JP5138313B2 - Biological structure - Google Patents

Description

  The present invention relates to a biological structure composed of a micro-molded product having a through-hole, and more particularly, used for a biological tissue filling material such as a bone filling material or a cell culture carrier to fix and carry cells that become bones or blood vessels. It is related with the structure for biological bodies suitable for making it propagate, culture | cultivate and culture | cultivate.

Conventionally, it has been studied to use a molded body made of metal or ceramic as a biological tissue filling material or a cell culture base for bone defect or cell culture due to bone tumor removal or trauma. A porous body having a large number of pores for invading, fixing, proliferating or culturing cells such as blast cells is known. However, since it is difficult to control the size and distribution of pores in the production of a normal porous body, there are many cases where cells do not smoothly enter and there is a problem that growth is not sufficiently promoted. For this reason, various studies have been made such as foam-like ones and honeycomb-like ones having a large number of through holes in a certain direction. For example, a foam-shaped molded body is obtained by impregnating a ceramic slurry in a resin foam, degreasing the resin portion and then sintering, and is known as a three-dimensional network structure, which is compared with that of a porous body. The pores can be enlarged and at the same time the pore diameter can be set to some extent, and it has multi-directional characteristics. However, there is a problem in that a crack is easily generated in the skeleton part due to manufacturing, and the strength becomes extremely low, and since there is no single penetration part, it is not enough to promote cell proliferation. As another example, honeycomb-shaped ones obtained by extrusion molding and the like can easily control the pores, and a single through-hole having a uniform diameter is obtained, so that sufficient cell growth is desired and the strength is stable. However, since all the through holes are oriented in a certain direction, it is difficult to enter cells from other directions, and a sufficient effect cannot be obtained depending on the location. For this reason, a method is known in which bead-shaped molded bodies having through-holes, that is, aggregates mainly composed of spherical shapes, are used together (see Patent Document 1). By using this method, a structure having a through-hole with a certain length and extending in multiple directions is possible.
JP 2003-335574 A

  However, in the above-mentioned method, for example, when used as a bone grafting material, beads are gathered as they are in the defective part and are embedded as they are, so that they move after implantation or scatter during implantation. In addition, there is a problem in that randomness in the direction of the through holes is not clearly obtained even when the beads are joined together.

The present invention is a living body structure in which the above-mentioned problems are solved, and is a structure formed by assembling and fixing columnar micromolded articles having at least one through-hole in the longitudinal direction. up direction of the through-hole greens are located randomly in the three-dimensional direction, the gap between the micro-molded product is set and fixed is to form pores of a three-dimensional network, even smaller moldings each other is self-sticking Thus, the first gist is that the self-adhesion has a structure in which the micro-molded products are fixed by firing .

Furthermore, the second gist is that the main component of the micro-molded product is calcium phosphate.

  In the biological structure of the present invention, the through-holes of the micromolded article have moderate linearity, and the pore direction is randomly oriented in an arbitrary direction. At the same time, cell entry from multiple directions is facilitated. Therefore, it is possible to easily embed without worrying about the way and direction of embedding, and further, the diameter and length of the through holes, and the structure in which these are assembled and fixed can be changed to any size. Since it is possible, it has various advantages such as being able to be formed into a shape suitable for the type and amount of cells to be cultured or the place of supplement.

  The biological structure of the present invention achieves the purpose of allowing cells from multiple directions to enter and promoting cell generation and growth. Next, the biological structure of the present invention will be described with reference to the drawings.

  FIG. 1 is a front view showing a living body structure 1 of the present invention, and FIG. 2 is a perspective view showing a micromolded product 2. The micro-molded product 2 of the present invention is cylindrical and has one through-hole 3 in the longitudinal direction, and the micro-molded product 2 is assembled and fixed by randomly positioning the direction of the through-hole 3 in a three-dimensional direction. The three-dimensional network-like pores 4 are formed in the gaps between the micromolded products 2 constituting the living body structure 1 and assembled and fixed.

  As the external shape of the micro-molded product 2, a columnar shape is used, and examples thereof include a columnar shape, a triangular column shape, a quadrangular column shape, a hexagonal column shape, and the like, and these can be used in combination. By making it columnar, it becomes easy to arrange each micro-molded product 2 at random in the three-dimensional direction, and as a result, the desired pores 4 are easily obtained in the gaps between the micro-molded products 2. That is, when the columnar materials are randomly assembled, only a part of the outer peripheral surface is joined to each other, and most of the outer peripheral surface is in a three-dimensionally complicated state without being joined. The voids present three-dimensional network pores. Any column may be used as long as it is columnar, but a columnar shape is particularly preferable in that a three-dimensional network-like pore 4 having a clear shape is easily obtained.

