JP2019024339A - Method of producing culture scaffold - Google Patents

Abstract

To efficiently produce culture scaffold provided with fibers aligned in one direction in a non-loose state.SOLUTION: A method of producing a culture scaffold comprises: a deposition step for forming a fiber assembly 20 by discharging fiber raw material liquid to create fibers while depositing the fibers around the circumferential surface of a winding rotary body 10; a substrate preparation step of preparing a substrate 30 provided with an adhesive 40; a transfer step of transferring the fiber assembly 20 to the substrate 30 via the adhesive 40 while rotating the winding rotary body 10; wherein a plurality of belt-like protrusions 10P are provided so as to extend along the direction of the rotary axis of the winding rotary body 10 on the circumferential surface of the winding rotary body 10 and, in the transfer step, a starting point Pwhere peeling off of the fiber assembly 20 starts from one of the protrusions 10P thereof and an end point Pwhere peeling ends are adhered to the adhesive 40.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a method for manufacturing a culture scaffold, and in particular, to an improvement in productivity of a culture scaffold having 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 deposition step, a base material preparation step of preparing a base material provided with an adhesive, and a transfer step of transferring the fiber assembly to the base material via the adhesive while rotating the winding rotary body. A plurality of belt-like convex portions extending in a direction along a rotation axis of the winding rotary body are disposed on the peripheral surface of the winding rotary body, and in the transfer step, the fiber assembly It relates to a method for producing a culture scaffold, wherein a starting point at which peeling from any of the convex portions starts and an end point at which the peeling ends are adhered to the adhesive.

  According to the production method of the present invention, it is possible to efficiently produce a culture scaffold provided with fibers arranged in one direction without slack.

It is a side view which shows typically a winding rotary body and a base material in a transfer process of a manufacturing method concerning the present invention ((a)-(c)). 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 a decomposition | disassembly side view which shows the other example of the winding rotary body which concerns on this invention. It is a perspective view which shows the further another example of the winding rotary body which concerns on this invention. It is a side view which shows typically the winding rotary body and other base material in the transfer process of the manufacturing method which concerns on 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)-(c)). It is a schematic top view of the one part area | region of the fiber assembly for demonstrating the arrangement | sequence of a fiber. It is a side view which shows typically the winding rotary body and base material in a transcription | transfer process in case the point where peeling of a fiber assembly is started is not adhere | attached on the adhesive agent.

  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 this embodiment, in order to transfer the fiber assembly to the base material while maintaining the alignment of the fibers in one direction, the fiber is stretched in the direction along the rotation axis of the winding rotating body. A plurality of belt-like convex portions are arranged. Thereby, the fiber assembly (fiber assembly) arranged so as to circulate around the circumferential surface of the winding rotary body is easily peeled off from the winding rotary body.

  Furthermore, an adhesive is disposed on at least a part of the surface of the substrate. For this reason, in the transfer step, the convex portion and the adhesive are brought into close contact with each other via the fiber assembly, whereby the fiber aggregate is transferred from the convex portion to the base material via the adhesive. At this time, the start point at which peeling from an arbitrary convex part of the fiber assembly starts and the end point at which peeling ends are simultaneously or sequentially bonded to the adhesive. As a result, the fiber assembly is easily transferred to the substrate without sagging while maintaining the fiber arrangement.

Hereinafter, the transfer process will be described in detail with reference to the drawings. FIG. 1 is a side view schematically showing a winding rotary body and a substrate in a transfer process of the manufacturing method according to the present embodiment. 1 (a) is a side view of a prior separation of the fiber assembly 20 on any of the projecting portion 10P is started, FIG. 1 (b), a side view of the start point P _S to which the peeling is started , and the FIG. 1 (c) is a side view of the end point P _E where the peeling is completed. In the illustrated example, the fiber assembly 20, the convex portion 10P, and the adhesive 40 are hatched for convenience.

  In the transfer step, the fiber assembly 20 deposited on the peripheral surface is transferred to the substrate 30 while rotating the winding rotary member 10 (FIG. 1A). An adhesive 40 is disposed on at least a part of the base material 30, and the fiber assembly 20 is transferred to the base material 30 via the adhesive 40.

If the starting point P _S of the fiber assembly 20 is not adhered to the adhesive 40, as shown in FIG. 8, the delamination by the winding rotary member 10 is rotated, the substrate 30 and the convex portion 10P It starts when the distance becomes large enough. At this time, a large tension T is applied to the fiber assembly 20. For this reason, the fibers forming the fiber assembly 20 may be broken or the fiber assembly 20 itself may be torn. Furthermore, as a result of the tearing of the fiber assembly 20, a part of the fiber assembly 20 may remain on the winding rotary body 10. Incidentally, FIG. 8 is a side view of the winding rotary member and the base material shown schematically in the transfer step in the case where the start point P _S of the fiber assembly 20 is not adhered to the adhesive 40.

