JP2019024342A - Method for producing culture scaffold and production device - Google Patents

Abstract

To efficiently produce a culture scaffold provided with fibers aligned in one direction.SOLUTION: A method of producing a culture scaffold comprises: a deposition step of forming a fiber assembly by discharging fiber raw material liquid from a nozzle to create fiber while depositing the fiber around the circumferential surface of a winding rotary body; a heating step of heating the fiber assembly deposited on the circumferential surface of the winding rotary body; and a transferring step of transferring the heated fiber assembly onto a substrate while rotating the winding rotary body; wherein a plurality of belt-like heating layers are arranged on the circumferential surface of the winding rotary body so as to extend along the direction of the rotary axis of the winding rotary body and, in the heating step, the fiber assembly is heated due to the heating layer.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a method for manufacturing a scaffold for culture and an apparatus for manufacturing the same, and in particular, to an improvement in productivity of a scaffold for culture including fibers arranged in one direction.

  In recent years, fiber base materials have attracted attention as a culture scaffold for culturing biological tissues and microorganisms (see Patent Document 1). The fiber substrate is, for example, a woven fabric, a knitted fabric, or a non-woven fabric, and has a three-dimensional structure. Therefore, biological tissues and microorganisms can be cultured in a state close to a physiological environment in vitro.

Special table 2010-517590

  When directionality is seen in the growth of biological tissues and microorganisms, it is desirable that the fibers constituting the fiber base material are arranged in a certain direction. This is because biological tissues and microorganisms are easy to grow. However, usually, the fiber base material is held in shape by entanglement of fibers, and does not have the above arrangement.

  One aspect of the present invention is to form a fiber assembly by discharging a fiber raw material liquid from a nozzle to generate the fiber and depositing the fiber so as to circulate on a peripheral surface of a winding rotary body. A heating step of heating the fiber aggregates deposited on the peripheral surface of the winding rotary body, and transferring the heated fiber aggregates to the substrate while rotating the winding rotary body A plurality of belt-like heating layers extending in a direction along the rotation axis of the winding rotary body are disposed on the peripheral surface of the winding rotary body, and in the heating step, The present invention relates to a method for producing a culture scaffold, wherein the fiber assembly is heated by the heating layer.

  According to another aspect of the present invention, a fiber raw material liquid is discharged from a nozzle to generate the fiber, and the fiber is deposited so as to circulate on a peripheral surface of a winding rotary body. And a transfer unit that transfers the fiber assembly to a base material while rotating the winding rotary body, and the winding rotary body has the winding rotation on the circumferential surface thereof. An apparatus for manufacturing a scaffold for culture, comprising a plurality of belt-like heating layers extending in a direction along the rotation axis of the body, wherein the fiber assembly heated by the heating layer is transferred to the substrate in the transfer section About.

  According to the manufacturing method and the manufacturing apparatus according to the present invention, it is possible to efficiently manufacture a culture scaffold including fibers arranged in one direction.

It is the perspective view (a) and top view (b) which show an example of the winding rotary body which concerns on this invention. It is sectional drawing which shows typically the principal part of the winding rotary body concerning 1st Embodiment of this invention. It is sectional drawing which shows typically the principal part of the other winding rotary body concerning 1st Embodiment of this invention. It is sectional drawing which shows typically the principal part of the winding rotary body concerning 2nd Embodiment of this invention. It is a side view which shows typically the winding rotary body and / or base material in each process of the manufacturing method which concerns on this invention ((a) and (b)). It is a decomposition | disassembly side view which shows the other example of the winding rotary body which concerns on this invention. It is a schematic top view of the one part area | region of the fiber assembly for demonstrating the arrangement | sequence of a fiber.

  The fiber assembly formed on the peripheral surface of the winding rotator by spinning the fiber with the winding rotator is useful as a scaffold for culture having high alignment. However, it is not easy to transfer to the substrate while maintaining the alignment. This is because the fibers are not entangled to such an extent that the arrangement can be maintained when the fiber assembly is peeled from the winding rotary body.

  In the present embodiment, a heating layer is disposed on the peripheral surface of the winding rotary body in order to transfer the fiber assembly to the substrate while maintaining the arrangement of the fibers in one direction. By heating the fiber assembly before the transfer step, the fiber assembly is softened and easily peeled off from the winding rotary body. Therefore, the fiber assembly is easily transferred to the substrate while maintaining the fiber arrangement. Furthermore, since the fiber assembly is transferred to the base material in a softened state, the adhesion between the fiber assembly and the base material is improved. Thereby, it is not always necessary to use an adhesive for the close contact between the fiber assembly and the substrate, which is advantageous in terms of productivity and cost.

