Apparatus for freezing and transferring a graft and method for freezing and transferring a graft

Abstract

The present invention addresses the problem of providing a means with which it is possible to efficiently and promptly detach a transplant from a device without causing any damage or creasing to the transplant. This medical device for transferring a transplant to a target region includes a transplant and a support which has the transplant placed on one surface thereof. The transplant and the support having the transplant placed thereon are in a frozen state, and by defrosting the frozen transplant placed on the support, the transplant can be detached from the support and transferred to a target region.

Description

[Technical field]

[0001] The present invention relates to a medical device for cryotransporting a graft to a target site and a method for cryotransporting a graft using said medical device. [Background technology]

[0002] In recent years, attempts have been made to transplant various cells to repair damaged tissues, etc. For example, attempts have been made to use fetal cardiomyocytes, skeletal myoblasts, mesenchymal stem cells, cardiac stem cells, ES cells, iPS cells, etc. to repair myocardial tissue damaged by ischemic heart disease such as angina pectoris and myocardial infarction (Non-Patent Document 1).

[0003] As part of such efforts, cell structures formed using scaffolds and sheet-like cell cultures in which cells are formed into a sheet have been developed (Non-Patent Document 2). Regarding the applications of sheet-type cell cultures in treatment, research is underway on the use of cultured epidermal sheets to treat skin injuries caused by burns etc., the use of corneal epithelial sheet-type cell cultures to treat corneal injuries, and the use of oral mucosa sheet-type cell cultures for endoscopic resection of esophageal cancer, and some of these have already reached the stage of clinical application. Non-Patent Document 3 describes that skeletal myoblast cell sheets can be used to heal pancreatic fistula and gastric perforation in animal models. In recent years, endoscopic submucosal dissection (ESD) has attracted attention as a minimally invasive method for removing early-stage tumors. This involves injecting a localized solution into the submucosal layer of the lesion, artificially inducing edema, and then resecting the elevated mucosal lesion together with the submucosal layer. However, it has been reported that ESD, particularly of the duodenum, can cause complications such as perforation with a probability of about 30% due to the operability of the endoscope and the thinness of the intestinal wall.

[0004] Regarding surgical methods for administering sheet-shaped cell cultures to target sites, endoscopic surgery is widely used as a minimally invasive surgical method for the human body, and various instruments have been proposed for delivering and administering sheet-shaped cell cultures to target sites. For example, the delivery and administration device described in Patent Document 1 has a sheet support member that is tubular and stored inside an outer cylinder, thereby reducing the degree of invasiveness to the human body and enabling the delivery of a sheet-like therapeutic substance to the transplantation site.

[0005] The sheet application device described in Patent Document 2 can peel off a rod-shaped member arranged along the surface of a sheet support part by moving it along the surface of the sheet support part, thereby allowing a sheet-like substance to be applied to a target area. The transport and administration device described in Patent Document 3 can administer a sheet using a sheet detachment means that can apply negative pressure to the sheet support section to adsorb and retain the sheet-form therapeutic substance, and positive pressure to detach the sheet-form therapeutic substance from the sheet support section. The delivery device described in Patent Document 4 is capable of applying a sheet-type therapeutic substance by ejecting fluid from a plurality of air holes provided on the surface of a head holding the sheet-type therapeutic substance. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2009-511 A [Patent Document 2] JP 2016-187601 A [Patent Document 3] JP 2008-173333 A [Patent Document 4] International Publication No. 2014 / 069292 [Non-patent literature]

[0007] [Non-Patent Document 1] Haraguchi et al., Stem Cells Transl Med. 2012 Feb;1(2):136-41 [Non-Patent Document 2] Sawa et al., Surg Today. 2012 Jan;42(2):181-4 [Non-Patent Document 3] Tanaka et al., Surg Today. 2017 Jan;47(1):114-121 Summary of the Invention [Problem to be solved by the invention]

[0008] In the course of developing a means for efficiently transferring a graft to a target site, the inventors of the present invention faced problems such as the difficulty of detaching the graft from the device without causing damage or wrinkles. Therefore, an object of the present invention is to solve such problems and realize a medical device that is simply configured and rational. [Means for solving the problem]

[0009] In the course of intensive research to solve the above problems, the inventors of the present invention have noticed that a support on which a graft is placed can be frozen, delivered to a target site, and then thawed to allow the graft to be properly detached. They have found that a graft can be efficiently transported to a target site by using a medical device including a support on which a graft can be placed and frozen on one surface, and as a result of further research, have completed the present invention.

