System for forming a reinforcing layer on a sheet-shaped cell culture, method for forming a reinforcing layer on a sheet-shaped cell culture, and program

Abstract

Provided are a system for forming a reinforcing layer on a sheet-shaped cell culture, a method for forming a reinforcing layer on a sheet-shaped cell culture, and a program for forming a reinforcing layer made of fibrin gel at predetermined positions including the peripheral portion of the sheet-shaped cell culture, in an appropriate and easy manner. [Solution] The formation system 100 has an imaging unit 110 that photographs the sheet-shaped cell culture 10, a processing unit 120 that performs processing to form a reinforcing layer 30 made of fibrin gel on the sheet-shaped cell culture, a detection unit 131 that detects the peripheral portion 13 of the sheet-shaped cell culture based on image information acquired by the imaging unit, and a control unit 130 that controls the operation of the processing unit so as to form a reinforcing layer on the peripheral portion of the sheet-shaped cell culture.

Description

[Technical Field]

[0001] The present invention relates to a system for forming a reinforcing layer on a sheet-shaped cell culture, a method for forming a reinforcing layer on a sheet-shaped cell culture, and a program. [Background technology]

[0002] Sheet-shaped cell cultures (cell sheets) are widely known for use in fields such as regenerative medicine. Sheet-shaped cell cultures are produced by storing and culturing cells collected from humans or non-human animals in a culture substrate (culture vessel) containing a culture medium, and then allowing them to adhere and aggregate into a sheet.

[0003] Because the sheet-shaped cell culture is constructed in the form of a thin film sheet, it is physically fragile and therefore requires careful handling, as it is prone to wrinkling and tearing during isolation from the culture substrate, transportation and storage of the sheet-shaped cell culture, and transplantation into a patient's body.

[0004] To solve the above problems, a method has been proposed in which a fibrinogen solution and a thrombin solution are applied to a sheet-shaped cell culture, a reinforcing layer made of fibrin gel is formed on the sheet-shaped cell culture, and a laminate consisting of the sheet-shaped cell culture and the reinforcing layer is produced (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication No. 2016-52272 Summary of the Invention [Problem to be solved by the invention]

[0006] The laminate produced by the method of Patent Document 1 has the physical strength of part or all of the sheet-shaped cell culture reinforced by the reinforcing layer, which effectively prevents wrinkling and tearing when handled by workers.

[0007] However, in the method of Patent Document 1, the fibrin treatment (application of fibrinogen solution and application of thrombin solution) to form the reinforcing layer is performed manually. Therefore, when the method of Patent Document 1 is adopted, the position of the reinforcing layer formed on the sheet-shaped cell culture depends on the intuition, skill, experience, etc. of the worker performing the fibrin treatment. Therefore, it is not easy to form the reinforcing layer appropriately and simply.

[0008] In particular, it is desirable that the reinforcing layer formed on the sheet-shaped cell culture be formed in a portion including the peripheral edge of the sheet-shaped cell culture in order to more effectively improve the handling properties when handling the sheet-shaped cell culture, but it is even more difficult for an operator to manually form the reinforcing layer appropriately in such a position.

[0009] The present invention aims to provide a system for forming a reinforcing layer on a sheet-shaped cell culture, a method for forming a reinforcing layer on a sheet-shaped cell culture, and a program that enable the appropriate and easy formation of a reinforcing layer made of fibrin gel at a predetermined position, including the peripheral portion of the sheet-shaped cell culture. [Means for solving the problem]

[0010] The present invention is achieved by any one of the following means (1) to (7).

[0011] (1) an imaging unit that captures an image of the sheet-shaped cell culture; a processing unit that performs a process to form a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a detection unit that detects the peripheral edge of the sheet-shaped cell culture based on the image information acquired by the imaging unit; A system for forming a reinforcing layer on a sheet-shaped cell culture, comprising: a control unit that controls the operation of the processing unit so as to form the reinforcing layer on the peripheral portion of the sheet-shaped cell culture.

[0012] (2) A system for forming a reinforcing layer on a sheet-shaped cell culture described in (1), wherein the control unit controls the operation of the processing unit so that the reinforcing layer is formed extending outside the peripheral edge of the sheet-shaped cell culture.

