JP4388260B2 - Articular cartilage regeneration member - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
  The present invention relates to articular cartilage.ofMore specifically, the cartilage peculiar to the joint part.ofThe present invention relates to a reproduction member that can be suitably used for reproduction.
[0002]
[Prior art]
The joint is a connecting part where the bones are movably connected to each other, and the surfaces (joint surfaces) of the bone ends of the connecting part are covered with articular cartilage. The periosteum at the epiphyses of each other forms a joint capsule so as to integrally wrap the connecting portion. A space called a joint cavity is formed between the bones covered with the joint capsule, and the inside is filled with joint fluid.
[0003]
The cartilage formed on the joint surface is usually about 2 mm in thickness at a human knee joint, and it is 1 to 4 mm due to trauma or disease.²If damaged to some extent, there is a possibility of regeneration due to natural healing, but 20mm²If it is damaged, it is difficult to reproduce it by itself, and it is generally accompanied by great pain.
Further, when articular cartilage is completely lost due to various causes such as tumor and necrosis, for example, a treatment such as embedding an artificial joint in the corresponding part is performed to restore the joint function.
[0004]
However, an artificial joint is artificially constructed to resemble a joint function to the last, and is a foreign body for a living body, so it is difficult to maintain biocompatibility.
In addition, since artificial joints are required to perform complex operations in a severe environment in a living body, it is difficult to maintain them for more than 20 years. Deterioration or wear of resin or metal used as the material is difficult. The powder or the like may cause functional deterioration and pain, and it cannot be said that the durability is sufficient.
[0005]
Therefore, a technique for regenerating articular cartilage itself is desired as an alternative to artificial joint treatment.
Further, in the treatment of cartilage dysplasia where cartilage itself is difficult to form, there is a demand for a technique for regenerating articular cartilage as a living tissue without using artificial materials.
[0006]
Several proposals have been made on the technique for regenerating cartilage, but all of them are to the extent that cartilage in the previous stage in the process of ossification where normal bone is formed is scattered in the gaps in the bone. It was a thing.
For example, Japanese Patent Application Laid-Open No. 7-88174 discloses that a callus-like osseous protuberance including bone and cartilage including bone and cartilage is formed by an implant using atelocollagen.
[0007]
However, in the above graft, the amount of cartilage is not sufficient, as with a callus-like osseous protuberance, and it does not have continuity, thickness and amount that can be used as a joint. .
As described above, articular cartilage is difficult to regenerate. Conventionally, there is no example of articular cartilage that has been regenerated continuously in the form of a film or layer. Development of a technique capable of continuously obtaining cartilage in a sufficient amount has been demanded.
[0008]
In a recent research presentation, it was announced that articular cartilage is regenerated by perforating the joint surface and placing collagen containing bone morphogentic protein (BMP) at the desired site. .
[0009]
[Problems to be solved by the invention]
However, the regenerated articular cartilage is not formed continuously with the adjacent existing articular cartilage and cannot be said to be completely regenerated.
Collagen tends to be avoided from being applied to living bodies due to problems such as BSE (bovine spongiform encephalopathy), so-called mad cow disease.
[0010]
Therefore, it has been desired to regenerate complete articular cartilage in a continuous state without a boundary between the regenerated part and the existing part, using only materials that are approved for application to living bodies.
[0011]
  The present invention has been made in order to solve the above technical problem, and is integrated with the existing surrounding articular cartilage adjacent to each other in a good condition in an environment close to nature. Articular cartilage that can regenerate early thickness of articular cartilageofIt aims at providing the member for reproduction | regeneration.
[0012]
[Means for Solving the Problems]
  Regeneration of articular cartilage according to the present inventionMaterialsIsJoint surfaceTo be embedded deeper than the lower surface of the articular cartilage layerA member for regenerating articular cartilage, having a porosity of 50% or more and 90% or less, and a porous body having communication holes through which cells can invade and move as a whole.It is characterized by that.
  Here, the term “reproduction” in the present invention is used in a sense including a new formation.
  the aboveRecycling materialAccording to the present invention, bone cells are introduced into the porous body, subchondral bone is formed on the upper surface of the porous body, and the upper surface has a thickness equivalent to that of the adjacent surrounding articular cartilage. Can regenerate articular cartilage.