Similarly, when the end point P _E of the fiber assembly 20 is not adhered to the adhesive 40, the peel, the distance between the substrate 30 and the convex portion 10P is terminated by again becomes sufficiently large. Also at this time, the fiber assembly 20 is still under great tension. Therefore, the fiber assembly 20 transferred to the substrate 30 and released from the tension is likely to be loosened, and the fiber arrangement is likely to be disturbed.

In the present embodiment, the start point P _S peeling starts from any protrusions 10P of the fiber assembly 20 is adhered to the adhesive 40. That is, the start point _{P S} of the fiber aggregate 20 is peeled from convex portion 10P in a state of being adhered to the adhesive 40 (Figure 1 (b)). Furthermore, end point _{P E} of the fiber aggregate 20 is also peeled from the protrusion 10P in a state of being adhered to the adhesive 40 (FIG. 1 (c)). Therefore, hardly takes tension on the fiber, thus, without loosening the fiber assembly 20 between the start point P _S and the end point P _E, and, while maintaining the sequence, readily transferred to the substrate 30 Is done.

In the transfer step, at least a part of the rotating convex part 10P and at least a part of the adhesive 40 are brought into close contact with each other via the fiber assembly 20, whereby the projected shape of the convex part 10P is reflected. A close contact region (not shown) between the body 20 and the adhesive 40 is formed. Starting point P _S, of the contact region, a end portion along the extending direction D _P of the convex portion 10P _(see FIG. 2), which is the end which is in close contact with the first adhesive 40. End point P _E is the end opposite to the starting point P _S of the contact area. Note that the close contact region may be different from the region where the convex portion 10P and the fiber assembly 20 are in contact after the deposition step and before the transfer step. This is because, in the transfer process, the convex portion 10P rotates and is pressed against the base material 30 to be deformed.

(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.

  An example of the winding rotary body 10 is shown in FIGS. FIG. 2A is a perspective view showing an example of the winding rotary body 10, and FIG. 2B is a plan view thereof. In FIG. 2, a part of the fibers 21 (fiber assembly 20) deposited on the peripheral surface of the winding rotary body 10 is also shown.

The fibers 21 are deposited on the circumferential surface of the winding rotator 10 while being arranged in a direction (hereinafter referred to as an arrangement direction D ₂₁ ) around the circumferential surface of the winding rotator 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 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 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.

Protrusion 10P is a strip, the circumferential surface of the winding rotary member 10, extends in the extending direction D _P along the rotation axis A of the winding rotary member 10. Extending direction _{D P} is not limited to the case it is parallel to the rotation axis A, the angle between the rotational axis A to the stretching direction _{D P θ P} (However, θ _P <90 °), for example, 0 ° or more, 30 ° or less. Especially, from a viewpoint of the peelability of the fiber assembly 20, it is preferable that angle (theta) _P is 0 degree or more and 20 degrees or less.

Extending direction _{D P} is a direction intersecting the arrangement direction _{D 21} of the fiber 21. The angle between the stretching direction _{D P} to the arrangement direction _{D 21} theta (However, theta ≦ 90 °), for example, 60 ° or more and 90 ° or less. Incidentally, the stretching direction D _P, when viewed protrusion 10P in the normal direction of the peripheral surface of the winding rotary member 10, a longitudinal centerline L _CP of the convex portion 10P is the direction of stretching. If the center line L _CP contains a curve, the extending direction D _P is the minimum rectangular center line surrounding the center line L _CP is the direction of stretching. Extending direction D _R to be described later rib 10R may be obtained in the same manner.

The shape of the convex portion 10P is not particularly limited as long as it is a belt shape. The strip, the length of the extending direction D _P of the convex portion 10P is a shape longer than the length in the direction perpendicular to the extending direction D _P. Examples of the shape when the convex portion 10P is viewed from the normal direction of the peripheral surface of the winding rotary body 10 include a rectangle and a trapezoid.

  The number of the convex portions 10P is not particularly limited and may be two or more. Among these, from the viewpoint of peelability of the fiber assembly 20, three or more are preferably arranged on the peripheral surface of the winding rotary body 10, and ten or more are preferably arranged. Further, from the same viewpoint, it is preferable that the convex portions 10P are arranged at equal intervals. As will be described later, prior to the transfer step of the fiber assembly 20 to the base material 30 (see FIG. 10C), the fiber assembly 20 is cut in a state of being wound around the winding rotary member 10. The fiber assembly 20 is cut between the protrusions 10P so that at least a part of the cut fiber assembly 20 is in contact with the protrusions 10P. Thereby, the arrangement of the fibers 21 is easily maintained. In this case, it is preferable that the interval between the convex portions 10P of the planned cutting location C (see FIG. 3) is smaller than the interval between the convex portions 10P in other portions.

