JP2005111129A - Bone replacement material and its manufacturing method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a bone replacement material capable of realizing cell adhesion in an early stage at the time of replacing a bone defective part even where a periosteum is remarkably broken, accelerating bone formation and performing replacement to an autologous bone in a short period of time, and its manufacturing method. <P>SOLUTION: The bone replacement material 1 for which calcium phosphate is a scaffold material comprises a replacing material main body 2 composed of the calcium phosphate, the bone marrow and platelet-rich plasma, and a coating part 3 composed of a collagen sheet covering the replacement material main body 2. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a method for manufacturing a bone prosthetic material to be compensated for a bone defect in a human body.

  In recent years, it has become possible to regenerate a bone and repair the bone defect by replenishing the bone defect caused by bone tumor extraction, trauma, or the like with a bone filling material. As a bone grafting material, calcium phosphate typified by hydroxyapatite is known, but from the idea that no foreign matter remains in the body, for example, a porous body of calcium phosphate such as β-tricalcium phosphate (β-TCP) ( Bone prosthetic materials made of porous sintered bodies are increasingly used. When this β-TCP is kept in contact with the bone tissue of the bone defect part, osteoclast-like cells absorb β-TCP, and cells involved in bone formation (such as osteoblasts) form new bone. So-called remodeling is performed. That is, the bone prosthetic material compensated for in the bone defect portion is replaced with autologous bone over time. Note that β-TCP is a porous body having a predetermined porosity, and when it is embedded and compensated in the human body, cells can sufficiently penetrate into a large number of pores. It is because it can form earlier.

However, if the bone grafting material is composed of only calcium phosphate, it cannot be said that the adhesiveness between the cells and the calcium phosphate after filling is still sufficient. In other words, even if calcium phosphate is used as a porous material to allow cells to enter the inside, it takes time for the cells to adhere to the cells in the pores, and thus it takes a long time to replace the cells with autologous bone. It was a fact. For this reason, the inventors of the present application have proposed a bone grafting material comprising a complex in which calcium phosphate such as β-TCP or the like is used as a scaffold, and bone marrow, platelet-rich plasma (PRP) or the like is mixed with β-TCP.
JP-A-6-304242 (paragraphs 0003-0004, paragraphs 0020-0026)

  By using a bone grafting material composed of such a complex, cell adhesion can be realized earlier and replacement with autologous bone can be performed in a shorter time. However, the periosteum around the bone defect is also significantly lost. If so, there were still challenges. That is, since it becomes impossible to cover the bone grafting material with the periosteum, it has been difficult to sufficiently spread the circulating tissue such as blood to the back of the bone grafting material. For this reason, in the absence of periosteum, cell proliferation / differentiation is not uniformly performed throughout the bone grafting material, and as a result, replacement with autologous bone cannot be performed early and accurately.

  Thus, the inventors of the present application have made an independent study and came up with the idea of using a collagen sheet, which is a natural material and has high water absorption, as a material suitable for ensuring the function as a substitute for the periosteum.

  In addition, what is described in patent document 1, for example is already known as a composite material for biological bodies formed by mixing collagen with calcium phosphate. However, in the invention described in this document, a specific type of calcium phosphate having a chemical activity such as α-tricalcium phosphate (α-TCP) is used, and finally chemically bonded to a material containing collagen, Is converted to hydroxyapatite or the like and integrated with the living hard tissue, and is completely different in technical idea from the present invention.

  The present invention has been made in view of the above circumstances, and even when a bone defect part in which the periosteum is remarkably deficient is compensated, cell adhesion is realized early to promote bone formation, and replacement with autologous bone can be achieved in a short period of time. An object of the present invention is to provide a bone prosthetic material that can be used and a method for producing the same.

  The invention according to claim 1 is a bone prosthetic material using calcium phosphate as a scaffolding material, and a covering material portion comprising the calcium phosphate, bone marrow, and platelet-rich plasma, and a collagen sheet covering the filling material main body. It is characterized by having.

  The invention according to claim 2 is the bone grafting material according to claim 1, characterized in that the calcium phosphate is a granule having a particle size in the range of 0.01 μm to 3 mm.

  The invention according to claim 3 is a method for producing a bone grafting material using calcium phosphate as a scaffolding material, wherein the calcium phosphate is mixed with bone marrow and platelet-rich plasma and then molded, and the bone grafting material filling material And a covering material forming process for forming a covering portion covering the filling material body by winding a collagen sheet around the filling material body.

  Invention of Claim 4 is a manufacturing method of the bone grafting material of Claim 3, Comprising: The said calcium phosphate was made into the granule whose particle size is the range of 0.01 micrometer-3 mm, It is characterized by the above-mentioned.