[0010] That is, the present invention relates to the following. [1] A medical device for transporting a graft to a target site, comprising a graft and a support having the graft mounted on one surface thereof, the graft and the support being frozen with the graft mounted on the support, and the graft can be detached from the support and transported to the target site by thawing the frozen graft mounted on the support. [2] A medical device according to [1], wherein the liquid adhering to the graft is frozen between the graft and the support. [3] The medical device described in [2], wherein the liquid includes a cryoprotectant. [4] The medical device according to any one of [1] to [3], wherein the support has a plurality of holes. [5] The medical device according to any one of [1] to [4], wherein the support is made of a material with high thermal conductivity. [6] A medical device for transporting a graft to a target site, comprising a support on which a graft can be placed and frozen, and by thawing the frozen graft placed on the support, the graft can be detached from the support and transported to the target site.

[0011] [7] A method for transporting a graft to a target site, the method comprising the steps of: providing a medical device including a graft and a support having the graft mounted on one surface thereof; freezing the graft and the support; bringing the support having the graft mounted thereon close to the target site; thawing the frozen graft mounted on the support; and peeling the graft from the support and transporting it to the target site. [8] The method according to [7], wherein thawing is carried out by warming only the support. [9] The method according to [7] or [8], wherein the thawing is carried out by contacting the support on which the graft is placed with the target site.

[10] The method according to any one of [7] to [9], wherein delivery to the target site is achieved by inserting a support carrying the graft into a tubular body inserted transperitoneally into a body cavity.

[11] The method according to any one of [7] to

[10] , for transperitoneally inserting a graft into a body cavity and attaching it to a target site. Effect of the Invention

[0012] According to the present invention, the graft can be easily peeled off from the support and transferred to the target site. In addition, the graft can be fixed to the target site while maintaining its shape without causing damage or wrinkles. Furthermore, by freezing the support on which the graft is placed, the graft can be reliably transferred to the target site even when the device is facing upward, downward, or sideways. [Brief description of the drawings]

[0013] [Figure 1]FIG. 1 is a schematic diagram of one embodiment of the device of the present invention. [Diagram 2] FIG. 2 is a schematic diagram of one embodiment of the delivery of an implant to a target site using the device of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] In the present invention, the term "graft" refers to a structure for transplantation into a living body, and in particular to a transplantation structure containing living cells as a component. Preferably, the graft is a transplantation structure that does not contain any structure (e.g., a scaffold, etc.) other than living cells and substances derived from living cells. Examples of the graft of the present invention include, but are not limited to, sheet-shaped cell cultures, spheroids, cell aggregates, etc., and are preferably sheet-shaped cell cultures or spheroids, and more preferably sheet-shaped cell cultures.

[0015] In the present invention, the term "sheet-shaped cell culture" refers to a sheet-shaped product in which cells are connected to each other. The cells may be connected to each other directly (including via cellular elements such as adhesion molecules) and / or via an intervening substance. The intervening substance is not particularly limited as long as it is a substance that can at least physically (mechanically) connect the cells to each other, and examples thereof include extracellular matrix. The intervening substance is preferably derived from cells, particularly from cells that constitute the cell culture. The cells are at least physically (mechanically) connected, but may also be functionally connected, for example, chemically or electrically. The sheet-shaped cell culture may be one composed of one cell layer (single layer) or one composed of two or more cell layers (laminated (multilayered) body, for example, two layers, three layers, four layers, five layers, six layers, etc.). The sheet-shaped cell culture may have a three-dimensional structure with a thickness exceeding that of a single cell, without the cells showing a clear layer structure. For example, in a vertical cross section of a sheet-shaped cell culture, the cells may not be uniformly aligned in the horizontal direction but may be arranged unevenly (eg, in a mosaic pattern).