  A heating layer is arrange | positioned at the strip | belt shape extended | stretched in the direction in alignment with the rotating shaft of a winding rotary body. On the other hand, the fibers constituting the fiber assembly are arranged so as to circulate on the peripheral surface of the winding rotary body, that is, in a direction intersecting with the heating layer. The fibers accumulated on the peripheral surface of the winding rotary body are intermittently heated by crossing the stretching direction of the heating layer and the fiber arrangement direction, and the base material is used as an aggregate (fiber aggregate). It is even easier to transfer to the surface. Furthermore, since the peripheral surface of the winding rotary body is partially heated, the thermal efficiency is increased.

(Heating layer)
Hereinafter, the heating layer will be described in detail with reference to the drawings. FIG. 1 is a perspective view (a) and a plan view (b) showing an example of a winding rotary body including a heating layer. FIG. 1 also shows a part of the fibers (fiber assembly) deposited on the peripheral surface of the winding rotary body.

The heating layer 60 has a belt shape and extends in the extending direction D ₆₀ along the rotation axis A of the winding rotary body 10 on the circumferential surface 10S of the winding rotary body 10. The stretching direction D ₆₀ is not limited to being parallel to the rotation axis A, and the angle θ ₆₀ (where θ ₆₀ <90 °) between the stretching direction D ₆₀ and the rotation axis A is, for example, 0 ° or more, 30 ° or less. Especially, from a viewpoint of the peelability of the fiber assembly 20, the angle θ ₆₀ is preferably 0 ° or more and 20 ° or less.

The drawing direction D ₆₀ is a direction that intersects the arrangement direction D ₂₁ of the fibers 21. An angle θ (where θ ≦ 90 °) formed by the stretching direction D ₆₀ and the arrangement direction D ₂₁ is, for example, 60 ° or more and 90 ° or less. Incidentally, the stretching direction D _60, when viewed heating layer 60 from the normal direction of the peripheral surface 10S of the winding rotary member 10, the center line L _C of the longitudinal direction of the heating layer 60 is the direction of stretching. When the center line L _C includes a curve, the extending direction D ₆₀ is a direction in which the minimum rectangular center line surrounding the center line L _C extends.

The shape of the heating layer 60 is not particularly limited as long as it has a strip shape. The strip, the length in the stretching direction D ₆₀ of the heating layer 60 is a longer shape than the length in the direction perpendicular to the stretching direction D _60. Examples of the shape of the heating layer 60 when viewed from the normal direction of the peripheral surface 10S of the winding rotary body 10 include a rectangle and a trapezoid.

  The number of heating layers 60 is not particularly limited and may be two or more. Especially, from a viewpoint of the peelability of the fiber assembly 20, it is preferable to arrange 3 or more on the circumferential surface 10S of the winding rotary body 10, and it is preferable to arrange 10 or more. Further, from the same viewpoint, it is preferable that the heating layers 60 are arranged at equal intervals.

Direction orthogonal to the stretching direction D ₆₀ of the heating layer 60 (hereinafter, the short referred to as direction) length of the (width) is not particularly limited. In particular, from the viewpoint of the peelability of the fiber assembly 20, the total area of all the heating layers 60 in contact with the peripheral surface 10S of the winding rotary body 10 is 10% of the surface area of the peripheral surface 10S of the winding rotary body 10. The width of each heating layer 60 is preferably determined so that it is 80% or less, particularly 30% or more and 70% or less. The length of the extending direction D ₆₀ of the heating layer 60 is not particularly limited. Especially, it is preferable that the heating layer 60 is extended over the area | region where the fiber 21 can accumulate at least among the surrounding surfaces 10S of the winding rotary body 10. FIG.

  The principle of heat generation in the heating layer 60 is not particularly limited. For example, a method may be used in which an eddy current generated by IH (Induction Heating) is caused to flow through the heating layer 60 and the generated Joule heat is used, or a current is directly passed through the heating layer 60 and generated. A method using Joule heat may also be used. In these cases, examples of the material of the heating layer 60 include a metal material and a conductive resin.

  When the peripheral surface 10S of the winding rotary body 10 has thermal conductivity, it is preferable that a heat insulating layer is disposed between the heating layer and the peripheral surface 10S. Thereby, it is suppressed that the surrounding surface 10S whole is heated, and while being able to heat a fiber intermittently, thermal efficiency improves further.

  Hereinafter, with reference to the drawings, the heating layer is formed of a metal material (first embodiment) and the heating layer is formed of a conductive resin composition (second embodiment). Details will be described with reference to FIG. FIG. 2A is a cross-sectional view schematically showing a main part of the winding rotator according to the first embodiment, and FIG. 2B schematically shows a main part of another winding rotator according to the first embodiment. It is sectional drawing shown. FIG. 2C is a cross-sectional view schematically showing a main part of the winding rotary body according to the second embodiment.

