* NOTICE *
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`JPO and INPIT are not responsible for any damages caused by the use of this translation.
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`1. This document has been translated by computer. So the translation may not reflect the original precisely.
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`2. **** shows a word which cannot be translated.
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`3. in the drawings, any words are not translated.
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`Publication Number
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`JP2019024340A
`
`Bibliography
`
`(19) [Publication country] JP
`
`(12) [Kind of official gazette] A
`
`(11) [Publication number] 2019024340
`
`(43) [Date of publication of application] 20190221
`
`(54) [Title of the invention} CULTURE SCAFFOLD AND METHOD OF PRODUCING
`
`SAME
`
`(51) [International Patent Classification]
`
`
`
`C12M=3/00 (2006.01)
`
`
`
`DO4H=1/541 (2012.01)
`
`
`
`DO4H==1/74 (2006.01)
`
`C12N
`
`5/02
`
`(2006.01)
`
`[Fl]
`
`
`
`C12M=3/00 A
`
`DO4H=1/541
`
`DO4H=1/74
`
`C12N
`
`5/02
`
`(21) [Application number] 2017144348
`
`(22) [Filing date] 20170726
`
`(71) [Applicant]
`
`[Name] PANASONIC IP MANAGEMENT CORP
`
`(72) [Inventor]
`
`[Full name] IKEDA KOJI
`
`[Full name] NAKAMURA TAICHI
`
`[Full name] EBIHARA YUTO
`
`[Theme code (reference)]
`
`

`

`4B029
`
`4B065
`
`ALO47
`
`[F-term (reference) ]
`
`4B029AA02
`
`4B029AA21
`
`4B029BB11
`
`4B028CC10
`
`4B029DG08
`
`4BO65AA90X
`
`4B065AC12
`
`4B065BC41
`
`4B065CA44
`
`4LO47AA28
`
`4L047BA09
`
`4L047BD02
`
`4L047BD03
`
`4L047CC03
`
`Abstract
`
`(57) [Overview]
`
`PROBLEM TO BE SOLVED: To reduce disordering of the alignment of fibers in a culture
`
`scaffold provided with a fiber assembly comprising a plurality of aligned fibers.
`
`SOLUTION: A culture scaffold comprises a substrate and a fiber assembly arranged on
`
`the substrate. The fiber assembly comprises a plurality of first fibers arranged along one
`
`direction and a plurality of second fibers that crossover theplurality offirst fibers. Of the
`
`portions of the plurality of first fibers and plurality of second fibers that cross over, the
`
`first fibers and second fibers are integrated at least at one of the portions that cross over.
`
`SELECTED DRAWING: Figure 2
`
`Claim
`
`{Patent Claims]
`
`[Claim 1]
`
`A substrate includes a substrate and a fiber assembly disposed on the substrate.
`
`The fiber assembly includes a plurality of 1 fibers arranged along one direction and a
`
`plurality of 1 fibers intersecting the plurality of 2 fibers.
`
`

`

`A culture scaffold for culturing, wherein at least a part of the crossing part of intersections
`
`of a plurality of 1 fibers and a plurality of 2 fibers is integrated with the 1 fibers and the 2
`
`fibers.
`
`{Claim 2]
`
`The culture scaffold according to claim 1, wherein the fiber assembly has a 1
`
`layer
`
`structure comprising a 1 fiber layer composed of the plurality of 7 fibers and a 2 fiber
`
`layer overlapping the 2 fiber layer and composed ofthe plurality of 2 fibers.
`
`{Claim 3]
`
`A culture scaffoid according to claim 1 or 2, wherein said plurality of 2 fibers is interposed
`
`between said plurality of 1 fibers and said substrate.
`
`[Claim 4]
`
`The culture scaffold according to claim 1 or 2, wherein a ratio S 1 of the area of the 1
`
`fiber occupying a unit area of the fiber aggregate is larger than a ratio S 2 of an area of
`
`the 2 fiber occupying a unit area of the fiber aggregate.
`
`[Claim 5]
`
`Further, a frame bodyis provided which includes a 1 surface, a 2 surface opposite to the
`
`first surface, and one or more through holes penetrating from the 1 surface to the 2
`
`surface, and the frame body is mounted on the substrate such that the 1 surface faces
`
`the first surface.
`
`The fiber assembly is interposed between the substrate and the 1 surface.
`
`The culture scaffold according to any one of claims 1 to 4, wherein at least a portion of
`
`the fiber aggregate is exposed from a 1 opening formed on the 7 surface by the through
`
`hole.
`
`{Claim 6]
`
`The culture scaffold according to any one of claims 1 to 5, wherein the plurality of 2 fibers
`
`are arranged along one direction.
`
`[Claim 7]
`
`A culture scaffold according to claim 6, wherein the plurality of 1 fibers and the plurality
`
`of 2 fibers intersect in a lattice pattern.
`
`[Claim 8]
`
`A culture scaffold according to claim 6 or 7, wherein an average angle at which the 1
`
`fiber and the 2 fiber intersect is greater than 60 ° and less than or equal to 90 °.
`
`[Claim 9]
`
`The culture scaffold according to any one of claims 1
`
`to 8, wherein an average fiber
`
`diameter of the 7 fiber is larger than an average fiber diameter of the 2 fiber.
`
`[Claim 10]
`
`

