted into the defect part, the contact between the artificial bone particles and host bones is unstable, and particularly, the problems of looseness and instability of the artificial bone particles due to blood washing exist, so that the stability of the artificial bone material at the defect part is low, and the implantation effect of the artificial bone material is influenced.

Disclosure of Invention

The present disclosure has been made in view of the above circumstances, and an object thereof is to provide an artificial bone material for repairing a bone defect and a method for producing artificial bone granules, which can improve the stability of the artificial bone material at a defect site.

To this end, the present disclosure provides, in a first aspect, an artificial bone material for repairing a bone defect, including a plurality of artificial bone particles stacked on one another to form an artificial bone material having a porosity of 60% to 90%, the artificial bone particles including a body portion and a plurality of supporting pillars formed on the body portion, the body portion being elongated and having an upper surface and a lower surface which are oppositely disposed, the body portion having a through hole penetrating between the upper surface and the lower surface; the plurality of support columns are disposed around the main body portion along a length direction of the main body portion, the support columns extending along the length direction and protruding from the main body portion. In the present disclosure, the porosity of the artificial bone material for repairing a bone defect is 60 to 90%, which is formed by stacking a plurality of artificial bone particles on one another. The artificial bone particle comprises a strip-shaped main body part and a plurality of supporting columns formed on the main body part, wherein the main body part is provided with an upper surface and a lower surface which are oppositely arranged, and a through hole penetrating through the upper surface and the lower surface. The plurality of support columns are arranged around the main body along the longitudinal direction of the main body, and the support columns extend along the longitudinal direction and protrude from the main body. In this case, the artificial bone particles having the protrusions can be better adapted to the implantation defect site; when the artificial bone is implanted into a defect part, the protrusion of the support column can improve the contact stability between the artificial bone particles and host bones; in addition, the support column of the artificial bone particles can slow down the impact force of blood scouring on the main body part, so that the problems of looseness and instability caused by the blood scouring of the artificial bone particles are improved to a certain extent, the stability of the artificial bone material at the defect part is improved, and the implantation effect of the artificial bone material is improved.

In the artificial aggregate according to the present disclosure, the main body may have a plurality of first through holes communicating with the through holes, the main body may have a plurality of first side surfaces provided between adjacent support columns, and the first through holes may communicate from the first side surfaces to the through holes. Thereby, the adhesion, growth or creeping of osteoblasts on the artificial bone particles can be facilitated.

In the artificial bone according to the present disclosure, optionally, the first side surface is formed by a first plane, a second plane, and a third plane that are connected in this order, a normal line of the first plane, a normal line of the second plane, and a normal line of the third plane are orthogonal to the longitudinal direction, respectively, an included angle between the first plane and the second plane and an included angle between the third plane and the second plane are obtuse angles, respectively, and the first through hole communicates from the second plane to the through hole. In this case, the area of the first side surface of the main body can be increased, and the impact force generated when the blood washes the first side surface of the main body can be reduced to some extent.

In the artificial aggregate according to the present disclosure, the support column may have a plurality of second through holes communicating with the through hole and the first through hole. Thereby, the adhesion, growth or creeping of osteoblasts on the surface of the artificial bone particles can be further facilitated.

In the artificial bone material related to the present disclosure, optionally, an included angle between the first plane and the second plane is equal to an included angle between the third plane and the second plane. In this case, the third plane and the first plane are symmetrical with respect to the second plane. Therefore, when the blood washes the first side surface of the main body part, the third plane and the first plane can be uniformly stressed.

In the artificial bone material to which the present disclosure relates, optionally, the artificial bone particles have a size of 0.25mm to 20 mm. Therefore, artificial bone particles with different sizes can be selected according to different application scenes.

The second aspect of the present disclosure provides a method for preparing artificial bone particles, which includes: preparing a surface modifier solution, calcium-phosphorus-based ceramic powder with bioactivity and agate balls, mixing the calcium-phosphorus-based ceramic powder and the agate balls according to a preset material-ball ratio, adding the surface modifier solution for grinding to obtain slurry, and then drying and filtering the slurry to obtain target ceramic powder; preparing photosensitive resin, mixing the photosensitive resin with the target ceramic powder, adding a dispersing agent and graphene, and grinding to obtain ceramic slurry for printing; designing a model of the artificial bone particles by using design software, and printing by using the ceramic slurry for printing in 3D printing equipment based on the model to obtain an artificial bone particle blank; and cleaning the artificial bone particle blank, drying, and sintering the artificial bone particle blank to obtain the artificial bone particles.

In the disclosure, the preparation of the artificial bone particles by using the calcium-phosphorus-based ceramic powder with bioactivity is convenient for the degradation of the artificial bone particles after the artificial bone particles are implanted into the defect part; the ceramic powder, the surface modifier solution, the photosensitive resin and the graphene can be used for preparing slurry with good fluidity; the graphene can be converted into gas in subsequent sintering, so that the artificial bone particles leave a microporous structure, and the microporous structure is favorable for the degradation of the artificial bone particles and the growth of new bones; utilize 3D printing apparatus to print can the save raw materials, obtain the artificial bone granule that has higher wholeness.

In the preparation method of the artificial bone particles related to the present disclosure, optionally, in the sintering process, the initial temperature is set to 25 ℃, and the temperature is raised to 300 ℃ at a temperature raising rate of 2 ℃ for 2 minutes, and the temperature is maintained for 1 hour at the temperature of 300 ℃; heating from 300 ℃ to 600 ℃ at a heating rate of 1 ℃ for 2 minutes, and preserving heat for 5 hours at the temperature of 600 ℃; heating from 600 ℃ to 1100 ℃ at the heating rate of 2 ℃ for 2 minutes, and preserving heat for 2 hours; then naturally cooling to room temperature. Thus, the artificial bone particle blank can be sintered into desired artificial bone particles by the sintering process.

In the preparation method of the artificial bone particles related to the present disclosure, optionally, the surface modifier solution is prepared by adding palmitic acid into anhydrous ethanol; the photosensitive resin is prepared from a photoinitiator and a monomer of the photosensitive resin; the calcium-phosphorus-based ceramic powder is one or more of Hydroxyapatite (HA) ceramic powder, tricalcium phosphate (beta-TCP) ceramic powder or Biphase Calcium Phosphate (BCP) ceramic powder; the photoinitiator is one or more of 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide, 1-hydroxy-cyclohexyl-phenyl ketone, phenyl bis (2,4, 6-trimethylbenzoyl) phosphine oxide, methyl benzoylformate, isopropyl thioxanthone or 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone; the monomer of the photosensitive resin is one or more of 1, 6-hexanediol diacrylate, dipropylene glycol diacrylate, tripropylene glycol diacrylate and hydroxyethyl methacrylate; the dispersant is a phosphate dispersant.

In the preparation method of the artificial bone particles according to the present disclosure, optionally, the predetermined ball-to-ball ratio is 1:1.5 to 1:2, the mass of the graphene is 0.5% -1% of the mass of the ceramic slurry for printing, and the mass ratio of the dispersant to the graphene is 3:1 to 1:1. Thereby, artificial bone particles having a smooth surface can be obtained.

According to the present disclosure, an artificial bone material for repairing a bone defect and a method for preparing an artificial bone particle, which can improve the stability of the artificial bone material at a defect site, can be obtained.

Drawings

The disclosure will now be explained in further detail by way of example only with reference to the accompanying drawings, in which:

fig. 1 is a scene schematic diagram illustrating an artificial bone material according to an example of the present disclosure.

Fig. 2 is a perspective view illustrating an artificial bone particle according to an example of the present disclosure.

Fig. 3 is a front view illustrating an artificial bone particle according to an example of the present disclosure.

Fig. 4 is a top view illustrating an artificial bone particle according to an example of the present disclosure.

Fig. 5 is a partial cross-sectional view illustrating an artificial bone particle according to an example of the present disclosure.

