WO2012117739A1

WO2012117739A1 - Bone filling material

Info

Publication number: WO2012117739A1
Application number: PCT/JP2012/001441
Authority: WO
Inventors: 佐藤　仁; 茂夫藤井
Original assignee: 株式会社リメディオ
Priority date: 2011-03-02
Filing date: 2012-03-02
Publication date: 2012-09-07
Also published as: JP2014100151A

Abstract

The bone filling material (10) comprises a fiber web wherein fibrous calcium phosphate has been molded into a disc or block form. The bone filling material (10) is used by imbedding same under the mucosa or under the mucoperiosteum of a bone defect, alveolar ridge extraction socket, etc. A surface layer (11) that is on at least a portion of the outer surface of the fiber web is smooth. The front face of the bone filling material (10) is protected by the hard surface layer (11). The core (12) contacts the blood in the mucosa and is smoothly absorbed into the somatic tissue.

Description

Bone filling material

The present invention relates to a bone grafting material that promotes bone regeneration.

Bone regeneration material for bone regeneration is a medical material used by being embedded in the mucous membrane of a bone defect. The bone filling material implanted under the mucous membrane is itself degraded by phagocytosis of macrophages, osteoclasts, fibroblasts, etc., and promotes the growth of osteoblasts to regenerate bone tissue.

Regarding this type of technology, Patent Document 1 describes a bone grafting material made of a porous material. This porous body has hollow particles made of calcium phosphate ceramics such as hydroxyapatite or glass as a shell-like skeleton, and has open pores that communicate with the entire porous body and closed pores formed inside the particles. ing. This document describes that a bone prosthetic material having high connectivity and high porosity can be produced by having a porous body having both open pores and closed pores.

Patent Document 2 describes that a nonwoven fabric formed by spinning a calcium phosphate such as hydroxyapatite by solution spinning is used as an implant material.

JP 2008-195595 A JP 61-174460 A

However, since the bone grafting material described in Patent Document 1 is a hollow particle having closed pores, the inside thereof is a closed dead end (closed end). For this reason, there is a problem in that the contact with blood is poor inside the hollow particles and the progress of phagocytosis of macrophages is delayed. For this reason, there is a possibility that the growth rate of osteoblasts may become uneven, or cause local infection or mucosal inflammation. Moreover, since the implant material described in Patent Document 2 is a cotton-like non-woven fabric, there is a problem that the melting rate is high when it is embedded in a body tissue, and the regeneration of the tissue is not sufficient.

The present invention has been made in view of the above-mentioned problems, and provides a bone grafting material that can be used safely by sufficiently promoting the uniform and rapid growth of osteoblasts.

The bone prosthetic material of the present invention includes a fiber entangled body obtained by forming fibrous calcium phosphate into a plate shape or a block shape.

According to the above invention, since the calcium phosphate is formed into a fiber shape, the fiber entangled body has a large surface area and no dead end occurs. For this reason, blood makes good contact with the entire bone filling material inside the embedded mucous membrane. As a result, the growth of osteoblasts is improved, and local infection and inflammation in the mucous membrane are suppressed. Further, since the fiber entangled body is formed into a plate shape or a block shape instead of a sheet shape or cotton shape, it takes a predetermined time for blood to reach the inside of the bone grafting material embedded in the body tissue. For this reason, a time difference will arise in the timing which contacts the blood between the surface and the inside of a bone grafting material. Therefore, a predetermined period (for example, several weeks to several months) from when the surface of the bone grafting material is decomposed by the phagocytosis of macrophages or fibroblasts and osteoblast growth starts until bone tissue is fully regenerated. (Preferably 4 to 8 months), the fiber entangled body remains in the bone prosthetic material and can continue to exert the effect of promoting bone regeneration.

In the bone grafting material of the present invention, as a more specific embodiment, at least a part of the outer surface of the fiber entangled body may be smoothed.
This bone prosthetic material may be formed by folding or winding a calcium phosphate long fiber nonwoven fabric into a plate shape or block shape.
This bone prosthetic material may be formed into a plate shape in which a plurality of through holes are formed.
This bone grafting material includes a surface layer portion and a core portion covered with the surface layer portion, and the density of calcium phosphate in the surface layer portion may be different from the density of calcium phosphate in the core portion.
The bone grafting material includes a base portion and a curved surface portion protruding above the base portion, and the density of calcium phosphate in the curved surface portion may be larger than the density of calcium phosphate in the base portion.
The bone prosthetic material may have an outer shell shape having a hollow portion that communicates with the outside.
In this bone grafting material, the fiber entangled body may be impregnated with the growth factor component, or the surface of the fiber entangled body may be coated.
In this bone grafting material, the growth factor component may be a hydrophobic polysaccharide or aggregated fine particles.
This bone prosthetic material may be formed into a disk shape having a thickness of 1.5 mm to 6 mm and an outer diameter of 10 mm to 40 mm.
This bone prosthetic material may have an annular shape with through holes formed in the thickness direction, and growth factor components may be adhered to the outer peripheral surface and the inner peripheral surface.
The bone filling material may have a porosity of 0.1% to 78%.
In the bone filling material, the fiber diameter of the fiber entangled body may be not less than 0.5 μm and not more than 100 μm.
In the bone filling material, the calcium phosphate fiber may have a streak-like recess formed along the fiber direction.

According to the present invention, there is provided a bone grafting material that can be used safely by sufficiently promoting uniform and rapid growth of osteoblasts.

The above-described object and other objects, features, and advantages will be further clarified by a preferred embodiment described below and the following drawings attached thereto.

FIG. 1A is a perspective view showing a bone grafting material according to a first embodiment of the present invention. 1B is a cross-sectional view taken along the line BB of FIG. 1A. FIG. 1C is an electron micrograph of a cross section of the bone grafting material. FIG. 2A is a perspective view showing a bone grafting material of the second embodiment. FIG. 2B is a schematic diagram showing a use state of the bone grafting material. 3A to 3E are schematic views of bone prosthetic materials according to third to seventh embodiments, respectively. FIG. 4A to FIG. 4D are schematic views for explaining the usage state of the bone grafting material of the fifth embodiment. FIG. 5A to FIG. 5E are schematic views for explaining the usage state of the bone grafting material of the sixth embodiment. It is a schematic diagram which shows the manufacturing apparatus of a bone grafting material. FIGS. 7A to 7C are electron micrographs showing the state of the apatite fibers according to Examples 1 to 3 before firing. 8A and 8B are enlarged views of an apatite fiber before firing according to Example 3. FIG. 9A to 9D are electron micrographs of fired sheet-like fiber entangled bodies according to Reference Examples 1 to 4, respectively. 10A is an enlarged view of a sheet-like fiber entangled body after firing according to Reference Example 3. FIG. FIG. 10B is an enlarged view of the surface of the bone prosthetic material of the block-shaped embodiment 1 after firing.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. In all the drawings, the same reference numerals are given to the same components, and the description will be omitted as appropriate.

FIG. 1A is a perspective view showing a bone grafting material 10 according to a first embodiment of the present invention, and FIG. 1B is a cross-sectional view taken along line BB of FIG. 1A. FIG. 1C is an electron micrograph in which the cross section of the bone grafting material 10 is magnified 3000 times.

