JP2010233914A - Artificial bone and method of manufacturing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an artificial bone comprising a calcium phosphate/collagen composite holding a substance having a physiological activity function. <P>SOLUTION: The method of manufacturing the artificial bone includes: a composite manufacturing step S1 of manufacturing a sponge-like calcium phosphate/collagen composite by mixing and crosslinking fibrous collagen and β tricalcium phosphate; a physiologically active substance containing gel manufacturing step S2 of manufacturing the gel or xerogel of non-crosslinked collagen containing a physiologically active substance; and a laminating step S3 of laminating the calcium phosphate/collagen composite manufactured by the composite manufacturing step S1 and the gel or the xerogel manufactured by the physiologically active substance containing gel manufacturing step S2. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an artificial bone and a method for manufacturing the same.

Conventionally, artificial bone containing calcium phosphate such as apatite has biocompatibility with autologous bone, and thus has been clinically applied in various fields including orthopedics.
However, the mechanical properties and physiological properties of ceramic-based artificial bones such as apatite are not the same as those of autogenous bones, and ceramic-based artificial bones have the disadvantage that they are harder and more brittle than autogenous bones.

  In order to solve this problem, an apatite / collagen composite in which collagen is contained in a ceramic artificial bone has been proposed (for example, see Patent Document 1). This apatite / collagen composite is formed by putting a slurry in which the material constituting the apatite / collagen composite is dispersed in water into a mold, freezing and drying, and then crosslinking, and then forming a desired shape. It is designed to be used after cutting.

  On the other hand, substances having a physiologically active function for promoting bone growth, such as DBM (demineralized water bone matrix), are known. Therefore, in order to impart a physiologically active function to an artificial bone, it is desired that the collagen complex contains a substance having a physiologically active function such as DBM.

International Publication No. 2004/041320 Pamphlet

  However, the collagen complex needs to be cross-linked so as to increase the mechanical strength and retain its shape for a desired time in a state implanted in the body. Crosslinking of collagen can be performed using methods such as physical crosslinking using γ rays, ultraviolet rays, electron beams, thermal dehydration, and the like, and chemical crosslinking using a crosslinking agent or a condensing agent. In this case, if a substance having a physiologically active function is contained in the production of the collagen complex, there is a disadvantage that the physiological activity is lost due to crosslinking.

  This invention is made | formed in view of the situation mentioned above, Comprising: It aims at providing the artificial bone which consists of a calcium-phosphate / collagen composite holding the substance which has a bioactive function.

In order to achieve the above object, the present invention provides the following means.
The present invention provides a composite production step of producing a sponge-like calcium phosphate / collagen composite by mixing and cross-linking fiberized collagen and β-tricalcium phosphate, and an uncrosslinked collagen containing a physiologically active substance. A bioactive substance-containing gel production step for producing a gel or xerogel, a calcium phosphate / collagen complex produced by the complex production step, and a gel or xerogel produced by the bioactive substance-containing gel production step are laminated. A method for producing an artificial bone including a laminating step is provided.

  According to the present invention, a crosslinked sponge-like calcium phosphate / collagen complex and an uncrosslinked collagen gel or xerogel are laminated to produce an artificial bone containing a physiologically active substance in the collagen gel or collagen xerogel. Is done. Since the organizing active substance is contained in an uncrosslinked gel or xelgel, the deactivation of the physiological activity due to crosslinking is prevented, and the bone growth can be promoted by exerting the physiologically active function after transplantation. Further, by laminating with a crosslinked sponge-like calcium phosphate / collagen complex, it is possible to prevent inconvenience that the physiologically active substance flows out rapidly after transplantation and maintain mechanical strength.

In the said invention, the said bioactive substance containing gel manufacturing step may freeze-dry after mixing a bioactive substance with a collagen gel.
The complex manufacturing step forms a recess on the surface of the calcium phosphate / collagen complex, and the laminating step adds a physiologically active substance to the collagen gel on the surface of the calcium phosphate / collagen complex provided with the recess. A mixture may be arranged.
Thereby, what mixed the bioactive substance with the collagen gel can be hold | maintained to a recessed part, and it can be made hard to flow out, and a bioactive function can be maintained over a long time.

In the above invention, in the complex production step, two calcium phosphate / collagen complexes are produced, and an uncrosslinked collagen gel containing a physiologically active substance between the produced two calcium phosphate / collagen complexes or You may decide to pinch a xerogel.
Moreover, in the said invention, you may decide to depressurize, after laminating | stacking the said calcium phosphate / collagen composite and the gel or xerogel manufactured by the said bioactive substance containing gel manufacturing step.
By doing so, the collagen gel can be drawn into the pores of the sponge-like calcium phosphate / collagen complex by depressurization, can be made difficult to flow out, and the bioactive function can be maintained for a long time. it can.

  The present invention also provides a sponge-like calcium phosphate / collagen complex produced by mixing and crosslinking fiberized collagen and β-tricalcium phosphate, and an uncrosslinked collagen gel containing a physiologically active substance or An artificial bone obtained by laminating xerogel is provided.

  According to the present invention, it is possible to provide an artificial bone made of a calcium phosphate / collagen complex holding a substance having a physiologically active function.

It is a front view which shows the artificial bone which concerns on one Embodiment of this invention. It is a flowchart which shows the manufacturing method of the artificial bone of FIG. It is a longitudinal cross-sectional view which shows the modification of the artificial bone of FIG. It is a longitudinal cross-sectional view which shows the other modification of the artificial bone of FIG.