Fig. 6 is a schematic diagram illustrating a body portion of an artificial bone particle according to an example of the present disclosure.

Fig. 7 is a schematic diagram illustrating a support column for an artificial bone particle according to an example of the present disclosure.

Fig. 8 is a schematic diagram illustrating a modification of the artificial bone particle according to the example of the present disclosure.

Fig. 9 is a schematic diagram illustrating example 1 of an artificial bone particle according to an example of the present disclosure.

Fig. 10 is a schematic diagram illustrating example 2 of an artificial bone particle according to an example of the present disclosure.

Fig. 11 is a schematic diagram illustrating example 3 of an artificial bone particle according to an example of the present disclosure.

Fig. 12 is a schematic diagram illustrating example 4 of an artificial bone particle according to an example of the present disclosure.

Fig. 13 is a schematic diagram illustrating example 5 of an artificial bone particle according to an example of the present disclosure.

Fig. 14 is a flowchart illustrating a method of preparing artificial bone particles according to an example of the present disclosure.

Fig. 15 is a flowchart illustrating a sintering process method of artificial bone particles according to an example of the present disclosure.

Fig. 16 is a staining graph showing 12 week slices implanted at a canine bone defect site for artificial bone particles according to examples of the present disclosure.

The main reference numbers illustrate:

1 … artificial bone material, 10 … artificial bone particles, 11 … main body part, S1 … upper surface, S2 … lower surface, 111 … through hole, 112 … first through hole, S3 … first side surface, S₃₁… first plane, S₃₂… second plane, S₃₃… third plane, N₁、N₂、N₃… normal, α 1, α 2 … included angle, S4 … second side, 12 … supporting column, 121 … second through hole, 122 … third through hole, 123 … end, L … length direction, D₁… diagonal line, D₂… side length, third side of S5 ….

Detailed Description

Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the following description, the same components are denoted by the same reference numerals, and redundant description thereof is omitted. The drawings are schematic and the ratio of the dimensions of the components and the shapes of the components may be different from the actual ones.

It is noted that the terms "comprises," "comprising," and "having," and any variations thereof, in this disclosure, for example, a process, method, system, article, or apparatus that comprises or has a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include or have other steps or elements not expressly listed or inherent to such process, method, article, or apparatus. It will be understood by those within the art that, in general, terms used in the present disclosure are generally intended as "open" terms (e.g., the term "including" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "includes" should be interpreted as "includes but is not limited to," etc.). Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

In addition, the headings and the like referred to in the following description of the present disclosure are not intended to limit the content or scope of the present disclosure, but merely serve as a reminder for reading. Such a subtitle should neither be understood as a content for segmenting an article, nor should the content under the subtitle be limited to only the scope of the subtitle.

The present disclosure relates to an artificial bone material 1 for repairing a bone defect and a method for preparing artificial bone particles 10, which can improve the stability of the artificial bone material 1 at a defect site. The artificial bone 1 for repairing a bone defect may be simply referred to as an artificial bone 1. The artificial bone material 1 related to the present disclosure can be suitable for alveolar ridge expansion, filling and repairing of bone defects around periodontal and implant, bone defect repair requiring bone grafting and filling in oral maxillofacial surgery or plastic surgery, bone fusion between spinal interbody, transverse process and vertebral lamina, bone defect repair after scraping of bone tuberculosis lesions, bone defect repair after excision of benign bone tumor or tumor-like lesion, bone defect repair caused by various trauma or operation, bone defect repair in artificial joint replacement or revision, and bone grafting treatment of aseptic necrosis of femoral head.

Fig. 1 is a scene schematic diagram illustrating an artificial aggregate 1 according to an example of the present disclosure. In the present disclosure, as shown in fig. 1, the artificial bone material 1 may be used, for example, to repair a bone defect of a host bone 2. The disclosed artificial bone material 1 has high stability at a bone defect site of a host bone 2.

Fig. 2 is a perspective view illustrating an artificial bone particle 10 according to an example of the present disclosure. Fig. 3 is a front view showing an artificial bone particle 10 according to an example of the present disclosure. Fig. 4 is a top view illustrating an artificial bone particle 10 according to an example of the present disclosure. Fig. 5 is a partial sectional view showing an artificial bone particle 10 according to an example of the present disclosure.

In the present embodiment, the artificial bone material 1 for repairing a bone defect may include a plurality of artificial bone particles 10. A plurality of artificial bone particles 10 are stacked on each other to form an artificial bone material 1 (see fig. 1 and 2). The artificial bone material 1 formed by stacking the artificial bone particles 10 may have a porous structure.

In some examples, the porosity of the artificial bone material 1 may be 60% to 90%. In this case, the artificial bone material 1 simulates the anatomical structure of the tissue of a natural bone, and is advantageous in that osteoblasts adhere to, grow on and creep on the surface of the artificial bone particles 10 of the artificial bone material 1, and in that the conditions for regenerative repair of bone tissue are satisfied. Meanwhile, the mutually communicated (namely three-dimensional communicated) knots among the pores can ensure the transmission of nutrient substances and metabolic waste. For example, the porosity may be 60%, 70%, 80%, 90%.

In some examples, the macropore diameter in the pores may be 100-. For example, the macropore diameters may be 100 μm, 200 μm, 500 μm, 800 μm, 1000 μm. In some examples, 70% to 80% of the macropores in the pores are open pores. In some examples, the macropores in the pores may be interconnected.

In the artificial bone material 1 according to the present disclosure, the size (dimension) of the artificial bone particles 10 may be 0.25mm to 20 mm. Thereby, it is possible to select artificial bone particles 10 of different sizes according to different application scenarios. In some examples, the size of the artificial bone particle 10 may be 0.25mm to 2 mm. For example, the size of the artificial bone particle 10 may be 0.25mm, 0.3mm, 0.5mm, 0.7mm, 1mm, 1.2mm, 1.5mm, 1.8mm, 2 mm. The artificial bone particles 10 with the size of 0.25mm-2mm can be suitable for repairing the defects of oral cavity and maxillofacial bone. In some examples, the size of the artificial bone particle 10 may be 2mm-20 mm. For example, the size of the artificial bone particle 10 may be 2mm, 5mm, 8mm, 10mm, 12mm, 15mm, 18mm, 20 mm. The artificial bone particles 10 having a size of 2mm to 20mm may be suitable for spinal and trunk bone repair.

In some examples, the size of the artificial bone particle 10 may be represented by the distance between 2 relatively disposed support columns (described in detail later) that are farthest away. For example, as shown in the artificial bone particle 10 of FIG. 4, the size of the artificial bone particle 10 may pass through the diagonal line D₁Is shown. The size of the artificial bone particle 10 is 0.25mm-20mm, that is, the diagonal line D of the artificial bone particle 10₁The length of (A) is 0.25mm-20 mm.

In some examples, the artificial bone particle 10 as shown in FIG. 4, the artificial bone particle 10 having a size of 0.25mm to 20mm has a side length D₂The length of (d) may be 200 μm to 4000 μm. E.g. side length D₂The length of (B) may be 200. mu.m, 500. mu.m, 800. mu.m, 1000. mu.m, 1500. mu.m, 2000. mu.m, 2500. mu.m, 3000. mu.m, 3500. mu.m, 4000. mu.m.

In some examples, the artificial bone particle 10 is degradable. The artificial bone particles are usually coated with new bone tissue on the outside, and as the artificial bone particles 10 are degraded, the positions of the artificial bone particles 10 are replaced by new bone.

In some examples, each face of the artificial bone particle 10 may have a microporous structure. Therefore, as the artificial bone particles 10 are degraded, new bone gradually replaces the artificial bone particles 10 through the micropores, and the osteogenesis capability is good.