The bone grafting material 10 of the present embodiment includes a fiber entangled body obtained by forming fibrous calcium phosphate into a plate shape or a block shape. The bone filling material 10 is used by being embedded in a mucous membrane such as a bone defect part or an extraction fossa of an alveolar ridge. The bone filling material 10 is a material that is decomposed into macrophages or osteoclasts under the mucosa or submucosa periosteum, and is absorbed and replaced by bone tissue. The bone grafting material 10 includes a fiber entangled body containing one or more calcium phosphates as a main component. The fiber entangled body may contain subcomponents other than calcium phosphate such as hydrocarbons and inorganic antibacterial agents. The bone grafting material 10 may include both a plate-like or block-like three-dimensional portion and a flexible portion such as cotton or sheet. The bone prosthetic material 10 may include an encapsulated drug or a packaging agent such as an oblate as an element other than the fiber entangled body.

The calcium phosphate used in the present embodiment is selected from the group consisting of apatite typified by hydroxyapatite, α-tricalcium phosphate (α-TCP), β-tricalcium phosphate (β-TCP), and tetracalcium phosphate (TTCP). At least one selected. Hydroxyapatite (HAp) is a calcium phosphate biomaterial, and its chemical formula is represented by Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ . Biomaterial means a material intended to be transplanted into a human body in the medical field.

An example of a method for forming calcium phosphate into a fiber includes a melt blow (melt spinning) method in which a slurry in which calcium phosphate is dispersed in a solvent is sprayed from a die and formed into a fiber. By blending a binder component made of a hydrocarbon material into the slurry, the calcium phosphate in the molded fiber is stabilized, and the binder component can be removed by a firing step. As the binder component, edible water-soluble polysaccharides are preferable, and pullulan is particularly preferable. In addition, examples of polysaccharides used in the present embodiment include agar, carrageenan, alginic acid, alginates, xanthan gum, dextran, guar gum, pectin, glucomannan, starch, gelatin, karaya gum, chitin, chitosan, methylcellulose, tamarind gum, Men can mention gum arabic.

The fiber length and fiber diameter in the fiber entangled body after firing can be variably adjusted by adjusting the amount of the binder component to be blended in the slurry and the injection speed.
The mass ratio of calcium phosphate to the mass of the solvent is preferably 0.2 or more and 0.4 or less. Further, the mass ratio of the binder component to the mass of the solvent is preferably 0.1 or more and 0.4 or less. The viscosity of the slurry is preferably 10,000 poise or more and 100,000 poise or less, that is, 1 × 10 ³ pascal second or more and 1 × 10 ⁴ pascal second or less.

An aqueous dispersant may be added to the slurry. As the aqueous dispersant, a polycarboxylic acid dispersant, a polysulfonic acid dispersant, a polyphosphoric acid dispersant, an anionic dispersant, and the like can be used.

The fiber diameter of the fiber entangled body can be 0.5 μm or more and 100 μm or less, and preferably 10 μm or less. Within this range, the speed at which the bone grafting material 10 embedded in the mucous membrane is absorbed by the body tissue and the speed at which osteoblasts grow are balanced, so that good bone regeneration is performed. A more preferable fiber diameter is 0.5 μm or more and 6 μm or less. By setting it as this range, the fiber diameter becomes a scale equivalent to the phagocytosis of macrophages, and therefore the osteoinductivity by the bone grafting material 10 is particularly suitable. The fiber diameter can be obtained by image processing of an electron micrograph of the cross section of the bone grafting material 10. As an example, the fiber diameter of the fiber entangled body can be obtained by measuring the fiber diameters at a plurality of locations (for example, 10 locations) in the electron micrograph illustrated in FIG. 1C and taking the average.

The shape of the fiber entangled body constituting the bone grafting material 10 is a plate shape or a block shape, and specifically, various shapes can be taken. Here, that the fiber entangled body is plate-shaped or block-shaped means that the fiber entangled body has a predetermined thickness and shape retention (morphological stability) that does not deform during a medical procedure.

The main surface shape of the plate-shaped bone grafting material 10 is not particularly limited, such as a rectangular shape, a circular shape, or an ellipse diameter. Regarding the plate thickness, it may be uniform as a whole or may have a region where the plate thickness changes continuously or discontinuously.
The specific shape of the block-shaped bone filling material 10 is not particularly limited. Examples include rectangular parallelepiped (including cube) shapes, columnar shapes such as cylinders and prisms, tablet shapes such as disk shapes and spindle shapes, spherical shapes, dome shapes (prone shape), and frustum shapes. Can do. The block shape in the present invention is not limited to a three-dimensional shape composed of only a flat surface, but includes a curved solid body having a curved surface. Among these, the bone grafting material 10 of this embodiment is formed in a disk shape having a thickness of 1.5 mm to 6 mm and an outer diameter of 10 mm to 40 mm as an example of a block shape.

As shown in FIG. 1B, the bone grafting material 10 of this embodiment includes a surface layer portion 11 and a core portion 12 covered with the surface layer portion 11. The thickness of the surface layer portion 11 is preferably 0.5 mm or more and 2 mm or less. FIG. 1C is an electron micrograph of the core portion 12.

The porosity (porosity) of the bone grafting material 10 can be 0.1% or more and 78% or less. The porosity of the bone grafting material 10 can be 0.5% or more, preferably 20% or more, and preferably 50% or less. The porosity of the bone grafting material 10 may be selected according to the affected area where the bone grafting material 10 is used. The porosity can be obtained by the following formula (1).

Porosity (%) = [1− (volume of calcium phosphate in bone substitute) / (apparent volume of bone substitute)] × 100 (1)

Since the bone grafting material 10 of the present embodiment is substantially composed only of calcium phosphate, the (volume of calcium phosphate in the bone grafting material) in the formula (1) can be obtained by the mass of the bone grafting material / specific gravity of calcium phosphate.

The surface layer portion 11 is a dense structure that is harder and smoother than the core portion 12, and has a structure that approximates cortical bone. The density of calcium phosphate in the surface layer portion 11 is larger than the density of calcium phosphate in the core portion 12. The core portion 12 is porous like cancellous bone and is softer than the surface layer portion 11. The bone filling material 10 of this embodiment is embedded under the mucosa or the mucosa periosteum with the core portion 12 facing the inner side of the mucous membrane and the surface layer portion 11 facing the surface side of the mucosa.

In the bone grafting material 10 of the present embodiment, the fiber entangled body is formed in a block shape, and at least a part (surface layer portion 11) of the outer surface is smoothed. Thereby, the surface side of the bone grafting material 10 is protected by the hard surface layer part 11. On the other hand, the core portion 12 comes into contact with blood in the mucous membrane and is smoothly absorbed into the body tissue.

