Patent Application
20070112434
The present invention relates to a material for repairing biological tissues used for repairing a defect in biological tissues, and a process for producing the same.
Recently, it has become possible to repair a defect in biological tissue such as bone caused by osteoncus extraction, trauma, or the like by regenerating the bone by filling a material for repairing biological tissues such as a bone substitute or the like. For such a bone substitute, hydroxyapatite (HAP) and tricalcium phosphate TCP) are known. However, from the viewpoint of leaving no foreign matter inside the body, a scaffold made of a porous calcium phosphate material, for example, such as β-TCP is used. If the β-TCP is left in contact with bone cells of a defect part of bone, so-called remodeling is performed in which osteoclasts eat the β-TCP and osteoblasts form a new bone. That is, the bone substitute filled in the defect part of the bone is replaced by autologous bone as time goes by (for example, refer to: Uemura and two others, “Tissue engineering in bone using biodegradable β-TCP porous material—a new material strengthened in vivo Osferion”, Medical Asahi, The Asahi Shimbun Company, Oct. 1, 2001, Vol. 30, No. 10, p. 38-41).
When the bone substitute is to be filled into a defect part of the bone, in order to increase the adhesiveness with the bone tissue, various inventions have been proposed in which: the surface to be in contact with the defect part of the bone is made uneven by plasma spraying (for example, refer to Japanese Patent No. 3166352); or a binding packing made from a nonwoven fabric is arranged on the surface in contact with the defect part of the bone (for example, refer to Japanese Unexamined Patent Application, First Publication No. 2003-19149).
On the other hand, according to the condition of the defect part of the bone, there is a case where the bone forming function is promoted by adding growth factors to the bone substitute in order to increase the activity of the cells surrounding the defect part of the bone.
As a method of adding the growth factors in this case, there is known a method wherein the bone substitute is provided with various sizes of holes which are filled with biodegradable viscous material such as collagens containing the growth factors, and the bone substitute is applied as a filling.
However, the binding force between the abovementioned conventional bone substitute, which is provided only with the uneven part or the binding packing, and the surrounding bone tissue is weak, so that the bone substitute and the bone tissues may become separated before the bone has grown.
Therefore, although such a structure has been employed, bone regeneration still takes a long time and it has been difficult to sufficiently demonstrate the bone regenerating function.
Moreover, in the abovementioned conventional bone substitute, although micropores are reliably in communication with each other inside of the porous body, there has been a problem in that straight penetrating holes are not provided and blood vessels can not be sufficiently formed. Moreover, there has been a problem in that growth factors of sufficient types and amounts can not be added, so that supply with a sustained-release property where they are leaked out into the biological tissue surrounding the defect as time goes by cannot be achieved, and therefore, the effect can not be maintained for a long time.
In view of the above problems, an object of the present invention is to provide a material for repairing biological tissues which sustains a sufficient binding force after application to a biological tissue and promotes biological tissue formation.
Moreover, the present invention has an object of providing a material for repairing biological tissues which can provide agonistic factors of sufficient types and amounts to a biological tissue, and can control the sustained-release dose thereof.
The present invention employs the following solution in order to solve the above problems.
In the material for repairing biological tissues of the present invention, a plurality of grooves are formed in the surface of a plate-type base member.
Since a plurality of grooves are formed in the surface of the base member, the material for repairing biological tissues, can be more in contact with the biological tissues. As a result, places where the biological tissue formation is induced, are increased. Moreover, for example, if it is used as a bone substitute, it is filled so that its groove side is pressed against and inserted into the cancellous bone inside the bone, and its base plate side is in contact with the cortical bone being the outer layer, so that the adhesiveness with the cancellous bone is increased. As a result, even if a load is applied in a separation direction, the connection of the bone substitute with the biological tissues can be maintained, and the effect of forming a biological tissue can be maintained, enabling an increase in the healing speed.
Moreover, in the material for repairing biological tissues according to the present invention, it is preferable that the grooves be formed along almost the same direction.
According to the material for repairing biological tissues, since a plate-type base member can be readily formed into a curved shape along the direction where the grooves are extending, it can be provided in an optimum shape for defects in biological tissue.
A process for producing a material for repairing biological tissues of the present invention comprises: a step for supplying a raw material formed in a slurry form into a mold, and forming a compact in which a plurality of penetrating holes extending in a single direction are separated from each other by partition wall members having an almost uniform thickness; and a step for cutting and dividing the compact by a plane in parallel with the direction in which the penetrating holes are extending.
According to the process for producing the material for repairing biological tissues, by dividing the penetrating holes formed in the compact, grooves are formed by the partition wall members that divided the penetrating holes in the compact, and by pressing these grooves against the biological tissue, the adhesiveness thereof with the biological tissue can be improved. Moreover, since the compact is formed by supplying the raw material formed in a slurry form into the mold, the size and the shape of the penetrating holes which become the grooves, and the thickness of the partition wall member can be freely controlled, and the material for repairing biological tissues can be formed in an optimum shape and size considering the position to be repaired and the adhesiveness with the biological tissue.
The compact may have a honeycomb shape.
