JP2009225896A - Medical material for three-dimensional culture - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medical material for three-dimensional culture, which is used for cell culture and tissue culture or as a scaffold for the growth of cells inside a living body, and has high culture efficiency and growth efficiency,. <P>SOLUTION: The medical material 10 for three-dimensional culture is obtained by laminating a plurality of mesh sheets 11 where longitudinal wires 12 and horizontal wires 13 made of titanium wires, are aligned in a mesh shape. A woven fabric where multiple vertical wires 12 and horizontal wires 13 are braided in a woven metal wire shape or a honeycomb woven fabric with polygonal mesh is adopted as the mesh sheet 11. The upper and lower layers of the laminated mesh sheets 11 may be connected to each other by connection lines vertically or diagonally extending. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a three-dimensional culture medical material. More specifically, the present invention relates to a three-dimensional culture medical material that is three-dimensionally configured by arranging or braiding a plurality of titanium wires. In this specification, “titanium” includes titanium alloy in addition to pure titanium.

WO2006 / 033435 JP 2004-16398 A

  Conventionally, it is known to use a web made of a nonwoven fabric entangled and sintered with titanium fibers as a culture base for cell culture or tissue culture (see Patent Document 1). It is also known that a similar nonwoven fabric is embedded in a bone defect and used as a scaffold for bone regeneration (Patent Document 2). Patent Document 2 also proposes that titanium fibers are wound in multiple layers around a core material to form a three-dimensional rod shape.

  Medical materials such as culture bases and scaffolds made of these non-woven fabrics have a three-dimensional structure. Therefore, when cells or tissues are seeded, and an appropriate culture solution and oxygen are supplied, the cells are separated from the non-woven fabric (voids). ) And grow and divide according to the shape of the culture base and scaffolding material. Further, since it has a predetermined three-dimensional structure, it can be guided to a three-dimensional shape for the purpose of cell or tissue growth. Further, when these medical materials are embedded in the living body, osteoblasts enter the scaffold and are fixed, and eventually bone tissue is formed around the scaffold.

  Since the conventional three-dimensional culture medical material uses titanium fiber, it has high affinity with a living body. Moreover, the size of the space between the fibers can be set to some extent to the size preferred by the cells. However, in a three-dimensional structure wound around a web or core material intertwined with titanium fibers, the gaps between the fibers are not uniform, and other than the voids that are preferred by the cells, voids that are too small or voids that are too large There are many. For this reason, cells and tissues may not spread over the entire three-dimensional structure, but may solidify and grow only in specific places where the sizes of the voids are uniform. An object of the present invention is to provide a three-dimensional culture medical material that can be used as a scaffold for cell culture, tissue culture, or cell growth in vivo, and has high culture efficiency and growth efficiency.

  The three-dimensional culture medical material of the present invention is characterized in that a plurality of mesh sheets in which titanium wires are arranged in a net shape are overlapped (claim 1). The “superposition” here includes not only a case where a plurality of mesh sheets are overlapped but also a case where a single mesh sheet is wound a plurality of times to form a multilayer. In such a three-dimensional culture medical material, as the mesh sheet, a woven fabric in which a large number of vertical lines and horizontal lines are braided in a wire mesh shape can be adopted (Claim 2). In this specification, the woven fabric includes a knitted fabric. In addition, a honeycomb-shaped woven fabric having a polygonal mesh can be adopted as the mesh sheet. The three-dimensional cultured medical material preferably has a three-dimensional woven structure by connecting upper and lower layers of the overlapped mesh sheet by connecting lines extending vertically or obliquely (Claim 4).

  The 2nd aspect of the three-dimensional culture medical material of this invention consists of the 1st titanium wire group arranged in a spiral in one direction, and the 2nd titanium wire group arranged in a spiral in the opposite direction. And having a mesh sheet formed in a tube shape (claim 5). As such a three-dimensional cultured medical material, a material in which a second titanium wire group is superimposed on the first titanium wire group can be employed (Claim 6). Further, the first titanium wire group and the second titanium wire group may be braided (Claim 7). Furthermore, it is preferable that the mesh sheet configured in a tube shape is overlapped with a plurality of layers (Claim 8).