`

`A method of manufacturing a scaffold for culture includes a substrate and a fiber
`
`assembly disposed on the substrate.
`
`The fiber assembly includes a plurality of 1 fibers arranged along one direction and a
`
`plurality of 1 fibers intersecting the plurality of 2 fibers.
`
`The method for manufacturing a scaffold for culture includes a step of integrating the 1
`
`fibers and the 2 fibers in at least a part of the intersection of the plurality of 1 fibers and
`
`the plurality of 2 fibers.
`
`[Claim 14]
`
`The method of manufacturing a scaffold for culturing according to claim 10, wherein in
`
`the step of integrating, the 1 fiber and the 2 fiber are fused.
`
`[Claim 12]
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`A step of preparing the substrate ;
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`The method of manufacturing a culture scaffold according to claim 10 or 11, further
`
`comprising : disposing the plurality of 2 fibers on the substrate via the plurality of 7 fibers.
`
`Description
`
`[Detailed description of the invention]
`
`[Technical field]
`
`{000 1]
`
`The presentinvention relates to a culture scaffold containing a plurality of fibers arranged
`
`and a method for producing the same.
`
`[Backgroundof the Invention]
`
`{0002}
`
`in recent years, a fiber substrate has attracted attention as a scaffold for culturing
`
`biological tissues and microorganisms (see Patent Document 1}. The fibrous substrate
`
`is, for example, a woven fabric, a knitted fabric or a nonwoven fabric and has a three
`
`dimensional structure. Therefore, biological tissue and microorganisms can be cultured
`
`in vitro in a state close to physiological environment.
`
`[Prior art reference]
`
`[Patent document]
`
`{0003}
`
`{Patent document 1JJP 2010-517590A
`
`{Summary of the invention]
`
`[Problem to be solved by the invention]
`
`[0004]
`
`

`

`Whena fiber assembly in which a plurality of fibers are arranged is used as a scaffold
`
`for culture, a certain degree of rigidity can be secured in an arrangement direction of
`
`fibers (a length direction of fibers). However,
`
`in the direction perpendicular to the
`
`thickness direction of the fiber assembly and the direction of arrangementof the fibers,
`
`the rigidity becomes flow and the arrangementof the fibers tends to be disturbed.
`
`[Means for solving the problem]
`
`fO005]
`
`An aspect of the invention includes a substrate and a fiber assembly disposed on the
`substrate.
`
`The fiber assembly includes a plurality of 1 fibers arranged along one direction and a
`
`plurality of 1 fibers intersecting the plurality of 2 fibers.
`
`in at least one of the crossing portions of the plurality of 1 fibers and the plurality of 2
`
`fibers, at least a part of the crossing portions is integrated with the 1 fibers and the 2
`
`fibers.
`
`[0006]
`
`According to another aspect of the present invention, there is provided a method of
`
`manufacturing a scaffold for culture comprising the stepsof:
`
`The fiber assembly includes a plurality of 1 fibers arranged along one direction and a
`
`plurality of 71 fibers intersecting the plurality of 2 fibers.
`
`A method of manufacturing a scaffold for culture includes a step of integrating the 1 fiber
`
`and the 2 fiber in at least a part of the intersection part of the plurality of 1 fibers and the
`
`plurality of 2 fibers.
`
`[Effect of the Invention]
`
`[0007]
`
`To reduce the disorder of an arrangementof fibers in a scaffold for culture comprising a
`
`fiber aggregate containing a plurality of arrangedfibers.
`
`[Brief Description of the Drawings]
`
`fO008]
`
`[Fig. 1]FIG.
`
`1
`
`is a top view schematically showing a scaffold for culture according to an
`
`embodiment of the present invention ;
`
`[Fig. 2]FIG. 4 is a top view schematically showing a fiber assembly exposed from a
`
`through-hole of FIG.
`
`14
`
`;.
`
`[Fig. 3]FiG. 3 is an enlarged view schematically showing the region of FIG. 2 ;.
`
`[Fig. 4]JFIG. 4 is a cross-sectional view taken along line IV-IV of FIG. 3 ;.
`
`[Fig. 5]FIG. 3 is a cross-sectional view taken along line V-V of FIG. 2 ;.
`
`[Fig. 6]FIG. 1 is a schematic top view of a first or 2 fiber in a fiber assembly for describing
`
`