In the present embodiment, the artificial bone particle 10 may include a body part 11 and a supporting column 12. The support posts 12 may be disposed around the main body portion 11. The support post 12 may extend along the length direction L and protrude from the main body 11. Under the condition, the artificial bone particle can better adapt to the implantation defect part, and the contact stability between the artificial bone particle 10 and the host bone 2 is improved; the impact force of blood scouring on the main body part 11 is slowed down, the problems of looseness and instability caused by the scouring of the artificial bone particles 10 by the blood are improved to a certain extent, the stability of the artificial bone 1 at the defect part is improved, and the implantation effect of the artificial bone 1 is improved.

Fig. 6 is a schematic view showing the body portion 11 of the artificial bone particle 10 according to the example of the present disclosure.

In some examples, as described above, the artificial bone particle 10 may include the body portion 11 (see fig. 2). The body portion 11 may have an elongated shape.

In some examples, the body portion 11 may be cylindrical. For example, the body portion 11 may have a prismatic shape (see fig. 6). Examples of the present disclosure are not limited thereto, and the body portion 11 may have a cylindrical shape.

In some examples, the body portion 11 may have an upper surface S1 and a lower surface S2 (see fig. 2-3) that are oppositely disposed. In some examples, the upper surface S1 and the lower surface S2 may be parallel and equal. In some examples, the upper surface S1 or the lower surface S2 may be polygonal or circular. For example, the upper surface S1 or the lower surface S2 may be a regular polygon (see fig. 2 to 3). Examples of the present disclosure are not limited thereto, and the upper surface S1 or the lower surface S2 may be an irregular polygon.

In some examples, the body portion 11 may have a first side S3. The number of the first side S3 may be plural. For example, the number of the first sides S3 may be four (see fig. 2 to 6). The first side surface S3 may intersect both the upper surface S1 and the lower surface S2. Examples of the present disclosure are not limited thereto, and each of the first sides S3 may intersect the upper surface S1 or the lower surface S2.

In some examples, the first side surface S3 may be formed by sequentially connected first planes S₃₁A second plane S₃₂And a third plane S₃₃And (4) forming. First plane S₃₁A second plane S₃₂Or a third plane S₃₃May be quadrangular, for example rectangular (see fig. 6). Examples of the present disclosure are not limited thereto, the first plane S₃₁A second plane S₃₂Or a third plane S₃₃May be curved.

In other examples, the first side S3 may be a plane or a curved surface. The plane may be, for example, a polygonal plane. The curved surface may be, for example, a spherical surface.

In some examples, as shown in fig. 3 and 6, the first plane S₃₁Normal line N of₁May be orthogonal to the longitudinal direction L of the main body 11. Second plane S₃₂Normal line N of₂May be orthogonal to the longitudinal direction L of the main body 11. Third plane S₃₃Normal line N of₃May be orthogonal to the longitudinal direction L of the main body 11.

In some examples, as shown in fig. 6, the first plane S₃₁And a second plane S₃₂May intersect. First plane S₃₁And a second plane S₃₂May be represented as α 1, angle α 1 may be an obtuse angle, and third plane S₃₃And a second plane S₃₂May intersect. Third plane S₃₃And a second plane S₃₂May be represented as α 2 the angle α 2 may be an obtuse angle examples of the disclosure are not limited thereto and the angle α 1 or α 2 may be a right angle, an acute angle, or a straight angle.

In some examples, when the included angles α 1 and α 2 are straight angles, the first side surface S3 can be regarded as a plane.

In some examples, the first plane S₃₁And a second plane S₃₂May be equal to the third plane S₃₃And a second plane S₃₂In this case, the third plane S₃₃And a first plane S₃₁About a second plane S₃₂And (4) symmetry. Thus, when the blood washes the first side surface S3 of the main body 11, the third plane S₃₃And a first plane S₃₁Can be evenly stressed.

In some examples, the first side S3 may be disposed between adjacent support posts 12 (described in detail later) (see fig. 2).

In some examples, the body portion 11 may have a second side S4. The number of the second side S4 may be plural. For example, the number of the second side faces S4 may be four (see fig. 2 to 6). The second side surface S4 and the first side surface S3 may constitute a set of side surfaces of the main body portion 11. The body portion 11 may have multiple sets of sides. For example, the main body portion 11 may have four sets of sides (see fig. 2 to 6).

In some examples, the second side S4 may intersect both the upper surface S1 and the lower surface S2. Examples of the present disclosure are not limited thereto, and each of the second side surfaces S4 may intersect the upper surface S1 or the lower surface S2.

In some examples, the second side surface S4 may be defined by an adjacent fourth plane S₄₁And a fifth plane S₄₂And (4) forming. Fourth plane S₄₁Or a fifth plane S₄₂May be quadrangular, for example rectangular (see fig. 6). Examples of the present disclosure are not limited thereto, the fourth plane S₄₁Or a fifth plane S₄₂May be curved.

In other examples, the second side S4 may be a curved surface. The curved surface may be, for example, a spherical surface.

In some examples, as shown in fig. 6, a fourth plane S₄₁And a fifth plane S₄₂May intersect. Fourth plane S₄₁And a fifth plane S₄₂The included angle of (a) may be an acute angle, a right angle or an obtuse angle.

In some examples, the body portion 11 may have a through hole 111. The through hole 111 may penetrate the upper surface S1 and the lower surface S2. That is, the body portion 11 may have a through hole 111 (see fig. 2 to 6) penetrating between the upper surface S1 and the lower surface S2. Thereby, it is possible to facilitate adhesion, growth and creeping of osteoblasts on the surface of the artificial bone particle 10.

In some examples, the through-hole 111 may be a polygonal hole. For example, the through-hole 111 may be a quadrangular hole (see fig. 6). Examples of the present disclosure are not limited thereto, and the through-holes 111 may be circular holes.

In some examples, the through-holes 111 may include through-holes of various sizes. Specifically, the through-holes 111 may include through-holes of different hole diameters or different side lengths. For example, the through-holes 111 may include a first through-hole 111a and a second through-hole 111b (see fig. 6). The first through-hole 111a may have a larger side than the second through-hole 111 b.

In some examples, the first through hole 111a may be disposed in the middle of the body part 11. Specifically, the center axis of the first through hole 111a may overlap the center axis of the main body 11.

In some examples, the second through hole 111b may be disposed around the first through hole 111 a. Among them, the respective second through holes 111b disposed around the first through hole 111a may be uniformly and symmetrically distributed (see fig. 2 and 4). Examples of the present disclosure are not limited thereto, and the respective second through holes 111b may be randomly distributed around the first through hole 111 a.

In some examples, the second through hole 111b may be provided in the body portion between adjacent support pillars 12 (described later in detail) (see fig. 4). The second through hole 111b of the body portion located between the adjacent supporting columns 12 may be one or more.

In some examples, the body portion 11 may have a plurality of first through holes 112. Thereby, it is possible to facilitate the adhesion, growth and creeping of osteoblasts on the artificial bone particles 10.

In some examples, the first through hole 112 may be a polygonal hole. For example, the first through-hole 112 may be a quadrangular hole (see fig. 6). Examples of the present disclosure are not limited thereto, and the first through hole 112 may be a circular hole.

In some examples, the first through hole 112 may communicate with the through hole 111. In some examples, the first through hole 112 may communicate with the first through hole 111 a. The first through hole 112 may communicate with the second through hole 111b (see fig. 5).

In some examples, the first through hole 112 may communicate from the first side surface S3 to the through hole 111. This can facilitate adhesion, growth, or creeping of osteoblasts on the surface of the artificial bone particles 10 of the artificial bone material 1. The first through hole 112 may communicate with the first through hole 111a from the first side surface S3. The first through hole 112 may communicate with the second through hole 111b from the first side surface S3 (see fig. 5). In some examples, the first through hole 112 may communicate from the first side surface S3 with a second through hole 111b of the main body portion located between adjacent support pillars 12 (described later in detail) (see fig. 5).