  The titanium wire constituting the mesh sheet may be a single titanium wire. Furthermore, the titanium wire constituting the mesh sheet may be a stranded wire obtained by twisting sub-titanium strands (claim 10).

  In the case of the laminated structure, it is preferable that the mesh size of each mesh sheet and the distance between the upper and lower layers are substantially the same (claim 11). In any case, the mesh size of the mesh sheet is preferably 50 to 600 μm.

  Since the three-dimensional culture medical material of the present invention (Claim 1) uses a mesh sheet in which titanium wires are arranged in a mesh, the mesh size is uniform. Therefore, efficient cell and tissue culture can be performed by setting a desired size of cells and the like.

  When the mesh sheet is a woven fabric in which a large number of vertical lines and horizontal lines are braided in a wire mesh shape (Claim 2), the strength and the network structure are not easily broken, so the size and shape of the gaps are long. Maintained. Further, when the mesh sheet is made of a honeycomb-shaped woven fabric having a polygonal mesh (Claim 3), the strength is high and the network structure, the size and shape of the gap are not easily broken.

  In the case where the upper and lower layers of the overlapped mesh sheet are connected by connecting lines extending vertically or obliquely to form a three-dimensional woven structure (Claim 4), the bonding strength between the layers is high and the interlayer separation is high. Is unlikely to occur.

  Since the second aspect (Claim 5) of the three-dimensional culture medical material of the present invention is formed in a tube shape, cells and tissues are cultured in a tubular or elongated form like a tubular organ or bone. Suitable and easy to culture. Moreover, when a mesh is a rhombus, stretchability is high.

  In the case where the second titanium wire group is superimposed on the first titanium wire group (Claim 6), the manufacturing is easy. On the other hand, when the first titanium wire group and the second titanium wire group are braided (Claim 7), the strength is high and the mesh shape is stable.

  When a plurality of layers of the mesh sheet configured in the tube shape are overlaid (claim 8), a thick tubular structure is obtained. Thereby, it is useful as a scaffold for tubular organs and bones.

  When the titanium wire constituting the mesh sheet is a single titanium wire (Claim 9), a highly flexible three-dimensional culture medical material can be obtained. On the other hand, when the titanium wire constituting the mesh sheet is formed of a stranded wire obtained by twisting sub-titanium strands (claim 10), the strength is high.

  When the mesh size of each layer and the distance between the upper and lower layers are substantially the same size (claim 11), the gap between the upper, lower, left and right lines is aligned, so that the culture efficiency is further increased. When the mesh size of the mesh sheet is 50 to 600 [mu] m (Claim 12), since the size is preferred by the cells, the culture efficiency is high.

  Next, an embodiment of a three-dimensional culture medical material (hereinafter simply referred to as medical material) of the present invention will be described with reference to the drawings. FIG. 1 is a perspective view showing an embodiment of the medical material of the present invention, FIGS. 2a and 2b are cross-sectional views showing an embodiment of a mesh sheet constituting the medical material, and FIG. 3 is another view of the medical material of the present invention. FIG. 4A to FIG. 4E are schematic cross-sectional views showing an embodiment of the connecting structure of the upper and lower layers of the laminated medical material of the present invention, and FIG. 5 is still another implementation of the mesh sheet according to the present invention. FIG. 6a to FIG. 6c are perspective views showing still other embodiments of the medical material of the present invention, and FIGS. 7 and 8 are drawings for manufacturing still other embodiments of the medical material of the present invention, respectively. FIG. 9 is a side view showing still another embodiment of the medical material of the present invention, and FIG. 10 is a perspective view showing another embodiment of the titanium wire related to the medical material of the present invention.