  In addition, according to the porous body having the porosity and the pore shape as described above, mesenchymal cells, mesenchymal stem cells, bone marrow cells, etc. that are required for the formation of articular cartilage enter from inside the bone. Since it is easy to settle, the articular cartilage can be regenerated at an early stage.
[0013]
  The articular cartilage regeneration member according to the present invention is an articular cartilage regeneration member that is used by being embedded in a position deeper than the lower surface of the articular cartilage layer on the joint surface, and has a porosity of 50% or more and 90%. %, Average pore diameter is 100μm or more 600μm or less, and each pore is made of a porous body that communicates three-dimensionally with a communication hole..
  As described above, the porous body having such properties is suitable as a member for regenerating articular cartilage from the viewpoints of invasion, easiness of fixation, strength, etc. of mesenchymal cells, mesenchymal stem cells, bone marrow cells, and the like. Can be used.
[0014]
  It is preferable to embed the porous body so that at least a part of the porous body comes into contact with mesenchymal cells, mesenchymal stem cells or bone marrow cells in bone.
  By bringing the porous body into contact with the mesenchymal cells and the like, the regeneration of articular cartilage can be promoted.
[0015]
  The porous body is preferably embedded so that the upper surface (end surface on the joint surface side) is exposed on the joint surface.
  In order not to prevent the articular cartilage from being restored to the original damaged position at the original thickness, it is preferable to secure a space for accommodating the regenerated articular cartilage as described above.
[0016]
  The porous body is preferably made of hydroxyapatite.
  Hydroxyapatite is a main component of bone and has been already applied to the human body, and is a suitable material from the viewpoint of assimilation with bone, adhesion, strength, early recovery, and the like. It is also suitable as a cell scaffold.
[0017]
  Furthermore, as the porous body, those having pores formed by stirring foaming can be suitably used.
  The porous body in which pores are formed by stirring and foaming has a dense skeletal wall part that defines the pores, the pores are almost spherical, and high strength can be obtained. And the like, blood and the like easily penetrated. Moreover, since the surface area per unit volume is large, it is easy to obtain suitable properties as a scaffold for cells that have invaded.
[0018]
  Moreover, it is preferable that the pore inner surface of the porous body is coated with a mixed layer of a bioabsorbable member and an osteogenic factor.
[0019]
  The osteogenic factor is preferably any one of osteoinductive factors, transforming growth factors, osteogenic inducing factors, insulin-like growth factors, platelet-derived growth factors, and fibroblast growth factors.
[0020]
  The osteogenic factor is a human osteoinductive factor, and particularly preferably a recombinant human osteoinductive factor.
[0021]
  The bioabsorbable material is preferably an organic compound.
[0022]
  The bioabsorbable material is particularly preferably a polymer material having both hydrophobic and hydrophilic properties.
[0023]
DETAILED DESCRIPTION OF THE INVENTION
  Hereinafter, the present invention will be described in more detail with reference to some drawings.
  The articular cartilage of the present inventionUsing a recycling memberPlayback methodInEmbeds the porous body deeper than the lower surface of the articular cartilage layer on the joint surface.Ru.
  By the above method, bone cells are introduced from the inside of the bone to the inside of the porous body, and a bone layer called a subchondral bone that does not include the porous body is formed on the upper surface of the porous body. Then, the articular cartilage is regenerated on the upper surface of the subchondral bone with a thickness equivalent to that of the adjacent existing articular cartilage.
[0024]
  the aboveIn the reproduction method, first, the joint capsule is incised to expose the joint surface. For example, FIG. 1 shows a schematic diagram when the articular cartilage of the knee joint is regenerated.
  As shown in FIG. 1, in the knee joint of the femur 1, the bone is ground and drilled in a depth direction from the joint surface at a desired site where the regeneration of the articular cartilage 2 is required. Then, the porous body 4 having a shape substantially equal to the perforation is embedded in the perforation at a position deeper than the lower surface of the articular cartilage 2 layer.
[0025]
As shown in FIG. 1, at least a part of the porous body 4 is embedded up to a position where it is in contact with a site where many mesenchymal cells, mesenchymal stem cells, bone marrow cells and the like are present.