Both the surface layer portion 11 and the core portion 12 are made of a fiber entangled body. The bone grafting material 10 of the present embodiment is a material in which long fibers substantially consisting of only calcium phosphate (hydroxyapatite) are entangled two-dimensionally (planarly) or three-dimensionally (three-dimensionally), and optionally an antibacterial agent Or a growth factor component (Growth Factor) may be supplementarily added. Growth factor components include fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), bone morphogenetic protein (rBMP), beta-type mutant growth Examples include one or more selected from a factor (TGF-β: transforming factor-beta), an epidermal growth factor (rEGF), or a statin.

In addition, a hydrophobic polymer obtained by introducing a hydrophobic molecule into a water-soluble polymer may be added to the bone grafting material 10. The hydrophobized polymer is dissolved in an aqueous solvent such as blood or physiological saline, and self-organized a large number of associated fine particles (nano-aggregate fine particles, nanoparticle associated with a predetermined diameter of 1 μm or less, preferably 100 nm or less). Hereinafter referred to as “nanogel”). When the bone grafting material 10 to which the hydrophobized polymer is added is placed inside the mucous membrane, the fiber entangled body is absorbed into the body tissue in a state where the fiber entangled body is decomposed into fine particles having the above particle diameter by the hydrophobized polymer. For this reason, the growth of fibroblasts and osteoblasts is promoted. In this specification, a polymer that dissolves in water to form a nanogel (hereinafter referred to as a polymer gel), such as a nanogel and the above-described hydrophobic polymer, is included in the growth factor component. Examples of the polymer gel include hydrophobized polysaccharides, specifically, hydrophobized pullulans such as cholesterol-substituted pullulan (Cholesterol-bearing pullulan). That is, the bone grafting material 10 may be added with hydrophobic polysaccharides or aggregated fine particles as a growth factor component. The average particle diameter of the nanogel can be determined as an average value of the long diameters of a plurality of nanogels included in the enlarged image of the bone grafting material 10, and is preferably 1 μm or less.

The bone grafting material 10 of the present embodiment can be produced by three-dimensionally entanglement of calcium phosphate fibers and then press molding as necessary. In addition, the bone grafting material 10 can also be produced by folding or winding a calcium phosphate sheet-like long fiber nonwoven fabric into a plate shape or a block shape. More specifically, the sheet-like long-fiber nonwoven fabric is folded once or a plurality of times, or wound into a roll shape, and formed into a three-dimensional three-dimensional fiber entangled body having a desired thickness. Thereafter, the fiber entangled body is press-molded into a plate shape or a block shape.
When the block-shaped bone grafting material 10 is produced, a sheet-like long fiber nonwoven fabric is folded or wound to first form a plate-like fiber entangled body, which is then cut into a desired shape to form a block shape. Good.

The fiber of calcium phosphate constituting the bone grafting material 10 may be long fiber or short fiber, but long fiber is preferable. By using long fibers, the bone filling material 10 is prevented from being broken into a large number of pieces until the bone filling material 10 is absorbed into the body, and displacement under the submucosa or submucosa periosteum hardly occurs. Here, the long fiber means a fiber having a fiber length to fiber diameter ratio of 100 times or more, and the short fiber means a fiber having the ratio of less than 100 times.

The surface layer portion 11 and the core portion 12 may be integrally formed with a common long fiber, or may be formed by joining and integrating each portion separately with separate fiber entanglements. In other words, one or more long fibers may be included across the surface layer portion 11 and the core portion 12, or the separation interface of the fiber entangled body exists between the surface layer portion 11 and the core portion 12. May be.

When the surface layer portion 11 and the core portion 12 are integrally formed with a common long fiber, as will be described later in the examples, the fibrous calcium phosphate located on the surface of the core portion 12 is dispersed with a solvent to obtain a denser structure. The surface layer portion 11 can be formed.

FIG. 2A is a perspective view showing the bone grafting material 10 of the second embodiment. FIG. 2B is a schematic diagram showing a usage state of the bone grafting material 10. The upper side of FIG. 2A corresponds to the upper surface side of the bone grafting material 10. A surface layer portion 11 is formed on the upper surface side of the bone grafting material 10, and a core portion 12 is formed on the lower surface side. The surface layer part 11 is harder and denser than the core part 12.

The bone grafting material 10 of the present embodiment has an annular shape with through-holes formed in the thickness direction. Bone-forming protein (BMP: bone morphogenetic protein) or fibroblasts (not shown) are formed on the outer peripheral surface 14 and the inner peripheral surface 18. Growth factor components such as cell growth factor and polymer gel are applied. Growth factor components may also be applied to the front and back surfaces of the bone grafting material 10. The growth factor component may be impregnated in the fiber entangled body of the bone grafting material 10, or may be formed on the surface (front and back surfaces) of the fiber entangled body.

Bone morphogenetic protein is a growth factor for osteoblasts. As used herein, osteoblasts include bone cells, osteoprogenitor cells, and osteoblast stem cells.

The through-hole 15 for inserting the bolt 20 into one or a plurality of locations around the inner peripheral surface 18 is formed in the annular bone filling material 10 of the present embodiment. A counterbore 16 that accommodates the bolt head of the bolt 20 is formed on the upper surface side of the through hole 15. The bone grafting material 10 of this embodiment shown in each drawing of FIG. 2 has a pair of through holes 15 at positions facing each other at 180 degrees around the inner peripheral surface 18. The bolt 20 is preferably made of a biodegradable material such as polylactic acid.

As shown in FIG. 2B, the bone grafting material 10 is an auxiliary agent for regenerating an intervertebral disc (cartilage) that is used by being sandwiched between vertebrae 110 adjacent to each other. An intervertebral disc 112 exists between normal vertebrae 110, but when this is lost, by filling the bone filling material 10 of this embodiment, chondroblasts grow and the intervertebral disc is regenerated. By providing growth factor components such as bone morphogenetic protein and fibroblast growth factor on the outer peripheral surface 14 and the inner peripheral surface 18 of the bone grafting material 10, the growth of chondroblasts is promoted.

The bone filling material 10 is fixed to one of the vertebrae 110 by bolts 20. In order to prevent the bone filling material 10 from being crushed, a spacer 100 made of a metal material such as titanium or a titanium alloy may be inserted between the vertebrae 110. The spacer 100 has a thickness dimension substantially equal to that of the bone grafting material 10. The spacer 100 is inserted into the vertebra 110 on the outer peripheral side (the body surface side in FIG. 2B) from the mounting position of the bone grafting material 10.

3A to 3E are schematic views of the bone grafting material 10 according to the third to seventh embodiments.

The bone filling material 10 of the third embodiment shown in FIG. 3A is formed by winding a nonwoven fabric sheet 22 in which long fibers of calcium phosphate are two-dimensionally entangled in a roll shape. The bone grafting material 10 according to the present embodiment is formed by cutting a long roll of a nonwoven fabric sheet 22 along cutting lines C arranged at a predetermined width interval W. The cut bone substitute material 10 has a disk shape with a thickness W. In other words, the bone grafting material 10 of this embodiment is formed by spirally winding a strip-shaped nonwoven fabric sheet 22 having a width W.

Like this embodiment, the long fiber longer than the outer diameter of the bone grafting material 10 is extended in the circumferential direction of the bone grafting material 10 by winding the nonwoven fabric sheet 22 of the long fiber in a roll shape. It becomes. In this way, the bone filling material 10 containing long fibers maintains morphological stability when it is decomposed and absorbed by the mucosa, so that it does not collapse or shift its position under the mucosa or the mucosa periosteum.

