CN112221543B

CN112221543B - Cell sheet transfer device, transport device, and method for transferring cell sheet

Info

Publication number: CN112221543B
Application number: CN201910637375.1A
Authority: CN
Inventors: 高爽; 杜志宏; 靳新; 吴峥; 常德华
Original assignee: BOE Technology Group Co Ltd; BOE Regenerative Medicine Technology Co Ltd
Current assignee: BOE Technology Group Co Ltd; BOE Regenerative Medicine Technology Co Ltd
Priority date: 2019-07-15
Filing date: 2019-07-15
Publication date: 2024-05-10
Anticipated expiration: 2039-07-15
Also published as: CN112221543A; WO2021008472A1

Abstract

A cell sheet transfer device, a cell sheet transport apparatus, and a method of transferring a cell sheet using the cell sheet transport apparatus, the cell sheet transfer device comprising: a base plate and a lifting portion provided at an edge of the base plate, wherein the base plate is configured to carry the cell sheet; the bottom plate has a liquid passage configured to penetrate the bottom plate in a thickness direction of the bottom plate. The cell sheet transferring device can ensure that the cell sheet is not damaged in the process of transporting the cell sheet, and can rapidly and accurately transfer and attach the cell sheet to the surface of an organ or tissue to be repaired.

Description

Cell sheet transfer device, transport device, and method for transferring cell sheet

Technical Field

Embodiments of the present disclosure relate to a cell sheet transfer device, a cell sheet transport apparatus, and a method of transferring a cell sheet using a cell sheet transport apparatus.

Background

Cell sheets (cell sheets) are a research hotspot in the field of tissue engineering, and have wide application in the treatment of diseases related to skin, cornea, heart, liver, periodontal, bone marrow and the like. Cell sheets are formed by in vitro culture of primary cells, for example, neural cells, bone marrow stromal cells and the like, have become hot spots in the field of regenerative medicine, and a set of mature methods have been used for preparing cell sheets.

BRIEF SUMMARY OF THE PRESENT DISCLOSURE

At least one embodiment of the present disclosure provides a cell sheet transfer device comprising: a base plate and a lifting portion provided at an edge of the base plate, wherein the base plate is configured to carry the cell sheet; the bottom plate has a liquid passage configured to penetrate the bottom plate in a thickness direction of the bottom plate.

For example, in a cell sheet transfer device provided in at least one embodiment of the present disclosure, the lift and the base plate are movably connected at a connection such that an angle between the lift and a major surface of the base plate is adjustable.

For example, in the cell sheet transfer device provided in at least one embodiment of the present disclosure, the lifting portion is provided at two positions opposite to each other at the edge of the bottom plate.

For example, in the cell sheet transfer device provided in at least one embodiment of the present disclosure, the planar shape of the bottom plate is rectangular or circular.

For example, in the cell sheet transfer device provided in at least one embodiment of the present disclosure, the planar shape of the liquid channel is at least one of a circle, rectangle, square, triangle, oval, diamond, or fan.

For example, in a cell sheet transfer device provided in at least one embodiment of the present disclosure, the material of the base plate and the lifting portion are both biocompatible materials.

For example, in a cell sheet transfer device provided in at least one embodiment of the present disclosure, the biocompatible material comprises at least one of titanium, titanium alloy, polycaprolactone, polylactic acid, polyethylene, polypropylene, polyethylene glycol, polystyrene, nylon, polyacetal, polycarbonate, polyvinyl alcohol, polyethylenimine, polysulfone, polymethacrylate, polyurethane, polyterephthalic acid, sodium silicate borate, glass, or alumina.

At least one embodiment of the present disclosure also provides a cell sheet transport device, including: a preservation container, a cover layer and a cell sheet transfer device of any one of the preceding claims, wherein the preservation container comprises a recess having a side wall and a bottom surface; the cell sheet transfer device is arranged in the groove; the cover layer is provided on the holding container with the cell sheet transfer device between the holding container and the cover layer such that there is a gap between the cover layer and the bottom plate of the cell sheet transfer device in a direction perpendicular to the bottom surface.

For example, in the cell sheet transport device provided in at least one embodiment of the present disclosure, a support column is disposed in the groove, and the support column protrudes toward a side facing away from the bottom surface.

For example, in the cell sheet transport apparatus provided in at least one embodiment of the present disclosure, the cell sheet transfer device is disposed on a side of the support column near the cover layer, and the gap has a size of 0.1mm to 0.5mm.

For example, in the cell sheet transport apparatus provided in at least one embodiment of the present disclosure, the support column penetrates the cell sheet transfer device at the liquid passage, and a distance between a surface of the support column, which is away from the bottom surface, and the cover layer is 0.1mm to 0.5mm in a direction perpendicular to the bottom surface.

For example, in a cell sheet transport device provided in at least one embodiment of the present disclosure, the cover layer is detachably coupled to the preservation container.