The length (width) in the short direction of the convex portion 10P is not particularly limited. Among these, from the viewpoint of the peelability of the fiber assembly 20, the total area in contact with the peripheral surface of the winding rotary body 10 of all the convex portions 10 </ b> P is 10% or more of the surface area of the peripheral surface of the winding rotary body 10, It is preferable to determine the width of each convex portion 10P so that it is 80% or less, particularly 30% or more and 70% or less. The length of the extending direction D _P of the convex portion 10P is not particularly limited. Especially, it is preferable that the convex part 10P is extended over the area | region where the fiber 21 can accumulate on the surrounding surface of the winding rotary body 10 at least.

  The height of the convex portion 10P is not particularly limited. Especially, it is preferable that the height of the convex part 10P is not excessively high at the point which suppresses the slack of the fiber 21 and it is easy to maintain the arrangement | sequence in one direction. From the viewpoint of peelability of the fiber assembly 20 and suppression of slackness of the fibers 21, the height of the convex portion 10P is preferably 100 to 5000 μm. The height of the convex portion 10 </ b> P is an average value in the normal direction of the peripheral surface of the winding rotary body 10.

  The material of the convex part 10P is not specifically limited, Various resin materials are mentioned. Especially, it is preferable that the convex part 10P is provided with a silicone rubber layer at least in a contact part with the fiber 21. This is because the peelability of the fiber assembly 20 is further improved. On the other hand, since the silicone rubber has appropriate adhesiveness, the fiber assembly 20 is prevented from peeling from the peripheral surface of the winding rotary body 10 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. Of course, the entire protrusion 10P may be formed of silicone rubber. As will be described later, when the fiber 21 is produced by an electrospinning method, the convex portion 10P preferably has conductivity.

  From the viewpoint of handleability, it is preferable that the convex portion 10 </ b> P is arranged in a state where it can be attached to and detached from the winding rotary body 10. For example, as shown in FIG. 3, a concavo-convex sheet 12 including a support sheet 121 and a silicone rubber 122 arranged in a strip shape on the surface of the support sheet 121 is prepared, and the concavo-convex sheet 12 is placed around the rotating base 11. You may turn. At this time, the silicone rubber 122 corresponds to the convex portion 10P. With this configuration, the protrusions 10P can be easily arranged and can be easily replaced when the protrusions 10P deteriorate.

  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 is also preferably provided with 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. Examples of the silicone rubber 122 include the compounds described above.

  Further, in the process of transferring to the base material 30, the fiber 21 is easily maintained in the arrangement, and is stretched in the direction intersecting the rotation axis A as shown in FIG. It is preferable to arrange the ribs 10R.

(adhesive)
The adhesive 40 is disposed at a position corresponding to at least the start point P _S and end point P _E of the substrate 30. The adhesive 40 may be disposed in a band shape at a start point P _S , an end point P _E , and a position corresponding to between the start point P _S and the end point P _E. In this case, the length (width) of the adhesive 40 in the short direction of the convex portion 10P is larger than the length (width) of the convex portion 10P in the short direction. Incidentally, if the width of the convex portion 10P (length in the short direction) is small, and the starting point P _S and the end point P _E, close, further, may overlap. As shown in FIG. 5, the adhesive 40 is disposed in a band shape at a position corresponding to a start point P _S , an end point P _E , and a part between the start point P _S and the end point P _E. Also good.

  The kind of adhesive 40 is not specifically limited, For example, a silicone resin, hot melt resin, or ultraviolet curable resin is mentioned.

  The silicone resin is also referred to as a pressure-sensitive adhesive, and adheres the fiber assembly 20 and the base material 30 due to its adhesiveness. Examples of the silicone resin include dimethyl silicone and methylphenyl silicone. The hot melt resin is disposed on the base material 30 in a heated state, and is cooled, thereby bonding the fiber assembly 20 and the base material 30 together. The material of the hot melt resin is not particularly limited. For example, a polyester such as polyurethane (PU) or PET, a copolymer polyester such as urethane-modified copolymer polyester, a thermoplastic resin such as PA or polyolefin (for example, PP or PE) is used. It is included as a main component (component occupying 50% by mass or more).

  The ultraviolet curable resin adheres the fiber assembly 20 and the substrate 30 by being polymerized and cured by ultraviolet irradiation. The kind of ultraviolet curable resin is not specifically limited, An acrylic resin, an epoxy resin, etc. are mentioned. When an ultraviolet curable resin is used, it is preferable to irradiate the ultraviolet curable resin with ultraviolet rays before the transfer step so as to be in a semi-cured state. In this case, after the fiber assembly 20 and the base material 30 are in contact with each other in the transfer step, ultraviolet irradiation is further performed to completely cure the ultraviolet curable resin. The ultraviolet irradiation in the transfer process is performed from the base material 30 side, for example.