The bone grafting material 10 of 4th embodiment shown to FIG. 3B is provided with the surface layer part 11 and the core part 12 covered with this surface layer part 11. FIG. The density of the calcium phosphate in the surface layer portion 11 and the density of the calcium phosphate in the core portion 12 are different. More specifically, the core portion 12 of the bone grafting material 10 of the present embodiment has a lower calcium phosphate density than the surface layer portion 11.

The core part 12 may be completely embedded in the surface layer part 11 or a part of the core part 12 may be exposed from the surface layer part 11.

The fiber diameter of the surface layer portion 11 of this embodiment is larger than the fiber diameter of the core portion 12. The fiber density of the surface layer part 11 is higher than the fiber density of the core part 12. The fiber density refers to the number of fibers per unit volume.

The bone filling material 10 of the present embodiment is decomposed over a predetermined time by macrophages in the blood that have permeated the core portion 12 from the surface layer portion 11 inside the mucous membrane. The core portion 12 having a low fiber density is rapidly decomposed to grow fibroblasts. During this time, the surface layer portion 11 having a high fiber density and a slow degradation rate can remain under the mucosa or the mucosal periosteum for a predetermined period as a scaffold for regeneration of the hard tissue (osteoblasts). At this time, since the surface layer portion 11 corresponding to the side of the living tissue such as mucous membrane or mucosal periosteum remains for a long period of time, the positional stability of the bone grafting material 10 in the affected area is good.

However, depending on the site where the bone grafting material 10 is used, it may be preferable that the surface layer portion 11 is first decomposed using the inner core portion 12 as a scaffold. In this case, it may replace with this embodiment and the density of the calcium phosphate in the core part 12 may be made larger than the density of the calcium phosphate in the surface layer part 11. That is, the fiber diameter of the core portion 12 may be larger than the fiber diameter of the surface layer portion 11, and the fiber density of the core portion 12 may be higher than the fiber density of the surface layer portion 11. Thereby, even when the degradation rate of the bone grafting material 10 is low, such as when used for an affected part with a small amount of blood, the outer surface layer part 11 having a low fiber density is well decomposed to grow fibroblasts, and the core The part 12 can be used as a scaffold to prevent the displacement of the bone grafting material 10.

The bone grafting material 10 according to the fifth embodiment shown in FIG. 3C includes a base portion 30 and a curved surface portion 32 protruding above the base portion 30. In the present embodiment, the density of calcium phosphate in the curved surface portion 32 is greater than the density of calcium phosphate in the base portion 30.

The curved surface portion 32 has a mountain shape that is curved in a dome shape, and the upper surface of the base portion 30 bulges upward corresponding to the curved surface portion 32. Similarly to the third embodiment, the bone grafting material 10 of the present embodiment is also formed by cutting a fiber entangled body formed in a long rod shape by a cutting line C having a predetermined width into a block shape.

The bone filling material 10 of the sixth embodiment shown in FIG. 3D is composed of a curved plate-like main body 34. A through hole 36 may be optionally formed in the plate-like main body 34. The bone grafting material 10 of the present embodiment is composed of a plate-like main body 34 in which a plurality of through holes 36 are formed to penetrate in the plate thickness direction.

The bone prosthetic material 10 (plate body 34) of the present embodiment has an outer shell shape having a hollow portion (curved concave portion 40) communicating with the outside. The term “hollow portion communicates with the outside” means that the hollow portion has an opening rather than a sealed independent hole. The curved recess 40 opens downward. Further, the curved recess 40 communicates with the outside through the through hole 36.

The through-hole 36 has a sufficient diameter that can be clearly distinguished from pores in a fiber entangled body (porous) of calcium phosphate long fibers. Although the specific dimension and shape of the through-hole 36 are not specifically limited, As an example, it may be a circular hole having a diameter of 0.5 to 10 mm, preferably a diameter of 2 to 5 mm.

The arrangement of the through holes 36 is not particularly limited. For example, the through holes 36 can be arranged in a lattice pattern, a staggered pattern, or randomly. Alternatively, the diameters of the individual through holes 36 may be different from each other, or all the through holes 36 may have the same diameter.
The distance between the centers of the through holes 36 and the distance between adjacent edges of the adjacent through holes 36 are not particularly limited, but from the viewpoint of ensuring blood circulation of the mucosal periosteal valve 124 (see FIG. 5) described later, the through holes 36. The distance between adjacent edges is preferably smaller than the diameter of the through hole 36.
The plate thickness of the plate-like main body 34 may be uniform, or the plate thickness of the curved top portion 38 may be different from the plate thickness of the side edge portion 39. Specifically, the plate thickness of the top portion 38 may be larger than the plate thickness of the side edge portion 39. Thereby, when the bone grafting material 10 (plate-shaped main body 34) is embedded under the mucous membrane of the bone defect portion, the top portion 38 of the plate-shaped main body 34 is prevented from being broken.

The specific curved shape of the outer shell-like plate body 34 of the present embodiment is not particularly limited. FIG. 3D illustrates a plate-like main body 34 having a partially cylindrical shape (half-cylindrical shape) and an arc-shaped cross section. Although the central angle of the arc-shaped cross section is not particularly limited, FIG. 3D illustrates a case where the central angle is 180 degrees. In addition, the curved shape of the plate-like main body 34 may be a dome shape (prone shape). Another fiber entanglement body of calcium phosphate can be fitted into the curved concave portion 40 corresponding to the inside of the curved plate-shaped main body 34 and used. That is, the bone grafting material 10 of this embodiment may be used alone or in combination with other fiber entangled bodies. For example, the dome-shaped base 30 in the fifth embodiment (FIG. 3C) may be fitted and used. This use state will be described later with reference to FIG.

The plate-like main body 34 may be produced by stacking a plurality of long-fiber nonwoven fabric sheets 22 and press-molding them with a pair of male and female ridges. Alternatively, the bone prosthetic material 10 preformed in a cylindrical block shape may be cut and cut to be processed into a curved plate shape.

The bone prosthetic material 10 of the seventh embodiment shown in FIG. 3E has a shallow bottomed tubular shape (a petri dish shape). In FIG. 3E, the bone grafting material 10 which consists of the cylindrical surrounding wall part 42 which equips the inside with the recessed part 41, and the disk-shaped bottom part 43 is illustrated. The bone grafting material 10 of the present embodiment is a molded container in which calcium phosphate long fibers are molded into a block shape, and can be embedded in a living body such as a temporomandibular joint in a state in which, for example, a cartilage culture is accommodated in the recess 41. is there.