For example, in the cell sheet transport device provided in at least one embodiment of the present disclosure, the cover layer is a water-blocking and air-permeable layer.

For example, in the cell sheet transport device provided in at least one embodiment of the present disclosure, the material of the cover layer includes polyurethane rubber or silicone rubber.

For example, at least one embodiment of the present disclosure provides a cell sheet transport device, further comprising: and the bearing layer is arranged on the cell sheet layer transfer device, wherein the bending strength of the material of the bearing layer is smaller than that of the cell sheet layer transfer device.

For example, in the cell sheet transport device provided in at least one embodiment of the present disclosure, the holding container includes a plurality of the grooves, and the cell sheet transfer means is provided in each of the grooves.

At least one embodiment of the present disclosure further provides a method for transferring a cell sheet using the cell sheet transport apparatus of any one of the above, the method for transferring a cell sheet comprising: placing the cell sheet in the cell sheet transport apparatus, wherein the cell sheet is positioned between the cover layer and the cell sheet transfer device; removing the cover layer, and taking out the cell sheet and the cell sheet transfer device by extracting the extracting section; transferring the cell sheet onto the tissue or organ to be repaired.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings of the embodiments will be briefly described below, and it is apparent that the drawings in the following description relate only to some embodiments of the present disclosure, not to limit the present disclosure.

FIG. 1 is a schematic illustration of a cell sheet transfer process;

FIG. 2 is a schematic plan view of a cell sheet transfer device according to an embodiment of the present disclosure;

FIG. 3 is a schematic plan view of a cell sheet transfer device according to another embodiment of the present disclosure;

FIG. 4 is a schematic plan view of a cell sheet transfer device according to another embodiment of the present disclosure;

FIG. 5 is a schematic plan view of a cell sheet transfer device according to another embodiment of the present disclosure;

FIG. 6 is a schematic plan view of the cell sheet transfer device of FIG. 5 after the lift portion is flattened;

FIG. 7 is a schematic plan view of a cell sheet transfer device according to another embodiment of the present disclosure;

FIG. 8 is a schematic cross-sectional view of a cell sheet transport device according to an embodiment of the disclosure;

FIG. 9 is a schematic cross-sectional view of a cell sheet transport device according to still another embodiment of the present disclosure;

FIG. 10 is a schematic plan view of the cell sheet transfer device of FIG. 9 with a carrier layer disposed thereon;

FIG. 11 is a schematic plan view of a cell sheet transport device according to an embodiment of the disclosure;

FIG. 12 is a schematic cross-sectional view of a cell sheet transport device according to another embodiment of the present disclosure; and

Fig. 13 is a flowchart of a method for transferring a cell sheet by a cell sheet transport apparatus according to an embodiment of the present disclosure.

Reference numerals:

11-cell sheet; 12-a layer of carrier material; 20-cell sheet transfer device; 201-a bottom plate; 202-a lifting part; 203-a liquid channel; 204-a handle; 205-first connection; 206-a second connection; 207-a carrier layer; 30-cell sheet transport means; 31-a preservation container; 32-a cover layer; 311-grooves; 3111-sidewalls; 3112-bottom surface; 33-gap; 34-support columns.

Detailed Description

For the purpose of making the objects, technical solutions and advantages of the embodiments of the present disclosure more apparent, the technical solutions of the embodiments of the present disclosure will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present disclosure. It will be apparent that the described embodiments are some, but not all, of the embodiments of the present disclosure. All other embodiments, which can be made by one of ordinary skill in the art without the need for inventive faculty, are within the scope of the present disclosure, based on the described embodiments of the present disclosure.

Unless defined otherwise, technical or scientific terms used in this disclosure should be given the ordinary meaning as understood by one of ordinary skill in the art to which this disclosure belongs. The terms "first," "second," and the like, as used in this disclosure, do not denote any order, quantity, or importance, but rather are used to distinguish one element from another. The word "comprising" or "comprises", and the like, means that elements or items preceding the word are included in the element or item listed after the word and equivalents thereof, but does not exclude other elements or items. The terms "connected" or "connected," and the like, are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "upper", "lower", "left", "right", etc. are used merely to indicate relative positional relationships, which may also be changed when the absolute position of the object to be described is changed.

All terms (including technical or scientific terms) used in this disclosure have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs, unless specifically defined otherwise. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

For example, the preparation process of cell sheets is generally complicated, the preparation period is long, and the preparation cost is high. The cell sheet is thin and fragile, has a three-dimensional structure, and is easy to tear, fold or fracture in the processes of culturing, stripping, washing, storing and transporting the cell sheet and the like, so that the use of the subsequent cell sheet is affected, and great difficulty is brought to the application of the cell sheet in clinical medicine. For example, FIG. 1 is a schematic diagram of a cell sheet transfer process. As shown in fig. 1, the cell sheet 11 is laid flat on the carrier material layer 12 before the cell sheet 11 is transferred from the carrier material layer 12, and the cell sheet 11 is maintained in a complete round shape, and after the cell sheet 11 is separated from the carrier material layer 12, the edges of the cell sheet 11 become no longer flat, and the cell sheet 11 is damaged or wrinkled.