[0016] The sheet-shaped cell culture preferably does not include a scaffold (support). A scaffold may be used in the art to attach cells to its surface and / or inside and maintain the physical integrity of the sheet-shaped cell culture; for example, a membrane made of polyvinylidene difluoride (PVDF) is known, but the sheet-shaped cell culture of the present invention can maintain its physical integrity even without such a scaffold. In addition, the sheet-shaped cell culture of the present invention preferably consists only of substances derived from the cells that constitute the sheet-shaped cell culture, and does not include other substances.

[0017] The cells constituting the sheet-shaped cell culture are not particularly limited as long as they can form a sheet-shaped cell culture, and include, for example, adhesive cells (adherent cells). Adherent cells include, for example, adhesive somatic cells (e.g., cardiomyocytes, fibroblasts, epithelial cells, endothelial cells, hepatic cells, pancreatic cells, kidney cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells, synovial cells, chondrocytes, etc.) and stem cells (e.g., myoblasts, tissue stem cells such as cardiac stem cells, embryonic stem cells, pluripotent stem cells such as iPS (induced pluripotent stem) cells, mesenchymal stem cells, etc.). Somatic cells may be differentiated from stem cells, particularly iPS cells (iPS cell-derived adhesive cells). Non-limiting examples of cells constituting the sheet-shaped cell culture include myoblasts (e.g., skeletal myoblasts, etc.), mesenchymal stem cells (e.g., derived from bone marrow, adipose tissue, peripheral blood, skin, hair roots, muscle tissue, endometrium, placenta, umbilical cord blood, etc.), cardiomyocytes, fibroblasts, cardiac stem cells, embryonic stem cells, iPS cells, synovial cells, chondrocytes, epithelial cells (e.g., oral mucosal epithelial cells, retinal pigment epithelial cells, nasal mucosal epithelial cells, etc.), endothelial cells (e.g., vascular endothelial cells, etc.), hepatic cells (e.g., hepatic parenchymal cells, etc.), pancreatic cells (e.g., pancreatic islet cells, etc.), kidney cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells, etc. Non-limiting examples of iPS cell-derived adhesive cells include iPS cell-derived cardiomyocytes, fibroblasts, epithelial cells, endothelial cells, hepatic cells, pancreatic cells, kidney cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells, synovial cells, chondrocytes, etc.

[0018] In the present invention, the term "support" refers to a structure having a surface capable of supporting a graft while maintaining its shape. The support can be made of a material that can freeze and heat the graft with the graft placed on one surface and can also handle rapid temperature changes. When the graft is placed on the support and frozen, the liquid adhering to the graft is frozen between the graft and the support and acts as an adhesive. When the support has multiple holes, the liquid adhering to the graft is frozen in the multiple holes, so that the graft can be held firmly by the support. From the viewpoint of warming the graft to thaw it and peel it off from the support, it is preferable that the support is made of a material with high thermal conductivity. In order to prevent rapid heat transfer to the graft, a material with lower thermal conductivity than the high thermal conductivity material can be placed on the material with lower thermal conductivity, and the graft can be placed on the material. The thermal conductivity of the support is not particularly limited, but may be 0.15 to 360 [W / mK], preferably 10 to 360 [W / mK], and more preferably 50 to 360 [W / mK]. The graft can also be detached by naturally thawing the graft placed on the support without heating the support. In one embodiment, the support has flexibility and moderate softness, and can be curved while supporting the graft and stored along the inside of the cylindrical body, and when exposed from the cylindrical body, can be unfolded into a flat shape due to its restoring property. The material of the support is not particularly limited, and various known materials can be used alone or in combination. Examples of such materials include metals, soft polyvinyl chloride resins, polyurethane resins, silicone rubber, natural rubber, synthetic rubber, styrene-ethylene-butylene-styrene copolymers (SEBS), styrene-ethylene-propylene-styrene copolymers (SEPS), ethylene vinyl acetate copolymers (EVA), polyamide resins and polyamide elastomers such as nylon, polyester resins and polyester elastomers such as polyethylene terephthalate (PET), olefin resins such as polyethylene, fluororubbers, fluororesins, etc., and one or more of these can be used in combination.

[0019] In the present invention, "multiple holes" refers to two or more through holes provided in the support, and the graft can be peeled off from the supporting surface and attached by feeding a fluid from the surface of the support opposite to the surface supporting the graft and discharging the fluid through the holes. The hole may be capable of discharging the fluid, and at least one hole may be provided in the support. In addition, the "multiple holes" preferably have a pore size large enough to allow liquid adhering to the graft to enter and be held by surface tension when the graft is placed on the support, whereby the graft, the support, and the liquid that has entered the multiple holes are frozen, thereby firmly holding the graft to the support.