In some examples, the first via 112 may be from the second plane S₃₂And communicates with the through hole 111. In this case, canThe area of the first side surface S3 of the body 11 can be increased to reduce the impact force generated when the blood washes the first side surface S3 of the body 11 to some extent. Wherein the first through hole 112 may be from the second plane S₃₂Communicates with the first through-hole 111a (see fig. 2 to 5). The first through-hole 112 may be from the second plane S₃₂Communicating with the second through hole 111b (see fig. 5).

Fig. 7 is a schematic view showing a support column 12 of the artificial bone particle 10 according to an example of the present disclosure.

In some examples, as described above, the artificial bone particle 10 may include a support post 12 (see fig. 2). The number of the support columns 12 may be plural. For example, the number of support posts 12 may be 4. A plurality of support columns 12 may be formed at the main body portion 11. Under the condition, the supporting columns 12 of the artificial bone particles 10 can reduce the impact force of blood scouring on the main body part 11, so that the problems of looseness and instability caused by the blood scouring of the artificial bone particles 10 are improved to a certain extent, the stability of the artificial bone material 1 at the defect part is improved, and the implantation effect of the artificial bone material 1 is improved.

In some examples, a plurality of support posts 12 may be disposed around the body portion 11. Specifically, a plurality of support columns 12 may be provided around the main body portion 11 along the length direction L of the main body portion 11 (see fig. 2 to 4).

In some examples, the support posts 12 may be elongated. In some examples, the support posts 12 may be cylindrical. For example, the support post 12 may be prismatic (see fig. 7). Examples of the present disclosure are not limited thereto, and the support column 12 may have a cylindrical shape. In some examples, the support post 12 may have a plurality of second through holes 121. Thereby, it is possible to facilitate adhesion, growth and creeping of osteoblasts on the surface of the artificial bone particle 10.

In some examples, the second through hole 121 may be a polygonal hole. For example, the second through-hole 121 may be a quadrangular hole (see fig. 7). Examples of the present disclosure are not limited thereto, and the second through hole 121 may be a circular hole.

In some examples, the second through hole 121 may communicate with the through hole 111. In some examples, the second through hole 121 may communicate with the second through hole 111b (see fig. 5). This further contributes to adhesion, growth, or creeping of osteoblasts on the surface of the artificial bone particles 10 of the artificial bone material 1. In some examples, the second through hole 121 may communicate with the second through hole 111b of the body portion located between the adjacent support pillars 12 (see fig. 5).

In some examples, the second through hole 121 may communicate with the first through hole 112 (see fig. 5). This further contributes to adhesion, growth, or creeping of osteoblasts on the surface of the artificial bone material 1.

In some examples, the support post 12 may have a plurality of third through holes 122. The third through hole 122 may be a polygonal hole. For example, the third through-hole 122 may be a quadrangular hole (see fig. 7). Examples of the present disclosure are not limited thereto, and the third through hole 122 may be a circular hole.

In some examples, the third through hole 122 may be disposed at an end of the support post 12 near the lower surface S2 (see fig. 3). In some examples, the third through hole 122 may be provided to a portion of the support stand 12 protruding from the lower surface S2 of the main body portion 11 (see fig. 3).

In some examples, the third through hole 122 may penetrate the support post 12 in a direction intersecting the length direction L. The direction intersecting the longitudinal direction L may be a direction orthogonal to the longitudinal direction L.

In addition, in some examples, each face of the artificial bone particle 10 may have a microporous structure. Therefore, the artificial bone material 1 formed by stacking the artificial bone particles 10 has a good bone forming effect. The respective faces of the artificial bone particle 10 include, but are not limited to, the upper and lower surfaces and the respective side faces of the body portion 11, and the side faces of the support post 12 (described later).

In some examples, the support post 12 may extend along the length direction L and protrude from the body portion 11. In this case, the protrusions of the support columns 12 can improve the stability of the contact between the artificial bone particles 10 and the host bone 2 when implanted into the defect site, and thus the artificial bone particles 10 having the protrusions can be better adapted to the implantation defect site.

In some examples, the support post 12 may extend along the length direction L and protrude from the upper surface S1 or the lower surface S2 of the body portion 11. In some examples, the support post 12 may extend along the length direction L and protrude from the upper surface S1 and the lower surface S2 of the body portion 11 (see fig. 3).

In some examples, the protrusions may be embodied as prismoid-like ends 123 (see fig. 3 and 7). This can reduce damage to the host bone 2.

In some examples, the support post 12 may have a third side S5. The support post 12 may have a plurality of third sides S5. For example, the support column 12 may have 2 third sides S5, that is, the support column 12 may have 4 sides (see fig. 7). The third side surface S5 may be defined by an adjacent sixth plane S₅₁And a seventh plane S₅₂And (4) forming. Sixth plane S₅₁Or a seventh plane S₅₂May be quadrangular, for example rectangular (see fig. 7). Examples of the present disclosure are not limited thereto, the sixth plane S₅₁Or a seventh plane S₅₂May be curved.

In other examples, the third side S5 may be a curved surface. The curved surface may be, for example, a spherical surface.

In some examples, as shown in fig. 7, a sixth plane S₅₁And a seventh plane S₅₂May intersect. Sixth plane S₅₁And a seventh plane S₅₂The included angle of (a) may be an acute angle, a right angle or an obtuse angle. Sixth plane S₅₁And a seventh plane S₅₂Is equal to the fourth plane S₄₁And a fifth plane S₄₂The included angle of (a).

In some examples, the sixth plane S₅₁Can be aligned with the fourth plane S₄₁Bonding, seventh plane S₅₂May be aligned with the fifth plane S₄₂In this case, the support column 12 can be formed in the main body portion 11. The supporting columns 12 and the body 11 form the artificial bone particle 10.

In the present disclosure, the porosity of the artificial bone material 1 for repairing a bone defect is 60 to 90%, which is formed by stacking a plurality of artificial bone particles 10 on one another. The artificial bone particle 10 includes a body 11 having an elongated shape and a plurality of support columns 12 formed on the body 11, the body 11 having an upper surface S1 and a lower surface S2 which are oppositely disposed, and a through hole 111 penetrating between the upper surface S1 and the lower surface S2. The plurality of support columns 12 are provided around the main body 11 along the longitudinal direction L of the main body 11, and the support columns 12 extend along the longitudinal direction L and protrude from the main body 11. In this case, the artificial bone particle 10 having the protrusion can be better adapted to the implantation defect site; the protrusion of the support post 12 can improve the stability of the contact between the artificial bone particles 10 and the host bone 2 when implanted into the defect site; in addition, the supporting columns 12 of the artificial bone particles 10 can reduce the impact force of blood washing on the main body part 11, so that the problems of looseness and instability caused by blood washing of the artificial bone particles 10 are improved to a certain extent, the stability of the artificial bone 1 at the defect part is improved, and the implantation effect of the artificial bone 1 is improved. In addition, the artificial bone particles 10 according to the present disclosure can be tightly packed when being implanted into a defect site, and the cavities between the artificial bone particles 10 are relatively small.

Fig. 8 is a schematic diagram illustrating a modification of the artificial bone particle 10 according to the example of the present disclosure.

The artificial bone particle 10a shown in fig. 8 is a modification of the above-described artificial bone particle 10. The main differences compared to the artificial bone particle 10 described above are: the artificial bone particle 10a may have a body part 11a and a supporting column 12 a. The main body 11a has a first side surface which is a curved surface compared to the main body 11 of the artificial bone particle 10. The supporting column 12a has a cylindrical shape, compared to the supporting column 12 of the artificial bone particle 10 described above, of the supporting column 12 a. The end of the projection of the support post 12a is a circular truncated cone.