The inventors of the present disclosure found that, when the cell sheet 11 and the carrier material layer 12 are taken out of the culture liquid after the transportation of the cell sheet is completed, the carrier material layer 12 needs to be tilted to pour out the culture liquid thereon, which easily causes the cell sheet 11 to slide off the carrier material layer 12, thereby damaging the cell sheet, without providing a channel for the liquid to circulate on the carrier material layer 12 shown in fig. 1. Even if the cell sheet 11 does not slip, the cell sheet 11 is easily damaged when the cell sheet 11 is transferred from the carrier material layer 12 by, for example, bringing the cell sheet 11 and the carrier material layer 12 into a state of being easily separated by cooling and then scooping up the cell sheet 11 with a cell scoop or pinching up the cell sheet 11 with a special forceps to peel the cell sheet 11 from the carrier material layer 12 during the process of collecting the cell sheet 11.

The inventors of the present disclosure have also found that the carrier material layer 12 shown in fig. 1 is typically provided on opposite side walls of the recess to ensure that the nutrient solution in the recess flows and that the nutrient solution is allowed to pass through the carrier material layer 12 to provide nutrition to the cell sheet 11, but that the recess is relatively wide in opening, the carrier material layer 12 has a certain bending capability, which may result in that during transportation of the cell sheet 11, the cell sheet 11 and the carrier material layer 12 leak into the recess, and that shear forces of the liquid in the nutrient solution may also damage the cell sheet 11. Therefore, the method of transferring the cell sheets shown in fig. 1 cannot ensure that the cell sheets are not damaged during the transportation of the cell sheets, and cannot rapidly and accurately transfer and attach the cell sheets to the surface of the organ or tissue to be repaired. Therefore, there is a need for a specific cell sheet transport device that ensures that the cell sheet is in a flat environment, reduces the damage to the cell sheet caused by liquid shear forces, and also has a need for containing a quantity of cell culture fluid (including transport protection fluid) to provide the cell sheet with the nutrients required during transport and for a certain shelf life.

At least one embodiment of the present disclosure provides a cell sheet transfer device comprising: a base plate and a lifting portion provided at an edge of the base plate, the base plate configured to carry a cell sheet; the bottom plate has a liquid passage configured to penetrate the bottom plate in a thickness direction of the bottom plate. The lifting part and the liquid channel in the cell sheet transferring device are matched with each other, so that the cell sheet is not damaged in the process of transporting the cell sheet, and the cell sheet can be transferred and attached to the surface of an organ or tissue to be repaired rapidly and accurately.

For example, fig. 2 is a schematic plan view of a cell sheet transfer device according to an embodiment of the present disclosure. As shown in fig. 2, the cell sheet transfer device 20 includes: a base plate 201 and a lifting portion 202 provided at an edge of the base plate 201, the base plate 201 being configured to carry a cell sheet (the cell sheet is not shown in fig. 2); the bottom plate 201 has a liquid passage 203, and the liquid passage 203 is arranged to penetrate the bottom plate 201 in the thickness direction of the bottom plate 201. When transferring the cell sheet, the cell sheet is located on the bottom plate 201, so that the cell sheet is tiled to avoid the cell sheet from wrinkling, the lifting part 202 at the edge of the bottom plate 201 can ensure that the cell sheet is stably removed from the culture solution, and the bottom plate 201 is provided with the liquid channel 203 so that the culture solution can be leaked without tilting the bottom plate.

For example, in FIG. 2, the number of the lifting portions 202 is two, and the two lifting portions 202 are provided at two positions where the edges of the bottom plate 201 are opposite to each other, so that the cell sheet can be more smoothly removed from the culture solution. The cell sheet transferring device can be directly attached to the surface of the tissue or organ to be repaired on the side provided with the cell sheet so as to ensure that the cell sheet is transferred to the surface of the tissue or organ to be repaired more stably. In other embodiments of the present disclosure, the number of the lifting portions 202 may be more or 1, which is not limited herein.

For example, fig. 3 is a schematic plan view of a cell sheet transfer device according to still another embodiment of the present disclosure. As shown in fig. 3, the number of the lifting parts 202 is 1, and the lifting parts 202 are provided only at one position of the edge of the bottom plate 201, so that the structure of the cell sheet transfer device 20 is simplified while ensuring that the cell sheet can be smoothly removed from the culture solution.

For example, the planar shape of the base plate 201 is rectangular or circular, and the shape of the base plate 201 is circular in both fig. 2 and 3. The rectangular or circular planar shape of the bottom plate 201 can ensure that the bottom plate 201 is more stably fixed in an area defined by a groove in a cell sheet transport device to be referred to later, thereby enabling a cell sheet to be more stably stored in a culture solution.