  The L / D (L: length, D: outer diameter) of the micro-molded product 2 is arbitrary, but is preferably 1.5 or more, and particularly preferably 3 or more. When L / D is less than 1.5, it becomes infinitely disk-shaped or spheroidized, so that it is easy to overlap closely even if the hole directions of the through holes are randomly positioned. Is difficult to manufacture. As a result, it is difficult to obtain the desired pores in the gaps between the micromolded products.

  The pore diameter of the through-hole 3 included in the micro-molded product 2 may be set as long as cells, blood vessels, bones and the like can be sufficiently generated and grown, and can be appropriately set according to use conditions. A range of 200 to 1000 μm, which is a diameter suitable for cell invasion, is preferable. The number of through-holes is at least one, and typically a pipe-shaped one as shown in FIG. 2 is preferable, but a honeycomb-shaped one having a plurality of through-holes can also be used. The thing which has a through-hole from which the hole diameter differs in the thing can also be used. The cross-sectional shape of the through hole is arbitrary, such as a circle, an ellipse, a triangle, a quadrangle, and a hexagon, but usually a circle is preferably used.

  As the main material of the micro-molded product 2, any material may be used as long as it is a conventionally known material used for bone filling materials, cell culture carriers, and the like, and examples thereof include metals, ceramics, and resins. Among them, ceramics such as aluminum oxide, zirconium oxide, and calcium phosphate are preferable, and in particular, calcium phosphate-based ceramic is suitable because it has characteristics close to that of biological materials. , Calcium pyrophosphate, tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, hydroxyapatite, Ca-deficient hydroxyapatite, and the like. Other materials may be added in addition to the main material. For example, ceramics other than the materials used for the main material, resin, bioabsorbable polymer substances such as collagen and gelatin, and suitable for living organisms such as carbon The material currently used for is mentioned.

  The structure after assembling and fixing a large number of micromolded products 2 is characterized in that the directions of the through holes 3 of each micromolded product are randomly positioned in a three-dimensional direction. By being positioned at random, cell invasion from multiple directions becomes possible. Further, by fixing the micro-molded product 2 at random, pores 4 having a three-dimensional network structure due to random arrangement are formed in the gaps between the micro-molded products 2 in addition to the through-holes 3. By mixing the through-holes 3, further cell growth and promotion are achieved.

  Examples of the fixing structure for obtaining the above structure include coating fixing and self-fixing. Application fixing is a structure in which the micromolded product is joined by forming an adhesive material or carbon on the outer periphery of the micromolded product 2, and examples of the adhesive material include natural resin, synthetic resin, collagen, gelatin, and the like. Carbon is obtained by baking an adhesive material. It is a fixed structure obtained by applying or spraying the adhesive material on the outer periphery of a micro-molded product, or immersing it in a solution of the adhesive material and drying or baking. That is, in the case of only drying without firing, the adhesive material itself serves as a medium, and in the case of firing, the carbon obtained by firing the adhesive material serves as a medium for linking the micro-molded products. Here, when the adhesive material or carbon applied to the outer periphery of the micro-molded product and the material contained in the micro-molded product are the same material, the bonding force is improved, and it is particularly difficult to break. This is preferable.

  Self-adhesion is an adhering structure that utilizes the self-adhesive force of the micro-molded product 2 itself without using an adhesive material. In other words, it uses a binder such as resin, collagen, gelatin, etc. used as a raw material when producing the micro-molded product 2, or carbon obtained from the binder by firing or sintering power of the main material itself. The molding materials are arranged randomly, and at the same time, the bonding materials contained in each other at the contact portions of the micro molding materials are joined together by pressing, activated by water, etc., joined, dried or baked. In this structure, the molded products 2 are fixed to each other. In the case of drying, the encapsulated binding material binds the micro-molded products, and when fired, they are bound by the sintering force of carbon and / or the main material obtained from the binding material. In the case of this structure, the extra material does not enter, and the ease of manufacturing is good and the complexity of the process is small, so that the degree of randomness can be sufficiently improved, and as a result, the gap between the micro-molded products 2 is clear as it is. It is preferable in that it has a variety of advantages such as being easy to obtain a state in which such a shape is maintained and enabling effective utilization of the mesh-like pores 4. Furthermore, in any of the above-mentioned fixed structures, the structure is maintained only by joining the contact portions that are part of the surface, but a set of highly compact micro-molded products that are randomly entangled and combined in three dimensions. Since it is shaped, it has a feature that it is difficult to be crushed and broken.