  Thus, the main body of the filling material made of calcium phosphate, bone marrow, and platelet-rich plasma is covered with the covering portion made of the collagen sheet. Therefore, the circulating tissue in the body such as blood can be absorbed and permeated into the collagen sheet and transferred through the sheet. In other words, the same function as that of the periosteum is ensured in this covering part, and it can be in a state similar to the presence of blood vessels around the main body of the prosthesis, and the circulating tissue in the body can be spread all over the bone prosthesis. It is possible to carry oxygen and nutrients sufficiently and accurately into the bone marrow and platelet-rich plasma in the main body of the filling material. As a result, various natural forming factors (autologous growth factors) contained in bone marrow cells and platelet-rich plasma contained in the bone marrow can be uniformly and suitably activated throughout the bone filling material. Even if the bone defect part which is markedly lost is compensated, cell adhesion can be realized at an early stage to promote bone formation, and replacement with autologous bone can be performed in a short period of time.

  Since collagen is a natural material, it has higher biocompatibility than a bioabsorbable polymer such as polylactic acid (PLA) or polyglycolic acid (PGA), and remains as a foreign substance in the body. There is no fear.

  In addition, since bone marrow and platelet-rich plasma that can be collected directly from the patient are used, a series of operations can be performed during the bone repair operation. The manufacture can be completed and then immediately implanted into the patient's body. Since both bone marrow and platelet-rich plasma are returned from the patient and returned to the same patient's body, there is no risk of rejection and the like, and an extremely reliable operation can be performed accurately.

Embodiments of the present invention will be described below.
The method for manufacturing a bone filling material according to the present embodiment is a bone comprising a filling material main body 2 and a covering portion 3 during a surgery (bone filling surgery) for filling a bone defect material in a bone defect portion of a patient. The filling material 1 (shown in FIG. 2) is manufactured, and has two processes of a filling material main body manufacturing process and a covering portion forming process.

First, as a preparatory work before surgery, a porous granule made of β-tricalcium phosphate (β-TCP) as a kind of calcium phosphate is prepared. This β-TCP granule is used as a scaffold as a base of the bone prosthetic material 1. For example, a product produced by a mechanochemical method described in Japanese Patent No. 2597355 is finely ground. It is granulated. The particle diameter of the β-TCP granules is preferably set in the range of 0.01 μm to 3 mm.
Moreover, the collagen sheet which comprises the coating | coated part 3 is also prepared beforehand.

  Then, bone marrow and platelet-rich plasma (PRP) are added to and mixed with the β-TCP granule, and then molded to produce the filling material body 2 (filling material body production process). From here, it becomes work during surgery. Bone marrow is collected from a patient's bone defect or the like, and PRP is extracted from blood collected from the patient. The extraction of PRP is performed by, for example, a known centrifugation method. These bone marrow and PRP are added to and mixed with β-TCP granules to form a slurry fluid. At this time, the bone marrow and the PRP are sufficiently spread within the pores of β-TCP.

In this way, if bone marrow and β-TCP are mixed, bone marrow cells contained in the bone marrow are seeded on β-TCP. Therefore, a bone filling material in a state where bone marrow cells are seeded in advance is used. Can do.
In addition, if bone marrow is left as it is after being collected, a coagulation reaction takes place inside, so that its viscosity gradually increases and gradually solidifies. That is, the slurry-like fluid composed of β-TCP granules, bone marrow and PRP is gradually changed into a clay-like and solid form. A solid consisting of a bone marrow / PRP / β-TCP complex is obtained. This solid is used as the filling material main body 2 shown in FIG. In addition, as a coagulant for controlling the coagulation time, for example, thrombin may be appropriately added.

  PRP contains various natural forming factors (autologous growth factors) such as TGF-β1, PDGF, and IGF-1, and cells involved in bone formation (such as osteoblasts) by these forming factors. It has been found that activation of is promoted. For this reason, if β-TCP containing such PRP is compensated for in the bone defect part, peripheral osteoblasts and the like are immediately activated, and quickly enter into the pores of β-TCP and enter β-TCP. Cell adhesion is realized early and bone formation is promoted.

  That is, by mixing PRP and bone marrow with β-TCP, the behavior of osteoblasts and the like contained in the bone marrow on β-TCP is active in an in-vitro state by the action of the PRP forming factor. It becomes. When β-TCP containing PRP and bone marrow is used as a bone grafting material to fill a bone defect, as described above, osteoblasts around the bone grafting material are immediately activated by the action of the PRP forming factor. And rapidly penetrates into the pores of β-TCP, thereby realizing early cell adhesion to β-TCP. At this time, since the osteoblasts on β-TCP are in an activated state in advance, these cells try to integrate quickly in β-TCP. As a result, cell adhesion to β-TCP is realized more quickly and accurately.

  As described above, the slurry-like fluid composed of β-TCP granules, bone marrow, and PRP spontaneously coagulates when left alone without using any other chemicals. Therefore, it can be molded into a desired shape and size by pouring into a mold set in a desired shape and size at the stage of the slurry fluid and leaving it for a predetermined time. In other words, during the operation, a mold corresponding to the shape and size of the bone defect to be compensated is made from a predetermined material such as paper, and by using this mold, the filling material body 2 can be manufactured very easily during the operation. can do.

  Alternatively, solidification may proceed until it becomes semi-solid like clay, cut with a blade or the like, molded, and then allowed to stand until the solidification reaction is completed to manufacture the filling material body 2. . The shape and size of the bone defect may not be clearly understood unless the surgery is actually started, and even if it can be predicted in advance, it must be changed suddenly depending on the surgical situation. In some cases. If the prosthetic material body 2 is molded in this way, it is possible to respond quickly and accurately even during surgery, and surgery can be performed efficiently in a short time.