  As the adhesive 40, a hot melt resin and a silicone resin are preferable in that a special step for curing can be omitted. Further, a silicone resin is preferable in that a heating device for melting the adhesive is unnecessary. . Moreover, an ultraviolet curable resin is preferable at the point that hardening progresses rapidly.

The application amount of the adhesive 40 is not particularly limited, and is appropriately set according to the number and width of the convex portions 10P. 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

[Production method]
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 deposited so as to circulate around the circumferential surface of the winding rotary body 10. The fiber assembly 20 is bonded to the base material 30 while rotating the winding rotary body 10 while the deposition step for forming the fiber assembly 20, the base material preparation step for preparing the base material including the adhesive, and the winding rotary body 10 are rotated. And a transfer step of transferring via. At this time, a plurality of belt-like convex portions 10 </ b> P extending in the direction along the rotation axis A of the winding rotator 10 are arranged on the peripheral surface of the winding rotator 10. Further, in the transfer step, the end point P _E that any starting point P _S and the peeling peeling starts from the convex portion 10P of the fiber assembly 20 is completed, is adhered to the adhesive 40.

  For example, the above-described culture scaffold discharges the raw material liquid of the fiber 21 from the nozzle to generate the fiber 21 and deposits the fiber 21 so as to circulate on the peripheral surface of the winding rotary body 10. It is manufactured by an apparatus that includes a deposition unit that forms the assembly 20 and a transfer unit that transfers the fiber assembly 20 to a base material that includes an adhesive while rotating the winding rotary member 10. The At this time, the winding rotary body 10 includes a plurality of belt-like convex portions 10P on the peripheral surface thereof.

  Hereinafter, the manufacturing method of the culture scaffold according to the present embodiment will be described in detail with reference mainly to FIG. 6A to 6C 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 process (FIG. 6 (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 of the winding rotary body 10 one or more times. Thereby, the fiber assembly 20 is formed on the peripheral surface 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 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 adhere to the peripheral surface. Then, by rotating the winding rotary body 10 while discharging the raw material liquid 22, the fibers 21 are deposited while circling around the circumferential surface of the winding rotary body 10, as in the solution spinning method and the melt spinning method. It covers at least a portion of the peripheral surface of the winding rotary member 10, the fiber aggregate 20 comprising the fibers 21 arranged in the arrangement direction D ₂₁ is formed.

(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 the electrospinning method, the block polymer and the styrene resin can be easily dissolved in the solvent and the high spinnability can be ensured when the mass ratio is in such a range.

  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. 7 is a schematic top view of a fiber assembly for explaining the arrangement of the fibers. In FIG. 7, 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. 7) connecting a point where a certain fiber 21 intersects the two opposite sides is defined as an 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. 7) is obtained. Another two fibers 21 are selected, and an angle (for example, θ2 in FIG. 7) 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) Substrate preparation process (FIG. 6B)
In this step, the base material 30 including the adhesive 40 is prepared.

(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 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.

(3) Transfer process (FIG. 6C)
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 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 convex portion 10 </ b> P 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.

  The culture scaffold and fiber assembly obtained by the present invention are provided with fibers arranged in one direction in a slack-free state, and in particular, a culture scaffold for culturing a biological tissue or microorganism having a direction of growth. Useful as.

DESCRIPTION OF SYMBOLS 10: Winding rotary body 10P: Convex part 10R: Rib 11: Rotating base 12: Concavity and convexity sheet 121: Support sheet 122: Silicone rubber 20: Fiber aggregate 21: Fiber 22: Raw material liquid 30: Base material 40: Adhesive 51 : Nozzle 52: XZ stage 53: Mount 100: Scaffold for culture

Claims (4)

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 base material preparation step of preparing a base material provided with an adhesive;
A transfer step of transferring the fiber assembly to the base material via the adhesive while rotating the winding rotary body,
A plurality of belt-like convex portions extending in a direction along the rotation axis of the winding rotator are disposed on the peripheral surface of the winding rotator,
In the transfer step, a culture scaffolding manufacturing method, wherein a starting point at which peeling of the fiber assembly from an arbitrary convex portion starts and an end point at which the peeling ends are adhered to the adhesive.   The manufacturing method of the scaffold for culture | cultivation of Claim 1 whose said adhesive agent is silicone resin, hot-melt resin, or ultraviolet curable resin.   The manufacturing method of the scaffold for culture | cultivation of Claim 1 or 2 provided with a silicone rubber layer in the contact part with the said fiber at least of the said convex part. The winding rotary body includes a rotating base and a support sheet wound around the rotating base,
The manufacturing method of the scaffold for culture | cultivation as described in any one of Claims 1-3 with which the said convex part is arrange | positioned at the said support sheet.

Images