[0013] (3) the detection unit detects a peripheral edge of the reinforcing layer, The control unit controls the operation of the processing unit so that a reinforcing portion made of fibrin gel is formed on the peripheral portion of the reinforcing layer or in a portion extending outward from the peripheral portion of the reinforcing layer. (2) A system for forming a reinforcing layer on a sheet-shaped cell culture.

[0014] (4) the sheet-shaped cell culture has a substantially circular planar shape, The system for forming a reinforcing layer on a sheet-shaped cell culture described in any one of (1) to (3), wherein the control unit controls the operation of the processing unit so that the reinforcing layer is formed along the arc of the peripheral edge of the sheet-shaped cell culture.

[0015] (5) The control unit controls the operation of the processing unit so that the reinforcing layer is not formed at the center of the sheet-shaped cell culture in a planar view, or so that the reinforcing layer formed at the center is thinner than the reinforcing layer formed at the peripheral portion.

[0016] (6) an imaging unit capturing an image of the sheet-shaped cell culture; a step in which a detection unit detects the peripheral portion of the sheet-shaped cell culture based on image information of the sheet-shaped cell culture acquired by the imaging unit; A method for forming a reinforcing layer on a sheet-shaped cell culture, comprising: a processing unit forming a reinforcing layer made of fibrin gel along the peripheral edge of the sheet-shaped cell culture.

[0017] (7) A system having a processing unit for performing a process to form a reinforcing layer made of fibrin gel on a sheet-shaped cell culture, detecting a peripheral portion of the sheet-shaped cell culture based on image information of the sheet-shaped cell culture; and controlling the operation of the processing unit so as to form the reinforcing layer on the peripheral portion of the sheet-shaped cell culture. [Effects of the Invention]

[0018] According to the system, method, and program for forming a reinforcing layer on a sheet-shaped cell culture of the present invention, the detection unit detects the peripheral portion of the sheet-shaped cell culture based on image information of the sheet-shaped cell culture acquired by the imaging unit, and the processing unit performs fibrin treatment (application of fibrinogen solution and application of thrombin solution) to form a reinforcing layer on the peripheral portion of the sheet-shaped cell culture based on the results of detection by the detection unit. Therefore, according to the present invention, a reinforcing layer made of fibrin gel can be appropriately and simply formed at a predetermined position, including the peripheral portion of the sheet-shaped cell culture. [Brief explanation of the drawings]

[0019] [Figure 1] FIG. 1 is a block diagram showing a system for forming a reinforcing layer on a sheet-shaped cell culture according to an embodiment. [Figure 2] 1 is a flowchart showing the steps of a method for forming a reinforcing layer on a sheet-shaped cell culture according to an embodiment. [Figure 3]FIG. 10 is a plan view illustrating a method for forming a reinforcing layer on a sheet-shaped cell culture according to an embodiment. [Figure 4] 10A and 10B are cross-sectional views illustrating a method for forming a reinforcing layer on a sheet-shaped cell culture according to an embodiment. [Figure 5] FIG. 10 is a plan view illustrating a method for forming a reinforcing layer on a sheet-shaped cell culture according to an embodiment. [Figure 6] FIG. 10 is a plan view illustrating a method for forming a reinforcing layer on a sheet-shaped cell culture according to an embodiment. [Figure 7] 10A and 10B are cross-sectional views illustrating a method for forming a reinforcing layer on a sheet-shaped cell culture according to an embodiment. [Figure 8] FIG. 10 is a plan view illustrating a method for forming a reinforcing layer on a sheet-shaped cell culture according to an embodiment. [Figure 9] 10A and 10B are cross-sectional views illustrating a method for forming a reinforcing layer on a sheet-shaped cell culture according to an embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0020] Hereinafter, embodiments of the present invention will be described with reference to the drawings. Note that the dimensional proportions in the drawings are exaggerated for the sake of explanation and may differ from the actual proportions.

[0021] Fig. 1 is a simplified block diagram showing the overall configuration of a system 100 (hereinafter also referred to as "forming system 100") for forming a reinforcing layer 30 on a sheet-shaped cell culture 10 according to this embodiment. Fig. 2 is a flowchart showing each step of a method (hereinafter also referred to as "forming method") for forming a reinforcing layer 30 on a sheet-shaped cell culture 10 according to this embodiment.