[0020] The multiple holes are preferably arranged discretely on the surface of the support that supports the graft so that the graft can be detached or held at an adjustable position. For example, at least one of the multiple holes can be provided near the edge of the support, so that the graft can be detached from the edge. The multiple holes can be arranged in a row x column matrix, for example, 2 x 2 to 40 x 40, 5 x 5 to 20 x 20, etc., and the spacing between the holes can be, for example, 0.05 mm to 10 mm, 0.5 mm to 2 mm, and the diameter of the holes can be, for example, 0.05 mm to 10 mm, 0.3 to 0.6 mm, but are not limited thereto, and a person skilled in the art can freely select the size of the graft, the degree of adhesion between the graft and the support, etc. The matrix arrangement of the multiple holes can also be achieved by making the structure of the support a mesh structure.

[0021] In the present invention, the term "fluid" refers to a general term for gas and liquid that can be pushed out and detached without damaging the graft. The liquid is composed of at least one component, and the component is not particularly limited, but may be, for example, water, an aqueous solution, a non-aqueous solution, a suspension, or an emulsion. The components that compose the liquid are not particularly limited as long as they have little effect on the graft. When the graft is a membrane made of a biomaterial, it is preferable that the components that compose the liquid are biocompatible, that is, do not cause undesirable effects such as inflammatory reactions, immune reactions, and toxic reactions on biological tissues and cells, or at least have such effects small.

[0022] In the present invention, the term "target site" refers to the part to which the graft is applied (attached). Examples of the target site include a site in a hollow organ where an injury (wound) exists, and the opposite side of the hollow wall corresponding to the site where an injury exists. "Hollow organ" refers to an organ having an inner cavity housed in a body cavity, that is, an organ having a tubular or bag-like structure, and examples thereof include organs of the digestive system, circulatory system, urinary system, respiratory system, and female reproductive system. Typically, it is an organ of the digestive system. In addition, "luminal wall" refers to an organ wall that constitutes a tube or bag of a hollow organ. The luminal wall has an inner part facing the inner cavity and an outer part that forms the outer surface of the organ, and when "one side of the luminal wall" is mentioned, it means either the inside or the outside of the luminal wall, and the outside relative to the inside or the inside relative to the outside is called the "opposite side". In addition, the area located exactly opposite the luminal wall to a certain area on one side is called the "corresponding opposite side". In one embodiment, in luminal tissue having damage on at least one side of the luminal wall, tissue healing can be promoted by transplanting a sheet-shaped cell culture to the opposite side of the site of the damage. This is particularly effective even for damage formed by treatments such as ESD, making it possible to prevent complications after these treatments and improve prognosis.

[0023] In the present invention, a "liquid" is composed of at least one component, and the component is not particularly limited, but may be, for example, water, an aqueous solution, a non-aqueous solution, a suspension, an emulsion, a culture medium, or a physiological buffer solution.

[0024] The components constituting the liquid are not particularly limited as long as they have little effect on the graft. When the graft is made of a biomaterial, the components constituting the liquid are preferably biocompatible from the viewpoint of biological stability and long-term storage potential, that is, components that do not cause undesirable reactions such as inflammatory reactions, immune reactions, and toxic reactions in biological tissues and cells, or at least have small such effects. Examples of the components include water, physiological saline, physiological buffer solutions (e.g., HBSS, PBS, EBSS, Hepes, sodium bicarbonate, etc.), culture media (e.g., DMEM, MEM, F12, DMEM / F12, DME, RPMI1640, MC, etc.), and the like. DB, L15, SkBM, RITC80-7, IMDM, etc.), sugar solution (sucrose solution, Ficoll-paque (registered trademark) PLUS, etc.), seawater, serum-containing solution, Renografin (registered trademark) solution, metrizamide solution, meglumine solution, glycerin, ethylene glycol, ammonia, benzene, toluene, acetone, ethyl alcohol, benzole, oil, mineral oil, animal fat, vegetable oil, olive oil, colloidal solution, liquid paraffin, turpentine oil, linseed oil, castor oil, etc.