Examples of the present disclosure are not limited thereto, and in other examples, the artificial bone particle 10 and the artificial bone particle 10a may be stacked on each other to form an artificial bone material. In other examples, the artificial bone particles 10 may be stacked with artificial bone particles of other structures (e.g., a twist, square, cross, or tetrapod structure) to form an artificial bone material. Wherein, the artificial bone material formed by mixing and stacking can have continuous gradient porosity of 60-90%.

Fig. 9 is a schematic diagram illustrating example 1 of an artificial bone particle according to an example of the present disclosure. In other examples, as shown in fig. 9, the structure of the artificial bone particle 20a may beReferred to as four feet. The artificial bone particle 20a may include 4 protrusions 21. The protrusion 21 may be columnar. The axes of the 4 protrusions are M respectively₁、M₂、M₃And M₄. Axis M₁、M₂、M₃And M₄Intersecting at point O. The included angle theta between any 2 axes is equal. The included angle theta is 109.47 degrees. As shown in fig. 9, each protrusion extends from the point O in the direction of the arrow on the axis. The diameter of the columnar projection 21 is tapered from the point O end to the tip end. The tip of the protrusion 21 may have a circular truncated cone shape. In example 1, the respective protrusions are the same in shape. Examples of the present disclosure are not limited thereto.

Fig. 10 is a schematic diagram illustrating example 2 of an artificial bone particle according to an example of the present disclosure. In other examples, as shown in fig. 10, the configuration of the artificial bone particle 30a may be referred to as a torquing. The artificial bone particle 30a may include a body 31, a first protrusion 32, and a second protrusion 33. The body 31, the first protrusion 32, and the second protrusion 33 are all columnar. The first protrusion 32 and the second protrusion 33 are located at both ends of the body 31, respectively. The axes of the main body 31, the first projection 32 and the second projection 33 are respectively E₁、E₂And E₃. Axis E₁And the axis E₂Intersect at the point O₁And angle β is 90 degrees₁And the axis E₃Intersect at the point O₂And the included angle is equal to β DEG axis E₂And the axis E₃Not in the same plane. In some examples, axis E₂Perpendicular to axis E₃. The body 31 is along the axis E₁The diameter is unchanged in the direction. First projection 32 is from point O₁Along axis E₂Extending towards both ends and having a diameter of the first protrusion 32 from point O₁Tapering end to end. Second projection 33 is from point O₂Along axis E₃Extending towards both ends and having a diameter of the second protrusion 33 from point O₂Tapering end to end.

Fig. 11 is a schematic diagram illustrating example 3 of an artificial bone particle according to an example of the present disclosure. In other examples, as shown in fig. 11, the structure of the artificial bone particle 40a may be referred to as a wrenche. The artificial bone particle 40a may include a

body

41, 4

first protrusions

42, and 2 second protrusions 43. The body 41 is a quadrangular prism. The 4 first protrusions 42 are located at both ends of the body portion. The 2 second protrusions 43 are located at the middle of the body portion. The extending direction of the protrusion is orthogonal to the longitudinal direction L1 of the main body 41. The extending direction of the first protrusion 42 is perpendicular to the extending direction of the second protrusion 43. The two first protrusions 42 at the same end extend in opposite directions. The extending direction of the first projection 42 at one end is parallel to the extending direction of the first projection 42 at the other end. The 2 second protrusions 43 extend in opposite directions.

In example 3, the first protrusion 42 may be a truncated pyramid, for example, may be a truncated quadrangular pyramid (see fig. 11). As shown in FIG. 11, the upper bottom surface X of the first protrusion 42₁Parallel to the length direction L1. The lower bottom surface of the first protrusion 42 and the side surface Y of the body 41₁And (6) attaching. The first protrusion 42 has a plurality of sides. Side surface X of first projection 42₂And the side Y of the main body 41₂The intersection angle can be represented by γ 1. The included angle γ 1 may be, but is not limited to, 170.54 degrees. Side Y₁And side Y₂May intersect the side edge U, and the side edge V of the first protrusion 42 intersects the side edge U at an angle, which may be represented by γ 2. The included angle γ 2 may be, but is not limited to, 71.80 degrees. The side edge W of the second protrusion 43 intersects the side edge U at an angle, which may be designated by γ 3. Included angle y 3 may be, but is not limited to, 80.66 degrees.

Fig. 12 is a schematic diagram illustrating example 4 of an artificial bone particle according to an example of the present disclosure. Fig. 13 is a schematic diagram illustrating example 5 of an artificial bone particle according to an example of the present disclosure. In other examples, as shown in fig. 12, the structure of the artificial bone particle 50a may be referred to as a square. The artificial bone particle 50a may be cubic. The artificial bone particle 50a may include a first through-hole 51 penetrating the upper and lower surfaces of the cube, a second through-hole 52 penetrating the left and right surfaces of the cube, and a third through-hole 53 penetrating the front and rear surfaces of the cube. The first through-hole 51, the second through-hole 52, and the third through-hole 53 may be circular or square. The first through-hole 51, the second through-hole 52, and the third through-hole 53 communicate with each other. In other examples, as shown in fig. 13, the structure of the artificial bone particle 60a may be referred to as a cross. The artificial bone particle 60a may be formed by combining 7 artificial bone particles 50 a. Specifically, the artificial bone granules 60a are formed by disposing one artificial bone granule 50a on each of 6 surfaces of one artificial bone granule 50 a.

The disclosure also relates to a preparation method of the artificial bone particles. The artificial bone particle 10 can be obtained by the following method for preparing an artificial bone particle. It should be noted that the preparation method of the artificial bone particle according to the present disclosure can also prepare artificial bone particles with other structures. Such as wrenches, squares, crosses, or tetrapods. The preparation method of the artificial bone particle related to the present disclosure can save raw materials and obtain the artificial bone particle 10 with higher integrity. The following detailed description is made with reference to the accompanying drawings.

Fig. 14 is a flowchart illustrating a method of preparing the artificial bone particle 10 according to an example of the present disclosure. Fig. 15 is a flowchart illustrating a sintering process method of the artificial bone particle 10 according to an example of the present disclosure.

In the present disclosure, as shown in fig. 14, a method of preparing the artificial bone particle 10 may include preparing a surface modifier solution, a bioactive calcium-phosphorus-based ceramic powder, and agate balls, mixing the calcium-phosphorus-based ceramic powder and the agate balls at a predetermined material-to-ball ratio, and adding the surface modifier solution to grind to obtain a slurry, followed by drying and filtering the slurry to obtain a target ceramic powder (step S100).

In some examples, the surface modifier solution may be selected from one of higher fatty acids, higher phosphate ester salts, unsaturated fatty acids, unsaturated organic acids.

In some examples, the surface modifier solution in step S100 may be formulated by adding palmitic acid to anhydrous ethanol. The mass ratio of the absolute ethyl alcohol to the palmitic acid can be 15:1 to 150:1, for example, 15:1, 20:1, 30:1, 40:1, 50:1, 60:1, 80:1, 90:1, 100:1, 120:1, and 150: 1.

In some examples, the mass ratio of the surface modifier to the calcium-phosphorus-based ceramic powder may be 1:1 to 2:1, for example, may be 1:1, 1.2:1, 1.5:1, 2: 1.

In some examples, in step S100, the calcium-phosphorus-based ceramic powder body may be a degradable biomaterial. In addition, the calcium-phosphorus-based ceramic powder may be one or more of Hydroxyapatite (HA) ceramic powder, tricalcium phosphate (β -TCP) ceramic powder, or Biphasic Calcium Phosphate (BCP) ceramic powder. In addition, the calcium-phosphorus-based ceramic powder may also be referred to as calcium-phosphorus-based bioactive ceramic powder.

In some examples, the calcium-phosphorus-based bioactive ceramic powder can be added with degradable high molecular materials, so that the toughness of the artificial bone particles can be increased. The degradable high molecular material can be one or more of polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), polyglycolic acid (PGA), Polycaprolactone (PCL) and collagen.