[0022] Figures 3 to 9 are diagrams for explaining the formation method. Figures 3, 5, 6, and 8 are plan views of the sheet-shaped cell culture 10 (laminate 20) and the container 220 as viewed from the direction of arrow III shown in Figure 1. Figure 4 is a cross-sectional view taken along arrow IV-IV shown in Figure 3, Figure 7 is a cross-sectional view taken along arrow VII-VII shown in Figure 6, and Figure 9 is a cross-sectional view taken along arrow IX-IX shown in Figure 8.

[0023] The arrows X1, X2, Y1, and Y2 in each figure indicate directions parallel to the surface direction of the sheet-shaped cell culture 10, and the arrows Z1 and Z2 indicate the thickness direction perpendicular to the surface direction of the sheet-shaped cell culture 10 (laminated body 20).

[0024] <Sheet-shaped cell culture 10> The sheet-shaped cell culture 10 used in this embodiment can contain any cells capable of constituting the sheet-shaped cell culture 10. Cells constituting the sheet-shaped cell culture 10 include, for example, somatic stem cells (adult stem cells), mesenchymal stem cells, or cardiomyocytes derived from iPS cells (induced pluripotent stem cells). Somatic stem cells preferably include skeletal myoblasts (myoblast cells), fibroblasts, synovial cells, epithelial cells, and endothelial cells. Furthermore, the term "sheet-shaped cell culture" as used herein refers to a sheet-like (thin film-like) structure in which cells are interconnected.

[0025] As shown in Figure 3, the sheet-shaped cell culture 10 can be configured to have, for example, a substantially circular planar shape in its natural state without the application of external force. The planar shape of the sheet-shaped cell culture 10 is not limited to a circle, and may be, for example, a rectangle, a triangle, an oval, or any other geometric shape. There are also no particular limitations on the specific size or thickness of the sheet-shaped cell culture 10.

[0026] The sheet-shaped cell culture 10 has a surface 10a, a back surface 10b located opposite the surface 10a and arranged to face the bottom 223 of the container 220, and a peripheral edge 13 having a circular outer shape.

[0027] In this embodiment, a certain range including the central position o1 of the sheet-shaped cell culture 10 in the plan view shown in Fig. 4 is defined as the central region 11. The peripheral edge portion 13 is located in a range spaced further outward (radially outward) from the central position o1 than the central region 11, and is a predetermined range (region) extending from the outer peripheral surface (side surface) of the sheet-shaped cell culture 10 toward the central position o1.

[0028] When the sheet-shaped cell culture 10 has a rotationally symmetric shape such as a circle, square, or equilateral triangle, the center position o1, which serves as the reference for defining the central region 11, can be the center of symmetry. When the sheet-shaped cell culture 10 has a shape other than a rotationally symmetric shape, the position of the center position o1 can be set to any position near the center according to the planar shape of the sheet-shaped cell culture 10.

[0029] In this embodiment, the laminate in which the reinforcing layer 30 is formed in a position overlapping at least a portion of the sheet-shaped cell culture 10 is defined as a laminate 20 (see FIGS. 6 and 7).

[0030] The formation method described below can be carried out in a state where the sheet-shaped cell culture 10 is housed in a predetermined container 220 (see FIGS. 5 to 9).

[0031] The container 220 is, for example, a culture substrate used for culturing the sheet-shaped cell culture 10. When the container 220 is a culture substrate, the container 220 can be made of a material that is impermeable to liquids such as liquid culture media. When the container 220 is a culture substrate, before starting the formation method, an operation of discharging the solution (liquid culture media, etc.) used for the culture from the container 220 is appropriately performed.

[0032] As shown in FIG. 4, the container 220 has an opening 221 that opens upward, a bottom 223 on which the back surface 10b of the sheet-shaped cell culture 10 is placed, and a sidewall 225 that surrounds the periphery of the bottom 223.