By bringing the porous body 4 into contact with the mesenchymal cells, mesenchymal stem cells, bone marrow cells, etc., regeneration of articular cartilage can be promoted.
[0026]
At this time, as shown in FIG. 4, it is more preferable that the perforation is deeply formed to a site where many bone marrow cells exist, and the lower end thereof reaches the vicinity of the bone marrow.
By drilling to a depth position near the bone marrow, sufficient bone marrow cells can be introduced into the porous body 4.
Note that the deep part of such deep perforations may be filled with a porous granule or the like, or may be left hollow.
[0027]
When the growing cartilage layer 3 is present, the porous body 4 is preferably embedded to a depth where at least a part thereof reaches the growing cartilage layer 3.
In general, the growing cartilage layer 3 disappears with growth and aging. However, when the growing cartilage layer 3 is present, the porous body 4 is moved to a position in contact with the growing cartilage layer 3 as described above. It has been confirmed that by embedding, a superior articular cartilage regeneration effect tends to be obtained as compared with the case where the growing cartilage layer 3 is not contacted.
[0028]
In addition, the thinner the porous body 4 is, the smaller the depth of drilling the bone by drilling, the less damage is given to the bone, but the invasion of cells and the like from the inside of the bone is reduced. From the viewpoint of easiness and the like, it is preferable that the thickness be sufficiently fixed in the hole.
[0029]
Further, according to the method of the present invention, the articular cartilage is restored to the original damaged position at the original thickness, so that there is no hindrance in the portion where the articular cartilage is to be regenerated. In other words, the porous body is preferably embedded so that the upper surface of the porous body 4 is exposed.
[0030]
FIG. 2 shows an enlarged view of a portion where the porous body 4 is embedded in FIG.
As shown in FIG. 2, the porous body 4 is embedded and fixed at a position deeper by d than the lower surface of the existing articular cartilage 2 layer, that is, in a state where the recess P is formed. Then, with the upper surface of the porous body 4 exposed to the joint surface, the joint capsule is sutured to complete the treatment.
After the treatment is completed, the mesenchymal cells, mesenchymal stem cells, bone marrow cells, blood, and the like contained in the bone penetrate the porous body 4 from the inside of the bone or from the side of the recess P over time. That is, it is supplied to the concave portion P from the direction indicated by the arrow B.
[0031]
Then, bone cells enter the porous body 4 and the articular cartilage is regenerated in the state shown in FIG.
That is, in the portion where the porous body 4 is embedded, the bone is formed in the portion including the porous body 4. At the same time, as shown in FIG. 3, a new bone layer called subchondral bone 5 that does not include the porous body 4 is formed on the upper surface of the porous body 4.
Further, the articular cartilage 2 is formed on the upper surface of the subchondral bone 5. The regenerated articular cartilage is formed with a thickness equivalent to that of the adjacent surrounding articular cartilage and is integrated in good condition. Moreover, the boundary portion of the surface is formed in a continuously smooth state without cracks, scratches, irregularities and the like.
[0032]
On the other hand, when the upper surface of the porous body 4 is embedded at a depth position equivalent to the lower surface of the layer of the existing articular cartilage 2 or shallowly, that is, when the recess P is not formed. No articular cartilage is formed, nor is subarticular bone formed.
[0033]
Note that the articular cartilage lower surface A at the boundary portion tends to be slightly thicker than the articular cartilage layer in other portions.
Since the formation state of the articular cartilage lower surface A of the boundary portion differs depending on the depth position of the upper surface of the embedded porous body 4, this is because the supply state of mesenchymal cells and the like from inside the bone is 1 This is considered to be one factor.
As described above, by implanting the porous body 4 at a position deeper than the lower surface of the layer of the existing articular cartilage 2 by d, that is, in a state where the recess P is formed, mesenchymal cells and the like However, it is assumed that the articular cartilage layer is thickened on the lower surface A of the articular cartilage at the boundary portion because the natural healing power that tries to repair the damaged portion quickly works due to the supply from the side portion of the concave portion P. Is done.
[0034]
In the above treatment, it is preferable that the joint capsule is filled with the joint fluid after the porous body is embedded and the joint capsule is sutured.
It is considered that at least a part of the porous body is subjected to some kind of stimulation when it comes into contact with joint fluid, and regeneration of articular cartilage is promoted.