[0025] When the graft is a sheet-shaped cell culture, the components constituting the liquid are preferably ones that can stably preserve the cells, contain the minimum amount of oxygen, nutrients, etc. necessary for cell survival, and do not destroy the cells due to osmotic pressure or the like. Examples of such liquids include, but are not limited to, physiological saline, physiological buffer solutions (e.g., HBSS, PBS, EBSS, Hepes, sodium bicarbonate, etc.), culture media (e.g., DMEM, MEM, F12, DMEM / F12, DME, RPMI1640, MCDB, L15, SkBM, RITC80-7, IMDM, etc.), sugar solutions (sucrose solution, Ficoll-paque PLUS (registered trademark), etc.), etc. In the present invention, the "liquid" may further include a cryoprotectant used for freezing the cells. The freezing operation of the graft may be performed after immersing the graft in a culture solution or a physiological buffer solution, or after a treatment such as adding a cryoprotectant to protect the cells from freezing and thawing operations to the culture solution or replacing the culture solution with a cryopreservation solution containing a cryoprotectant. The cryoprotectant used for freezing the graft is not particularly limited as long as it exhibits a cryoprotective effect on the cells, and includes, for example, dimethyl sulfoxide (DMSO), glycerol, ethylene glycol, propylene glycol, sericin, propanediol, dextran, polyvinylpyrrolidone, polyvinyl alcohol, hydroxyethyl starch, chondroitin sulfate, polyethylene glycol, formamide, acetamide, adonitol, perseitol, raffinose, lactose, trehalose, sucrose, mannitol, etc. The cryoprotectant may be used alone or in combination of two or more kinds.

[0026] The step of freezing the graft and the support with the graft placed thereon can be carried out by any known method used for freezing grafts containing cells, etc. Examples of such methods include, but are not limited to, subjecting the support with the graft placed thereon to a freezing means, such as a freezer, a deep freezer, or a low-temperature medium (e.g., liquid nitrogen, etc.). The temperature of the freezing means is not particularly limited as long as it is a temperature at which a part, preferably the whole, of the graft can be frozen, but is typically about 0°C or lower, preferably about -20°C or lower, more preferably about -40°C or lower, and even more preferably about -80°C or lower. The cooling rate in the freezing operation is not particularly limited as long as it does not significantly impair the survival rate or function of the cells after freezing and thawing, but is typically about 1 hour to about 5 hours, preferably about 2 hours to about 4 hours, and particularly about 3 hours from 4°C until the temperature reaches -80°C (slow freezing). Specifically, for example, the cooling can be carried out at a rate of about 0.46°C / min. Such a cooling rate can be achieved by subjecting the support on which the graft is placed directly or in a freezing container to a freezing means set at a desired temperature. The freezing container may have a function of controlling the rate at which the temperature inside the container drops to a predetermined rate. Any known freezing container, such as BICELL® (Nippon Freezer), can be used as such a freezing container.

[0027] Hereinafter, devices according to preferred embodiments of the present invention will be described in detail with reference to the drawings. As shown in Figs. 1 and 2, the device 1 according to the first embodiment of the present invention includes a graft S and a support 2 on one surface of which the graft S is placed, and the graft S and the support 2 are frozen with the graft S placed thereon. Such a device 1 can be realized, for example, by taking out the graft S immersed in a liquid 4 (which may contain a cryoprotectant) and placing it on one surface of the support 2, and freezing the graft S, the liquid 4, and the support 2. That is, the liquid 4 attached to the graft S is frozen between the graft S and the support 2, thereby acting as an adhesive, and the graft S can be appropriately held on the support 2. Therefore, even if the device 1 is placed facing upward, downward, or sideways, the graft S can be transported to the target site A without being detached.

[0028] In one embodiment, the support 2 may have a plurality of holes 3. As a result, the liquid 4 attached to the graft S enters the plurality of holes 3 (FIG. 2B), and the liquid 4 is frozen, so that the graft S is firmly held by the support 2. In addition, by releasing fluid from some of the plurality of holes 3, the graft S can be peeled off from the support 2 and fixed to the target site A more reliably. In one embodiment, the support 2 can be made of a material with high thermal conductivity (such as a metal filter). As a result, by simply heating the support 2, heat can be indirectly transferred to the graft S to thaw it, and the graft S can be appropriately peeled off without causing direct thermal damage to the graft S. In addition, the graft placed on the support can be peeled off by naturally thawing it.