`

`an arrangementoffibers ;.
`
`{Mode for carrying out the invention]
`
`fOO09]
`
`A culture scaffold according to an embodiment of the present invention includes a
`
`substrate and a fiber assembly disposed on the substrate. The fiber assembly includes
`
`a plurality of 1 fibers arranged along one direction and a plurality of 2 fibers intersecting
`
`with the plurality of 1 fibers, and at least a part of the intersection of the plurality of 2
`
`fibers and the plurality of 1 fibers is integrated with the 1 fibers and the 2 fibers.
`
`[0010]
`
`in general, a fiber aggregate composed of a plurality of fibers arranged along one
`
`direction has low rigidity in a direction perpendicular to the arrangement direction of the
`
`fibers (a length direction of the fibers) and a thickness direction, and the arrangement of
`
`the fibers tends to be disordered. Whena biological tissue or a cell is cultured, a scaffold
`
`for culture may be immersed in a liquid medium, a liquid medium or a washing liquid may
`
`be pouredinto a culture scaffold, or a poured washing liquid may be sucked and removed.
`
`in these cases, the arrangementof the fibers may be disturbed due to the surface tension
`
`of the liquid, and the adjacent fibers may stick together. In other words, it is difficult to
`
`maintain a high degree of alignment even if an array of fibers arranged once is formed.
`
`On the other hand, according to the present embodiment, since the plurality of 1 fibers
`
`and the plurality of 2 fibers arranged along one direction intersect each other and the 1
`
`fibers and the 2 fibers are integrated at the intersection portion, the disturbance of the
`
`arrangementof the 1 fibers can be reduced or suppressed.
`
`{001 14]
`
`Note that the intersection portion is a portion where the 1 fiber and the 2 fiber intersect.
`
`The integration of the 1 fiber and the 2 fiber includes a state in which the 1 fiber and the
`
`2 fiber are directly bonded at the intersection portion, e.g., a fused (or welded) state ora
`
`bonded state.
`
`[0012]
`
`The scaffoid for culturing according to the present embodiment can be manufactured by
`
`a method of manufacturing a scaffold for culture including a step of integrating a 1 fiber
`
`and a 2 fiber at an intersection of at least a part of intersections of a plurality of 1 fibers
`
`and a plurality of 2 fibers.
`
`Hereinafter, a scaffold for culturing according to an embodimentof the present invention
`
`and a method of manufacturing the scaffold will be described in more detail with
`
`reference to the accompanying drawings, if necessary.
`
`