[0033] The container 220 has a substantially circular shape in the plan view shown in Fig. 3. The bottom 223 of the container 220 has a size (inner diameter) larger than the outer shape of the sheet-shaped cell culture 10 before the reinforcing layer 30 is formed.

[0034] There are no particular restrictions on the specific form of the sheet-shaped cell culture 10 (e.g., manufacturing method, physical properties, function, etc.) and the specific form of the culture substrate (e.g., material, function, structure and shape, type of liquid medium used, etc.), and publicly known content (e.g., Patent Publication No. 2011-155869, Patent Publication No. 2022-106986, Patent Publication No. 2021-106609, etc.) can be taken into consideration as appropriate.

[0035] <Forming system 100> 1, 3, 6, and 7, the formation system 100 comprises an imaging unit 110 that photographs the sheet-shaped cell culture 10, a processing unit 120 that performs processing to form a reinforcing layer 30 made of fibrin gel on the sheet-shaped cell culture 10, a detection unit 131 that detects the peripheral portion 13 of the sheet-shaped cell culture 10 based on image information acquired by the imaging unit 110, and a control unit 130 that controls the operation of the processing unit 120 so as to form the reinforcing layer 30 on the peripheral portion 13 of the sheet-shaped cell culture 10.

[0036] The image capturing unit 110 can be configured, for example, by a known camera device capable of acquiring still image data and / or video data.

[0037] 1, the imaging unit 110 can be laid out above the stage 210 on which the container 220 containing the sheet-shaped cell culture 10 is placed. By laying out the imaging unit 110 in this manner, it becomes possible to capture the entire sheet-shaped cell culture 10 within the imaging field of view from above the stage 210. The placement of the imaging unit 110 is not particularly limited as long as it is possible to photograph the sheet-shaped cell culture 10, and it can also be laid out below the container 220, for example.

[0038] As shown in Figures 1 and 5, the processing unit 120 can be configured to have a first application unit 121 that applies fibrinogen liquid (liquid containing fibrinogen) L1 to the sheet-shaped cell culture 10, and a second application unit 122 that applies thrombin liquid (liquid containing thrombin) L2 to the sheet-shaped cell culture 10.

[0039] The first applicator 121 can be configured to include, for example, a mechanism for dripping the fibrinogen liquid L1 onto the sheet-shaped cell culture 10. Examples of the mechanism for dripping the fibrinogen liquid L1 include a known syringe or pipette.

[0040] The second applicator 122 can be configured to include, for example, a mechanism for spraying the thrombin solution L2 onto the sheet-shaped cell culture 10. The mechanism for spraying the thrombin solution L2 can be, for example, a known spray.

[0041] The fibrinogen solution L1 and the thrombin solution L2 are not particularly limited as long as they react with each other and solidify to form a fibrin gel. There are also no particular limitations on the concentrations of the solutions L1 and L2, the amounts applied per unit time, the volume ratio of the solutions L1 and L2, the application pressure, etc. The specific forms of the solutions L1 and L2 used in this embodiment can be determined by referring to known information (e.g., JP 2016-52272 A, etc.).

[0042] The control unit 130 is configured to comprehensively control each part of the forming system 100. The control unit 130 is configured with a CPU (Central Processing Unit), memories such as RAM (Random Access Memory) and ROM (Read Only Memory), and a storage unit, and controls each of the above parts and performs various arithmetic processing according to a program.

[0043] The storage unit is configured with an HDD (Hard Disk Drive) or an SSD (Solid State Drive) and stores various programs and data. The storage unit can store a series of programs necessary for controlling the operation of the forming system 100. The above programs can incorporate algorithms for causing the control unit 130 to function as the detection unit 131 and the determination unit 132.

[0044] The operational control executed by the control unit 130 includes the operation of forming the reinforcing layer 30 by the formation system 100. In carrying out the above operation, the control unit 130 controls the operation of the formation system 100 to execute the following steps: the imaging unit 110 photographs the sheet-shaped cell culture 10; the detection unit 131 detects the peripheral edge 13 of the sheet-shaped cell culture 10 based on the image information acquired by the imaging unit 110 (detects the boundary between the outer edge (arc) of the sheet-shaped cell culture 10 and the container 220 (culture substrate)); and the processing unit 120 forms the reinforcing layer 30 made of fibrin gel along the peripheral edge 13 of the sheet-shaped cell culture 10. Specific steps of the formation method will be described later.