  A medical material 10 shown in FIG. 1 is a laminate of a large number of mesh sheets 11. Each mesh sheet 11 includes vertical lines 12 arranged at substantially equal intervals in the horizontal direction and horizontal lines 13 arranged at substantially equal intervals in the vertical direction. The interval L1 between the vertical lines 12 and the interval L2 between the horizontal lines 13 are preferably substantially the same. The intervals L1 and L2 are set to a size preferred by the cells or tissues to be cultured, but are usually about 50 to 600 μm, preferably about 100 to 400 μm, and more preferably about 150 to 200 μm. The thickness of the titanium wire used for the vertical line 12 and the horizontal line 13 is about 4 to 1000 μm, preferably about 5 to 150 μm. The thickness of the titanium wire may be changed depending on the site to be used. For example, a thick wire is used where strength is required. The titanium wire may be a single wire or a stranded wire obtained by twisting titanium wires (see FIG. 10).

  As shown in FIG. 2A, the vertical line 12 and the horizontal line 13 intersect with the minor number of vertical lines 12 by passing every other horizontal line 13 through the upper side and the lower side. Every other line 12 is crossed by passing up and down to form a wire mesh woven fabric as a whole. In addition, it is not every other, but every other two, or two or several can be bundled to form a mesh structure.

  As shown in FIG. 2b, it is also possible to adopt a form in which a large number of vertical lines 12 are arranged at substantially equal intervals on a large number of horizontal lines 13 arranged at approximately equal intervals. Each mesh sheet 11 may be integrated in advance by sintering, welding, diffusion bonding, or the like, or may not be integrated. In the case of sintering, in addition to sintering the whole, it is also possible to sinter and fix in spots every other several. Further, as shown in FIG. 1, a plurality of mesh sheets 11 may be stacked and then sintered, or may be stacked without being sintered. In FIG. 1, the vertical lines 12 and the horizontal lines 13 of the upper and lower mesh sheets 11 are aligned, but the directions may be changed for each layer or may be stacked obliquely. The weaving structure of the woven fabric may be a known woven or knitted form such as knitting or Lilian knitting in addition to the above-described wire netting.

  Since the medical material 10 configured as described above has a uniform mesh size, the culture efficiency is high if the size is set to be preferred by the cells. When immersed in a culture solution, the contact state with the culture solution is almost uniform, which is preferable. The arrangement in the culture fluid flow is preferable because the flow resistance becomes almost uniform. When the mesh sheet 11 is sintered, the network structure does not collapse and the size and shape of the mesh do not change, so that efficient cell culture can be performed over a long period of time.

  The medical material 15 shown in FIG. 3 employs a three-dimensional woven fabric having a so-called three-dimensional network structure composed of a plurality of mesh sheets 11 and connecting lines (connecting threads) 16 connecting upper and lower layers. Yes. Such a three-dimensional woven fabric can be used as the three-dimensional culture medical material of the present invention even if only one sheet is not stacked. The connecting line 16 may be a thread separate from the vertical line (warp thread) 12 and the horizontal line (weft thread) 13 constituting each layer. It is also possible to pass through the lower layer while weaving the vertical line 12 or the horizontal line 13. In that case, a part of the vertical line 12 or the horizontal line 13 becomes the connecting line 16. In the case of FIG. 3, a separate connecting line 16 is used, and a connecting structure 17 in which the upper and lower three layers are sewn in a zigzag shape is adopted. In this connection structure 17, since it can respond to the change of an up-and-down space | interval, it is highly flexible. The interval between the connecting lines 16 is about 150 to 500 μm.

  FIGS. 4 a-e show various embodiments of the connection structure of the upper and lower layers 18, 19 by the connection line 16. The connection structure 20 in FIG. 4a has a configuration in which upper and lower layers 18 and 19 are connected by a connection line 16 extending substantially perpendicularly therebetween. In this connection structure 20, the connection line 16 engages with the upper layer 18 and is passed from the position separated from the first line to the lower layer 19, and further passed from the position separated from the first line to the upper layer 18. In this way, one connecting line 16 is alternately engaged with the upper layer 18 and the lower layer 19 to maintain the three-dimensional structure. The interval between the connecting lines 16 is approximately the same as the mesh width of each of the layers 18 and 19, and is, for example, about 150 to 500 μm.

  In the connecting structure 21 of FIG. 4b, after the connecting line 16 is engaged with the upper layer 18, it immediately goes diagonally downward and is engaged with the lower layer 19, and immediately goes straight up, The upper and lower layers 18 and 19 are sewn together in the order of being engaged with each other. Since this connection structure 21 has a high density of the connection lines 16, the connection strength is high.