[First Embodiment]
In the present embodiment, the heating layer 60A is formed of a metal material. Furthermore, a heat insulating layer 61 is disposed between the heating layer 60A and the peripheral surface 10S.

(Heating layer)
The material of the heating layer 60A is not particularly limited as long as it is a metal material. Examples of the metal material include stainless steel, copper, aluminum, iron, nickel-chromium alloy, iron-chromium alloy, and tungsten. Of these, stainless steel is preferable in that it has moderate rigidity.

  The form of the metal material is not particularly limited, and may be, for example, a foil shape or a linear shape. For example, a plurality of linear metal materials are closely arranged or arranged side by side on the same plane at an interval to form the heating layer 60A.

  The thickness of the heating layer 60A is not particularly limited, and may be appropriately set according to a desired heat generation temperature. In the case of stainless steel, the thickness of the heating layer 60A is, for example, 2 to 50 μm.

(Insulation layer)
The material of the heat insulating layer 61 is not particularly limited as long as it has heat insulating properties. Examples of such materials include various resin materials. The resin material may include a synthetic resin (thermoplastic resin, thermosetting resin), natural resin, elastomer, natural rubber, and synthetic rubber (hereinafter the same). Of these, silicone rubber and fluororubber are preferable from the viewpoint of heat resistance.

  The thickness of the heat insulation layer 61 is not particularly limited, and may be set as appropriate according to the heat generation temperature. The thickness of the heat insulation layer 61 is, for example, 80 to 4900 μm.

It is preferable that the heat insulation layer 61 is arrange | positioned so that the whole surface by the side of the surrounding surface 10S of 60 A of heating layers may be opposed from a viewpoint of the heat insulation effect. The length in the short direction (width W _I ) of the heat insulating layer 61 is preferably equal to or larger than the length in the short direction (width W _H1 ) of the heating layer 60A. The heat insulating layer 61 may be disposed so as to cover the entire surface of the circumferential surface 10S.

(First resin layer)
In the present embodiment, the first resin layer 62 that covers at least a part of the heating layer 60A (surface of the metal material) and has peelability is further disposed on the circumferential surface 10S. Thereby, the fiber assembly 20 becomes easier to peel from the circumferential surface 10S. Especially, it is preferable that the entire surface of the heating layer 60 </ b> A (the entire surface of the metal material) is covered with the first resin layer 62.

  For example, as shown in FIG. 2A, the first resin layer 62 may be arranged in a strip shape so as to correspond to the heating layer 60A. In this case, unevenness due to the heating layer 60A and the first resin layer 62 is formed on the peripheral surface 10S. Thereby, peeling of the fiber assembly 20 becomes easier.

  The height of the unevenness provided on the peripheral surface 10S with the heating layer 60A is not particularly limited. Especially, it is preferable that the height of the unevenness is not excessively high in terms of suppressing the slackness of the fibers 21 and maintaining the alignment in one direction. The height of the unevenness is, for example, 100 to 5000 μm. The height of the unevenness is an average value in the normal direction of the peripheral surface 10S of the winding rotary body 10. The same applies to the thicknesses of the heating layer 60A, the heat insulating layer 61, and the first resin layer 62.

The length (width W _R ) of the first resin layer 62 in the short direction is the length in the short direction of the heating layer 60A when the heating layer 60A is viewed from the normal direction of the peripheral surface 10S of the winding rotary body 10. It is preferably larger than the width (width W _H1 ). Ratio of width W _R to width W _H1 : W _R / W _H1 may be greater than 1 and 2 or less.

Usually, tension is easily applied to the portion of the fiber 21 that contacts the edge 62E of the first resin layer 62, and heat generated in the heating layer 60A is likely to concentrate on the edge 62E. However, the width W _R of the first resin layer 62, to be larger than the width W _H1 of the heating layer 60A, at least one edge 62E vicinity hardly heated. Therefore, damage to the fiber 21 and further yarn breakage are easily suppressed.

  Or the 1st resin layer 62 may be arrange | positioned so that the whole surface 10S may be covered, as shown to FIG. 2B. In this case, the heat insulating layer 61 may be disposed so as to cover the entire surface of the circumferential surface 10S, or may be disposed in a band shape in a region corresponding to the heating layer 60A.

  The material of the 1st resin layer 62 is not specifically limited as long as it is the resin material (1st resin) which has peelability. Among these, silicone rubber is preferably exemplified as the first resin. Thereby, the peelability from the peripheral surface 10S of the fiber assembly 20 further improves. On the other hand, since the silicone rubber has appropriate adhesiveness, the fiber assembly 20 is prevented from peeling from the peripheral surface 10S before the transfer step.