[0045] As shown in FIG. 1, the formation system 100 may further include an image display unit 140 capable of displaying an image generated from image information (image data) acquired by the imaging unit 110, and a stage 210 capable of placing a container 220 containing a sheet-shaped cell culture 10.

[0046] The image display unit 140 can be configured, for example, by a known liquid crystal display or the like.

[0047] The forming system 100 can also be configured as a portable or non-portable information terminal device in which the imaging unit 110, the control unit 130, and the image display unit 140 are integrally incorporated.

[0048] <Formation method> Next, a forming method according to this embodiment will be described.

[0049] The specific work content of each step will be described below with reference to the flowchart shown in Fig. 2 and Fig. 3 to Fig. 9. The following description also describes an example in which the forming system 100 shown in Fig. 1 automatically performs steps S11 to S18 of the forming method.

[0050] To start the formation method, a container 220 is prepared, which contains the sheet-shaped cell culture 10 before the formation of the reinforcing layer 30, as shown in Figures 3 and 4. The container 220 is placed on a stage 210 (see Figure 1).

[0051] Next, the imaging unit 110 starts to capture an image of the sheet-shaped cell culture 10 (step S10). At this time, it is preferable that the sheet-shaped cell culture 10 has been detached from the container 220 (culture substrate) and is not adhered to the container 220.

[0052] Next, the detection unit 131 detects the peripheral portion 13 of the sheet-shaped cell culture 10 (step S11). The detection unit 131 detects the peripheral portion 13 of the sheet-shaped cell culture 10 based on the image information acquired by the imaging unit 110.

[0053] Next, as shown in Fig. 5, fibrin treatment is performed by the processing unit 120 (step S12). The control unit 130 controls the operation of each of the application units 121, 122 of the processing unit 120 to apply fibrinogen solution L1 and thrombin solution L2 along the peripheral edge 13 of the sheet-shaped cell culture 10 detected by the detection unit 131. The fibrinogen solution L1 may be applied in a circular shape along the peripheral edge 13 of the sheet-shaped cell culture 10. The fibrinogen solution L1 may also be applied in a spiral shape radially inward along the peripheral edge 13 of the sheet-shaped cell culture 10.

[0054] While Figure 5 shows an example in which the fibrinogen solution L1 and the thrombin solution L2 are simultaneously applied to the peripheral edge 13 of the sheet-shaped cell culture 10, the order of application may be controlled, for example, by applying the fibrinogen solution L1 first and then applying the thrombin solution L2 to the area where the fibrinogen solution L1 was applied. Alternatively, the fibrinogen solution L1 may be applied along the peripheral edge 13 of the sheet-shaped cell culture 10, and then the thrombin solution L2 may be applied from the top surface of the ring formed by the fibrinogen solution L1 or to the inner circumference of the ring. This more reliably forms the reinforcing layer 30 made of fibrin gel on the peripheral edge 13 of the sheet-shaped cell culture 10. Furthermore, the strength of the reinforcing layer 30 is greatest at the peripheral edge 13 of the sheet-shaped cell culture 10.

[0055] After causing the processing unit 120 to execute step S12, the control unit 130 waits for a predetermined time until the reaction (solidification) between the fibrinogen solution L1 and the thrombin solution L2 has progressed sufficiently and a fibrin gel is formed (step S13). When the reaction between the fibrinogen solution L1 and the thrombin solution L2 has progressed sufficiently to form a fibrin gel, a reinforcing layer 30 made of fibrin gel is formed along the peripheral edge 13 of the sheet-shaped cell culture 10, as shown in Fig. 6. This makes it possible to obtain a laminate 20 in which the sheet-shaped cell culture 10 is reinforced by the reinforcing layer 30.