  An example of the manufacturing method of the biological structure of the present invention will be described. A columnar microscopic material having at least one through-hole by adding a binder such as a resin to a main material such as ceramic and then performing extrusion molding, injection molding, press molding, or the like. The material of the molded product is produced, and the material is assembled randomly as it is or by applying an adhesive material and assembled randomly. When the adhesive material is not used, water is sprayed after gathering to wet the surface of the material, and the binding material contained in the material is activated. By this method, fixing is performed smoothly. These aggregated materials are dried or baked at a high temperature of 600 ° C. or higher, so that they are fixed with an external adhesive material or a binder inside the material, or carbonized and baked and fixed, or the main material itself It adheres by the sintering force of to make a biological structure. As another method, the material is fired to produce a micro-molded product, and an adhesive is applied to the outer periphery of the micro-molded product to randomly collect it, and then is fixed by drying or firing. There is also. Any of the above methods may be used. In particular, the method of self-adhering using a binder inside the material is most preferable from the viewpoint of ease of production and effective use of the gap between the minute molded products. Examples will now be described. The parts are “parts by weight”.

  100 parts of water is added to 80 parts of tricalcium phosphate as a main material and 20 parts of polyvinyl alcohol as a binder, and after kneading, extrusion molding is performed with a length of 2.0 mm, an outer diameter of 0.5 mm, and a pore diameter of 300 μm. A large number of cylindrical micromolded materials having holes were produced. This material was gathered randomly in a 0.5 cm cube, sprayed with water and lightly pressed. The bonding material inside the material was wetted with water and the surface of the material was activated, and a joined material was obtained. By firing this aggregate material in an oxygen atmosphere at a maximum temperature of 1100 ° C., a micro-molded product made of tricalcium phosphate is obtained, and at the same time, the direction of the through-holes of the micro-molded product is three-dimensionally within 0.5 cm cube. It was assembled and fixed to be random. At this time, the binding materials included in the contact portion between the materials are bonded to each other on the surface, the binding materials are sublimated in oxygen by firing, and at the same time, the micro-molded products are fixed to each other by the sintering force of the main material. A structural body was obtained. This biological structure is white and has a very good degree of randomness and is difficult to break. In addition, pores with a three-dimensional network structure are clearly formed in the gaps between micro-molded products. It was done. When this biological structure was embedded as a bone filler for a rabbit and taken out after 4 weeks, nerve cells proliferated in the through holes and in the pores of the gap, and sufficient growth was observed.

  The aggregate material produced in Example 1 was baked at a maximum temperature of 1100 ° C. in an argon atmosphere, and a micromolded product composed of tricalcium phosphate and carbon was assembled and fixed in the same manner as in Example 1. At this time, the binder became carbon by firing in an argon atmosphere, and the micro-molded products were fixed to each other by the sintering force of the carbon and the main material, and a biological structure was obtained. This living body structure had the same characteristics as in Example 1 except that it was black.

(Reference Example 1)
100 parts of water is added to 80 parts of tricalcium phosphate as a main material and 20 parts of gelatin as a binder, and after extrusion, it is extruded to have a length of 2.0 mm, an outer diameter of 0.5 mm, and a pore size of 300 μm. A large number of cylindrical micro-molded materials were prepared. This material was gathered randomly in a 0.5 cm cube, sprayed with water and lightly pressed. The bonding material inside the material was wetted with water and the surface of the material was activated, and a joined material was obtained. By drying the aggregate material, a micro-molded product composed of tricalcium phosphate and a binder was assembled and fixed. At this time, the micro-molded products were fixed to each other by the adhesive force of the encapsulating material contained therein, and a biological structure was obtained. This biological structure is white and has the same characteristics as in the first embodiment.

(Reference Example 2)
An aqueous solution of polyvinyl alcohol, which is an adhesive material, was applied to the outer peripheral surface of the micromolded material produced in Example 1, and assembled at random within a 0.5 cm cube and lightly pressed to obtain an aggregate material. The obtained aggregate material was fired at a maximum temperature of 1100 ° C. in an argon atmosphere, and a micro-molded product made of carbon obtained from tricalcium phosphate and a binder was assembled and fixed. At this time, the micro-molded products were fixed to each other by the black carbon obtained from the pressure-sensitive adhesive material by firing, and a biological structure was obtained. This biostructure is complicated in manufacturing because of the use of an adhesive material, and the degree of randomness is somewhat insufficient, and the resulting three-dimensional network pores are somewhat unclear, but included. The carbon obtained from the binding material and the surrounding adhesive material makes the bonding between the micro-molded products particularly strong, and has characteristics such as being black and difficult to break.