  Silicone rubber is a thermosetting compound whose main chain is formed by silicon-oxygen bonds (siloxane bonds). Examples of the silicone rubber include methyl silicone rubber, vinyl-methyl silicone rubber, phenyl-methyl silicone rubber, dimethyl silicone rubber, and fluorosilicone rubber.

  The thickness of the 1st resin layer 62 is not specifically limited, When the said unevenness | corrugation is formed in the surrounding surface 10S, what is necessary is just to set suitably in consideration of the height, the thickness of 60 A of heating layers, and the heat insulation layer 61. FIG. The thickness of the first resin layer 62 is, for example, 10 to 2000 μm.

[Second Embodiment]
In the present embodiment, the heating layer 60B is formed of a conductive resin composition. Moreover, the heating layer 60B includes a heat insulating layer 61 as in the first embodiment. In the present embodiment, irregularities including the heating layer 60 </ b> B and the heat insulating layer 61 are formed on the circumferential surface 10 </ b> S.

(Heating layer)
The resin composition that forms the heating layer 60B is, for example, a mixture of a conductive filler and various resin materials (second resin).

  The kind of conductive filler is not particularly limited, and examples thereof include copper, tin oxide, zinc oxide, titanium oxide, and carbon material. The blending amount of the conductive filler with respect to the second resin is not particularly limited, and may be appropriately set according to a desired heat generation temperature. The compounding quantity of the electroconductive filler with respect to 100 mass parts of 2nd resin is 20-200 mass parts, for example.

  The type of the second resin is not particularly limited. Especially, the resin material which has peelability is preferable. In this case, disposing the first resin layer 62 covering the heating layer 60B can be omitted. As the second resin, the same silicone rubber as the first resin can be preferably exemplified.

The thickness of the heating layer 60B is not particularly limited, and may be set as appropriate according to a desired heat generation temperature. However, when the unevenness is formed on the peripheral surface 10S, it is preferable to set the thickness of the heating layer 60B so that the height is 100 to 5000 μm. The thickness of the heating layer 60B is, for example, 80 to 3000 μm. It is preferable that the length (width W _H2 ) in the short direction of the heating layer 60B is the same as or smaller than the width W _I of the heat insulating layer 61.

[Manufacturing method and manufacturing apparatus]
In the manufacturing method of the scaffold for culture according to the present embodiment, the raw material liquid of the fiber 21 is discharged from the nozzle to generate the fiber 21, and the fiber 21 is circulated around the circumferential surface 10 </ b> S of the winding rotary body 10. A deposition process for depositing and forming the fiber assembly 20, a heating process for heating the fiber assembly 20 deposited on the circumferential surface 10 </ b> S of the winding rotary body 10, and a fiber while rotating the winding rotary body 10. A transfer step of transferring the aggregate 20 to the substrate 30. At this time, a plurality of belt-like heating layers 60 extending in the direction along the rotation axis A of the winding rotator 10 are arranged on the circumferential surface 10 </ b> S of the winding rotator 10. In the heating step, the fiber assembly 20 is heated by the heating layer 60.

  In the manufacturing method described above, the raw material liquid of the fiber 21 is discharged from the nozzle to generate the fiber 21, and the fiber 21 is deposited so as to circulate on the peripheral surface 10 </ b> S of the winding rotary body 10. And a transfer unit that transfers the fiber assembly 20 to the substrate while rotating the winding rotary member 10. At this time, the winding rotary body 10 includes a plurality of belt-shaped heating layers 60 on the peripheral surface 10S. In the transfer portion, the fiber assembly 20 heated by the heating layer 60 is transferred to the base material 30.

  Hereinafter, the method and apparatus for producing a culture scaffold according to the present embodiment will be described in detail with reference to the drawings. 3A and 3B are side views schematically showing the winding rotary body 10 and / or the base material 30 in each step of the present embodiment. In the present embodiment, the culture scaffold 100 includes a fiber assembly 20 and a base material 30.

(1) Deposition step (FIG. 3 (a))
In this step, the fibers 21 are generated from the raw material liquid 22, and the fibers 21 are deposited while rotating around the circumferential surface 10S of the winding rotary body 10 one or more times. Thereby, the fiber assembly 20 is formed on the circumferential surface 10S of the winding rotary body 10.

  The method (spinning method) for producing the fibers 21 from the raw material liquid 22 is not particularly limited, and may be appropriately selected according to the type of the fibers 21 to be produced. Examples of the spinning method include a solution spinning method, a melt spinning method, and an electrospinning method.

  The solution spinning method is a method in which a solution obtained by dissolving the raw material of the fiber 21 in a solvent is used as the raw material liquid 22. The solution spinning method using a solvent includes a so-called wet spinning method and a dry spinning method. Among these, the dry spinning method is preferable in that the fibers 21 are easily deposited while being arranged in one direction. In the dry spinning method, the fiber 21 is formed by discharging the raw material liquid 22 into the air and then removing the solvent by heating or the like.