Further, it is preferable that the joint can be moved and a stimulus such as a load change or a joint fluid pressure change is given. Giving such a stimulus is considered to contribute to the promotion of regeneration of articular cartilage.
[0035]
The porous body used in the present invention preferably has a porosity of 50% or more and 90% or less and has communication holes through which cells can invade and move as a whole.
Further, those having an average pore diameter of 100 μm or more and 600 μm or less and each pore communicating three-dimensionally with a communication hole are preferably used.
The average pore diameter can be measured by a resin embedding method.
The average pore diameter of the communication holes is preferably 20 μm or more, and more preferably 40 μm or more. The average pore diameter of the communication holes can be measured by a mercury porosimeter (mercury intrusion method).
Such a porous body is disclosed in, for example, Japanese Patent Application Laid-Open No. 2000-302567.
According to the porous body having the porosity and the pore shape as described above, mesenchymal cells, mesenchymal stem cells, bone marrow cells, blood and the like required for the formation of articular cartilage are transferred from inside the bone. Since it easily invades and settles, the articular cartilage can be regenerated early.
[0036]
When the porosity is less than 50%, it is difficult for the mesenchymal cells or the like to enter the porous body, and it becomes difficult to regenerate articular cartilage at an early stage.
On the other hand, when the porosity exceeds 90%, the mesenchymal cells and the like are poorly fixed, and in this case also, early regeneration of articular cartilage becomes difficult and sufficient strength cannot be obtained.
The porosity is more preferably 65% or more and 85% or less.
In addition, the porous body can be used as a granular body, if necessary.
[0037]
The porous body may be any of inorganic, organic, or inorganic and organic composite materials as long as the material does not have biological harm and has sufficient mechanical strength. Moreover, a bioabsorbable material may be sufficient.
Specifically, titanium, alumina, zirconia, silica, mullite, diopside, wollastonite, alite, belite, akermanite, montcelite, glass for biological use, calcium phosphate ceramics, lactic acid and / or glycolic acid A polymer or copolymer, collagen, or the like is preferably used.
Two or more of these materials may be used in combination.
[0038]
Among these, calcium phosphate ceramics that are excellent in biocompatibility and have already been applied to the human body are preferable. For example, hydroxyapatite, tricalcium phosphate, and fluorapatite are preferably used.
In the present invention, in particular, from the viewpoints of assimilation with bone, adhesion, strength, early recovery, etc., it is preferably made of hydroxyapatite which is the main component of bone.
[0039]
The porous body having the above configuration can be easily produced by stirring and foaming. The porous body in which pores are formed by stirring and foaming is dense in the skeleton wall itself that defines the pores, the pores are almost spherical, and high strength can be obtained. Cells, mesenchymal stem cells, bone marrow cells, blood and the like are easily invaded.
[0040]
Specifically, for example, the porous body as described above can be obtained by the following production method. A porous body made of hydroxyapatite will be described as an example.
First, polyethyleneimine or the like is added to a hydroxyapatite powder as a cross-linkable resin, mixed and crushed using water as a dispersion medium to prepare a slurry.
Next, polyoxyethylene lauryl ether or the like is added to the slurry as a foaming agent, and the mixture is stirred to foam.
Furthermore, by adding sorbitol glycidyl ether or the like as a cross-linking agent, casting the resulting foam slurry, drying it with the foam structure fixed, and then sintering at about 1100 to 1300 ° C., A porous body made of hydroxyapatite is obtained.
[0041]
When the porous body having the above structure is used as a member for regenerating articular cartilage, articular cartilage can be regenerated without using special factors such as osteogenic factors. In order to regenerate more reliably, it is preferable to use an osteogenic factor together with the porous body.
As the bone morphogenetic factor, various bone formation-related proteins that are components extracted from bone tissue can be used. For example, bone morphogentic protein (BMP), transforming growth factor (TGF-β), osteoinductive factor (OIF), insulin derived growth factor (IGF) ), Platelet derived growth factor (PDGF) and fibroblast growth factor (FGF).
[0042]
Among these bone morphogenetic factors, in order to be applied to the human body, human osteoinductive factor (hBMP) that is substantially free from other human-derived proteins is preferable.