Cartilage tissue is a tissue that is difficult to heal spontaneously because it has no blood vessels, and its regeneration requires culture of chondrocytes. As in the present embodiment, the bone filling material 10 that is provided with the concave portion 41 for accommodating the cartilage culture and is decomposed over a predetermined period in the living body holds the cartilage culture in the cartilage defect in the living body for a long period of time. This makes it possible to culture cartilage in vivo. That is, during the first half of the culture period, the cartilage culture is stored and held in the vicinity of the cartilage defect by the bone grafting material 10 of this embodiment so that the cartilage culture does not dissipate in vivo. In the second half of the culture period, the cartilage culture is fixed to the cartilage defect and the chondrocytes proliferate, and the bone filling material 10 is degraded in vivo and naturally disappears. Thus, in vivo cartilage culture using the bone grafting material 10 of the present embodiment is less invasive than surgery (autologous cartilage transplantation) in which autologous cultured cartilage is transplanted in vivo.

FIG. 4A to FIG. 4D are schematic views for explaining the usage state of the bone grafting material 10 of the fifth embodiment (see FIG. 3C). The bone filling material 10 of this embodiment is used to regenerate the alveolar bone 126 for implant treatment.

FIG. 4A shows a state in which the root portion 122 of the tooth 120 is covered with the mucosal periosteal valve 124 and grows on the alveolar bone 126. FIG. 4B shows a state where the tooth 120 is missing and the alveolar bone 126 is retracted. In this state, an incision 128 is formed in the mucosal periosteal valve 124 to expose the alveolar bone 126, and the bone prosthetic material 10 is attached to the upper portion of the alveolar bone 126. FIG. 4C shows a state in which the mucosal periosteal valve 124 is stretched, and the bone filling material 10 attached to the alveolar bone 126 is covered with the mucosal periosteal valve 124 and sutured with the suture thread 129.

The base 30 of the bone grafting material 10 is cut in advance according to the uneven shape of the upper surface of the alveolar bone 126. The curved surface portion 32 of the bone grafting material 10 is in close contact with and covered with the mucosal periosteal valve 124. The curved surface portion 32 of the present embodiment protrudes upward, and the mucosal periosteal valve 124 is sewn into a natural convex shape by closely contacting the mucosal periosteal valve 124 along the curved surface portion 32.

In the present embodiment, the bottom surface of the base 30 is formed in a concavo-convex shape and is in close contact with the top surface of the alveolar bone 126. Instead of the present embodiment, as in the sixth embodiment, a plate-shaped main body 34 (see FIG. 3D) having an outer shell shape having a hollow portion (curved concave portion 40) communicating with the outside is mounted on the upper surface of the alveolar bone 126. You may use it. The plate-like main body 34 is placed on the upper surface of the alveolar bone 126, and the mucosal periosteal valve 124 is sutured in a state where the hollow portion (curved concave portion 40) is held inside the bone filling material 10, so that the bone filling material 10 is mucous. It may be buried underneath. The hollow part inside the bone filling material 10 having the plate-shaped main body 34 as an outer shell is filled with blood. In the hollow portion, the inner surface of the plate-like main body 34 is gradually decomposed and absorbed by the living body, and the alveolar bone 126 grows. The mucosal periosteal valve 124 is sutured in a state where the hollow portion (curved concave portion 40) is filled with a powdery or granular bone filling material (not shown), and the bone filling material 10 is buried under the mucous membrane. Also good. Further, instead of this embodiment, the lower surface of the base 30 of the bone grafting material 10 is formed flat or convex, and a powdery or granular bone grafting material is filled between the alveolar bone 126 and the base 30. Also good. In other words, a powder or granular bone filling material may be filled between the mucosal periosteal valve 124 and the alveolar bone 126, and the bone filling material 10 may be placed thereon.

In this state, when a predetermined period (for example, several weeks to several months) elapses, the soft base portion 30 of the bone grafting material 10 is disassembled and replaced with the alveolar bone 126. On the other hand, the curved surface portion 32 contacts the mucosal periosteal valve 124, which has a larger blood volume than the alveolar bone 126. Here, in the bone grafting material 10 of the present embodiment, the curved surface portion 32 is configured to be harder and denser than the base portion 30. Therefore, the time difference between the speed (required time) at which the curved surface portion 32 is decomposed and absorbed into the mucosal periosteal valve 124 and the speed (required time) at which the base 30 is decomposed and absorbed into the alveolar bone 126 is small. For this reason, the bone filling material 10 of this embodiment is appropriately decomposed inside the mucosal periosteal valve 124, and fibroblasts and osteoblasts grow. As a result, the alveolar bone 126 which has been retracted as shown in FIG. 4B is regenerated, and the implant treatment can be performed satisfactorily. When the human alveolar bone 126 is regenerated, the curved surface portion 32 and the base portion 30 are preferably decomposed in 4 to 8 months.

Drawing 4D is a figure explaining the modification of the use state of bone grafting material 10 of this embodiment. Specifically, a state in which the bone grafting material 10 is embedded around the root portion 122 is shown. The bone grafting material 10 is also used for an affected part in which the tooth 120 is not missing, and the tooth root part 122 can be grown to increase the diameter by promoting the growth of osteoblasts. In the case of such a modification, it is preferable that the lower end side of the bone grafting material 10 is tapered and narrow so that the whole is a wedge shape. Thereby, the operation | work which inserts the bone grafting material 10 in the incision 128 of the mucosal periosteal valve 124 is easy.
That is, the bone grafting material 10 includes a base portion 30 on the lower end side having a sharp tip portion and a low fiber density, and a plate-like curved surface portion 32 attached to the upper end side and having a high fiber density. However, the formation of the curved surface portion 32 is optional, and the entire wedge-shaped bone grafting material 10 may be formed by the base 30 instead of the present embodiment.

In addition, regarding the bone grafting material 10 of the sixth and seventh embodiments (see FIGS. 3D and 3E), as shown in FIGS. 4A to 4D, it is between the mucosal periosteal valve 124 and the alveolar bone 126 or the root portion. It can be used by being embedded around 122.

FIG. 5A to FIG. 5E are schematic diagrams for explaining the usage state of the bone grafting material 10 of the sixth embodiment shown in FIG. 3D. The case of regenerating the alveolar bone 126 for implant treatment will also be described as an example for the bone grafting material 10 of the present embodiment.

FIG. 5A shows a state in which the root portion 122 of the tooth 120 is covered with the mucosal periosteal valve 124 and grows on the alveolar bone 126, and is the same as FIG. 4A. 5B and 5C show a state where the tooth 120 is missing and the alveolar bone 126 is absorbed and retracted. FIG. 5B shows a state of moderate absorption, and FIG. 5C shows a state of high absorption. In the case of moderate absorption, the trace of the root portion 122 remains in the alveolar bone 126 as a U-shaped recess, but in the case of high absorption, the trace disappears and the alveolar bone 126 becomes convex upward.

5B or 5C, an incision 128 is formed in the mucosal periosteal valve 124 to expose the alveolar bone 126, and the bone grafting material 10 is attached to the upper portion of the alveolar bone 126. The bone grafting material 10 of this embodiment is a combination of a base 30 having a low calcium phosphate density and a plate-like main body 34 having a higher calcium phosphate density than the base 30. The base 30 made in accordance with the shape of the upper surface of the alveolar bone 126 is mounted on the alveolar bone 126, and the plate-shaped main body 34 is mounted by fitting the upper surface of the base 30 into the curved recess 40 (see FIGS. 5D and 5E). reference).