  The melt spinning method is a method in which a melt obtained by heating and melting the raw material of the fiber 21 is used as the raw material liquid 22. The obtained raw material liquid 22 is solidified into a fibrous form by being cooled in the air and then cooled. In this case, normally, a solvent for dissolving the raw material of the fiber 21 is not used. Therefore, the melt spinning method is preferable in that the solvent removal operation can be omitted.

  The electrospinning method is common to the solution spinning method in that a solution obtained by dissolving the raw material of the fiber 21 in a solvent is used as the raw material liquid 22. However, in the electrospinning method, the raw material liquid 22 is discharged into the air while applying a high voltage. The solvent contained in the raw material liquid 22 volatilizes in the process until it reaches the peripheral surface 10S of the winding rotary body 10.

In the electrospinning method, in order to apply a high voltage to the raw material liquid 22, the raw material liquid 22 is charged positively or negatively. At this time, the discharge end of the raw material liquid 22 discharged into the air is attracted to the take-up rotary body 10 by grounding the winding rotary body 10 or charging it with a polarity opposite to that of the raw material liquid 22. And adheres to the peripheral surface 10S. Then, by rotating the winding rotary body 10 while discharging the raw material liquid 22, the fiber 21 is deposited while circling on the peripheral surface 10 </ b> S of the winding rotary body 10, as in the solution spinning method and the melt spinning method. covers at least a portion of the peripheral surface 10S of the winding rotary member 10, the fiber aggregate 20 comprising the fibers 21 arranged in the arrangement direction D ₂₁ is formed.

(Winding rotary body)
The configuration of the winding rotary body 10 is not particularly limited as long as it can rotate, and may be a drum shape or a belt stretched by a plurality of rolls. In the latter case, the belt is rotated by rotating at least one roll. Examples of the material of the winding rotary body 10 include metal materials, various resins, various rubbers, ceramics, and combinations thereof. When the winding rotary body 10 is a belt, the belt may be a metal belt or a resin belt. When the fiber 21 is spun by the electrospinning method, the resin belt preferably has conductivity. The outer shape of the winding rotary body 10 may be, for example, a cylinder or a prism.

The fibers 21 are deposited on the circumferential surface 10S of the winding rotary body 10 while being arranged in a direction (hereinafter referred to as an arrangement direction D ₂₁ ) around the circumferential surface 10S of the winding rotary body 10. The arrangement direction D ₂₁ is, for example, the rotational direction of the winding rotary member 10 (i.e., the direction perpendicular to the rotation axis A of the winding rotary member 10) is a direction along the. The angle θ ₂₁ (where θ ₂₁ ≦ 90 °) formed by the arrangement direction D ₂₁ and the rotation axis A may be, for example, 60 ° or more and 90 ° or less. Incidentally, the arrangement direction _{D 21} is when viewing the fiber 21 from the normal direction of the peripheral surface 10S of the winding rotary member 10, a longitudinal direction of the fiber 21 (see Figure 2 (b)). The longitudinal direction of the fiber 21 may be obtained by taking an approximate straight line of the fiber 21 when viewed from the normal direction of the peripheral surface 10S of the winding rotary body 10. Angle theta ₂₁ is the average value of the angle formed between the arrangement direction D ₂₁ of the plurality of fibers 21 and the rotary shaft A. The arrangement direction D ₂₁ of the plurality of fibers 21 deposited on the winding rotary member 10 may be different from each other within the above range.

  From the viewpoint of handleability, the heating layer 60 is preferably disposed in a state that it can be attached to and detached from the winding rotary body 10. For example, as shown in FIG. 4, a heating sheet 12 including a support sheet 121 and a heating layer 60 arranged in a band shape on the surface of the support sheet 121 is prepared, and the heating sheet 12 is placed around the rotating base 11. You may turn. With this configuration, the heating layer 60 can be easily disposed and can be easily replaced when the heating layer 60 is deteriorated. A heat insulating layer 61 and / or a first resin layer having a desired shape may be arranged on the heating sheet 12 together with the heating layer 60.

  The material of the support sheet 121 is not particularly limited, and examples thereof include polyester such as polyethylene terephthalate (PET), polyimide, and the like. When the fiber 21 is produced by an electrospinning method, the support sheet 121 preferably has conductivity. The thickness of the support sheet 121 is not particularly limited, and may be set as appropriate according to the material of the support sheet 121 and the like.