For example, fig. 4 is a schematic plan view of a cell sheet transferring device according to still another embodiment of the present disclosure, and as shown in fig. 4, a bottom plate 201 is rectangular in shape to better match the cross-sectional shape of a groove in a cell sheet transporting apparatus to be referred to later. For example, the rectangular base plate 201 is symmetrically provided with the lifting portions 202 on opposite sides.

For example, fig. 5 is a schematic plan view of a cell sheet transferring device according to still another embodiment of the present disclosure, and as shown in fig. 5, a lifting portion 202 and a bottom plate 201 are movably connected at a connection portion, so that an angle between the lifting portion 202 and a main surface of the bottom plate 201 can be adjusted, thereby enabling a cell sheet (not shown in the drawing) placed later to be transferred to a tissue or organ to be repaired better. For example, the angle between the lifting portion 202 and the main surface of the base plate 201 can be adjusted in the range of 90 ° to 180 °. The adjustable angle range is continuous and can be accurate to 0.1 °.

For example, the lifting portion 202 of the cell sheet transferring device 20 and the bottom plate 201 are movably connected at a connection portion, so that the cell sheet transferring device can be conveniently turned over after the cell sheet is fetched, and attachment of the cell sheet on a tissue or organ to be repaired is achieved, that is, the cell sheet transferring device can be used as a transplanting tool of the cell sheet.

For example, as shown in fig. 5, the lifting portion 202 and the base plate 201 are provided with a first connecting portion 205 at a connection, and the first connecting portion 205 may allow an angle between the lifting portion 202 and a main surface of the base plate 201 to be adjustable.

For example, FIG. 6 is a schematic plan view of the cell sheet transfer device of FIG. 5 with the lifting portion 202 flattened. As shown in fig. 6, the overturning process can be more conveniently performed by adjusting the angle between the lifting portion 202 and the main surface of the base plate 201 to be 180 °, so that the cell sheet layer can be more stably attached to the tissue or organ to be repaired. The angle between the lifting portion 202 and the main surface of the soleplate 201 may be adjusted to other suitable angles according to different application scenarios.

For example, fig. 7 is a schematic plan view of a cell sheet transfer device according to another embodiment of the present disclosure. As shown in fig. 7, the side of the lifting portion 202 remote from the base plate 201 is also provided with a handle 204. Since the side of the lifting portion 202 near the bottom plate is too thin, it is inconvenient to lift the cell sheet, which is equivalent to increasing the contact area of the lifting portion 202 by providing the handle 204, so that it is easier to smoothly remove the cell sheet from the culture solution.

In one example, the handle 204 may be configured with a rugged surface that may increase the roughness of the handle to facilitate removal of the cell sheet transfer device 20.

For example, the handle 204 and the lifting part 202 may be movably connected, and as shown in fig. 7, a second connecting part 206 is provided between the handle 204 and the lifting part 202, which facilitates operation in a limited space.

For example, the planar shape of the liquid channel 203 is at least one of a circle, rectangle, square, triangle, oval, diamond, or sector. The liquid channel 203 is designed to have the above-described regular shape to better achieve the penetration of the bottom plate 201 through the support column in the cell sheet transport device to be referred to later, so that the liquid channel and the support column can be more conveniently sized.

In fig. 2,3 and 5 to 7, the planar shape of the liquid passage 203 is exemplified as a fan shape. The area of each sector is equal, i.e. the area of each liquid channel 203 is equal. In the above description of fig. 4, the planar shape of the liquid passage 203 is exemplified as a right triangle, and the area of each right triangle is equal, that is, the area of each liquid passage 203 is equal. The equal area of each liquid channel 203 in FIGS. 2-7 may make the bottom plate 201 divided more uniformly, and the equal area of each liquid channel 203 may be more advantageous for uniformity of distribution of the culture solution.

For example, in some embodiments of the present disclosure, the materials of the sole plate 201 and the lift 202 are both biocompatible materials. By using a biocompatible material, adverse effects on the cell sheet can be reduced during and before transfer of the cell sheet.

For example, the material of the base plate 201 and the lifting portion 202 is hard, which is advantageous for structural stability.

For example, the biocompatible material includes a metal having good biocompatibility, such as titanium or a titanium alloy, etc.; the biocompatible material includes a non-metal with good biocompatibility, for example, at least one of polycaprolactone, polylactic acid, polyethylene, polypropylene, polyethylene glycol, polystyrene, nylon, polyacetal, polycarbonate, polyvinyl alcohol, polyethylenimine, polysulfone, polymethacrylate, polyurethane, polyterephthalic acid, sodium silicate borate, or glass; biocompatible materials also include biocompatible metal oxides such as alumina and the like.