  In order to suitably exhibit such actions and effects, it is preferable to set the particle size of the β-TCP granule in a range of 0.01 μm to 3 mm.

  Next, a collagen sheet is wound around and covered with the filling material main body 2 to form a covering portion 3 that covers the filling material main body 2 (covering portion forming process). The collagen sheet is a natural material having high absorbability, and can absorb and infiltrate circulating tissues in the body such as blood to be transferred through the sheet. Thus, the bone prosthetic material 1 composed of the prosthetic material body 2 and the covering portion 3 is completed.

  FIG. 3 shows a state in which the prosthetic material 1 is filled in the bone defect portion L of the patient. In this figure, reference numeral 10 denotes a bone, and reference numeral 11 denotes a periosteum. As shown in this figure, the covering portion 3 is in contact with the periosteum 11 or the bone 10 and can absorb and infiltrate the body circulation tissue such as blood from the adjacent living tissue. That is, the covering portion 3 can be ensured to have the same function as that of the periosteum, and the blood vessel can exist in the same state as that around the filling material body 2. For this reason, since it can be set as the state where the periosteum 11 is continuing from the surface of the bone 10 to the surface of the bone grafting material 1, it can spread | circulate a body circulation tissue to every corner in the body 2 of the grafting material. be able to. That is, oxygen, nutrients, and the like can be sufficiently and accurately carried into the bone marrow and PRP in the filling material body 2.

  As a result, bone marrow cells contained in the bone marrow and various natural forming factors (autologous growth factors) contained in the PRP can be suitably activated. However, cell adhesion can be realized at an early stage to promote bone formation, and replacement with autologous bone can be performed in a short period of time.

  In addition, since the collagen is gradually eluted or dispersed in the body circulation tissue or the like after the bone filling material 1 is filled, the covering portion 3 is finally removed from the surface of the bone filling material 1. However, there is no particular problem if the periosteum 11 near the bone defect L is sufficiently regenerated at this point. That is, various conditions such as the type of collagen used for the covering portion 3 and the film thickness thereof can be set so that the function as a substitute for the periosteum 11 can be maintained at least until the periosteum 11 can be sufficiently regenerated. Is important.

  In the bone prosthetic material 1 and the manufacturing method thereof according to the present embodiment, the prosthetic material body 2 made of β-TCP, bone marrow, and PRP is covered with the covering portion 3 made of a collagen sheet. It can absorb and permeate blood and other circulating tissues in the body. That is, the covering portion 3 ensures the same function as that of the periosteum, can be in a state similar to the presence of blood vessels around the main body 2 of the filling material, and circulates in the body in every corner of the main body 2 of the filling material. And oxygen and nutrients can be sufficiently and accurately carried into the bone marrow and PRP in the main body of the filling material. As a result, various natural forming factors (autologous growth factors) contained in bone marrow cells and platelet-rich plasma contained in the bone marrow can be suitably activated. However, cell adhesion can be realized at an early stage to promote bone formation, and replacement with autologous bone can be performed in a short period of time.

  Since collagen is a natural material, it has higher biocompatibility than a bioabsorbable polymer such as polylactic acid (PLA) or polyglycolic acid (PGA), and remains as a foreign substance in the body. There is no fear.

  Furthermore, since bone marrow and PRP, which can be directly collected from the patient, are used, a series of operations can be performed during the bone repair operation, and the bone filling material can be manufactured within a short time during the operation. Once completed, it can be quickly implanted and filled into the patient's body. Since both bone marrow and PRP are collected from the patient and returned to the same patient's body, there is no risk of rejection and the like, and an extremely reliable operation can be performed accurately.

It is a schematic perspective view which shows the prosthetic material main body of the bone prosthetic material which concerns on one Embodiment of this invention. It is a schematic perspective view which shows the bone grafting material which concerns on one Embodiment of this invention. FIG. 3 is a cross-sectional view showing a state where the bone defect material of FIG. 2 is filled in a bone defect portion.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Bone prosthetic material 2 Prosthetic material main body 3 Covering part 10 Bone 11 Periosteum

Claims (4)

A bone filling material using calcium phosphate as a scaffold,
A bone grafting material comprising: a filling material body made of the calcium phosphate, bone marrow, and platelet-rich plasma; and a covering portion made of a collagen sheet covering the filling material body. The bone grafting material according to claim 1, wherein the calcium phosphate is a granule having a particle size in a range of 0.01 µm to 3 mm. A method for producing a bone grafting material using calcium phosphate as a scaffold,
A process for producing a main body of a prosthetic material, which is formed after mixing bone marrow and platelet-rich plasma with the calcium phosphate,
A covering portion forming step of winding a collagen sheet around the filling material body to form a covering portion covering the filling material body;
A method for producing a bone grafting material, comprising: The method for producing a bone grafting material according to claim 3, wherein the calcium phosphate is a granule having a particle size in a range of 0.01 µm to 3 mm.

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