(Reference Example 3)
Using the micro-molded material produced in Example 1 and firing this material in an oxygen atmosphere at a maximum temperature of 1100 ° C. to produce a number of white micro-molded articles having one through-hole, the outer circumference of the micro-molded product A collagen solution, which is an adhesive material, was applied to the surface, randomly assembled within a 0.5 cm cube, and lightly pressed to obtain an aggregate material. By drying the aggregate material, micro-molded products made of tricalcium phosphate were assembled and fixed. At this time, the micro-molded products were fixed to each other by the adhesive force of the adhesive material, and a biological structure was obtained. Although this biostructure is complicated in manufacturing because of the use of an adhesive, the degree of randomness is somewhat insufficient, and the resulting three-dimensional network pores are somewhat unclear, but the fired pipe is Because it is used, it has a stable through-hole shape, white, and difficult to break.

(Reference Example 4)
Using the micro-molded material produced in Example 1 and firing this material in an oxygen atmosphere at a maximum temperature of 1100 ° C. to produce a number of white micro-molded articles having one through-hole, the outer circumference of the micro-molded product An aqueous solution of polyvinyl alcohol as an adhesive material was applied to the surface, randomly assembled within a 0.5 cm cube, and lightly pressed to obtain an aggregate material. The aggregate material was fired at a maximum temperature of 1100 ° C. in an argon atmosphere, and a micro-molded product made of tricalcium phosphate was assembled and fixed. At this time, the micro-molded products were fixed to each other by the black carbon obtained from the pressure-sensitive adhesive material by firing, and a biological structure was obtained. This living body structure had the same characteristics as in Example 5 except that it was black.

(Reference Example 5)
100 parts of water is added to 80 parts of tricalcium phosphate as a main material and 20 parts of collagen which is a binder, and after extrusion, it is extruded to have a through hole having a length of 2.0 mm, an outer diameter of 0.5 mm and a pore diameter of 300 μm. A large number of cylindrical micro-molded materials were prepared. A collagen solution, which is an adhesive material, was applied to the outer peripheral surface of this material, assembled randomly within a 0.5 cm cube, and lightly pressed to form an aggregate material. By drying the aggregate material, micro-molded products composed of tricalcium phosphate and collagen were assembled and fixed. At this time, the micro-molded products were fixed to each other by the adhesive force of the adhesive material, and a biological structure was obtained. This living body structure is complicated in manufacturing because of the use of an adhesive material, and the degree of randomness is somewhat insufficient, and the resulting three-dimensional network pores are slightly unclear, but a micromolded product Since the bonding material and the adhesive material contained in the same material are the same material, the bonding is particularly strong, and it is white and difficult to break.

(Comparative Example 1)
Using the materials and blends used in Example 1, a micro-molded material having through-holes having a length of 1 mm, an outer diameter of 1 mm and a pore diameter of 300 μm after extrusion was produced, and this was produced at a maximum temperature of 1100 ° C. in an argon atmosphere. After firing, it was processed into a substantially spherical bead shape to obtain a micro-molded product. An adhesive material was applied to the outer periphery of the micro-molded product and assembled in a 0.5 cm cube while lightly pressing so that the through holes were random in the three-dimensional direction. The obtained assembly was fired again to 1100 ° C. in an argon atmosphere, the adhesive material was carbonized, and the micro-molded products were fixed to form a biological structure. This living body structure is black, and the micro-molded product has a bead shape, so it overlaps multiplely. The degree of randomness of the through holes is not clear, and the gap between the micro-molded products is also clear. Pore having an original net-like structure was not obtained.

(Comparative Example 2)
After the micro-molded material of Comparative Example 1 is dried, it is processed into a substantially spherical bead shape, this is assembled so that the through-holes are random in three-dimensional directions, and water is sprayed to contact the surface of the material. The parts were joined to form a collective material. This aggregate material was fired to 1100 ° C. in an oxygen atmosphere, and the materials were fixed to form a biological structure. This living body structure is white, and, as in Comparative Example 1, the micro-molded products are overlapped multiple times, and the degree of randomness of the through holes is not clear, and the gap between the micro-molded products is also clear. No pores having the structure were obtained.

  The biological structure of the present invention promotes the formation of blood vessels and cell proliferation, and facilitates cell invasion from multiple directions. Therefore, the biological structure becomes a good bone filling material or cell culture carrier. Can be applied.

It is a front view which shows the structure for biological bodies of this invention. It is a perspective view which shows a micromolded product.

DESCRIPTION OF SYMBOLS 1 Structure for biological body 2 Micromolded article 3 Through-hole of micromolded article 2 4 Pore of structure 1 for biological body

Claims (2)

A longitudinally at least one through-micro-molded product to become by the set and fixed structure of columnar having a hole, Ri Na said being positioned randomly in the direction the three-dimensional direction of the through holes of the micro-molded product The gaps between the assembled and fixed micro-molded products form three-dimensional network pores, and the micro-molded products are self-adhered, and the self-adhering is fired to fix the micro molded products together. A structure for living body characterized by having a structure to be used.   The biological structure according to claim 1, wherein the main component of the micro-molded product is calcium phosphate.

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