[0056] In step S12, the control unit 130 controls the operation of the processing unit 120 (first applicator 121 and second applicator 122) so that the reinforcing layer 30 is formed so as to extend outward (radially outward) beyond the peripheral edge 13 of the sheet-shaped cell culture 10. By forming the reinforcing layer 30 at the peripheral edge 13 and at a position extending outward beyond the peripheral edge 13, an operator can grasp the portion of the reinforcing layer 30 extending outward beyond the peripheral edge 13 of the sheet-shaped cell culture 10 with a predetermined tool or the like when lifting and moving the sheet-shaped cell culture 10 or transplanting it into a patient's body. This makes it possible to suitably prevent the sheet-shaped cell culture 10 from wrinkling or tearing when the operator handles the sheet-shaped cell culture 10.

[0057] In the following description, the portion of the reinforcing layer 30 formed at a position overlapping the sheet-shaped cell culture 10 will be referred to as the "first region 31." Additionally, the portion of the reinforcing layer 30 extending beyond the peripheral edge 13 of the sheet-shaped cell culture 10 will be referred to as the "second region 32."

[0058] The control unit 130 causes the processing unit 120 to execute step S12, thereby forming a reinforcing layer 30 made of fibrin gel along the peripheral edge 13 of the sheet-shaped cell culture 10, as shown in Figures 6 and 7. This makes it possible to obtain a laminate 20 in which the sheet-shaped cell culture 10 is reinforced by the reinforcing layer 30.

[0059] As described above, the sheet-shaped cell culture 10 according to this embodiment has a substantially circular planar shape. Therefore, in step S12, the control unit 130 can control the operation of the processing unit 120 (first coating unit 121 and second coating unit 122) so that the reinforcing layer 30 is formed along the arc of the peripheral edge 13 of the sheet-shaped cell culture 10 (see FIG. 5). By controlling the operation of the processing unit 120 as described above, the control unit 130 can form the reinforcing layer 30 at an appropriate position along the peripheral edge 13 of the sheet-shaped cell culture 10 having a substantially circular planar shape (see FIG. 6).

[0060] The control unit 130 can control the operation of the processing unit 120 so that a reinforcing layer 30 is not formed at the central position o1 in a planar view of the sheet-shaped cell culture 10, or so that the reinforcing layer 30 formed at the central position o1 is formed thinner than the reinforcing layer 30 formed in the peripheral portion 13.

[0061] In this embodiment, as shown in FIGS. 6 and 7 , the operation of the processing unit 120 is controlled to provide a non-reinforced region 15, where the reinforcing layer 30 is not formed, in a portion of the central region 11 where the central position o1 is located. As a result, the reinforcing layer 30 is formed in a circular ring shape surrounding the central position o1 in the plan view shown in FIG. 6 . By providing the sheet-shaped cell culture 10 with the non-reinforced region 15 where the reinforcing layer 30 is not formed as described above, the flexibility of the sheet-shaped cell culture 10 can be ensured compared to when the reinforcing layer 30 is formed over the entire surface 10a of the sheet-shaped cell culture 10. This further improves the handleability of the sheet-shaped cell culture 10 when transporting or storing it, or when transplanting it into a patient's body.

[0062] Note that even when the reinforcing layer 30 formed at the central position o1 is formed thinner than the reinforcing layer 30 formed in the peripheral edge portion 13 (when the reinforcing layer 30 is formed so as to form a recess near the central position o1 in the cross-sectional view shown in Fig. 7), the effect of ensuring flexibility as described above can be achieved. Therefore, the reinforcing layer 30 may be formed so as to form a recess as described above.

[0063] After confirming the formation of the reinforcing layer 30, the control unit 130 can additionally perform the work of forming the reinforcing portion 40 (steps S15 to S18).

[0064] When an operator or the like operating the forming system 100 desires to form the reinforcing portion 40, the operator or the like can input a command to execute the above work in advance to the control unit 130. Note that when the control unit 130 (determination unit 132) does not receive a command to form the reinforcing portion 40 (step S14: NO), it ends the forming method of this embodiment.

[0065] When the control unit 130 (determining unit 132) receives a command to form the reinforcing portion 40 (step S14: YES), the control unit 130 starts capturing an image of the laminate 20 (step S15).