`

`{001 3]
`
`[Scaffold for culture]
`
`FIG.
`
`1
`
`is a top view schematically showing a scaffold for culture according to an
`
`embodiment of the present invention. A scaffold 100 for culture includes a substrate 110
`
`and a fiber aggregate 130 arranged on the substrate 110. The fiber assembly 130
`
`includes a plurality of 1 fibers 131 a arranged and a plurality of 7 fibers 137 b intersecting
`
`the plurality of 2 fibers.
`
`{0014}
`
`More specifically, the culture scaffold 100 includes a frame 120 mounted on a mounting
`
`surface 110 X of a substrate 110. The frame 120 includes a first main surface (1 main
`
`surface) 120 X and a second main surface (1 main surface) 120 Y opposite the 2 main
`
`surface 120 X, and is mounted on the substrate 110 such that the 1 surface 120 X faces
`
`the substrate 110. The frame 120 has a through hole 121 penetrating from the 1 surface
`
`120 X to the 2 surface 120 Y. When the through hole 121 penetrates the frame 120 in
`
`the thickness direction, a 2 opening 121 a is formed in the 1 surface 120 X, and a1
`
`opening 121 b is formed in the 2 surface 120 Y. In the illustrated example, the frame 120
`
`includes 4 through holes 121, but the present invention is not limited thereto and may
`
`include one or more through holes 121. When the frame 120 is used, itis easy to maintain
`
`high arrangementof the 1 fibers 131 a. In addition, it is easy to hold a liquid medium or
`
`the like in a recess formed by the through hole 121, and is particularly suitable for use in
`
`culture.
`
`{0015}
`
`The fiber assembly 130 is interposed between the substrate 110 and the frame 120. The
`
`plurality of 7 fibers 131 a are arranged along one direction, and together with a plurality
`
`of 2 fibers 131 b intersecting with a plurality of 1 fibers, constitute a fiber aggregate 130.
`
`The fiber aggregate 130 is small.
`
`Also, a part of the 1 surface 420 X is exposed through the 1 opening 121 a formedin the
`
`first surface 121 X.
`
`In addition,
`
`in the illustrated example, the fiber assembly 130 is
`
`disposed not on the entire surface of the substrate 110 on which the frame 120 is
`
`mounted but in a range facing the one main surface (the 1 surface 120 X) of the frame
`
`420.
`
`[0016]
`
`FIG. 2 is a top view schematically showing the fiber aggregate 130 exposed from the 1
`
`opening 1217 a of one through-hole 121 of FIG. 1. In the illustrated example, a plurality of
`
`2 fibers 131 b are also arrangedin one direction (specifically, in a direction perpendicular
`
`

`

`to an arrangement direction (length direction) of the 1 fibers 131 a). The plurality of 14
`
`fibers 134 a and the plurality of 2 fibers 131 b are in a state of crossing each other ina
`
`lattice pattern.
`
`f0017]
`
`FIG. 3 is aschematic enlarged viewof the region Ill of FIG. 2;. FiG. 4 is a cross-sectional
`
`view taken along line !V-IV of FIG. 3 ;.
`
`The region of lll includes an intersection 140 of the 7 fiber 131 a and the 2 fiber 131 b
`
`and its periphery. In the intersection portion 140, the 1 fiber 131 a and the 2 fiber 131 b
`
`are integrated. By integrating the 1 fibers 131 a and the 2 fibers 131 b at the intersection
`
`portion 140, the rigidity in the direction perpendicular to the arrangement direction of the
`
`1 fibers and the thickness direction of the fiber aggregate 130 is increased, and the
`
`disturbance of the arrangement of the 1 fibers can be suppressed.
`
`[0018]
`
`A plurality of intersecting portions 140 are present in the fiber assembly 130.
`
`It
`
`is
`
`sufficient for at least a part of the intersecting portions 140 to be integrated with the 1
`
`fibers 131 a and the 1 fibers 131 b at at least a part of the intersecting portions 140, but
`
`from the viewpoint of reducing the disturbance of the arrangement of the 2 fibers 731 a.
`
`It is preferred that the 1 fibers 131 a and the 2 fibers 131 b be integrated at an intersection
`
`140 of, for example, 90% or more of the entire plurality of intersection portions 140, and
`
`more preferably that the 1 fibers 131 a and the 2 fibers 131 b be integrated at all of the
`
`intersection portions 140. For example, as shownin FIG. 2, it is preferable that the ratio
`
`of the intersection portion 140 where the 1 fibers 131 a and the 2 fibers 137 b are
`
`integrated to the entire intersection portion 140 of the region exposed from the 1 opening
`
`421 ais 90% or more, and more preferably 100%.
`
`[0019]
`
`FIG. 5 is a cross-sectional view taken along line V-V of FIG. 2 ;. As shown in FIGS. 5
`
`and 4, in the fiber assembly 130, a plurality of 2 fibers 131 b are interposed between a
`
`plurality of 1 fibers 131 a and a substrate 110. In other words, in the culture scaffold 100,
`
`the plurality of 1 fibers 134 a arranged are reinforced by the plurality of 2 fibers 131 b
`
`from the rear side.
`
`[0020]
`
`Further, when the plurality of 1 fibers 131 a arrangedis a 1 fiber layer 132 a and a plurality
`
`of 2 fibers 131 bis a 2 fiber layer 132 b, the fiber assembly 130 can be said to have a 2
`
`layer structure of a 1 fiber layer 132 a and a 2 fiber layer 132 b.
`
`[0021]
`
`in such a culture scaffoid 100, itis possible to maintain a high degree of alignmentof the
`
`