The base 30 is formed as a block made of a calcium phosphate fiber entangled body formed into a cubic shape, a cylindrical shape, or the like, and this is used by cutting according to the shape of the upper surface of the alveolar bone 126. The plate-shaped main body 34 has a curved plate shape in which a large number of through holes 36 are formed, and is used by cutting according to the shape and dimensions of the base 30. As shown in FIG. 5E, the plate-like main body 34 may be used by being bent at a bent portion 37. Accordingly, the plate-like main body 34 can be embedded under the mucosa or the mucosal periosteum according to the shape of the alveolar bone 126 regardless of the initial curved shape and curvature of the plate-like main body 34.

Further, as shown in FIGS. 5D and 5E, the mucosal periosteal valve 124 is extended, and the bone filling material 10 (plate-like main body 34) attached to the alveolar bone 126 is covered with the mucosal periosteal valve 124 and sutured with a suture thread 129. . In this state, the base 30 is disassembled and replaced with the alveolar bone 126 while being held on the upper surface of the alveolar bone 126 by the plate-shaped main body 34. After the replacement of the base 30 with the alveolar bone 126 is started, the plate-like main body 34 is disassembled inside the mucosal periosteal valve 124.

According to the bone grafting material 10 of the present embodiment, since the blood circulation from the vascular network on the surface (bone surface) of the alveolar bone 126 to the mucosal periosteal valve 124 is resumed through the through hole 36 of the plate-like main body 34, the mucosa Dehiscence due to necrosis of the periosteal valve 124 can be prevented.

In addition, regarding the bone grafting material 10 of the fifth and seventh embodiments (see FIGS. 3C and 3E), as shown in FIGS. 5A to 5E, between the mucosal periosteal valve 124 and the alveolar bone 126 or the root portion It can be used by being embedded around 122.

FIG. 6 is a schematic diagram showing a manufacturing apparatus 200 for the bone grafting material 10. The manufacturing apparatus 200 according to the present embodiment is an apparatus that forms a long fiber by a melt blow method and entangles them with each other to manufacture a nonwoven fabric sheet 22, and further shapes and fires the nonwoven fabric sheet 22 to obtain the bone grafting material 10. . In the present embodiment, the nonwoven fabric sheet 22 is wound into a roll and then fired to form the bone grafting material 10.

The manufacturing apparatus 200 includes a hopper 202, a die 204, a drum roll 206, a heating unit 208, a take-up unit 210, a roll forming unit 220, and a firing unit 230.
The hopper 202 is a container for storing a polymer raw material (slurry) in which a polysaccharide such as pullulan and calcium phosphate such as hydroxyapatite are dispersed in a solvent such as water. A polysaccharide having solvent solubility is used. The polymer raw material may contain an antibacterial agent having a predetermined concentration.

The die 204 includes a large number of minute nozzles (not shown), and a blower 214 is provided on the upstream side of the die 204. The opening of the die 204 is preferably circular with a diameter of 0.05 mm to 1.0 mm. The polymer raw material supplied from the hopper 202 is ejected from the die 204 at a high speed to become a fiber. By dissolving the polysaccharide in the solvent, the high-viscosity polymer raw material is formed into a fiber shape, and calcium phosphate is dispersed in the fiber.

A drum roll 206 is disposed in front of the injection direction from the die 204. The long fibers 24 sprayed onto the surface of the drum roll 206 are entangled with each other to form the nonwoven fabric sheet 22.

The long fibers 24 ejected from the die 204 are heated inside the cylindrical casing 216 to remove the solvent. The heating unit 208 of the present embodiment is a ceramic heater, and is arranged in a plurality of stages in the injection direction from the die 204 (vertical direction in FIG. 6). The heating unit 208 irradiates the long fibers 24 with infrared rays (including far-infrared rays) to radiatively dry the long fibers 24. The long fibers 24 are made of a mixed material of polysaccharide (pullulan) and calcium phosphate (hydroxyapatite).

A blower 209 is provided behind the heating unit 208. The blower 209 blows cold air (including normal temperature) from the side against the long fibers 24 ejected from the die 204. Thereby, the solvent removed from the long fibers 24 is excluded from the housing 216, and drying of the long fibers 24 is promoted. In addition, a guide 218 having a tapered shape from the die 204 toward the drum roll 206 is provided inside the housing 216 so as to be opposed thereto. The guide 218 is made of a porous material such as a metal mesh, and allows both infrared rays radiated from the heating unit 208 and cold air from the blower unit 209 to pass therethrough. The long fibers 24 ejected from the die 204 converge in a bundle along the guide 218, interlaced with each other, and reach the surface of the drum roll 206. Here, the long fiber 24 converges suitably because the ventilation part 209 blows a cold wind from the side with respect to the long fiber 24. FIG.

The drum roll 206 is rotated about its axis by a rotation mechanism (not shown), and the formed nonwoven fabric sheet 22 is sent to the take-up unit 210. The rotational speed of the drum roll 206 can be variably adjusted, and the basis weight of the nonwoven fabric sheet 22 can be changed by the adjustment. The nonwoven fabric sheet 22 composed of the long fibers 24 is taken up at a predetermined speed by the take-up section 210 and formed into a predetermined thickness.

The roll forming unit 220 is a device that winds the nonwoven fabric sheet 22 into a roll having a predetermined diameter. The roll forming unit 220 may be wound into a roll shape after cutting the nonwoven fabric sheet 22 in advance. The roll forming unit 220 includes a restraining portion 221 that restrains the leading end of the nonwoven fabric sheet 22 in the feeding direction, and a blade portion 222 that cuts the nonwoven fabric sheet 22. The restraining part 221 and the blade part 222 can be moved up and down with respect to the take-up part 210. The non-woven fabric sheet 22 is wound by the conveying force of the take-up section 210 by the restraining portion 221 restraining the tip of the non-woven fabric sheet 22. When the nonwoven fabric sheet 22 is wound to a predetermined diameter, the blade portion 222 is lowered and cut. Since the nonwoven fabric sheet 22 contains polysaccharide (pullulan) and has adhesiveness, the wound nonwoven fabric sheet 22 is integrally fixed.

The nonwoven fabric sheet 22 wound and cut into a roll shape is baked by a baking unit 230 including a heater 231 and further cut and cut as necessary to become the bone grafting material 10. By firing the nonwoven fabric sheet 22, the polysaccharide contained in the long fibers 24 is thermally decomposed and disappears, and only calcium phosphate (hydroxyapatite) remains while maintaining the fiber shape. Moreover, the winding diameter (roll diameter) and the fiber diameter of the nonwoven fabric sheet 22 both decrease by the disappearance of the polysaccharide, and the calcium phosphate aggregates. Thereby, the bone filling material 10 after firing becomes a fiber entangled body of long fibers in which calcium phosphate is densely aggregated.

As mentioned above, the manufacturing method of the bone grafting material 10 of this embodiment is as follows.
(1) A fiberizing step in which a mixture of an aqueous solvent, a water-soluble edible polysaccharide, and calcium phosphate is sprayed from a die to form long fibers;
(2) A drying process in which the long fibers are entangled with each other while removing the aqueous solvent by heating the sprayed long fibers, and a fiber entangled body is obtained.
(3) a firing step of firing the fiber entangled body to remove the polysaccharide.
Note that some or all of the steps (1) to (3) may be performed at the same timing.