[0066] Next, the control unit 130 causes the detection unit 131 to detect the peripheral edge 32a of the reinforcing layer 30 (step S16). As shown in Figures 6 and 7, the peripheral edge 32a of the reinforcing layer 30 is located in a second region 32 that extends outward from the peripheral edge 13 of the sheet-shaped cell culture 10 in the reinforcing layer 30. The peripheral edge 32a of the reinforcing layer 30 is the region from the outer edge (end) of the sheet-shaped cell culture 10 to the outer edge (end) of the reinforcing layer 30 on the radially outer side.

[0067] Next, the control unit 130 performs fibrin treatment at a predetermined position on the peripheral edge 32a of the reinforcing layer 30 to form a reinforcing portion 40 (step S17). Specifically, in step S17, the control unit 130 operates the processing unit 120 (first applicator 121 and second applicator 122) so that a reinforcing portion 40 made of fibrin gel is formed on the peripheral edge 32a of the reinforcing layer 30 or in a portion of the reinforcing layer 30 extending outward from the peripheral edge 32a. In this step, at least one reinforcing portion 40 can be formed on the peripheral edge 32a of the reinforcing layer 30.

[0068] When forming the reinforcing portion 40, as in the case of forming the reinforcing layer 30, the fibrinogen liquid L1 and the thrombin liquid L2 may be applied simultaneously to the peripheral portion 13 of the sheet-shaped cell culture 10 and its surrounding area, or the order of application may be controlled so that after the fibrinogen liquid L1 is applied, the thrombin liquid L2 is applied to the area where the fibrinogen liquid L1 has been applied.

[0069] By operating the processing unit 120 as described above, the control unit 130 can form the reinforcing section 40 at a position that does not overlap with the sheet-shaped cell culture 10, as shown in FIGS. 8 and 9. By forming the reinforcing section 40 in the laminate 20, it becomes possible to connect various medical devices (e.g., sutures, etc.) to the reinforcing section 40 when transplanting the sheet-shaped cell culture 10 into a patient's body. This further improves the handleability of the sheet-shaped cell culture 10. Furthermore, by forming the reinforcing section 40 at a position that does not overlap with the sheet-shaped cell culture 10, it is possible to prevent the thickness of the sheet-shaped cell culture 10 from becoming excessively large. This ensures the flexibility of the sheet-shaped cell culture 10.

[0070] 8 and 9 show an example in which one reinforcing part 40 is provided in the laminate 20, but there is no particular limit to the number of reinforcing parts 40. There is also no particular limit to the shape, thickness, etc. of the reinforcing part 40, and they can be changed as desired.

[0071] The control unit 130 confirms that the reinforcing portion 40 has been formed in the laminate 20 (step S18). After confirming that the reinforcing portion 40 has been formed, the control unit 130 ends the forming method of this embodiment.

[0072] As described above, the formation system 100 of this embodiment includes an imaging unit 110 that photographs the sheet-shaped cell culture 10, a processing unit 120 that performs processing to form a reinforcing layer 30 made of fibrin gel on the sheet-shaped cell culture 10, a detection unit 131 that detects the peripheral portion 13 of the sheet-shaped cell culture 10 based on image information acquired by the imaging unit 110, and a control unit 130 that controls the operation of the processing unit 120 so as to form the reinforcing layer 30 on the peripheral portion 13 of the sheet-shaped cell culture 10.

[0073] In addition, the forming method according to this embodiment includes the steps of: an imaging unit 110 photographing the sheet-shaped cell culture 10; a detection unit 131 detecting the peripheral edge 13 of the sheet-shaped cell culture 10 based on image information of the photographed sheet-shaped cell culture 10; and a processing unit 120 forming a reinforcing layer 30 made of fibrin gel along the peripheral edge 13 of the sheet-shaped cell culture 10.

[0074] Furthermore, the program for executing the formation method according to this embodiment is a program for causing a formation system 100 having a processing unit 120 that performs processing to form a reinforcing layer 30 made of fibrin gel on the sheet-shaped cell culture 10 to execute the following steps: detecting the peripheral portion 13 of the sheet-shaped cell culture 10 based on image information of the sheet-shaped cell culture 10; and controlling the operation of the processing unit 120 so as to form the reinforcing layer 30 on the peripheral portion 13 of the sheet-shaped cell culture 10.