  In the connection structure 22 of FIG. 4c, the connection line 16 is immediately engaged obliquely downward, engaged with the lower layer 19, and is obliquely upwardly engaged with the upper layer 18, after being engaged with the upper layer 18. The upper and lower layers 18 and 19 are sewn in a zigzag shape in the order of going downward and diagonally again. This is highly flexible because the connecting line 16 between the upper and lower layers is long and connected obliquely. Therefore, cells and tissues can be cultured in a deformed state.

  The connection structure 23 of FIG. 4d has a configuration in which the same structure as the connection line 16 of the connection structure 22 of FIG. In this connection structure 23, the flexibility is high and the connection strength is high similarly to the connection structure 15 of FIG.

  The connection structure 24 of FIG. 4e is provided with a combination of the connection structure 20 of FIG. 4a and the connection structure 23 of FIG. 4d, and has high connection strength and is not easily deformed.

  The mesh sheets 11 of the medical materials 10 and 15 in FIGS. 1 and 3 are rectangular meshes with the vertical lines 12 and the horizontal lines 13 intersecting at right angles. However, as shown in FIG. It is also possible to employ a mesh sheet 26 of a honeycomb structure 25 having a mesh. Such a honeycomb structure can be manufactured by, for example, three-dimensional (three-dimensional) knitting or three-dimensional (three-dimensional) braiding. Furthermore, a honeycomb structure having a polygonal mesh such as a pentagon or an octagon can be employed. In these honeycomb structures, the vertical lines 12 and the horizontal lines 13 are engaged and separated in a complicated manner, so that the network structure is stabilized. As the mesh of the honeycomb structure, a three-dimensional knitted fabric used as a core material of fiber reinforced resin (FRP), for example, a three-dimensional knitted fabric such as a double raschel solid knitted fabric can be used.

  In any of the above embodiments, the three-dimensional structure is obtained by superimposing the planar mesh sheets 11. However, as shown in FIG. 6 a, the mesh sheet 11 on any one of the aforementioned planes is rounded into a cylindrical shape. The medical material 27 can also be obtained by making the structure. Further, as shown in FIG. 6b, the medical material 28 may be formed by winding the mesh sheet 11 a plurality of times. In addition, as shown in FIG. 6c, by using the medical material 29 in which the single-layered cylindrical sheets 27 are overlapped, a thick medical treatment with high strength can be obtained. Such medical materials 28 and 29 are suitable for regenerative medicine of tubular organs such as blood vessels and gastrointestinal tracts, and for the treatment of forming bone by introducing osteoblasts into bone defects.

  When the planar mesh sheet is formed into a cylindrical shape, the edges need to be overlapped and joined, but for example, as shown in FIG. 7, the titanium wires 30 and 32 can be formed into a cylindrical shape. In FIG. 7, the titanium wire 30 is spirally wound around the cylindrical core member 31 (first step S1), and another titanium wire 32 is wound in a reverse spiral shape (second step S2). A cylindrical medical material is used. Furthermore, in this embodiment, the third and fourth titanium wires 33 and 34 are spirally wound on the third and fourth titanium wires 33 and 34 alternately on the third and fourth titanium wires 33 and 34 (third step S3). Since the titanium wires 30 and 32 or the titanium wires 33 and 34 on the titanium wires 30 and 32 constitute a rhombus network structure, the deformation thereof is relatively easy. The overlapped titanium wires can be joined together by sintering or the like to be integrated together.

  FIG. 8 shows a cylindrical medical material 38 formed by braiding a large number of titanium wires 36 and 37 into a cylindrical shape. The braiding method is the same as the method of forming a reinforcing blade layer such as a hose or a netting layer. The titanium wires 37 are braided alternately so as to form a left spiral. Thereby, a cylindrical medical material 38 having a mesh structure with the same mesh shape and size as the wire mesh can be obtained.

  FIG. 9 shows a procedure for knitting bamboo baskets, in which a plurality of axially extending titanium wires 39 are arranged in an annular shape, and oblique titanium wires 40 and 41 are alternately knitted with respect to them. This is strong.