For example, the cell sheet transfer device provided by the embodiments of the present disclosure can facilitate removal of a cell sheet. The cell sheet transfer device is provided with a liquid channel, can mechanically support the cell sheet when the cell sheet is taken out, can enable liquid to flow through the liquid channel, and can prevent the cell sheet from being transferred and used more easily due to the attraction force of surface tension on the cell sheet when the cell sheet is separated from the liquid, so that the damage to the cell sheet caused by clamping the cell sheet by hard sharp instruments such as forceps is avoided.

For example, the handle of the cell sheet transfer device can be held to take out the cell sheet and the bottom plate can be turned over so that the side of the bottom plate bearing the cell sheet faces the position where the cell membrane needs to be attached, thereby accurately attaching the cell sheet carried by the cell sheet transfer device to the tissue or organ where the cell sheet needs to be attached, and facilitating the implementation of the operation.

At least one embodiment of the present disclosure also provides a cell sheet transport device. For example, fig. 8 is a schematic cross-sectional structure of a cell sheet transport device according to an embodiment of the disclosure. The cell sheet transport device 30 includes: the holding container 31, the cover layer 32, and the cell sheet transfer device 20 of any of the above embodiments, wherein the holding container 31 comprises a recess 311, the recess 311 having a side wall 3111 and a bottom surface 3112; the cell sheet transfer device 20 is disposed within the recess 311; the cover layer 32 is provided on the holding container 31, and the cell sheet transfer device 20 has a gap between the cover layer 32 and the bottom plate 201 of the cell sheet transfer device 20 in a direction perpendicular to the bottom surface 3112 between the holding container 31 and the cover layer 32.

For example, the cell sheet transport device can maintain the flatness of the cell sheet surface and reduce the damage of liquid shear force to the cell sheet. Meanwhile, the cell sheet transport device can hold a certain amount of nutrient solution (such as transport protection solution) to provide a stable preservation environment for the cell sheet, maintain the balance of acid and alkali and osmotic pressure of the surrounding environment of the cell sheet and provide needed nutrient substances for the cell sheet. And the cell sheet transport device comprises a separable cell sheet transfer device which can conveniently take out and transfer the cell sheet to the tissue or organ to be repaired.

For example, as shown in fig. 8, a support column 34 is provided in the groove 311, and the support column 34 protrudes toward a side facing away from the bottom surface 3112. For example, the support columns 34 provide mechanical support for the cell sheet, such that the support columns 34 allow for a more stable presence of the cell sheet in the cell sheet transport device without slipping under its own weight into the grooves 311 forming wrinkles or being damaged, relative to the side walls 3111 without the support columns 34 having only grooves 311.

For example, the embodiment of the present disclosure is not particularly limited in the size of the bottom surface 3112 of the groove 311, as long as the size of the bottom surface 3112 of the groove 311 is adapted to the size of the cell sheet contained therein.

For example, a cell sheet may include one or more living cells, and a culture fluid (including a transport protective fluid) may be required to maintain the stability of the growth environment of the cell sheet during transport of the cell sheet and to provide a supply of culture fluid (including a transport protective fluid). Under the condition that the support columns are arranged in the grooves, the bottom surfaces of the preservation containers are mutually communicated, the capacity of the preservation containers in the limited space (comprising transportation protection liquid) is improved through the design of the mutual communication, meanwhile, circulation of the culture liquid is facilitated, nutrient substance exchange between the culture liquid and the cell sheets is facilitated, and stable environment and nutrient supply are provided for the cell sheets. In addition, the nutrient components in the culture solution can be uniform through the circulation of the culture solution, so that the nutrient substances and oxygen in the culture solution are fully utilized.

For example, buffer solutions for balancing pH in culture include: 4-hydroxyethylpiperazine ethane sulfonic acid (HEPE) and phosphate buffer solution.

For example, the major components of transport protective fluids are human blood proteins and human alpha globulin, beta globulin, sodium pyruvate, sodium chloride, magnesium sulfate, ethylenediamine tetraacetic acid (EDTA), glucose, and various amino acids.

For example, as shown in FIG. 8, support columns 34 penetrate cell sheet transfer device 20 at liquid channels (not shown in FIG. 8), and the spacing between the surface of support columns 34 remote from bottom surface 3112 and cover layer 34 in the direction perpendicular to bottom surface 3112 is 0.1mm to 0.5mm so that cell sheet transfer device 20 is more stably present in recess 311. Thus, in the process of transporting the cell sheet, the cell sheet is positioned on the support column, and the distance between the surface of the support column 34 far from the bottom surface 3112 and the cover layer 34 is just the thickness of the cell sheet, so that the movable space of the cell sheet is smaller, and the probability of wrinkling of the cell sheet can be reduced. When it is necessary to scoop up the cell sheet from the culture solution, the cell sheet transfer device 20 can be vertically taken out, so that when the bottom plate 201 of the cell sheet transfer device 20 is moved to the end of the support column 34 near the cover layer 32, the cell sheet falls onto the bottom plate 201 of the cell sheet transfer device 20, so that the cell sheet and the cell sheet transfer device 20 can be conveniently taken out through the extraction section 202.