`

`1 fibers 131 a until the time of culturing, and it is possible to reduce stress applied to the
`
`biological tissues and microorganisms due to the fact that the fibers are not entangled.
`
`Thus, biological tissues and microorganisms easily grow along the arrangementdirection
`
`(length direction) of the 1 fibers 131 a.
`
`f0022]
`
`For example, the scaffold 100 for culturing holds a medium for culturing a biological
`
`tissue or a microorganism and is used as a holder for supporting biological tissues or
`
`microorganisms. Further, the scaffold 100 for culturing may be used as a potential
`
`measuring device for measuring potentials of biological tissues or microorganisms in a
`
`state in which they hold biological tissues or microorganisms. The scaffold 100 for culture
`
`may be used for each use, if necessary, in a state in which it is stored in a holder or the
`
`like.
`
`[0023]
`
`In this specification, the term "biological tissue” refers to a biological tissue or a part
`
`thereof, a biological tissue or an organ.
`
`The cells (and the organizations or organs which are cultivated from the cell, these parts,
`
`etc.) which can specialize in organism organizations, organs, etc., such as *** and the
`
`iPS cell to accomplish, and an embryonic stem cell, shall be included.
`
`{0024}
`
`(Fiber Aggregate 130).
`
`The fiber assembly 130 is an aggregate of a plurality of 7 fibers 131 a and a plurality of
`
`2 fibers 131 b arranged along one direction.
`
`The arrangementof the plurality of 1 fibers 131 a along one direction means that, in the
`
`fiber aggregate 130, the 1 fibers 131 a do not intersect each other, or an average angle
`
`(an acute angle) at which the 1 fibers 131 a intersect each other is greater than 0 ° and
`
`less than or equal to 60 °. Preferably, this average angle is greater than 0 ° and less than
`
`or equal to 30 °. In this way, whenaplurality of 1 fibers 131 a are arranged, the 1 fibers
`
`131 a easily extend along the arrangementdirection of the 1 fibers 131 a, and thus stress
`
`on biological tissues and microorganisms is reduced. Thus, biological tissues and
`
`microorganisms easily grow along the arrangementdirection of the 1 fibers 131 a.
`
`{0025}
`
`The plurality of 2 fibers 131 b may or may not be arranged along one direction. The
`
`arrangement of the plurality of 2 fibers 131 b along one direction means that in the fiber
`
`assembly 130, the 2 fibers 131 b do not cross each other or the 2 fibers 131 b intersect
`
`each other at an average angie (an acute angle) exceeding 0 ° and not more than 60 °
`
`

`

`(preferably more than 0 °}. 30.
`
`[0028]
`
`it is preferable that the average angle (acute angle) at which the 1 fiber 131 a and the 2
`
`fiber 131 b intersect is greater than 60 ° and less than or equal to 90 °. Further,
`
`it is
`
`preferable that the 1 fiber 131 a and the 2 fiber 131 b intersect each other in a lattice
`
`shape. The term “intersecting in a lattice shape" means a case in which an average angie
`
`(an angie at an acute angle) at which the 1 fiber 131 a and the 2 fiber 131 b intersectis,
`
`for example, 75° or more and 90 ° or less. In these cases, it is possible to further increase
`
`the rigidity in the direction perpendicular to the arrangement direction of the fiber
`
`assembly 130 andin the thickness direction.
`
`[0027]
`
`Here, the average angle at whichthefibers intersect can be determined from the average
`
`iength of the fibers. The average length of the fibers can be determined based on, for
`
`example, a scanning electron microscope (SEM) photograph of the fiber assembly as
`
`viewed from its normal direction.
`
`{0028}
`
`FIG. 6 is a schematic top view of a 1 or 2 fiber in a fiber assembly 130 for explaining an
`
`arrangementoffibers. In FIG. 6, in the fiber aggregate 130 of an SEM photograph taken
`
`from a normaldirection of the fiber aggregate 130, a state in which the 1 fibers 131 a (or
`
`the 2 fibers 137 b) are arranged is simulated, and the other fibers are omitted. A square
`
`region R of a predetermined size (e.g., 1 x 1) is set as seen from a normal direction of
`
`the fiber aggregate 130. At this time, the region R is determined so that 8 or more 1 fibers
`
`131 a (or 2 fibers 131 b) enter into the region R and more than 50% of the 1 fibers 131
`
`a (or 2 fibers 131 b) positioned in the region R intersect the opposing 2 sides of the region
`
`R.
`
`In this region R, a direction of a straight line (a dotted line in FiG. 6) connecting
`
`between 2 points at which a certain 1 fiber 131 a (or a 2 fiber 131 b) intersects with the
`
`2 opposing sides is an average length direction of the 7 fiber 131 a (or the 2 fiber #31 b).
`
`{0029}
`
`The average angle at which the fibers intersect with each other, for example, is arbitrarily
`
`selected in the region R. From (for example, 12) 1 fibers 131 a (or 2 fibers 131 b), further
`
`optionally, 2 1 fibers 131 a (or 2 fibers 1374 b) are selected, and an angle (e.g., 8 7 in FIG.
`
`6) where an average length direction of each 1 fiber 131 a (or 2 fibers 131 b) intersects
`
`is determined. 2 other 1 fibers 131 a (or 2 fibers 137 b) are selected and an angle {e.g.,
`
`8 2 of FIG. 6) at which the average length direction of the 1 fibers 131 a (or the 2 fibers
`
`431 b) intersect with each other is determined.
`
`