In some examples, the calcium-phosphorus-based ceramic powder and the agate balls may be mixed at a predetermined ball-to-ball ratio in step S100, and the mixture may be ground by adding a surface modifier solution to obtain a slurry. Wherein the predetermined ball-to-ball ratio may be 1:1.5 to 1: 2. For example, the predetermined ball-to-ball ratio may be 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1: 2. The material-ball ratio can be the mass ratio of the calcium-phosphorus-based ceramic powder to the agate balls. Agate balls may be used for milling.

In some examples, the device that performs milling in step S100 may be a milling tank. For example, the milling jar may be an agate milling jar. Milling in an agate jar may also be referred to as ball milling.

In some examples, the prepared surface modifier solution may be introduced into an agate jar, and then the mixed calcium-phosphorus-based ceramic powder and agate balls may be placed in the jar. In other examples, the mixed calcium-phosphorus-based ceramic powder and the agate balls can be placed in a milling pot, and then the prepared surface modifier solution is added into the agate milling pot.

In some examples, the grinding may be performed at a first predetermined rotation speed in step S100 to obtain the slurry. For example, an agate jar may be ball milled at a first predetermined rotational speed to obtain a slurry. The first predetermined rotational speed may be 300r2min to 600r2 min. For example, the first predetermined rotational speed may be 300r2min, 400r2min, 500r2min, or 600r2 min. In addition, the ball milling time at the first predetermined rotational speed may be 4 to 6 hours. For example, the milling jar may be ball milled at the first predetermined rotational speed for 4 hours, 5 hours, and 6 hours.

In some examples, the slurry may be dried and filtered in step S100 to obtain the target ceramic powder. For example, the slurry can be placed in an oven with the temperature condition of 60 ℃ to 70 ℃ for standing and drying for 12 to 14 hours, and then filtered by a 250 or 270-mesh screen to obtain the target ceramic powder. Wherein, the temperature condition of the oven can be 60 ℃, 65 ℃ or 70 ℃. The time for standing to dry may be 12 hours, 13 hours or 14 hours.

In the present disclosure, as shown in fig. 14, a method of preparing the artificial bone particle 10 may include preparing a photosensitive resin, mixing the photosensitive resin with a target ceramic powder, adding a dispersant and graphene, and grinding to obtain a ceramic slurry for printing (step S200).

In some examples, in step S200, the photosensitive resin may be formulated by a photoinitiator and a monomer of the photosensitive resin. That is, the photoinitiator may be used to polymerize monomers of the photosensitive resin under irradiation of ultraviolet light having a predetermined wavelength to obtain the photosensitive resin. Specifically, the photoinitiator may be mixed with a monomer of the photosensitive resin, stirred by a stirrer, and polymerized by the photoinitiator under irradiation of ultraviolet light having a certain wavelength to obtain the photosensitive resin. The predetermined wavelength may be 405 nm.

In some examples, the photoinitiator may be at least one of a free radical initiator. In some examples, the photoinitiator may be one or more of 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide, 1-hydroxy-cyclohexyl-phenyl-methanone, phenylbis (2,4, 6-trimethylbenzoyl) phosphine oxide, methyl benzoylformate, isopropylthioxanthone, or 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone.

In some examples, the monomer of the photosensitive resin may be one or more of 1, 6-hexanediol diacrylate, dipropylene glycol diacrylate, tripropylene glycol diacrylate, and hydroxyethyl methacrylate.

In some examples, the mass ratio of the photoinitiator to the monomers of the photosensitive resin may be 1:30 to 1:120, for example, may be 1:30, 1:50, 1:80, 1:100, 1: 120.

In some examples, the mass of the calcium-phosphorus-based ceramic powder accounts for 30% to 80% of the total mass of the surface modifier solution, the calcium-phosphorus-based ceramic powder, and the photoinitiator, and may be 30%, 40%, 50%, 60%, 70%, or 30%, for example.

In some examples, the photosensitive resin may be mixed with the target ceramic powder in step S200, and the dispersant and the graphene may be added to perform grinding, thereby obtaining the printing ceramic paste. Specifically, the photosensitive resin and the target ceramic powder are mixed and then placed in a grinding tank, and then the dispersant and graphene are added into the grinding tank, and then grinding is performed at a second predetermined rotation speed to obtain the printing ceramic slurry.

In some examples, the dispersant may be a phosphate-based dispersant. The dispersant can be one or more of nonyl phenol polyether phosphate, styrene-based polyether phosphate and fatty alcohol ether phosphate.

In some examples, the graphene may have a particle size in the range of 200nm to 600 nm. For example, the particle size of the graphene may be 200nm, 250nm, 300nm, 350nm, 400nm, 450nm, 500nm, 550nm, 600 nm.

In some examples, the graphene may be 0.5% to 1% by mass of the ceramic paste for printing. For example, the mass ratio of graphene to the ceramic paste for printing may be 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1%. Therefore, the fluidity of the ceramic slurry for printing can be improved, and the surface of the printed finished product (namely the artificial bone particle blank) is smooth.

In some examples, graphene may function as a lubricant and micropore placeholder. In some examples, the mass ratio of dispersant to graphene may be 3:1 to 1:1. For example, the mass ratio of dispersant to graphene may be 3:1, 2:1, or 1:1. Thereby, the artificial bone particle 10 having a smooth surface can be obtained.

In some examples, the mass ratio of the photosensitive resin to the target ceramic powder may be 1:1 to 55: 45.

In some examples, the total mass of the dispersant and graphene accounts for 2% -3% of the total mass of the photosensitive resin, the target ceramic powder, the dispersant, and graphene, and may be, for example, 2%, 2.5%, or 3%.

In some examples, the second predetermined rotational speed may be 600-. For example, the second predetermined rotational speed may be 600r2min, 650r2min, 700r2min, 750r2min, or 800r2 min. In addition, the second predetermined rotational speed may be for a grinding time of 6 to 8 hours. For example, the milling jar may be ball milled at the second predetermined rotational speed for 6 hours, 7 hours, and 8 hours.

In the present disclosure, as shown in fig. 14, the method for preparing the artificial bone particle 10 may include designing a model of the artificial bone particle 10 using design software, and printing using ceramic slurry for printing based on the model in a 3D printing apparatus to obtain an artificial bone particle blank (step S300).

In some examples, the model of the artificial bone particle 10 may be designed using design software in step S300. The design software may include, but is not limited to, 3D design software such as soildworks. The structure of the artificial bone particle 10 may be various structures as described above. That is, a model of the artificial bone particle 10 may be designed based on the artificial bone particle 10 of various structures as described above. In addition, the model of the artificial bone particle 10 needs to be designed with reference to the size of the defect site.

In some examples, the artificial bone particle blank may be obtained by printing with a ceramic slurry for printing based on a model in a 3D printing apparatus in step S300. Specifically, the model may be imported into the 3D printing device, and the printing parameters of the 3D printing device may be set. The printing parameters may include, among other things, the particle size and the particle side length of the artificial bone particle 10. In addition, the ceramic slurry for printing can be placed in a material box of 3D printing equipment, and photocuring 3D printing is carried out to obtain the artificial bone particle blank.

In some examples, the particle size and particle side length of the artificial bone particle 10 in the printing parameters are related to the size of the defect site.

In this disclosure, use 3D to print can avoid unnecessary cutting waste to produce, processing is swift and the cost is lower, and material utilization can reach more than 95%. The 3D printing equipment occupies a small area. The artificial bone particles 10 obtained by 3D printing have good integrity.

In the present disclosure, as shown in fig. 14, a method for preparing the artificial bone particle 10 may include washing and drying an artificial bone particle blank, and then sintering the artificial bone particle blank to obtain the artificial bone particle 10 (step S400).