In particular, it is a recombinant human osteoinductive factor (rhBMP) obtained by a genetic recombination technique in view of the fact that it is possible to obtain a large amount of materials with stable clinical quality such as immunity and stable quality. preferable. That is, it is prepared by culturing a transformant such as a cell or microorganism containing a recombinant DNA containing a base sequence encoding a human osteoinductive factor, and isolating and purifying the rhBMP produced by the transformant. is there.
[0043]
Among these rhBMPs, rhBMP-2 or rhBMP-7 is preferable for cartilage regeneration because rhBMP-2 or rhBMP-7 is highly effective, and rhBMP-2 is particularly preferable.
[0044]
In addition, these bone morphogenetic factors, when singly coated directly on the porous body, flow out immediately, and therefore have a sustained release property of the bone morphogenetic factor, and are not harmful to the living body. It is preferable to use the bioabsorbable member uniformly mixed in a bioabsorbable member that gradually absorbs bone formation factors while being gradually absorbed by the in vivo tissue.
[0045]
The bioabsorbable member may be an inorganic material such as tricalcium phosphate, but is preferably an organic compound from the viewpoint of ease of control of the bioabsorbable time. In the case of an organic compound, the sustained release period can be adjusted by adjusting the molecular weight, and further, the bone formation factor can be spread uniformly and widely within the pores of the porous body.
In addition, it is more preferable to use the organic compound obtained by a synthesis | combination from a viewpoint of eliminating the infection by a microbe etc.
[0046]
As the bioabsorbable material, specifically, a polymer material having both hydrophobic and hydrophilic properties is preferably used. For example, a polymer of lactic acid and / or glycolic acid, a block copolymer of a polymer of lactic acid and / or glycolic acid and polyethylene glycol, a copolymer of lactic acid and / or glycolic acid, p-dioxanone and polyethylene glycol ( PLA-DX-PEG), atelocollagen and the like.
[0047]
As described above, the articular cartilage regeneration member according to the present invention is a specific porous body made of hydroxyapatite that has already been approved for use in the human body without using special factors such as bone formation factors. Then, the articular cartilage can be regenerated at the original thickness at an early stage.
[0048]
  As mentioned aboveAccording to the method, for example, for a patient who has damaged articular cartilage over a wide area due to severe exercise or the like, the function of the articular cartilage is not so important. It is also possible to perform such a treatment that the articular cartilage regeneration member according to the present invention is embedded in the hole of the side surface portion generated thereby to supplement the collected articular cartilage.
[0049]
Further, by using the articular cartilage regeneration member according to the present invention, chondrocytes, mesenchymal cells, mesenchymal stem cells, bone marrow cells and the like collected from a patient are similar to joint portions in vivo outside the body. It is also possible to form an environment, culture articular cartilage in the environment, and transplant it to the affected area. This makes it possible to establish a treatment method that replaces the conventional artificial joint treatment, which has been a burden and pain for the patient.
[0050]
【Example】
EXAMPLES Hereinafter, although this invention is demonstrated more concretely based on an Example, this invention is not restrict | limited by the following Example.
[Example 1]
A porous body made of hydroxyapatite having a porosity of 75% and a pore diameter of 200 μm was produced by stirring and foaming, and processed into a cylindrical body having a diameter of 4 mm and a length of 4 mm.
A rabbit's knee joint is incised, and the femoral joint surface is 4 mm in diameter and drilled to a depth where a part reaches the growth cartilage layer 3. The resulting porous body is inserted into the hole, and the surface thereof is articular cartilage. After embedding so as to be 1 mm deeper than the layer, that is, d = 1 mm in FIG. 2, the joint was returned to its original position, and the incision was sutured to make it movable.
The above treatment was performed on 5 rabbits (n = 5).
[0051]
[Example 2]
A porous body made of hydroxyapatite similar to that in Example 1 was prepared.
The depth of embedding of the porous body is set to be 2 mm deeper than the articular cartilage layer, that is, d = 2 mm in FIG. The knee joint was treated.
[0052]
[Comparative Example 1]
A porous body made of hydroxyapatite similar to that in Example 1 was prepared.