An artificial bone 1 according to an embodiment of the present invention will be described below with reference to the drawings.
As shown in FIG. 1, the artificial bone 1 according to the present embodiment includes two sponge layers 2 made of a sponge-like calcium phosphate / collagen complex, and a collagen layer 3 made of collagen xerogel. It has a three-layer structure in which sponge layers 2 are laminated on both sides of the sheet.

The sponge layer 2 is constituted by mixing fiberized collagen and β tricalcium phosphate to crosslink the fiberized collagen. Crosslinking can be performed using a method such as physical crosslinking using γ rays, ultraviolet rays, electron beams, thermal dehydration, or the like, or chemical crosslinking using a crosslinking agent or a condensing agent.
The collagen layer 3 is composed of a collagen xerogel obtained by lyophilizing collagen containing a physiologically active substance in an uncrosslinked state. The physiologically active substance is, for example, DBM.

The artificial bone 1 according to this embodiment is manufactured as follows.
That is, the method for producing the artificial bone 1 according to the present embodiment, as shown in FIG. 2, mixes fiberized collagen and β-tricalcium phosphate and crosslinks to form a sponge-like calcium phosphate / collagen composite. A composite production step S1 for producing a sponge layer 2 comprising, a bioactive substance-containing gel production step S2 for producing a non-crosslinked collagen xerogel containing a bioactive substance, and 2 produced by these steps S1 and S2. It includes a laminating step S3 for laminating two sponge layers 2 and a collagen layer.

  According to the artificial bone 1 according to the present embodiment configured as described above, the fibrillated collagen of the sponge-like calcium phosphate / collagen composite is cross-linked, thereby resembling autologous bone having mechanical strength and flexibility. It has properties. In addition, since the collagen layer 3 sandwiched between the sponge layers 2 contains a physiologically active substance, the physiologically active substance oozes out after transplantation into a bone defect and exerts a physiologically active function, thereby developing bone growth. This has the advantage that the bone defect can be repaired quickly by promoting the above.

  In this case, according to the present embodiment, the two sponge layers 2 made of calcium phosphate / collagen complex and the collagen layer 3 made of collagen xerogel are produced in separate steps S1 and S2, thereby preventing the non-crosslinked collagen. The layer 3 can contain a physiologically active substance. As a result, it is possible to prevent the disadvantage that the physiologically active substance is deactivated by crosslinking, maintain the physiologically active function, and promote bone growth.

In the present embodiment, the collagen layer 3 is freeze-dried while being uncrosslinked to form a xerogel. Instead, the collagen layer 3 is laminated in a gel state without being freeze-dried. It may be.
In the present embodiment, as shown in FIGS. 3 and 4, in the complex production step S1, the sponge layer 2 made of a calcium phosphate / collagen complex having a recess 4 at the center of one surface is produced. It may be. In this case, it is preferable to arrange the concave portion 4 so that a part or all of the collagen layer 3 is accommodated.

  By doing in this way, the collagen layer 3 is hold | maintained at the recessed part 4 of the sponge layer 2, and the outflow of the collagen layer 2 in the state transplanted by the biological body can be suppressed. In addition, by accommodating the entire collagen layer 3 in the recess 4, the sponge-like calcium phosphate / collagen composite layers can be brought into contact with each other to obtain high mechanical strength.

  Moreover, in this embodiment, after laminating the sponge layer 2 and the collagen layer 3 in the laminating step S3, the pressure may be reduced to a predetermined pressure. By doing in this way, it can attract | suck so that the collagen layer 3 may enter into the pore of the sponge layer 2, and the sponge layer 2 and the collagen layer 3 can be combined more firmly.

  In the present embodiment, an artificial bone having a three-layer structure in which the collagen layer 2 is sandwiched between the sponge layers 3 is exemplified, but the present invention is not limited to this, and an arbitrary number of layers having a two-layer structure or more are laminated. A thing may be adopted.

1 Artificial bone 2 Sponge layer (calcium phosphate / collagen complex)
4 Recess S1 Complex production step S2 Bioactive substance-containing gel production step S3 Lamination step

Claims (6)

A composite production step of producing a sponge-like calcium phosphate / collagen composite by mixing and cross-linking fiberized collagen and β tricalcium phosphate;
A bioactive substance-containing gel production step for producing an uncrosslinked collagen gel or xerogel containing a bioactive substance;
A method for producing an artificial bone, comprising: a laminating step of laminating a calcium phosphate / collagen complex produced by the complex producing step and a gel or xerogel produced by the physiologically active substance-containing gel producing step.   The method for producing an artificial bone according to claim 1, wherein in the step of producing a gel containing a physiologically active substance, the collagen gel is mixed with a physiologically active substance and then freeze-dried. The complex manufacturing step forms a recess on the surface of the calcium phosphate / collagen complex,
The method for producing an artificial bone according to claim 1 or 2, wherein the laminating step arranges a collagen gel mixed with a physiologically active substance on the surface of the calcium phosphate / collagen complex provided with the recess. Producing two calcium phosphate / collagen complexes in the complex production step;
The method for producing an artificial bone according to any one of claims 1 to 3, wherein an uncrosslinked collagen gel or xerogel containing a physiologically active substance is sandwiched between the two produced calcium phosphate / collagen complexes.   The artificial bone according to any one of claims 1 to 4, wherein the laminating step decompresses after laminating the calcium phosphate / collagen complex and the gel or xerogel produced by the bioactive substance-containing gel producing step. Production method. A sponge-like calcium phosphate / collagen composite produced by mixing and cross-linking fiberized collagen and β-tricalcium phosphate;
An artificial bone formed by laminating an uncrosslinked collagen gel or xerogel containing a physiologically active substance.

Images