(Raw material liquid)
The raw material liquid 22 used in the solution spinning method and the electrospinning method includes the raw material of the fiber 21 and a solvent. The raw material liquid 22 used in the melt spinning method includes a raw material of the melted fiber 21. In the melt spinning method, it is not necessary to consider the solubility of the raw material in the solvent, so that the choice of the raw material is expanded.

  The raw material of the fiber 21 is not particularly limited as long as it can be used as a scaffold for culturing biological tissue or microorganisms. Among them, the raw material of the fiber 21 includes a block polymer containing a polystyrene block and a polybutadiene block, a block polymer containing the polystyrene block and a polybutadiene block, because it has a high affinity for the biological tissue and microorganism and is difficult to give stress to the biological tissue and microorganism. Preferably contain different styrene resins.

  The block polymer may be, for example, a diblock body in which a polybutadiene (PB) block and a polystyrene (PS) block are connected, but a polyblock body of a triblock body or more in which PB blocks and PS blocks are alternately connected. Is preferred. The block polymer preferably contains a PS block at least at the end from the viewpoint of ensuring affinity with the styrene resin. The PB block increases the flexibility and elongation of the obtained fiber 21.

  The content of the PB block in the block polymer is, for example, 10 to 30% by mass, preferably 15 to 30% by mass, and more preferably 20 to 30% by mass or 20 to 25% by mass. When the content of the PB block is in such a range, the affinity with the styrene resin is increased, and the homogeneous fibers 21 are easily generated. Moreover, the obtained fiber 21 has high flexibility and elongation. Furthermore, when the fiber 21 is produced by an electrospinning method, high spinnability is ensured.

  As the styrene resin, a polymer different from the above block polymer is used. Examples of the styrene resin include polystyrene (styrene homopolymer), and a copolymer of styrene and another copolymerizable monomer. A styrene resin may be used alone or in combination of two or more.

  In the case of the solution spinning method or the electrospinning method, the mass ratio of the block polymer to the styrene resin (= block polymer: styrene resin) is, for example, 2: 1 from the viewpoint of achieving both flexibility and easy formation of the fibers 21. ˜1: 5, preferably 1: 1 to 1: 4. In particular, when the fiber assembly 20 is formed by an electrospinning method using a solution, when the mass ratio is in such a range, the block polymer and the styrene resin are easily dissolved in a solvent, and high spinnability is ensured. You can also.

  The solvent is not particularly limited as long as it dissolves the raw material of the fiber 21 and can be removed by volatilization or the like, and can be appropriately selected from water and an organic solvent according to the kind of raw material and production conditions. As the solvent, an aprotic polar organic solvent is preferable. Examples of such a solvent include amides such as N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAc), and N-methyl-2-pyrrolidone (NMP) (chain or cyclic amide). A sulfoxide such as dimethyl sulfoxide; These solvent may be used individually by 1 type, and may be used in combination of 2 or more type.

  Although the solid content concentration of the raw material liquid 22 can be adjusted according to the kind of solvent etc., it is 5-50 mass%, for example, and may be 10-30 mass%. The raw material liquid 22 may further contain an additive as necessary.

  In the case of the melt spinning method, the mass ratio of the block polymer (preferably a diblock body) to the styrene resin (= block polymer: styrene resin) may be, for example, 5: 1 to 1: 1. It may be 1-2: 1.

(fiber)
The fiber 21 produced | generated from the said raw material liquid 22 contains the said block polymer and a styrene resin, and also an additive as needed. The average fiber diameter of the fibers 21 is, for example, preferably 0.5 μm to 20, more preferably 1 to 8 μm, and particularly preferably 1.5 to 4 μm.

  The average fiber diameter is an average value of the diameters of the fibers 21. The diameter of the fiber 21 is a diameter of a cross section perpendicular to the length direction of the fiber 21. If such a cross section is not circular, the maximum diameter may be considered as the diameter. Further, the width in the direction perpendicular to the length direction of the fibers 21 when viewed from the normal direction of one main surface of the fiber assembly 20 may be regarded as the fiber diameter. The average fiber diameter is, for example, an average value of the diameters of arbitrary portions of arbitrary 10 fibers included in the fiber assembly 20.

(Fiber assembly)
The fiber aggregate 20 is an aggregate of a plurality of fibers 21. In the fiber assembly 20, the plurality of fibers 21 are arranged in one direction. That the plurality of fibers 21 are arranged in one direction means that in the fiber assembly 20, the fibers 21 do not intersect with each other or the average angle at which the fibers 21 intersect each other exceeds 0 ° and is 60 ° or less. Say something. In this way, when the plurality of fibers 21 are arranged, the fibers 21 are likely to extend along the arrangement direction of the fibers 21, so that stress on a biological tissue or microorganism can be reduced. Therefore, it becomes easy for biological tissues and microorganisms to grow along the arrangement direction of the fibers 21.