The embedding depth of the porous body is set so that the surface thereof is equal to the depth position of the lower surface of the articular cartilage layer, that is, d = 0 in FIG. Then, the knee joint of the rabbit was treated.
[0053]
[Comparative Example 2]
A porous body made of hydroxyapatite similar to that in Example 1 was prepared.
The embedding depth of the porous body is set so that the surface thereof is 0.5 mm shallower than the depth position of the lower surface of the articular cartilage layer. Otherwise, the rabbit knee joint is the same as in Example 1. Was treated.
[0054]
[Comparative Example 3]
As a control test, a rabbit knee joint was incised, a femoral joint surface was drilled with a diameter of 4 mm and a depth of 4 mm, nothing was embedded in the hole, the joint was returned to its original position, and the incision was further removed. It was sewn and allowed to move.
The above treatment was performed on 5 rabbits (n = 5).
[0055]
Three weeks later, the treated parts were observed in the above Examples and Comparative Examples.
As a result, when the porous body was embedded at a position deeper than the lower surface of the articular cartilage layer (Examples 1 and 2), the sub-articular bone was formed on the upper surface of the porous body in spite of a short period of 3 weeks. It was observed that about 60% of the articular cartilage was almost completely regenerated on the surface thereof, with a thickness equivalent to that of the adjacent healthy articular cartilage.
In the regenerated articular cartilage, the surface of the boundary portion was continuously and smoothly formed.
In addition, it was recognized that the articular cartilage was formed to be slightly thick on the lower surface of the boundary portion of the surrounding healthy articular cartilage adjacent to the regenerated articular cartilage.
[0056]
On the other hand, when the porous body was embedded at a depth equal to or shallower than the depth position of the lower surface of the articular cartilage layer (Comparative Examples 1 and 2), the articular cartilage was not regenerated at all.
From this, it is considered that articular cartilage is not regenerated when there is no room for formation of subchondral bone between the articular cartilage layer and the porous body.
As a control test, when the porous body was not embedded (Comparative Example 3), the articular cartilage was not regenerated at all.
[0057]
[Example 3]
PLA-DX-PEG (PLA: DX: PEG = 45: 17: 38 (molar ratio)) 100 mg composed of a copolymer having a number average molecular weight of 9300 composed of DL-lactide, p-dioxanone and polyethylene glycol, and rhBMP-2 Was mixed with 20 μg and diluted with acetone to prepare a gel mixture.
After this gel-like mixture was infiltrated into a porous material made of hydroxyapatite prepared in the same manner as in Example 1, it was allowed to stand for a while to evaporate acetone, and the pore inner surface of the apatite porous material was bioabsorbable. It was coated with a uniform mixed layer of the member and the osteogenic factor to obtain a member for regenerating articular cartilage.
Using this articular cartilage regeneration member, a rabbit knee joint was treated in the same manner as in Example 1.
[0058]
After 3 weeks, the treated part was observed, and when a joint cartilage regeneration member composed of a porous body coated with a bioabsorbable member and an osteogenic factor was used (Example 3), almost complete About 100% of the articular cartilage is regenerated in the state, and the reliability of the articular cartilage regeneration is higher than that of the articular cartilage regeneration member (Examples 1 and 2) made of only a porous body. It was found to be superior. In particular, it was confirmed that the thickness uniformity was excellent.
[0059]
[Example 4]
A porous body made of hydroxyapatite similar to that in Example 1 was prepared.
The rabbit knee joint was incised, and the femoral joint surface was drilled to a depth of 4 mm and not reaching the growth cartilage layer. Otherwise, treatment was performed on the rabbit knee joint in the same manner as in Example 1. gave.
The length of the porous body was finely adjusted as appropriate so as to be within the perforations.
[0060]
[Example 5]
A porous body made of hydroxyapatite similar to that in Example 1 was prepared.
The rabbit knee joint was incised, and the femoral joint surface was 4 mm in diameter and penetrated through the growth cartilage layer until it reached the bone marrow. Otherwise, the same procedure as in Example 1 was performed on the rabbit knee joint. Treatment was given.
In addition, the deep part of the said perforation was made into the state of a cavity.