`

`it asks. Such an operation is performed on the selected remaining 1 fibers 131 a (or 2
`
`fibers 131 b) (e.g., 8}. Then, an average of the respective angles is calculated as an
`
`average angle at which thefibers intersect.
`
`fO030]
`
`Note that in the case where a part of the fibers intersect each other in an SEM photograph
`
`of the fiber assembly 130 when viewed from the normal direction,
`
`it
`
`is difficult to
`
`distinguish betweenthe 1 fiber 131 a and the 2 fiber 131 b. In this case, when the average
`
`angle (acute angle) at which the fibers intersect each other is 60 ° or less, the 1 fiber 131
`
`a may be used, and when the average angle is larger than 60 °, the 2 fiber 131 b may
`
`be used.
`
`{003 14]
`
`The ratio S 1 of the area of the 7 fibers 131 a occupying the unit area of the fiber
`
`aggregate 130 may be equal to or less than the ratio S 2 of the area of the 2 fibers 131
`
`b occupying the unit area of the fiber aggregate 130, but may be larger than S 2. in the
`
`relation of S 1> S 2, the arrangementof the 17 fibers 131 a can be sufficiently reinforced,
`
`and the high degree of alignment of the 1 fibers 131 a can be utilized for the growth of
`
`biological tissues and cells.
`
`[0032]
`
`it is preferable that the ratio S 1 of the area of the 131 fibers 1 a is, for example, 10 to
`
`50%, and is uniformly dispersed and deposited at 30 to 40%. The ratio S 2 of the area
`
`of the 131 fiber 2 b is, for example, 0.2 to 20%, preferably 0.5 to 5%, and may be 0.5 to
`
`2%.
`
`in addition, a ratio of an area of the 1 fiber 131 a (or the 2 fiber 131 b) on one principal
`
`surface (for example, an upper surface) of the fiber aggregate 130 is a predetermined
`
`area in the fiber aggregate 130. For a region of (e.g., an ellipse with a short axis of 3x a
`
`long axis of 6), an area occupied by the 1 fiber 131 a (or the 2 fiber 131 b) from an image
`
`acquired by an optical microscope or the like is calculated and converted into an area
`
`ratio (%) per unit area. When calculating an area, an image may be binarization
`
`processing if necessary.
`
`{0033]
`
`The materials of the 1 fibers 131 a and the 2 fibers 131 b are not particularly limited as
`
`long as they can be used as a scaffold for culturing biological tissues or microorganisms.
`
`in particular, each of the fibers preferably contains a rubber-containing styrene resin in
`
`view of high affinity for biological tissues and microorganisms and difficulty in giving
`
`stress to biological
`
`tissues and microorganisms during culturing. As the rubber-
`
`containing styrene resin, a block polymer containing a poly (styrene block) and a
`
`