For example, fig. 9 is a schematic cross-sectional structure of a cell sheet transport apparatus according to still another embodiment of the present disclosure, where the cell sheet transfer device 20 is disposed on a side of the support column 34 near the cover layer 32, the cell sheet transfer device 20 is placed on the support column 34, the bottom plate 201 of the cell sheet transfer device 20 does not pass through the support column 34, and the gap 33 between the bottom plate 201 of the cell sheet transfer device 20 and the cover layer 32 is 0.1mm to 0.5mm, and the gap is approximately the thickness of the cell sheet, so that the space for cell sheet movement can be reduced, and the probability of wrinkling of the cell sheet is reduced.

For example, the gap 33 provides room for subsequent placement of the cell sheet, and is designed to be small enough that the cell sheet does not have excess room for folding or creasing, given that the cell sheet is flexible and subject to creasing.

For example, in the schematic cross-sectional structures of the cell sheet transport apparatus shown in fig. 8 and 9, a snap or lock portion may be designed at a position of the storage container 31 corresponding to the lifting portion 202 of the cell sheet transfer device 20, so that the cell sheet transfer device 20 and the cell sheet transport apparatus 30 can be more firmly combined, thereby preventing the cell sheet transfer device 20 from moving and damaging the cell sheet during transport of the cell sheet.

For example, in the schematic sectional structure of the cell sheet transport device shown in FIGS. 8 and 9, the cover sheet 32 is detachably combined with the holding container 31, so that the cover sheet 32 can be easily removed from the holding container 31.

For example, the cover layer 32 and the storage container 31 may be coupled by a simple mechanical engagement, and the cover layer 32 and the storage container 31 may be coupled by other means, such as a screw connection, a snap connection, or a hinge connection.

For example, the material of the cover layer 32 is a soft material or a hard material. When the material of the cover layer 32 is a hard material, better protection may be provided for the cell sheet transporter 30. When the material of the cover layer 32 is a soft material, the soft material can deform to a certain extent, so that more bubbles can be removed as much as possible, and damage to the cell sheet caused by liquid shear force in the transportation process is reduced.

For example, when the cover layer 32 is coupled to the holding container 31 by means such as a screw connection, a snap connection, or a hinge connection, different portions of the cover layer 32 may be formed of different materials. For example, a hard material is used for the screw fixing portion, and a soft material is used for the covering portion. This can simultaneously satisfy the stability of the connecting portion and minimize the gap between the cover portion holding container 31 and the cover layer 32, so that the space for the cell sheet to move becomes small.

For example, the cover layer 32 is a water-blocking breathable layer. The water-blocking breathable layer can prevent the transportation protection liquid from flowing out while not blocking the air flow. For example, the material of the water-blocking and air-permeable layer is polytetrafluoroethylene, and the covering layer 32 formed by the material with water-blocking and air-permeable properties can facilitate air exchange between the cell sheet layer and the external environment, i.e. exchange between the cell sheet layer and the external environment can be realized in the process of long-time transportation and preservation of the cell sheet layer, so that the balance of the oxygen concentration in the cell sheet layer transportation device is maintained, and the preservation of the cell sheet layer is facilitated.

For example, when the material of the cover layer 32 is a soft material, the material of the cover layer 32 includes urethane rubber or silicone rubber.

For example, when the transported cell sheet is formed of cells that are relatively fragile such as nerve cells, the cell sheet transport device 30 may further include: the carrier layer (the carrier layer is not shown in fig. 8 and 9 because the carrier layer is too thin) provided on the cell sheet transfer device 20. In the configuration shown in fig. 8, the carrier layer is disposed directly on the support posts 34 during transport of the cell sheet, and is not disposed directly on the cell sheet transfer device 20. When the cell sheet is scooped up, the carrier layer is located directly on the cell sheet transfer device 20. In the configuration shown in fig. 9, the cell sheet may also be disposed directly on a carrier layer disposed on the side of the cell sheet transfer device 20 adjacent to the cover layer 34.

For example, FIG. 10 is a schematic plan view of the cell sheet transfer device of FIG. 9 with a carrier layer disposed thereon. As shown in fig. 10, a carrier layer 207 is provided on the cell sheet transfer device 20, and the carrier layer 207 may cover the entire bottom plate 201 of the cell sheet transfer device 20 or may cover a part of the bottom plate 201 of the cell sheet transfer device 20.

For example, the flexural strength of the material of the carrier layer is less than the flexural strength of the cell sheet transfer device 20. Thus, the cell sheet layer can be attached to the bearing layer with smaller bending strength for transportation, and the integrity of the cell sheet layer can be ensured.

The bending strength refers to the maximum stress that the material can bear when being broken under the action of bending load or reaching a specified bending moment, the maximum stress is the maximum normal stress when the material is bent, the maximum stress is expressed in MPa (megapascal), the bending resistance of the material is reflected, the bending performance of the material is measured, and the greater the bending strength is, the greater the rigidity of the material is; the less the bending strength, the more flexible the material.