In this embodiment, after producing the sheet-like long fiber nonwoven fabric by the drying step (2) above, before the firing step (3) above,
(4) A forming step of forming the fiber entangled body into a plate shape or a block shape is further performed. In the forming step, the sheet-like long-fiber nonwoven fabric is folded or wound to form a plate or block having a predetermined thickness.
Through the above steps, the bone grafting material 10 of the present embodiment is produced.

A growth factor component such as bone morphogenetic protein, fibroblast growth factor or polymer gel is added to the plate-like or block-like fiber entangled body after firing. Although the specific addition method is not particularly limited, as an example, the fiber entangled body may be impregnated with the growth factor component by immersing the fiber entangled body in an aqueous solvent in which the growth factor component is dispersed for a short time. In addition, an aqueous solvent in which the growth factor component is dispersed may be spray-coated on the surface of the fiber entangled body. In this manner, the bone grafting material 10 in which the growth factor component is impregnated or coated on the fiber entangled body can be produced.

(Example)
Hereinafter, the present invention will be described in more detail based on examples. However, the present invention is not limited to the following examples.

Each slurry of hydroxyapatite (HAp) and pullulan was sufficiently dispersed in water (solvent) to prepare a slurry. The slurry was prepared at room temperature by changing the mass ratio of HAp: water: pullulan into three types as shown in Table 1 below (Examples 1 to 3 respectively). A small amount of an aqueous dispersant was added to the slurry.

These slurries were sprayed from the die 204 shown in FIG. 6 by the melt blow method and dried by heating in the heating unit 208 to remove water, thereby forming long fibers (apatite fibers) made of HAp and pullulan. The opening diameter of the die 204 was 0.3 mm.

FIG. 7A to FIG. 7C are electron micrographs showing the state before the three-dimensional molding (that is, before firing) of the nonwoven sheet made of apatite fibers according to Examples 1 to 3, respectively. The enlargement ratio is 75 times in FIGS. 7A and 7B and 35 times in FIG. 7C. 8A and 8B are enlarged views of the apatite fiber before firing according to Example 3 shown in FIG. 7C, and the enlargement ratios are 1000 times and 5000 times, respectively.

It was confirmed that all of the apatite fibers were formed into a long fiber shape with HAp dispersed in the pullulan by a melt blow method, and the fiber diameter (long fiber thickness) was 10 μm or less. Examples 4 to 7 were the same.

9A to 9D are electron micrographs of fiber entangled bodies obtained by firing the nonwoven fabric sheets according to Examples 1 to 4 under the following conditions without three-dimensional molding. 9A to 9D are electron micrographs of the fiber entangled bodies according to Reference Example 1 to Reference Example 4 fired into a sheet shape under the following conditions. 9A and 9B are 75 times, FIG. 9C is 100 times, and FIG. 9D is 200 times. On the other hand, as Examples 1 to 4, after the sheet-like fiber entangled body was laminated in multiple layers and press-molded with a roll compressor (calender device) to form a three-dimensional disk, the following conditions were satisfied. Baked in.

As baking conditions, it heated for 24 hours, heating up from normal temperature to 320 degreeC with the temperature increase rate of 13.3 degrees C / hour, and kept at 320 degreeC for 1 hour continuously. Thereafter, the mixture was further heated from 320 ° C. to 1100 ° C. at a heating rate of 50.0 ° C./hour for 17.6 hours, then heated to 1200 ° C. and fired for 2 hours.

As described above, the firing step of the present example includes the first firing step of heating while raising the temperature from 200 ° C. to 500 ° C. with the normal temperature as the initial temperature, and then further 800 ° C. to 1400 ° C. And a second baking step of heating while raising the temperature to within a temperature range.
In the first firing step, residual moisture of the apatite fibers is removed, and the intramolecular and intermolecular bonds of the binder made of a hydrocarbon material (in this embodiment, pullulan) are broken.
In the second firing step in which the apatite fibers are fired at a higher temperature than the first firing step, the binder is decomposed into carbon dioxide and water and removed from the apatite fibers. By performing the second firing step while increasing the temperature, the fiber diameter gradually decreases while the HAp maintains the fiber shape. In other words, by taking the first firing step and the second firing step as in the present embodiment, the fiber entangled body after firing is sintered in a fiber shape, so that a porous body having a large specific surface area is produced. .

As shown in each figure of FIG. 9, the property of the fiber entangled body after baking can be adjusted as desired by changing the ratio of HAp in the slurry.
Specifically, the ratio of the mass of HAp to the mass of the slurry excluding pullulan (hereinafter referred to as HAp mass ratio) is 7.4% in Example 1 (= 8.0 g / (8.0 g + 100 g)). 2 is 12.9% (= 14.8 g / (14.8 g + 100 g)) and Example 3 is 14.4% (= 16.8 g / (16.8 g + 100 g)). The HAp mass ratio of Example 4 is 19.4% (= 24.0 g / (24.0 g + 100 g)), and the HAp mass ratio of Example 5 is 44.4% (= 80.0 g / (80. 0g + 100 g)), the HAp mass ratio of Example 6 is 30.5% (= 43.8 g / (43.8 g + 100 g)), and the HAp mass ratio of Example 7 is 44.4% (= 80.0 g). /(80.0 g + 100 g)).
And as for the property after baking of Example 1 whose HAp mass ratio is less than 10%, as shown to FIG. 9A, it turned out that apatite fibers contact | adhere in the fiber width direction and it becomes a sea surface shape. On the other hand, the properties after firing of Example 2 and Example 3 in which the HAp mass ratio is 10% or more, preferably 12% or more, show that the apatite fibers are in close contact with each other in the fiber width direction as shown in FIGS. 9B and 9C. Without crossing, it was found that they crossed and bound into a mesh. That is, in Example 2 and Example 3, it can be said that the occurrence of dead ends in the fiber entangled body is more suitably suppressed and the specific surface area is larger than that in Example 1. The same tendency was confirmed in Examples 4 to 6.

FIG. 10A is an enlarged view of the apatite fiber after firing according to Reference Example 3 shown in FIG. 9C, and the enlargement ratio is 5000 times.
Comparing FIG. 8B and FIG. 10A, the surface of the apatite fiber before firing is flat (see FIG. 8B), whereas the surface of the apatite fiber after firing is scale-like (see FIG. 10A). I understand.

Moreover, the apatite fiber after firing in this example has a streak-like recess formed along the fiber direction. In other words, the cross-sectional shape of the apatite fiber before firing is a substantially circular shape, but after firing, the apatite fiber has a bowl shape (violin shape, figure 8 shape or dumbbell shape) crushed from opposite sides, and each fiber Have two streak-like recesses extending in the fiber direction at opposite positions of approximately 180 degrees. The mechanism by which such a streak-like recess is formed is not necessarily clear, but in the process where the pullulan disappears from the apatite fiber and the HAp shrinks, the HAp enters the pulling vane voids to form a circular shape. It is expected that the apatite fiber, which had a cross-section, fell into a wrinkle-shaped cross-section. The apatite fiber after firing is substantially sintered only of HAp fine particles, and its cross-sectional shape is smooth and sharp as a whole, including a narrow concave portion and a wide bulge portion in a bowl shape. There is no edge. In other words, the cross-sectional shape of the apatite fiber after firing is a blunt shape that is smoothly curved (see FIGS. 9D and 10A).