`

`polybutadiene block (including its hydrogenated product) is preferred. Each of the fibers
`
`may contain a rubber containing styrene resin, and may contain 2 or more kinds thereof.
`
`Eachfiber may also include a rubber-containing styrene resin (1 resin) and another resin
`
`(2 resin). As the 2 resin, a styrene resin is preferable from the viewpoint of high affinity
`
`with a rubber-containing styrene resin.
`
`if desired, each fiber may contain various
`
`additives.
`
`[0034]
`
`The block polymer may be, for example, a diblock body in which a polybutadiene (PB)
`
`block and a polystyrene (PS) block are linked together, and may be a triblock group or
`
`more of a triblock copolymer having a PB block and a PS block connected alternately.
`
`From the viewpoint of ensuring affinity with a styrene resin, it is preferable that the block
`
`polymer includes at least a PS block at a terminal thereof. PB blocks enhance the
`
`flexibility and elongation of the resulting fibers.
`
`{0035}
`
`The content of PB block in the block polymeris, for example, 10 to 50% by weight,
`
`preferably 10 to 30%by weight, or 15 to 30% by weight, more preferably 20 to 30% by
`
`weight. When the content of the PB block is within such a range, affinity with a styrene
`
`resin becomes high and uniform fibers tend to be formed. Also, the resulting fibers have
`
`high flexibility and elongation. Further, when each of the fibers is produced by an
`
`electrospinning method, high spinnability is secured.
`
`[0038]
`
`When each of the fibers contains 2 or more rubber-containing styrene resins, each of the
`
`rubber-containing styrene resins is used.
`
`Examples thereof include a rubber content and / or a different block structure.
`
`[0037]
`
`As the styrene resin, a polymer different from the block polymer is used. Examples of
`
`the styrene resin include polystyrene (styrene homopolymer) and a copolymerof styrene
`
`and another copolymerizable monomer. The styrene resin may be used alone or in
`
`combination of 2 or more. The ratio of rubber-containing styrene resin to styrene resin
`
`may be adjusted depending on the rubber content, the spinning method, and / or the
`
`application of the rubber containing styrene resin.
`
`{00338}
`
`The massratio of rubber-containing styrene resin to styrene resin (= rubber-containing
`
`styrene resin : styrene resin) can be selected from, for example, 90:10-3:97. For example,
`
`when the solution spinning method or the electrospinning method is employed, the mass
`
`

`

`ratio of the rubber-containing styrene resin and the styrene resin is preferably 70:30-3:97,
`
`and may be a 50:50-3:97.
`
`In the melt spinning method,
`
`it is possible to increase the
`
`degree of freedom such as a combination of resins, a mixing ratio, and a rubber content
`
`as compared with a solution-spinning method or an electrospinning method. For example,
`
`the massratio of the rubber-containing styrene resin to the styrene resin may be 90:10-
`
`50:50 or 90:10-70:30.
`
`[0039]
`
`The 1 fiber 131 a and the 2 fiber 131 b may be made of the same material or different
`
`materials. For example, the 1 fiber 131 a may be formed of a rubber-containing styrene
`
`resin, and the 2 fiber 131 b may be formed of polystyrene. Further, the 7 fibers 131 a
`
`and the 2 fibers 131 b may be formed of rubber-containing styrene resins having different
`
`rubber contents.
`
`[0040]
`
`The average fiber diameter of each of the 1 fiber 131 a and the 2 fiber 131 b is, for
`
`example, 0.5um-20pm. it is preferable that an average fiber diameter of the 1 fiber 131
`
`a is larger than an averagefiber diameterof the 2 fiber 131 b. In this case, itis preferable
`
`that the biological tissue and the cells grow along the arrangement cirection of the 1
`
`fibers 131 a. The average fiber diameter of the 1 fibers 131 ais, forexample, 1 umto8
`
`um, preferably 1 pm to 5 um. The average fiber diameter of the 2 fibers 131 b is, for
`
`example, 0.5 p mto 7 pm, preferably 0.5 to4 um.
`
`{004 1]
`
`Note that the average fiber diameter is an average value of diameters of respectivefibers.
`
`The diameter of eachfiber is the diameter of a cross section perpendicular to the length
`
`of each fiber.
`
`lf such a cross-section is not circular, a maximum diameter may be
`
`considered as a diameter. In addition, a width in a direction perpendicular to a length
`
`direction of each fiber when viewed from a direction of a normal direction of one principal
`
`surface of the fiber aggregate 130 may be regarded as a diameter of the fiber. The
`
`average fiber diameter is, for example, an average value of diameters at arbitrary
`
`portions of arbitrary 10 of the 1 fibers 131 a (or the 2 fibers 131 b) included in thefiber
`
`aggregate 130.
`
`[0042]
`
`(Substrate 110).
`
`The substrate 110 is not particularly limited and may be appropriately selected
`
`depending on the application. Examples of the material of the substrate inciude glass,
`
`quartz, a resin, and combinations thereof. The substrate may be a plate or a film, and
`
`may be porous. Examples of the substrate include a glass plate, a quartz plate, an acrylic
`
`