Or the material of the carrier layer has a modulus of elasticity that is less than the modulus of elasticity of the cell sheet transfer device. The elastic modulus is an index for measuring the degree of difficulty in generating elastic deformation of a material, and the larger the value is, the larger the stress for generating certain elastic deformation of the material is, namely the larger the rigidity of the material is, namely the smaller the elastic deformation is under the action of certain stress.

For example, the material of the carrier layer is a film or sheet material with good biocompatibility, and the material of the carrier layer can be subjected to surface treatment processing to improve the attaching capability of the cell sheet layer on the carrier layer. For example, the surface treatment process includes performing a cationic treatment or grafting an organic functional group, and the like.

For example, the cell sheet is supported by the supporting layer, so that the cell sheet can be closely attached to the supporting layer without any external force. In addition, the bearing layer is soft in texture and smooth in surface, so that the cell sheet layer is easy to lay on the bearing layer in a flat and wrinkle-free mode, and the bearing layer also has the effects of protecting and buffering the cell sheet layer.

For example, the material of the bearing layer comprises at least one temperature sensitive material of poly-N-isopropyl acrylamide (PIPAAm), a compound of N-isopropyl acrylamide and methacrylic acid and lysine short peptide. By adjusting the temperature, when the temperature sensed by the bearing layer reaches a specific condition, for example, when the temperature is raised/lowered to a specific temperature, the cell sheet layer is transformed from a state of being clung to the temperature sensitive material to a state of being easy to separate, thereby facilitating the harvesting and collection of the cell sheet layer.

For example, fig. 11 is a schematic plan view of a cell sheet transport device according to an embodiment of the disclosure. As shown in fig. 11, the cell sheet transfer means 20 in the cell sheet transport apparatus 30 is overlapped on the side wall 3111 of the recess 311, and the holding container 31 is an outer body of the cell sheet transport apparatus 30.

For example, fig. 12 is a schematic cross-sectional structure of a cell sheet transport device according to another embodiment of the present disclosure. As shown in fig. 12, a holding container 31 in a cell sheet transport apparatus 30 may include a plurality of grooves 311, each groove 311 having a cell sheet transfer device 20 disposed therein, the cell sheet transport apparatus 30 being provided with a cover layer 32.

For example, in fig. 8, 9 and 12, a seal ring may be further provided on the cover layer 32 to seal the protective container 31 when the cover layer 32 is provided on the protective container 31, preventing leakage of the protective transport liquid.

For example, in fig. 8, 9 and 12, a handle may be further provided on the protective container 31 to facilitate the user to carry the bulk cell sheet transport device 30.

For example, the cell sheet transport device is formed using additive manufacturing (Additive Manufacturing, AM) methods, i.e., 3D printing methods. The cell sheet transport device may be formed by casting.

Embodiments of the present disclosure also provide a method for transferring a cell sheet using the cell sheet transport apparatus of any of the above embodiments, for example, fig. 13 is a flowchart of a method for transferring a cell sheet using the cell sheet transport apparatus according to an embodiment of the present disclosure. As shown in fig. 13, the method for transferring cell sheets includes:

S101: placing a cell sheet in a cell sheet transport device, wherein the cell sheet is positioned between a cover layer and a cell sheet transfer device;

s102: removing the cover layer, and taking out the cell sheet and the cell sheet transfer device by extracting the extracting section;

s103: the cell sheet is transferred to the tissue or organ to be repaired.

For example, the angle between the extraction portion and the base plate may be adjusted prior to transferring the cell sheet to the tissue or organ to be repaired so that the cell sheet is more easily transferred to the tissue or organ to be repaired.

For example, detecting the condition of the cell sheet, such as detecting the shape, area, thickness, uniformity, flatness, distribution density, survival status, etc., of the cell sheet using a detection device, such as an optical detection device, is also included before transferring the cell sheet.

Embodiments of the present disclosure provide a cell sheet transfer device, a cell sheet transport apparatus, and a method of transferring a cell sheet using the cell sheet transport apparatus, having at least one of the following advantageous effects:

(1) The cell sheet transport device provided by at least one embodiment of the present disclosure can ensure that the cell sheet is not damaged during transport of the cell sheet.

(2) The cell sheet transport device provided by at least one embodiment of the present disclosure can rapidly and accurately transfer and attach a cell sheet to the surface of an organ or tissue to be repaired.

(3) The cell sheet transportation device provided by at least one embodiment of the present disclosure can exchange oxygen and carbon dioxide with the outside in the process of long-time transportation and preservation of the cell sheet, and is conducive to maintaining the balance of the oxygen concentration in the cell sheet transportation device, so as to facilitate preservation of the cell sheet.