[0029] In one embodiment, the support 2 is a plate-like body having flexibility and moderate softness, and can be curved while supporting the graft S and inserted (stored) into a cylindrical body 5 or the like. The support 2 can also be configured so that a part of its contour has a convex shape (for example, circular), and the top of the convex part is curved by abutting and pressing against the opening of the cylindrical body 5, making it easier to push the support 2 into the cylindrical body 5 or the like. When freezing the support 2 with the graft S placed on it, the graft S can be easily inserted into the cylindrical body 5 or the like by curving (rolling) it and freezing it.

[0030] In one embodiment, the support 2 can be configured so that it can be expanded into a planar shape due to its restoring property when pushed out (or pulled out) from the tubular body 5. For example, by using a port inserted transperitoneally into a body cavity used in endoscopic surgery or the like as the tubular body 5, the support 2 can be configured so that it is automatically expanded into a planar shape when pushed out from the port and brought close to the target site A. The support 2 supporting the graft S can be rolled up so that the graft S faces inward, and the peripheral portion of the support 2 can be inserted into the opening of the tubular body 5 from outside the body while being held with forceps 6 or the like, thereby appropriately transferring the graft S to the target site A without damaging it.

[0031] As shown in FIG. 2, when using the device 1 of the present invention, the support 2 supporting the frozen graft S is positioned close to the target site A, and the graft S, the liquid 4, and / or the support 2 can be thawed by naturally thawing the graft S placed on the support 2 or by heating the support 2. This weakens the adhesiveness of the liquid 4, which acted as an adhesive when frozen, and the graft S can be easily peeled off from the support 2 and transported to the target site A. Heating can be performed by heating the support 2 on which the graft S is placed, or by bringing the support 2 on which the graft S is placed into contact with the target site A. In other words, heating includes heating the graft S and / or the support 2.

[0032] Heating can be achieved by contacting the support 2 on which the graft S is placed with hot air or a heated member, by configuring the forceps 6 for grasping the support 2 to be temperature adjustable, or by configuring the support 2 itself to be temperature adjustable. When only the support 2 is heated, heat is indirectly transferred to the graft S (and the intervening liquid 4), and direct thermal damage to the graft S can be prevented. Configuring the support 2 itself to be temperature adjustable may include configuring the support 2 itself to be cooling adjustable. In other words, it is also possible to configure the support 2 so that the temperature of the support 2 can be lowered with the graft S placed on it, and the graft S and the support 2 can be frozen. In the case of natural thawing, the graft S is not heated, so that the graft S can be thawed without thermal damage.

[0033] The support 2 on which the graft S is placed may be heated, for example, by contacting (adhering) the support 2 on which the graft S is placed to the target site A. That is, by contacting the surface of the support 2 on which the graft S is placed to the target site A, the temperature of the target site A can be transferred to the graft S and / or the support 2 to heat it. This allows the graft S to be easily peeled off from the support 2. Also, in this case, the graft S can be brought into contact with the target site A while more appropriately maintaining its shape, and at the same time peeled off from the support 2, i.e., fixed to the target site A, so that the graft S can be transported without causing damage or wrinkles.

[0034] When the support 2 has a plurality of holes 3, the above-mentioned detachment of the graft S from the support 2 can be reliably performed by releasing fluid from some of the holes 3. After a portion (e.g., the peripheral portion) of the thawed graft S is fixed (attached) to the target site A, the support 2 can be moved to pull the graft S while detaching the other portion of the thawed graft S from the support 2. In other words, by pulling the graft S while detaching it, the graft S can be fixed to the target site A in a stretched state, making it difficult for wrinkles to form on the graft S.

[0035] When the device 1 of the present invention is used to transplant a graft S into a target site A such as an organ, the support 2 supporting the frozen graft S can be delivered directly into the abdominal cavity (body cavity), or the graft S can be delivered transperitoneally into the body cavity via a hollow port (cylindrical body 5) that penetrates the abdominal wall and is used in endoscopic surgery, etc. When the graft S is delivered transperitoneally, the frozen graft S and the support 2 are inserted into the hollow port (cylindrical body 5) and delivered into the body cavity. At this time, by rolling the support 2 as described above, the possibility of the graft S being damaged can be further prevented before delivery.