  Here, the average angle at which the fibers 21 intersect can be determined from the average length direction intersection of the fibers 21. The average length direction of the fibers 21 can be determined based on, for example, an SEM photograph when the fiber assembly 20 is viewed from the normal direction. FIG. 5 is a schematic top view of the fiber assembly for explaining the arrangement of the fibers. In FIG. 5, the state of the fiber assembly 20 in the SEM photograph which image | photographed the fiber assembly 20 from the normal line direction is imitated. A square region R having a predetermined size (for example, 100 μm × 100 μm) is set when the fiber assembly 20 composed of a plurality of fibers 21 is viewed from the normal direction. At this time, the region R is determined so that eight or more fibers 21 are included in the region R, and 50% or more of the fibers 21 located in the region R intersect two opposite sides of the region R. In this region R, the direction of a straight line (a dotted line in FIG. 5) connecting two points where a certain fiber 21 intersects the two opposite sides is defined as the average length direction of the fiber 21.

  For example, in the region R, the average angle at which the fibers 21 cross each other is selected from a plurality of (for example, twelve) fibers 21 that are arbitrarily selected, and two fibers 21 are arbitrarily selected. An angle at which the average length direction intersects (for example, θ1 in FIG. 5) is obtained. Another two fibers 21 are selected, and an angle (for example, θ2 in FIG. 5) at which the average length direction of each fiber 21 intersects is obtained. Such an operation is performed on the remaining selected fibers 21 (for example, eight). And the average of each angle is calculated and it is set as the average angle which the fibers 21 cross.

  The ratio of the area of the fiber 21 to the unit area of the fiber assembly 20 can be selected from 10 to 90%. For example, when used for cardiomyocyte culture or a potential measuring device, the fiber assembly 20 is very thin, and the proportion of the fibers 21 per unit area is 20 to 50%, and is uniformly dispersed at 30 to 40%. It is preferable to deposit. The ratio of the area of the fibers 21 is a region of a predetermined area (for example, an ellipse having a minor axis of 3 mm and a major axis of 6 mm) on one main surface (for example, the upper surface) of the fiber assembly 20. , The glossiness is measured with a glossiness meter, the area occupied by the fibers 21 is calculated based on the difference in glossiness between the fibers 21 and the region other than the fibers 21, and is converted into an area ratio (%) per unit area. Can be obtained.

(2) Heating step In this step, the fiber assembly 20 deposited on the circumferential surface 10S of the winding rotary body 10 is heated. The heating of the fiber assembly 20 is performed by the heating layer 60 disposed on the circumferential surface 10 </ b> S of the winding rotary body 10.

  The heating layer 60 generates heat when energized, for example. The exothermic temperature may be appropriately set in consideration of the softening point or melting point of the fiber 21. The heat generation temperature is adjusted so that the fiber 21 has a temperature of 80 to 140 ° C., for example.

(3) Transfer process (FIG. 3B)
In this step, the fiber assembly 20 is transferred to the substrate 30 while rotating the winding rotary member 10. Thereby, the scaffold 100 for culture | cultivation provided with the fiber assembly 20 and the base material 30 is obtained.

  Prior to the transfer step, the fiber assembly 20 is cut at the planned cutting position C in a state of being wound around the winding rotary body 10. For example, the planned cutting location C is set along the shape of the base material 30. The fiber assembly 20 is cut in a direction along the rotation axis A, for example. The fiber assembly 20 is transferred to the base material 30 using this cut portion as a trigger. It does not specifically limit as a cutting device, For example, a long cutter etc. are mentioned.

  The base material 30 is mounted on the pedestal 53 supported by the XZ stage 52 and conveyed. At this time, the base material 30 is preferably transported in the X-axis direction at a relatively higher speed than the moving speed (circumferential speed) of the peripheral surface 10S of the winding rotary body 10. Thereby, the fiber assembly 20 is transferred to the base material 30 in a state in which the slackness is further suppressed. The XZ stage 52 can transport the gantry 53, and by extension, the base material 30 placed on the gantry 53, in a direction perpendicular to the rotation axis A (X-axis direction) and an up-down direction (Z-axis direction).

  On the other hand, in the transfer step, the substrate 30 may be conveyed by the rotation of the winding rotary body 10. That is, after transporting the base material 30 to a predetermined position, the gantry 53 is raised and the base material 30 is pressed against the winding rotary body 10. Next, the winding rotary body 10 may be rotated, and the base material 30 may be conveyed by a frictional force generated between the peripheral surface 10 </ b> S and the base material 30. Thereby, the relative conveyance speed of the base material 30 becomes the same as the peripheral speed of the winding rotary body 10, and the slackness of the fiber assembly 20 is suppressed. Moreover, since the alignment of the base material 30 becomes easy, transfer deviation of the fiber assembly 20 is suppressed. After the fiber assembly 20 is transferred, the gantry 53 is quickly lowered to separate the base material 30 from the winding rotary body 10.