Moreover, another material for repairing biological tissues of the present invention comprises: a main body of a shape in which a plurality of penetrating holes extending in a single direction are formed separated from each other by partition wall members having an almost uniform thickness; and a biodegradable viscous member which is filled into at least one of the penetrating holes in the main body, and contains an agonistic factor capable of increasing cell activity.
In the main body of the material for repairing biological tissues, the size and shape of the penetrating holes can be freely controlled for molding. Moreover, since the biodegradable viscous member containing the agonistic factor is filled into the penetrating holes, then by controlling the position of the penetrating holes and the number thereof to be filled, the sequence of providing the agonistic factor into a defect, and the sustained-release dose can be controlled, so that the biological tissue formation can be effectively promoted.
The main body may be in a honeycomb shape.
Hereunder is a description of a material for repairing biological tissues according to a first embodiment of the present invention, with reference to
As shown in
Next is a description of a process for producing the bone substitute 10.
As shown in
In step (S01) for forming the honeycomb compact 15, firstly, for example by a method disclosed in Japanese Unexamined Patent Application, First Publication No. Hei 5-237178, an aqueous foamed slurry which has been mixed and foamed, is adjusted and mixed with granular compacts made from β-TCP so as to make a raw material which is formed in a slurry form.
The raw material is supplied into the honeycomb mold 14 to make a honeycomb prototype 16 shown in
As shown in
The width of the slits 18 and the intervals therebetween are previously determined considering the adhesiveness according to the shape and the size of the bone tissue to be repaired.
The obtained honeycomb prototype 16 is sintered after drying, for example in a method disclosed in Japanese Unexamined Patent Application, First Publication No. Hei 5-237178.
In this manner, the honeycomb compact 15 in which a plurality of penetrating holes 20 extending in a single direction are separated from each other by partition wall members 13, is obtained.
In the step (S02) for cutting and dividing the honeycomb compact 15, it is cut and divided by a plane (for example, the IV-IV position shown in
In this case, the bone substitute 10 wherein the wall 15a constituting the external surface of the honeycomb compact 15 is serving as the base member 11, and the respective penetrating holes 20 are serving as grooves 12, is obtained.
Next is a description of the effect of the bone substitute 10 of the present embodiment having the above structure.
As shown in
Moreover, since the bone tissue and the bone substitute 10 are in contact over a large area including the surface of the partition wall members 13 as well as the surface of the base member 11, the bone is formed over a large area.
According to the bone substitute 10, since it is formed by honeycomb molding, the size and the shape of the penetrating holes 20 serving as the grooves 12 can be freely controlled, and it can be formed in an optimum shape and size considering the adhesiveness of the bone substitute to the bone to be repaired and its vicinity. Moreover, since the grooves 12 are formed, the bone substitute can be in contact with the cancellous bone 22 over a large area, and the bone formation can be promoted so as to increase the healing speed after the repair, more than in the conventional case.
Next is a description of a material for repairing biological tissues according to a second embodiment of the present invention, with reference to
The point where the second embodiment is different from the first embodiment is that in the first embodiment the material of the base member 11 of the bone substitute 10 is β-TCP, whereas in the second embodiment the material is a bioabsorbent material such as polylactic acid (PLA).
As shown in
Next is a description of a process for producing the bone substitute 24.
As shown in
In step (S01) for forming the honeycomb compact 15, firstly, the raw material of PLA that has been formed into a slurry form is made.
Similarly to the first embodiment, the raw material is supplied into the honeycomb mold 14 to make a honeycomb prototype 16.
The obtained honeycomb prototype 16 is then dried, and as shown in
Next, the process proceeds to step (S02) for cutting and dividing the honeycomb compact 15. In this step, similarly to the first embodiment, as shown in
In the step (S13) for applying the β-TCP 26, the base member 11 is heated, and then as shown in
Then, as shown in
Next is a description of the effect of the bone substitute 24 of the present embodiment having the above structure.
As shown in
Meanwhile, since the β-TCP 26 applied onto the surface 25a, and the bone cells being the defect part of the bone are in contact, so-called remodeling is performed in which osteoclasts eat the β-TCP 26 and osteoblasts form a new bone. Then, the bone substitute 24 is replaced by the autologous bone as time goes by.
According to the bone substitute 24, since it is formed by honeycomb molding, the size and the shape of the penetrating holes 20 serving as the grooves 12 can be freely controlled. Moreover, since after molding the base member 11 is curved and inserted, the adhesiveness of the bone substitute to the bone to be repaired and its vicinity can be further improved. Furthermore, since the β-TCP 26 is applied, then even if the bone substitute 24 is absorbed into the body, the bone regeneration is accelerated due to the bone forming function, and the healing speed after the repair can be increased more than for the conventional case.
The technical scope of the present invention is not limited by the abovementioned first and second embodiments, and various modifications can be made thereto without departing from the gist of the present invention.
For example, in the present embodiments, the base plate 24 is curved by heating. However, a honeycomb mold 14 which has been previously curved into a predetermined shape may be used to form the honeycomb compact 15 comprising a curved wall 15a.