In some examples, the artificial bone granule embryo body may be washed with anhydrous ethanol in step S400. Thereby, the uncured ceramic slurry for printing on the surface of the artificial bone particle blank can be removed. In some examples, the sintering process of the artificial bone particle blank may be performed using a muffle furnace in step S400.

In some examples, as shown in FIG. 15, in step S400, the sintering process may include setting an initial temperature to 20-25 deg.C, raising the temperature to 300-320 deg.C at a temperature raising rate of 2 deg.C for 2 minutes, and maintaining the temperature at 300-320 deg.C for 1-2 hours (step S410). The initial temperature may be set at 20 deg.C, 21 deg.C, 22 deg.C, 23 deg.C, 24 deg.C or 25 deg.C.

In some examples, as shown in FIG. 15, the sintering process may include raising the temperature from 300-320 ℃ to 500-600 ℃ at a temperature raising rate of 0.8-1 ℃ for 2 minutes and maintaining the temperature at 500-600 ℃ for 5-6 hours (step S420).

In some examples, as shown in FIG. 15, the sintering process may include raising the temperature from 500-600 ℃ to 1050-1100 ℃ at a temperature raising rate of 2-3 ℃ for 2 minutes, and maintaining the temperature for 2-3 hours (step S430).

In some examples, as shown in fig. 15, the sintering process may include then naturally cooling to room temperature (step S440). Thus, the artificial bone particle blank can be sintered into the desired artificial bone particle 10 by the sintering process. The room temperature may be 25 to 30 ℃ and may be, for example, 25 ℃, 26 ℃, 27 ℃, 28 ℃, 29 ℃ or 30 ℃.

In some examples, sintering the artificial bone particle blank at a high temperature of 600 ℃ or higher can remove graphene, so that the graphene is transformed into micropores in situ. In other words, the graphene sintered at a high temperature of 600 ℃ or higher can be converted into harmless carbon dioxide gas, so that micropores are left on the artificial bone particles 10. In this case, the microporous structure facilitates the degradation of the artificial bone particles 10 and the new bone ingrowth.

Compared with the problems of poor fluidity of calcium-phosphorus slurry, poor surface smoothness of the artificial bone and compactness and non-porosity after sintering in the existing preparation method, in the method, the artificial bone particles 10 prepared by utilizing the calcium-phosphorus-based ceramic powder with bioactivity are convenient for degradation after the artificial bone particles 10 are implanted into defect parts; the ceramic powder, the surface modifier solution, the photosensitive resin and the graphene can be used for preparing slurry with good fluidity; the graphene can be converted into gas in subsequent sintering, so that the artificial bone particles 10 are provided with a microporous structure, and the microporous structure is favorable for the degradation of the artificial bone particles 10 and the growth of new bones; the raw materials can be saved by printing with the 3D printing equipment, and the artificial bone particles 10 with high integrity are obtained.

Fig. 16 is a staining graph showing 12 week slices implanted at a canine bone defect site for artificial bone particles according to examples of the present disclosure. Hereinafter, the effect of the method for preparing the artificial bone particle 10 of the present disclosure will be described in connection with examples and comparative examples of the method for preparing the artificial bone particle 10. It is to be noted that the present disclosure is not limited to the embodiments, and includes various modifications that may occur to those skilled in the art.

[ examples ] A method for producing a compound

In the examples, 0.8g of palmitic acid was added to 50g of absolute ethanol to prepare a surfactant solution. Weighing 50g of biphase calcium phosphate ceramic powder, placing the biphase calcium phosphate ceramic powder in an agate ball milling tank, introducing a prepared surfactant solution, and then adding a mixture with a material-ball ratio of 1:1.5 agate beads. And placing the agate ball milling tank in a ball mill to perform ball milling for 4 hours at the rotating speed of 300r2min to obtain fully mixed ball milling slurry. And (3) standing and drying the ball-milled slurry in an oven at 60 ℃ for 12 hours, and sieving the ball-milled slurry by a 250-mesh sieve to obtain the surface-modified biphase calcium phosphate ceramic powder.

In the examples, 1.2g of a photoinitiator (phenylbis (2,4, 6-trimethylbenzoyl) phosphine oxide) was weighed out and mixed with 40g of a monomer (1, 6-hexanediol diacrylate, HDDA) of a photosensitive resin, and stirred on a magnetic stirrer for 5 hours so that the photoinitiator was sufficiently dissolved in the monomer to obtain a photosensitive resin.

In the examples, 53g of photosensitive resin was mixed with 45g of surface-modified biphasic calcium phosphate ceramic powder, the mixture was put into an agate jar, 1.5g of dispersant (nonylphenol polyether phosphate) and 0.5g of graphene were added, and the mixture was ball-milled in a ball mill at 600r2min for 6 hours to uniformly disperse the surface-modified biphasic calcium phosphate ceramic powder in the photosensitive resin, thereby obtaining a photocurable printing ceramic slurry.

In the embodiment, printing parameters are set in DLP printing equipment, a model of the artificial bone particles 10 designed by Solidworks software is led into a 3D printer, the particle size and the side length are set according to the requirements of a bone grafting part, then ceramic slurry for photocuring printing is poured into a material box, and photocuring 3D printing is carried out to obtain artificial bone particle blanks.

In the examples, the uncured printing paste on the surface of the artificial bone particle embryo body is washed with absolute ethyl alcohol. After drying, the artificial bone particle embryo body is sintered in a muffle furnace. The sintering procedure was as follows: the temperature is raised from room temperature of 25 ℃ to 300 ℃ at the temperature raising speed of 2min, and then the temperature is kept at 300 ℃ for 1 h. Then heating from 300 ℃ to 600 ℃ at the heating rate of 1 ℃ for 2min, and preserving the heat for 5h at the temperature of 600 ℃; then heating from 600 ℃ to 1100 ℃ at the heating rate of 2 ℃ for 2min, and then preserving heat for 2 h; and finally, naturally cooling to room temperature of 25 ℃ to obtain the artificial bone particles 10.

Then, the artificial bone particles obtained in the examples and the artificial bone material formed by the artificial bone particles were characterized, and the characterization results are shown in table 1, and the specific characterization manner is as follows:

(1) microstructure of the micro-morphology: the artificial bone particles were observed by scanning electron microscopy at different magnifications. The magnification is 30 times, 10000 times and 20000 times respectively.

(2) And (3) porosity testing: take 1cm³The artificial bone particles are piled up to form an artificial bone material, the artificial bone material is placed in a transparent acrylic tube with the diameter of 8mm, and the porosity of the artificial bone material is counted and analyzed by adopting a micro-computer tomography (micro-CT) technology.

(3) And (3) testing the impact resistance: take 1cm³The artificial bone particles are piled up to form artificial bone materials which are placed in a transparent acrylic tube with the diameter of 8 mm.20mL of deionized water was injected at one end of the transparent acrylic tube at a water flow rate of 2mL2s to impact the artificial bone particles accumulated in the tube. Impact displacement (mm) of the piled artificial bone particles (i.e. artificial bone material) is calculated, wherein impact displacement is the length of particle pile after impact-the length of particle pile before impact.

(4) Bone formation effect test: manufacturing a cylindrical defect part with the diameter of 8mm and the height of 10mm on the lateral side of the femoral condyle of the beagle dog, taking out the residual bone fragments in the hole, and slowly filling artificial bone particles into the defect part until the defect part is tightly filled. The muscle, fascia and skin are sutured layer by layer. The materials are taken 12 weeks after the operation, the samples are prepared into hard tissue sections through the steps of fixing, embedding and the like, the osteogenesis effect of the artificial bone material formed by the accumulation of the artificial bone particles at the defect part is inspected by adopting H & E staining, and the H & E staining result is shown in figure 16.

Comparative example 1

Ceramic slurry for photo-curing printing was prepared in the same manner as in example, and then artificial bone particles were prepared by injection molding using a metal mold and characterized in the same manner as in example, with the results shown in table 1.