(Base material)
The base material 30 is mainly used for supporting the fiber assembly 20.
The base material 30 is not specifically limited, The thing utilized for the conventional scaffold for culture | cultivation can be used. Examples of the base material 30 include porous base materials such as resin films and nonwoven fabrics, substrates made of glass or resin materials, or combinations thereof, depending on the type of biological tissue or microorganisms to be cultured.

  The adhesive 40 may be applied to the base material 30 before the transfer process. Thereby, the adhesiveness of the fiber assembly 20 and the base material 30 further increases. The kind of adhesive 40 is not specifically limited, For example, a silicone resin, hot melt resin, or ultraviolet curable resin is mentioned.

  The adhesive 40 is preferably applied to a position corresponding to the heating layer 60 of the substrate 30. In this case, the fiber assembly 20 and the base material 30 are pressed by the heating layer 60 and the gantry 53 supported by the XZ stage 52 with the adhesive 40 interposed. Therefore, the adhesiveness between the fiber assembly 20 and the base material 30 is improved.

The adhesive 40 is disposed in a band shape at a predetermined position of the substrate 30 by, for example, a dispenser 55. A pressure sensitive adhesive such as a silicone resin may be disposed on the substrate 30 after being formed into a belt-like film. The application amount of the adhesive 40 is not particularly limited. Especially, from the viewpoint of preventing the culture of biological tissues and microorganisms from being inhibited while ensuring the adhesiveness between the fiber assembly 20 and the substrate 30, the applied amount of the adhesive 40 is 0.5 to 100 mg / cm ^2. It is preferable that

  Since the culture scaffold and fiber assembly obtained by the present invention have fibers arranged in one direction, they are particularly useful as a culture scaffold for culturing a biological tissue or microorganism having a direction of growth.

DESCRIPTION OF SYMBOLS 10: Winding rotary body 10S: Circumferential surface 11: Rotating base 12: Heating sheet 121: Support sheet 20: Fiber assembly 21: Fiber 22: Raw material liquid 30: Base material 40: Adhesive 51: Nozzle 52: XZ stage 53 : Stand 60, 60A, 60B: heating layer 61: heat insulating layer 62: first resin layer 62E: edge of first resin layer 100: scaffold for culture

Claims (8)

A deposition step of discharging a fiber raw material liquid from a nozzle to generate the fiber and depositing the fiber so as to circulate on a peripheral surface of a winding rotary body to form a fiber assembly;
A heating step of heating the fiber assembly deposited on the circumferential surface of the winding rotary body;
A transfer step of transferring the heated fiber assembly to a substrate while rotating the winding rotary body,
A plurality of belt-like heating layers extending in a direction along the rotation axis of the winding rotator are disposed on the peripheral surface of the winding rotator,
In the heating step, the fiber assembly is heated by the heating layer.   The manufacturing method of the scaffold for culture | cultivation of Claim 1 with which the heat insulation layer is arrange | positioned between the said heating layer and the said surrounding surface of the said winding rotary body. The heating layer is formed of a metal material;
The culture according to claim 1, wherein a resin layer that covers at least a part of the heating layer and includes a first resin having peelability is further disposed on the peripheral surface of the winding rotary body. Manufacturing method for scaffolds. When the heating layer is viewed from the normal direction of the peripheral surface of the winding rotary body,
The manufacturing method of the scaffold for culture | cultivation of Claim 3 whose width | variety of the said resin layer is larger than the width | variety of the said heating layer in the direction orthogonal to the extending | stretching direction of the said heating layer.   The manufacturing method of the scaffold for culture | cultivation of Claim 3 or 4 with which the said resin layer is formed with a silicone rubber.   The manufacturing method of the scaffold for culture | cultivation of Claim 1 or 2 with which the said heating layer is formed with the resin composition which has electroconductivity.   The manufacturing method of the scaffold for culture | cultivation of Claim 6 in which the said resin composition contains a silicone rubber and an electroconductive filler. A fiber raw material liquid is discharged from a nozzle to generate the fiber, and the fiber is deposited so as to circulate on the circumferential surface of the winding rotary body, thereby forming a fiber assembly,
A transfer unit that transfers the fiber assembly to a substrate while rotating the winding rotary body,
The winding rotary body includes a plurality of belt-shaped heating layers extending on a circumferential surface thereof in a direction along the rotation axis of the winding rotary body,
The transfer scaffold manufacturing apparatus for transferring a scaffold for culturing, wherein the fiber assembly heated by the heating layer is transferred to the substrate.

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