Moreover, the shape of the penetrating holes 20 is not limited to the quadrangular shape, and may be a hexagonal shape, a triangular shape, or a circular shape, according to the part to be repaired. Moreover, the size of the respective penetrating holes are not necessarily uniform, and may be nonuniform.
The material of the honeycomb compact it is not necessarily β-TCP nor PLA, and provided it has an affinity with the biological tissue, it may be other bioabsorbent materials such as hydroxyapatite (HAP), or combinations thereof.
Hereunder is a description of a material for repairing biological tissues according to a third embodiment of the present invention, with reference to
A bone substitute (material for repairing biological tissues) 110 according to the present embodiment is made from β-TCP as the raw material and comprises: a honeycomb shaped main body 113 in which a plurality of penetrating holes 111 extending in a single direction are formed and separated from each other by partition wall members 112 having an almost uniform thickness; and collagens (biodegradable viscous member) 115 which are impregnated with growth factors (agonistic factor) 114 for increasing the cell activity, and filled into a plurality of penetrating holes 111.
As shown in
The size of the penetrating holes 111 and the positions of the penetrating holes 111 that are filled with the collagens 115 are determined according to the sustained-release dose of the growth factors 114 which has impregnated into the collagens 115, and the amount of the collagens 115.
Next is a description of a process for producing the main body 113.
Firstly, for example, by a method disclosed in Japanese Unexamined Patent Application, First Publication No. Hei 5-237178, an aqueous foamed slurry which has been mixed and foamed, is adjusted and mixed with granular compacts made from β-TCP so as to make a raw material which is formed in a slurry form. By inserting the raw material into a honeycomb mold of a predetermined shape and size provided with slits, the honeycomb compact formed into a honeycomb shape is obtained, which is further sintered so as to obtain the main body 113.
As shown in
The collagen 115 is made into sol form at a temperature from 40° C. to 60° C., then added with growth factors 114. This is then poured into the penetrating holes 111, and cooled to make into gel form, to thereby fill the penetrating holes 111.
The growth factor 114 is a cytokine such as PRP (platelet-rich plasma), and has a function of promoting bone regeneration, blood vessel formation, and the like.
Next is a description of the effect of the bone substitute 110 of the third embodiment having the above structure.
When the bone substitute 110 is grafted into a defect part of the bone, the bone regeneration is started from the periphery of the main body 113 which is in contact with the bone tissue. In this case, as shown in
Even if such absorption and bone formation progresses, since the penetrating holes 111 arranged in the center of the main body 113 are also impregnated with growth factor 114, then the function of the growth factors continues, and bone regeneration is performed, until the whole main body 113 is absorbed.
According to the bone substitute 110, since it is also impregnated with growth factors 114, then compared to the case where only β-TCP carriers are grafted for the repair, the activity of the surrounding tissue cells can be increased, and bone formation can be promoted.
Moreover, since it is formed into a honeycomb shape, the positions and the number of the penetrating holes 111 to be filled with the collagen 115 including the growth factor 114 can be determined, considering optimum sustained-release.
Furthermore, since the size and the shape of the penetrating holes can be freely controlled when making the honeycomb shape, an optimum shape can be provided for the condition of the affected part to be filled with the bone substitute 110.
The technical scope of the present invention is not limited by the abovementioned embodiments, and various modifications can be made without departing from the gist of the present invention.
For example, the shape of the penetrating holes is not limited to a sector shape, and may be a polygonal shape such as with the hexagonal penetrating holes 116 shown in
For the material of the main body 113, it is not necessarily β-TCP, and provided it has an affinity with the biological tissue, it may be any material such as calcium phosphate ceramics, polylactic acid, or combinations thereof. Moreover, the agonistic factor is not limited to PRP, and may be any as long as it is required for the regeneration of biological tissues. Bone forming factors such as BMP (Bone Morphogenetic Protein), FGF (Fibroblast Growth Factor), TGF-β (Transforming Growth Factor-β), IGF (Insulin-like Growth Factor), PDGF (Platelet-Derived Growth Factor), VEGF (Vascular Endothelial cell Growth Factor), and the like can be filled solely or in combinations thereof.
The following effects are demonstrated in the above described present invention.
According to the material for repairing biological tissues of the present invention wherein a plurality of grooves are formed in the surface of the plate-type base member, there is a sufficient binding force after application to a biological tissue, and the effect of forming a biological tissue can be promoted, so as to increase the healing speed of a defect in the biological tissue.
Using the material for repairing biological tissues according to the present invention, which comprises a honeycomb shaped main body in which a plurality of penetrating holes extending in a single direction are formed and separated from each other by partition wall members having an almost uniform thickness and a biodegradable viscous member which is filled into at least one of the penetrating holes in the main body and contains an agonistic factor capable of increasing the cell activity, agonistic factors of sufficient types and amounts can be supplied to a biological tissue, and the sustained-release dose thereof can be controlled, so that regeneration of the biological tissue can be performed under optimum conditions.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2003-098031 | Apr 2003 | JP | national |
| 2003-098032 | Apr 2003 | JP | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/JP04/04637 | 3/31/2004 | WO | 9/21/2005 |