[0075] According to this embodiment, the detection unit 131 detects the peripheral edge 13 of the sheet-shaped cell culture 10 based on image information of the sheet-shaped cell culture 10 acquired by the imaging unit 110, and based on the results of detection by the detection unit 131, the processing unit 120 performs fibrin treatment (application of fibrinogen solution L1 and application of thrombin solution L2) to form a reinforcing layer 30 on the peripheral edge 13 of the sheet-shaped cell culture 10. Therefore, according to this embodiment, the reinforcing layer 30 made of fibrin gel can be appropriately and simply formed at a predetermined position including the peripheral edge 13 of the sheet-shaped cell culture 10.

[0076] Although the system for forming a reinforcing layer on a sheet-shaped cell culture, the method for forming a reinforcing layer on a sheet-shaped cell culture, and the program according to the present invention have been described through the embodiments, the present invention is not limited to the configurations described in the embodiments, and can be modified as appropriate based on the claims.

[0077] For example, the steps of forming the reinforcing portion 40 in the laminate 20 (steps S15 to S18 in FIG. 2) can be omitted as appropriate. [Explanation of symbols]

[0078] 10. Sheet-shaped cell culture 10a Surface of sheet-shaped cell culture 10b Backside of sheet-shaped cell culture 11 Central area 13 Periphery of sheet-shaped cell culture 15 Unreinforced area 20 laminate 30 Reinforcement layer 31 First area 32 Second area 32a Peripheral edge of reinforcing layer 40 Reinforcement 100 Formation System 110 Imaging unit 120 Processing section 121 First application section 122 Second application section 130 Control Unit 131 Detection unit 132 Judgment section 140 Image display unit L1 fibrinogen liquid L2 thrombin solution o1 Center position of sheet-shaped cell culture

Claims

1. an imaging unit that captures an image of the sheet-shaped cell culture; a processing unit that performs a process to form a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a detection unit that detects the peripheral edge of the sheet-shaped cell culture based on the image information acquired by the imaging unit; A system for forming a reinforcing layer on a sheet-shaped cell culture, comprising: a control unit that controls the operation of the processing unit so as to form the reinforcing layer on the peripheral portion of the sheet-shaped cell culture.

2. The system for forming a reinforcing layer on a sheet-shaped cell culture described in claim 1, wherein the control unit controls the operation of the processing unit so that the reinforcing layer is formed extending outside the peripheral edge of the sheet-shaped cell culture.

3. the detection unit detects a peripheral edge of the reinforcing layer, The system for forming a reinforcing layer on a sheet-shaped cell culture described in claim 2, wherein the control unit controls the operation of the processing unit so that a reinforcing portion made of fibrin gel is formed on the peripheral portion of the reinforcing layer or in a portion extending outside the peripheral portion of the reinforcing layer.

4. the sheet-shaped cell culture has a substantially circular planar shape, The system for forming a reinforcing layer on a sheet-shaped cell culture described in any one of claims 1 to 3, wherein the control unit controls the operation of the processing unit so that the reinforcing layer is formed along an arc of the peripheral edge of the sheet-shaped cell culture.

5. 2. The system for forming a reinforcing layer on a sheet-shaped cell culture described in claim 1, wherein the control unit controls the operation of the processing unit so that the reinforcing layer is not formed at a central position in a planar view of the sheet-shaped cell culture, or so that the reinforcing layer formed at the central position is formed thinner than the reinforcing layer formed at the peripheral portion.

6. an imaging unit capturing an image of the sheet-shaped cell culture; a step in which a detection unit detects the peripheral portion of the sheet-shaped cell culture based on image information of the sheet-shaped cell culture acquired by the imaging unit; A method for forming a reinforcing layer on a sheet-shaped cell culture, comprising: a processing unit forming a reinforcing layer made of fibrin gel along the peripheral edge of the sheet-shaped cell culture.

7. A system having a processing unit for performing a process to form a reinforcing layer made of fibrin gel on a sheet-shaped cell culture, detecting a peripheral portion of the sheet-shaped cell culture based on image information of the sheet-shaped cell culture; and controlling the operation of the processing unit so as to form the reinforcing layer on the peripheral portion of the sheet-shaped cell culture.

Images