In comparative example 1, the method of metal mold injection molding includes: ceramic slurry for printing was prepared in the same manner as in example; forming process: after the shape of the artificial bone particles was formed by CAD, a metal mold was fabricated according to the shape, and a mold including 12 cavities was used as the metal mold using SKD11 flash material. The structure of the metal mold is matched with the artificial bone particles 10, the ceramic slurry for printing is injection molded by a horizontal injection molding machine with a mold clamping force of 12 tons, the initial set value of the injection pressure is set to be 12Gpa, the temperature of a cylinder sleeve of the molding machine is set to be 1300 ℃, and the temperature of the metal mold is set to be 200 ℃; degreasing process: heating to 10000 ℃ at the maximum temperature in an atmospheric degreasing furnace under the atmospheric environment, keeping for 1 hour, and then cooling in the furnace. The degreasing process is 18 hours including cooling time, and 90% of alumina (with the porosity of 20%) is adopted as a positioner; and (3) sintering: heating to 10000 deg.C from atmospheric environment, maintaining for 1 hr, and cooling. The sintering time, including the cooling time, was 18 hours. The positioner directly adopts the positioner of degrease process. The artificial bone particles 10 are obtained.

Comparative example 2

In comparative example 2, which is different from the example in that graphene is not added in the preparation of the ceramic slurry for photo-curing printing, artificial bone particles were prepared and characterized in the same manner as the example, and the characterization results are shown in table 1.

Comparative example 3

In comparative example 3, which is different from the example in that the model of the artificial bone particle 10 is an existing sphere shape, artificial bone particles were prepared and characterized in the same manner as the example, and the characterization results are shown in table 1.

TABLE 1 comparison table of characterization results of artificial bone particles and artificial bone materials

Based on table 1, it can be seen that the artificial bone particles obtained by the preparation method of the present disclosure and the artificial bone material formed by stacking the artificial bone particles have a good bone formation effect, as compared to each of comparative examples 1 to 3. The artificial bone particles obtained by the preparation method of comparative example 1 are degraded too fast due to the existence of cracks, so the osteogenic effect of the artificial bone material is poor. The artificial bone particles obtained by the preparation method of comparative example 2 have no abundant micropores on the surface, so that new bone cannot grow in through the micropores, and thus the osteogenic effect of the artificial bone material is general. The artificial bone material obtained by stacking the artificial bone particles obtained in comparative example 3 has a general osteogenesis effect.

The impact resistance of the artificial bone is reflected by impact displacement, and the smaller the impact displacement is, the higher the impact resistance is. Based on table 1, it can be seen that the artificial aggregates of the present disclosure have higher impact resistance, in other words, have higher stability and better implantation effect at the defect site, as compared to each of comparative examples 1 to 3 in examples.

In some instances, numbers expressing quantities of ingredients, properties such as concentrations, reaction conditions, and so forth, used to describe and claim certain examples of the present disclosure are to be understood as being modified in some instances by the term "about". Accordingly, in some examples, the numerical parameters set forth in the written description and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the particular example. In some examples, the numerical parameter should be interpreted in terms of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some examples of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. The numerical values presented in some examples of the disclosure may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

While the present disclosure has been described in detail in connection with the drawings and examples, it should be understood that the above description is not intended to limit the disclosure in any way. Those of skill in the art will recognize many methods and materials similar or equivalent to those described herein that can be used in the practice of the present disclosure. Those skilled in the art can make modifications and variations to the present disclosure as needed without departing from the true spirit and scope of the disclosure, which fall within the scope of the disclosure.

Claims

1. An artificial bone material for repairing a bone defect, comprising a plurality of artificial bone particles stacked on one another to form an artificial bone material having a porosity of 60% to 90%, the artificial bone particles including a body portion and a plurality of supporting pillars formed on the body portion, the body portion being elongated and having an upper surface and a lower surface which are oppositely disposed, the body portion having a through-hole penetrating between the upper surface and the lower surface; the plurality of support columns are disposed around the main body portion along a length direction of the main body portion, the support columns extending along the length direction and protruding from the main body portion.

2. The artificial aggregate according to claim 1, characterized in that:

the main body portion has a plurality of first through holes communicating with the through holes, the main body portion has a plurality of first side surfaces provided between adjacent support columns, and the first through holes communicate from the first side surfaces to the through holes.

3. The artificial aggregate according to claim 2, characterized in that:

the first side face is composed of a first plane, a second plane and a third plane which are sequentially connected, a normal of the first plane, a normal of the second plane and a normal of the third plane are respectively orthogonal to the length direction, an included angle between the first plane and the second plane and an included angle between the third plane and the second plane are respectively an obtuse angle, and the first through hole is communicated from the second plane to the through hole.

4. The artificial aggregate according to claim 1, characterized in that:

the support post has a plurality of second through-holes communicating with the through-hole and the first through-hole.

5. The artificial aggregate according to claim 3, wherein:

and the included angle between the first plane and the second plane is equal to the included angle between the third plane and the second plane.

6. An artificial bone as claimed in any one of claims 1 to 5, wherein:

the size of the artificial bone particles is 0.25mm-20 mm.

7. A preparation method of artificial bone particles is characterized in that,

the method comprises the following steps:

preparing a surface modifier solution, calcium-phosphorus-based ceramic powder with bioactivity and agate balls, mixing the calcium-phosphorus-based ceramic powder and the agate balls according to a preset material-ball ratio, adding the surface modifier solution for grinding to obtain slurry, and then drying and filtering the slurry to obtain target ceramic powder;

preparing photosensitive resin, mixing the photosensitive resin with the target ceramic powder, adding a dispersing agent and graphene, and grinding to obtain ceramic slurry for printing;

designing a model of the artificial bone particles by using design software, and printing by using the ceramic slurry for printing in 3D printing equipment based on the model to obtain an artificial bone particle blank; and is

And cleaning the artificial bone particle blank, drying, and sintering the artificial bone particle blank to obtain the artificial bone particles.

8. The method of claim 7, wherein:

in the sintering treatment, the initial temperature is set to be 25 ℃, the temperature is increased to 300 ℃ at the temperature increasing speed of 2 minutes at 2 ℃, and the temperature is kept for 1 hour at the temperature of 300 ℃;

heating from 300 ℃ to 600 ℃ at a heating rate of 1 ℃ for 2 minutes, and preserving heat for 5 hours at the temperature of 600 ℃;

heating from 600 ℃ to 1100 ℃ at the heating rate of 2 ℃ for 2 minutes, and preserving heat for 2 hours;

then naturally cooling to room temperature.

9. The production method according to claim 7 or 8, characterized in that:

the surface modifier solution is prepared by adding palmitic acid into absolute ethyl alcohol;

the photosensitive resin is prepared from a photoinitiator and a monomer of the photosensitive resin;

the calcium-phosphorus-based ceramic powder is one or more of Hydroxyapatite (HA) ceramic powder, tricalcium phosphate (beta-TCP) ceramic powder or Biphase Calcium Phosphate (BCP) ceramic powder;

the photoinitiator is one or more of 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide, 1-hydroxy-cyclohexyl-phenyl ketone, phenyl bis (2,4, 6-trimethylbenzoyl) phosphine oxide, methyl benzoylformate, isopropyl thioxanthone or 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone;

the monomer of the photosensitive resin is one or more of 1, 6-hexanediol diacrylate, dipropylene glycol diacrylate, tripropylene glycol diacrylate and hydroxyethyl methacrylate;

the dispersant is a phosphate dispersant.

10. The production method according to claim 7 or 8, characterized in that:

the preset ball-to-ball ratio is 1: 1.5-1: 2, the mass of the graphene is 0.5-1% of the mass of the printing ceramic slurry, and the mass ratio of the dispersing agent to the graphene is 3: 1-1: 1.