(4) The cell sheet transfer device provided by at least one embodiment of the present disclosure has a liquid channel, and can mechanically support the cell sheet when the cell sheet is taken out, and meanwhile, liquid can flow through the liquid channel without inclining the bottom plate to leak the culture solution, so that the cell sheet is more easily transferred and used due to the attraction force of surface tension on the cell sheet when the cell sheet is separated from the liquid, and damage to the cell sheet caused by clamping the cell sheet by hard sharp instruments such as forceps is avoided.

(5) The cell sheet layer transferring device provided by at least one embodiment of the present disclosure, after the cell sheet layer is taken out, the handle of the cell sheet layer transferring device is held by hand, and by turning over, the loaded cell sheet layer can be accurately attached to the tissue or organ to which the cell sheet layer needs to be attached, so that the implementation operation of the operation is facilitated.

The following points need to be described:

(1) The drawings of the embodiments of the present disclosure relate only to the structures related to the embodiments of the present disclosure, and other structures may refer to the general design.

(2) In the drawings for describing embodiments of the present disclosure, the thickness of layers or regions is exaggerated or reduced for clarity, i.e., the drawings are not drawn to actual scale. It will be understood that when an element such as a layer, film, region or substrate is referred to as being "on" or "under" another element, it can be "directly on" or "under" the other element or intervening elements may be present.

(3) The embodiments of the present disclosure and features in the embodiments may be combined with each other to arrive at a new embodiment without conflict.

The foregoing is merely specific embodiments of the disclosure, but the scope of the disclosure is not limited thereto, and the scope of the disclosure should be determined by the claims.

Claims

1. A cell sheet transfer device comprising: a base plate and a lifting part arranged at the edge of the base plate, wherein,

The base plate is configured to carry the cell sheet;

The bottom plate has a liquid passage configured to penetrate the bottom plate in a thickness direction thereof;

The lift and the base are movably connected at a connection such that an angle between the lift and a major surface of the base is adjustable.

2. The cell sheet transfer device of claim 1, wherein the lift is disposed at two locations opposite each other at an edge of the base plate.

3. The cell sheet transfer device of claim 1 or 2, wherein the planar shape of the bottom plate is rectangular or circular.

4. The cell sheet transfer device of claim 3, wherein the planar shape of the liquid channel is at least one of circular, rectangular, square, triangular, oval, diamond, or fan-shaped.

5. The cell sheet transfer device of claim 4 wherein the material of the base and the lift are both biocompatible materials.

6. The cell sheet transfer device of claim 5, wherein the biocompatible material comprises at least one of titanium, titanium alloy, polycaprolactone, polylactic acid, polyethylene, polypropylene, polyethylene glycol, polystyrene, nylon, polyacetal, polycarbonate, polyvinyl alcohol, polyethylenimine, polysulfone, polymethacrylate, polyurethane, polyterephthalic acid, sodium silicate borate, glass, or alumina.

7. A cell sheet transport device comprising: a preservation container, a cover layer and a cell sheet transfer device according to any one of claims 1 to 6, wherein,

The holding container includes a recess having a sidewall and a bottom surface;

the cell sheet transfer device is arranged in the groove;

The cover layer is provided on the holding container, and the cell sheet transfer device has a gap between the cover layer and the bottom plate of the cell sheet transfer device in a direction perpendicular to the bottom surface between the holding container and the cover layer.

8. The cell sheet transport apparatus of claim 7, wherein a support post is disposed within the recess, the support post protruding toward a side facing away from the bottom surface.

9. The cell sheet transport apparatus according to claim 8, wherein the cell sheet transfer means is provided on a side of the support column near the cover layer, and the gap has a size of 0.1mm to 0.5mm.

10. The cell sheet transport apparatus according to claim 8, wherein the support column penetrates the cell sheet transfer device at the liquid passage, and a distance between a surface of the support column remote from the bottom surface and the cover layer in a direction perpendicular to the bottom surface is 0.1mm to 0.5mm.

11. The cell sheet transport apparatus according to any one of claims 7 to 10, wherein the cover layer is detachably combined with the preservation container.

12. The cell sheet transport apparatus of claim 11 wherein the cover layer is a water-blocking gas-permeable layer.

13. The cell sheet transport device of claim 12, wherein the material of the cover layer comprises polyurethane rubber or silicone.

14. The cell sheet transport device of claim 7, further comprising: and the bearing layer is arranged on the cell sheet layer transfer device, wherein the bending strength of the material of the bearing layer is smaller than that of the cell sheet layer transfer device.

15. The cell sheet transport apparatus of claim 7, wherein the holding container comprises a plurality of the recesses, each recess having the cell sheet transfer device disposed therein.

16. A method of transferring a cell sheet using the cell sheet transport apparatus of any one of claims 7-15, comprising:

Placing the cell sheet in the cell sheet transport apparatus, wherein the cell sheet is positioned between the cover layer and the cell sheet transfer device;

removing the cover layer, and taking out the cell sheet and the cell sheet transfer means by extracting the lifting portion;

transferring the cell sheet onto the tissue or organ to be repaired.