And, even if the apatite fiber before firing is formed into a predetermined shape by fiberizing a slurry in which calcium phosphate (HAp) is dispersed together with a hydrocarbon binder component (pullulan) as in this embodiment, The porosity in the fiber entangled body is not lost. This is because, since the binder component has a predetermined occupied volume in the fiber before firing, even if, for example, a high press pressure is applied to form a fiber entangled body into a block shape (fiber block), calcium phosphate is dispersed in the fiber. This is to maintain the state. In other words, by using the binder component, it is possible to form the apatite fiber before firing into a fiber block having a desired shape while maintaining the state in which the calcium phosphate is dispersed in the fiber. In addition, the yarn stringiness of the slurry can be increased or decreased by changing the component and concentration of the binder. Furthermore, it is possible to adjust the fiber diameter of the apatite fiber by adjusting the opening diameter of the die and the blow speed. Thereby, it is possible to make the calcium-phosphate density of the surface layer part 11 and the core part 12 (refer FIG. 1B) in the bone grafting material 10 after baking differ.

FIG. 10B is an enlarged view of the surface of the bone prosthetic material after firing in Example 1 formed into a disk shape (block shape) as shown in FIG. 1A. The enlargement ratio is 3000 times. The electron micrograph shown in FIG. 1C corresponds to a cross-sectional photograph of the bone grafting material according to this example. As can be seen by comparing FIG. 1C and FIG. 10B, the bone prosthetic material of this example has one main surface (upper end surface) corresponding to at least a part of the outer surface smoothed.

The bone prosthetic material of this example is a two-dimensional entangled body of apatite fibers blow-molded into a long fiber shape, subjected to a surface smoothing treatment in a state of being pressed into a disk shape and formed into a fiber block, It is fired after that. As the smoothing treatment, a solvent (for example, water) for dissolving the binder (pullulan) is preferably brought into contact with the surface of the fiber block in a small amount for a short time. Thereby, the binder on the surface of the fiber block is locally dissolved in the solvent, and the HAp in that portion is smoothed like a scale. Such a small amount of solvent (water) may be sprayed on the surface of the fiber block by, for example, spraying. By spraying the solvent after the fiber block is heated to room temperature or higher, the solvent in contact with the fiber block volatilizes in a short time, so that the HAp smoothing treatment is restricted from extending to the inside of the fiber block. The Thereby, only the partial thickness on the surface side of the fiber block is smoothed. By firing such a fiber block, the bone grafting material shown in the first embodiment including a hard and dense surface layer portion and a core portion having a higher porosity is produced.

The above embodiments and examples include the following technical ideas.
(1) A bone prosthetic material comprising a fiber entangled body obtained by forming fibrous calcium phosphate into a plate shape or a block shape.
(2) The bone grafting material according to (1), wherein at least a part of the outer surface of the fiber entangled body is smoothed.
(3) The bone grafting material according to the above (1) or (2), which is formed by folding or winding a calcium phosphate long fiber nonwoven fabric into a plate shape or a block shape.
(4) The bone grafting material according to any one of (1) to (3), wherein the bone grafting material is formed into a plate shape having a plurality of through holes.
(5) A surface layer portion and a core portion covered with the surface layer portion, wherein the density of the calcium phosphate in the surface layer portion is different from the density of the calcium phosphate in the core portion (1) ) To (4).
(6) A base portion and a curved surface portion protruding above the base portion, wherein the density of the calcium phosphate in the curved surface portion is larger than the density of the calcium phosphate in the base portion. The bone grafting material according to any one of (1) to (4).
(7) The bone grafting material according to any one of (1) to (4), wherein the bone grafting material is formed into a disk shape having a thickness of 1.5 mm to 6 mm and an outer diameter of 10 mm to 40 mm.
(8) The bone grafting material according to (7), wherein the bone grafting material has an annular shape with through holes formed in the thickness direction, and a growth factor component is deposited on the outer peripheral surface and the inner peripheral surface.
(9) The bone grafting material according to any one of (1) to (8), wherein the porosity is 10% or more and 78% or less.
(10) The bone grafting material according to any one of (1) to (9), wherein the fiber entangled body has a fiber diameter of 0.5 μm or more and 10 μm or less.
(11) The bone grafting material according to any one of (1) to (10), wherein the calcium phosphate fiber has a streak-like recess formed along the fiber direction.

This application claims priority based on Japanese Patent Application No. 2011-044720 filed on Mar. 2, 2011, the entire disclosure of which is incorporated herein.

Claims

Bone prosthesis material containing a fiber entangled body formed by molding fibrous calcium phosphate into a plate or block shape.
The bone grafting material according to claim 1, wherein at least a part of the outer surface of the fiber entangled body is smoothed.
The bone grafting material according to claim 1 or 2, which is formed by folding or winding a calcium phosphate long fiber nonwoven fabric into a plate shape or a block shape.
The bone grafting material according to any one of claims 1 to 3, wherein the bone grafting material is formed into a plate shape in which a plurality of through holes are formed.
A surface layer part, and a core part covered with the surface layer part,
The bone grafting material according to any one of claims 1 to 4, wherein a density of the calcium phosphate in the surface layer portion is different from a density of the calcium phosphate in the core portion.
The base portion and a curved surface portion protruding above the base portion, wherein the density of the calcium phosphate in the curved surface portion is larger than the density of the calcium phosphate in the base portion. 5. The bone filling material according to any one of 4 above.
The bone prosthetic material according to any one of claims 1 to 4, wherein the bone prosthetic material has an outer shell shape having a hollow portion communicated with the outside.
The bone prosthetic material according to any one of claims 1 to 7, wherein a growth factor component is impregnated in the fiber entangled body or is coated on the surface of the fiber entangled body.
The bone grafting material according to claim 8, wherein the growth factor component is a hydrophobized polysaccharide or aggregated fine particles.
The bone grafting material according to any one of claims 1 to 4, wherein the bone grafting material is formed into a disc shape having a thickness of 1.5 mm to 6 mm and an outer diameter of 10 mm to 40 mm.
The bone prosthetic material according to claim 10, wherein the bone prosthetic material has an annular shape with through holes formed in the thickness direction, and a growth factor component is adhered to the outer peripheral surface and the inner peripheral surface.
The bone grafting material according to any one of claims 1 to 11, which has a porosity of 0.1% to 78%.
The bone grafting material according to any one of claims 1 to 12, wherein a fiber diameter of the fiber entangled body is 0.5 µm or more and 100 µm or less.
The bone grafting material according to any one of claims 1 to 13, wherein the calcium phosphate fiber has a streak-like recess formed along a fiber direction.