[0061]
After 3 weeks, when the treated part was observed, a case was drilled to a depth position not reaching the growth cartilage layer (Example 4), and a case where drilling was performed until it reached the bone marrow through the growth cartilage layer In all of Examples (5), it was confirmed that sub-articular bone was formed on the upper surface of the porous body, and that articular cartilage was regenerated on the surface.
However, when drilling was performed up to a depth that does not reach the growing cartilage layer (Example 4), about 20% of the articular cartilage was regenerated in a nearly complete state. Some of the regenerated articular cartilage had a non-uniform thickness, and some of the regenerated articular cartilage required more time before it was fully regenerated.
On the other hand, in the case of drilling until the bone marrow layer is penetrated through the growth cartilage layer (Example 5), as in the case of drilling to a depth position where a part reaches the growth cartilage layer (Example 1), about 60 % Were found to have almost completely regenerated articular cartilage.
[0062]
【The invention's effect】
  Regeneration of articular cartilage according to the present inventionMaterialsAccording to the above, using only a member made of a material that has already been approved for application to the human body, it is integrated in a good condition with the adjacent surrounding articular cartilage in a natural condition, and is in a continuous state. Thus, the articular cartilage having the original thickness can be regenerated early.
  Further, by using the articular cartilage regeneration member according to the present invention, it becomes possible to culture the articular cartilage for transplantation in vitro and transplant it to a patient, which is a conventional artificial body that has been burdensome and painful to the patient. It can also contribute to establishing treatment methods that replace joint treatments.
[Brief description of the drawings]
FIG. 1 is a diagram schematically showing the vicinity of the articular cartilage of a femur in a rabbit knee joint.
FIG. 2 is an enlarged view schematically showing an embedded portion of a porous body in FIG.
FIG. 3 is an enlarged view schematically showing a regeneration part of articular cartilage.
FIG. 4 is a diagram schematically illustrating a case where a femoral joint surface of a rabbit knee joint is perforated so that the lower end reaches the vicinity of the bone marrow.
[Explanation of symbols]
1 Femur
2 Articular cartilage
3 Growing cartilage layer
4 Porous body
5 Subchondral bone
P recess
A Lower surface of articular cartilage at the boundary
B Flow of mesenchymal cells

Claims (12)

An articular cartilage regeneration member that is used by being embedded in a position deeper than the lower surface of the articular cartilage layer on the joint surface , having a porosity of 50% or more and 90% or less, and can invade and move as a whole. A member for regenerating articular cartilage, comprising a porous body having communication holes . A member for regenerating articular cartilage, which is used by being embedded in a position deeper than the lower surface of the articular cartilage layer on the joint surface, having a porosity of 50% to 90% and an average pore diameter of 100 μm to 600 μm, A member for regenerating articular cartilage, characterized in that each pore is made of a porous body that communicates three-dimensionally with a communication hole. The regeneration of articular cartilage according to claim 1 or 2 , wherein at least a part of the porous body is implanted so as to be in contact with mesenchymal cells, mesenchymal stem cells or bone marrow cells in bone. Materials . The member for regenerating articular cartilage according to any one of claims 1 to 3, wherein the porous body is embedded so that the upper surface is exposed to the joint surface. The member for regenerating articular cartilage according to any one of claims 1 to 4, wherein the porous body is made of hydroxyapatite. The member for regenerating articular cartilage according to any one of claims 1 to 5, wherein the pores of the porous body are formed by stirring and foaming. The articular cartilage regeneration member according to any one of claims 1 to 6, wherein an inner surface of pores of the porous body is coated with a mixed layer of a bioabsorbable member and an osteogenic factor. 8. The osteogenesis factor is any one of osteoinductive factor, transforming growth factor, osteogenesis inducing factor, insulin-like growth factor, platelet-derived growth factor, and fibroblast growth factor. The member for regeneration of articular cartilage as described. The member for regenerating articular cartilage according to claim 7, wherein the osteogenic factor is a human osteoinductive factor. The member for regenerating articular cartilage according to claim 9, wherein the human osteoinductive factor is a recombinant human osteoinductive factor. The member for regenerating articular cartilage according to any one of claims 7 to 10, wherein the bioabsorbable material is an organic compound. The member for regenerating articular cartilage according to any one of claims 7 to 11, wherein the bioabsorbable material is a polymer material having both hydrophobic and hydrophilic properties.

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