  Any of the titanium wires used in the embodiment can be constituted by a single titanium wire (titanium strand). However, as shown in FIG. 10, sub-titanium strands 42 are twisted together to form one strand. A multi-layer type stranded wire obtained by twisting a plurality of stranded wires 43 may be used. Such a stranded wire 43 can vary in thickness depending on the number of titanium wires and the number of layers. Therefore, for example, it is preferable to prepare a thin titanium wire of about 4 to 20 μm, twist an appropriate number of titanium wires according to the application, and twist the twisted wires together. The thickness of the stranded wire 43 is 4 to 1000 μm, preferably about 5 to 150 μm, similar to the above-described titanium wire (vertical line 12 and horizontal line 13 in FIG. 1). Use the appropriate thickness depending on the location.

  The medical material having a three-dimensional structure using the titanium wire can be used as a cell culture carrier or a tissue culture carrier by attaching or coating calcium phosphate, or by supporting collagen.

It is a perspective view which shows one Embodiment of the medical material of this invention. 2a and 2b are cross-sectional views each showing an embodiment of a mesh sheet constituting the medical material. It is a perspective view which shows other embodiment of the medical material of this invention. 4a to 4e are schematic cross-sectional views showing an embodiment of a connection structure for upper and lower layers of the laminated medical material of the present invention. It is a top view which shows other embodiment of the mesh sheet | seat in connection with this invention. 6a to 6c are perspective views showing still other embodiments of the medical material of the present invention. It is process drawing which shows the manufacturing method of further another embodiment of the medical material of this invention. It is process drawing which shows the manufacturing method of further another embodiment of the medical material of this invention. It is a side view which shows other embodiment of the medical material of this invention. It is a perspective view which shows other embodiment of the titanium wire in connection with the medical material of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Medical material 11 Mesh sheet 12 Vertical line 13 Horizontal line L1, L2 Space | interval 15 Medical material 16 Connection line 17 Connection structure 18 Upper layer 19 Lower layer 20, 21, 22, 23, 24 Connection structure 25 Honeycomb structure 26 Mesh sheet 27 , 28, 29 Medical material 30, 32 Titanium wire 31 Core material 33, 34 Titanium wire 35 Medical material 36, 37 Titanium wire 38 Medical material 39, 40, 41 Titanium wire 42 Titanium wire 43 Stranded wire

Claims (12)

  A three-dimensional cultured medical material made up of a plurality of mesh sheets in which titanium wires are arranged in a mesh.   The three-dimensional cultured medical material according to claim 1, wherein the mesh sheet is a woven fabric in which a number of vertical lines and horizontal lines are braided in a wire mesh shape.   The three-dimensional cultured medical agent according to claim 1, wherein the mesh sheet is made of a honeycomb-shaped woven fabric having a polygonal mesh.   The three-dimensional culture medical material according to claim 1, wherein the upper and lower layers of the overlapped mesh sheet have a three-dimensional woven structure by being connected by connecting lines extending vertically or obliquely.   Three-dimensional culture medical treatment having a mesh sheet formed in a tube shape, comprising a first titanium wire group spirally arranged in one direction and a second titanium wire group spirally arranged in the opposite direction material.   The three-dimensional cultured medical material according to claim 5, wherein a second titanium wire group is superimposed on the first titanium wire group.   The three-dimensional cultured medical material according to claim 5, wherein the first titanium wire group and the second titanium wire group are braided.   The three-dimensional culture medical material according to claim 5, wherein a plurality of layers of the mesh sheet configured in the tube shape are overlapped.   The three-dimensional culture medical material according to any one of claims 1 to 8, wherein the titanium wire constituting the mesh sheet is a single titanium wire.   The three-dimensional culture medical material according to any one of claims 1 to 8, wherein the titanium wire constituting the mesh sheet is a stranded wire obtained by twisting sub-titanium single wires.   The three-dimensional culture medical material according to any one of claims 1 to 4, wherein the mesh size of each mesh sheet and the distance between the upper and lower layers are substantially the same.   The three-dimensional culture medical material according to any one of claims 1 to 11, wherein the mesh size of the mesh sheet is 50 to 600 µm.