`

`plate, a porous substrate (such as a nonwoven fabric), or a combination thereof.
`
`[0043]
`
`The substrate 110 may be provided with the electrode if needed. Examples of such
`
`electrodes include a plurality of electrodes (1 electrode) insulated from each other. A
`
`plurality of 1 electrodes are arranged so as not to be in contact with the fiber aggregate
`
`730. The substrate 110 may further comprise a plurality of micro-electrodes (2
`
`electrodes) electrically connected to the 1 electrode and insulated from each other. A
`
`plurality of 2 electrodes are disposed to contact at least a portion of the fiber assembly
`
`130.
`
`[0044]
`
`The type and size of the 1 electrode and the 2 electrode, the distance between adjacent
`
`electrodes, and the like may be appropriately selected depending on the application.
`
`Examples of the 1 electrode and the 2 electrode include an ITO (indium tin oxide)
`
`electrode and a platinum electrode.
`
`{0045}
`
`(Frame)
`
`The frame 120 includes a 1 surface 120 X, a 2 surface 120 Y opposite thereto, and one
`
`or more through holes 121 extending from the 1 surface 120 X to the 2 surface 120 Y.A
`
`fiber aggregate 130 is arranged on the surface of the 1 surface 120 X so as to coverat
`
`least a part of the through hole 121. In other words, the fiber aggregate 130 is exposed
`
`from the opening (the 1 opening 121 a) of the through-hole 121 on the side of the 1
`
`surface 120 X.
`
`[0046]
`
`When the frame 120 is mounted on the substrate 110, the 1 opening 121 ais closed by
`
`the substrate 710 via the fiber assembly 130, and a recess is formed on the substrate
`
`710 by the through hole 121. A culture liquid containing biological
`
`tissue or
`
`microorganisms is injected into the recess from the opening (2 opening) on the side of
`
`the 2 surface 121 Y of the through-hole 120. The injected biclogical
`
`tissue or
`
`microorganisms grow as a scaffold in the fiber assembly 130. Since the plurality of 1
`
`fibers 131 a constituting the fiber assembly 130 are arranged, it is also possible to grow
`
`the biological tissue or the microorganisms along the length of the 1 fibers 1314 a.
`
`[0047]
`
`The material of the frame 120 is not particularly limited and may be glass or resin
`
`{including elastomer). The size of the frame 120 is not particularly limited as long as the
`
`entire surface of the 1 surface 120 X can be opposed to the substrate 110. When an
`
`

`

`electrode is arranged on the substrate 110, the size of the frame 120 may be adjusted
`
`so as not to disturb the wiring of the electrode.
`
`{0048}
`
`The numberof the through holes 121 is not particularly limited, and may be appropriately
`
`set according to the size and use of the frame 120. The shape and size of the 1 opening
`
`421 a and the 2 opening 121 b are not particularly limited, and may be appropriately set
`
`depending on the application and the like. The shape and size of the 1 opening 121 a
`
`and the 2 opening 127 b may be the sameor different. There is no particular limitation
`
`on the shape of the recess formed by the through hole 121. For example, if both the 1
`
`opening 121 a and the 2 opening 121 b are circular, the shape of the recess may be
`
`cylindrical or conical. From the viewpoint of easy injection of the culture liquid, as shown
`
`in the drawing, it is preferable that the 2 opening 121 b of the recess has a larger mortar
`
`shape than the 1 opening 121 a.
`
`{0049}
`
`(in addition to this)
`
`The substrate 110, the frame 120, and the fiber assembly 130 may be bonded to each
`
`other by an adhesive. The adhesive portion is formed of an adhesive (including a
`
`pressure-sensitive adhesive). Adhesives include pressure sensitive adhesives, hot melt
`
`adhesives, or curable adhesives.
`
`fOO50]
`
`[Method for Producing Scaffold for Culture]
`
`The culture scaffold 100 according to the present embodiment can be manufactured by
`
`a manufacturing method including a step (integration step) of integrating the 2 fibers 131
`
`a and the 1 fibers 131 b at at least a part of intersections of the intersecting portions of
`
`the plurality of 2 fibers 131 a and the plurality of 1 fibers 131 b arranged along one
`
`direction.
`
`In the scaffold 400 for culture obtained by such a manufacturing method,
`
`di