[0036] The movement of the support 2 within the port can be performed by grasping the support 2 with forceps 6 or the like and moving the forceps 6 forward and backward. The support 2 can be extended from the tip of the hollow port to position the support 2 relative to the target site A. Positioning of the support 2 at the target site A may be performed using another forceps (not shown) inserted into the abdominal cavity. After positioning the support 2, the graft S is allowed to thaw naturally or the support 2 is heated to detach the graft S and transplant it into the target site A. The support 2 can be heated by heating the support 2 on which the graft S is placed, or by bringing the surface of the support 2 on which the graft S is placed into contact with the target site A.

[0037] The device 1 may include at least a support 2 on one surface of which the graft S can be placed and frozen. As described above, the device 1 may include the frozen graft S and the support 2 on one surface of which the graft S is placed. As described above, the device 1 may further include forceps 6, another forceps (not shown), a cylindrical body 5, a temperature-adjustable member, and the like. The support 2 may have a plurality of holes 3. After the graft S is fixed to the target site A, the support 2 may be collected using a laparoscopic surgical resection bag (such as INZII (registered trademark)).

[0038] The device 1 of the present invention can be used, for example, by the following steps in sequence. (1) The graft S and the support 2 are frozen with the graft S placed thereon. (2) The frozen graft S and the support 2 are brought close to the target site A. (3) The graft S is thawed and detached from the support 2. (4) The detached graft S is fixed to the target site A. The graft S can be thawed by heating the support 2 on which the graft S is placed, or by bringing the surface of the support 2 on which the graft S is placed into contact with the target site A. The graft S placed on the support 2 can also be detached by natural thawing. The graft S to which a liquid containing a cryoprotectant is attached can also be frozen together with the support 2.

[0039] When the graft S placed on the support 2 is allowed to thaw naturally, or when the support 2 on which the graft S is placed is heated, the support 2 on which the graft S is placed can be brought close to the target site A while being spatially separated therefrom. At this time, the support 2 can be floated in midair so as not to come into contact with the target site A. This makes it possible to maintain a state in which the graft S does not come into contact with the target site A even after the graft S has been peeled off from the support 2 until the graft S is attached to the target site A. The graft S can be peeled off and attached to the target site A separately or simultaneously.

[0040] Furthermore, after the graft S is attached, a step of spraying a fluid onto the attached graft S may be added. This allows the graft S to be more reliably attached to the target site A. In this case, too, the graft S can be adhered to the target site A without the support 2 being in contact with the target site A. Furthermore, a reinforcing layer that reinforces the sheet-like material may be formed by spraying a gel and / or a polymer as the fluid.

[0041] As described above, according to the device 1 according to the first embodiment of the present invention, the graft can be easily peeled off from the support and transferred to the target site. In addition, the graft can be fixed to the target site while maintaining its shape without causing damage or wrinkles. Furthermore, by freezing the support on which the graft is placed, the graft can be reliably transferred to the target site even when the device is facing upward, downward, or sideways. Although the present invention has been described with reference to the illustrated embodiment, the present invention is not limited thereto. In the present invention, each component can be replaced with any component capable of exerting a similar function, or any component can be added. [Explanation of symbols]

[0042] 1 equipment 2 Support 3 Multiple holes 4 liquid 5. Cylindrical body 6 forceps S graft A Target area

Claims

1. 1. A method for delivering a graft to a target site, comprising: Providing a medical device comprising an implant and a support having the implant disposed thereon; Freezing the graft and support; Bringing the support on which the graft is placed close to the target site; thawing the frozen graft mounted on the support; and A step of peeling the graft from the support and transporting it to a target site. Including, The thawing is performed by contacting the support on which the graft is placed with the target site. The method.

2. The method of claim 1, wherein the thawing is performed by warming only the support.

3. 3. The method according to claim 1 or 2, wherein the delivery to the target site is carried out by inserting the support on which the graft is placed into a tubular body that is inserted transperitoneally into a body cavity.

4. The method according to any one of claims 1 to 3, for inserting the graft transperitoneally into a body cavity and attaching it to a target site.

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