METHOD FOR PRODUCING BIOLOGICAL TISSUE

Abstract

Method for producing biological tissue, in particular for medical treatment and/or pharmacological examinations, wherein a support for cell tissue is provided, wherein a printing medium containing living cells is provided, wherein the printing medium is printed onto the support through a printing screen and/or a printing stencil, and wherein the printed cells develop into tissue by the printing and/or after the printing.

Claims

1. A method for producing biological tissue (22, 24) in which a support (10) for cell tissue (22, 24) is provided, in which a printing medium containing living cells is provided, in which the printing medium is printed onto the support (10) through a printing screen and/or a printing stencil (14), and in which the printed cells develop into tissue (22, 24) as a result of the printing and/or after the printing.

2. The method according to claim 1, wherein: the printing medium is printed through the printing screen and/or the printing stencil (14) onto the support (10) with or without a scaffold, a matrix and/or a structural framework and/or the structural frameworks, matrices and/or scaffolds are provided on the support (10), and/or the structural frameworks, matrices and/or scaffolds are printed together with and/or contained in the printing medium.

3. The method according to claim 1, wherein: the printing medium is printed in layers and/or built up in layers, and/or a single printing layer and/or printing thickness is produced in a single printing operation, and/or a printing layer has a smaller thickness in the print build-up direction than the extent of the printing layer transverse to the print build-up direction.

4. The method according to claim 1, wherein the printing medium is conveyed through the printing screen and/or the printing stencil (14) and onto the support (10) by at least one blading process and/or at least one printing blade movement.

5. The method according to claim 1, wherein: the printing medium is printed onto the support (10) by at least one screen printing process, and/or the printing of the printing medium onto the support (10) is carried out using a screen printing process.

6. The method according to claim 1, wherein: by printing the printing medium onto the support (10) a three-dimensional cell culture and/or a three-dimensional cell agglomeration is generated, and/or after printing onto the support (10) the respective cell culture and/or cell agglomeration develops into a three-dimensional tissue (22, 24) and/or a three-dimensional tissue structure.

7. The method according to claim 1, wherein the printed printing medium and/or the printed cells and/or cell agglomerations by the printing or after the printing develop into organ tissue, and/or to a partial or complete organ, and/or consumable meat, and/or meat-containing food.

8. The method according to claim 1, wherein the printing screen and/or the printing stencil (14) has at least one cutout (18, 19) for the passage of the printing medium, and/or the printing screen and/or the printing stencil (14) has a plurality of cutouts (18, 19) for the passage of the printing medium, wherein the plurality of cutouts (18, 19) are formed separately from one another, and/or the printing screen and/or the printing stencil (14) has at least one cutout (18, 19) with sections merging into one another.

9. The method according to claim 1, wherein: different printing screens and/or printing stencils (14) are used for printing a tissue (22, 24) in order to produce differently shaped printing layers, and/or complex three-dimensional tissues (22, 24) and/or tissue structures are produced by the different shaping of different printing screens and/or printing stencils (14)

10. The method according to claim 1, wherein: different printing media and/or printing media with different cells are used for printing different layers for producing tissue (22, 24) with different layer properties and/or for producing different skin layers, and/or a variation of the printing medium is carried out in a printing build-up direction.

11. The method according to claim 1, wherein: a tissue variation is generated within a printing layer an x/y direction and/or transversely to a printing build-up direction, and/or tissue variations are generated by using different printing screens and/or printing stencils (14) per cell type and/or printing area.

12. The method according to claim 1, wherein: the printing medium is formed as printing paste and/or low-viscosity or medium-viscosity nutrient liquid and/or liquid suspension and/or sol-gel matrix, and/or the printing medium has a variable viscosity, and/or the viscosity of the printing medium can be changed by a drying step and/or a tempering step, and/or the printing medium is structurally viscous.

13. The method according to claim 1, wherein: a drying and/or tempering step of the printed printing medium is carried out between successive printing steps, and/or a sol-gel transition is generated after the printing of the printing medium by a drying and/or tempering step, and/or a further printing process is carried out after a generated sol-gel transition.

14. The method according to claim 1, wherein a support (10) for cell tissue (22, 24) is provided, wherein a printing medium containing living cells is printed onto the support (10) by means of screen printing, and wherein the printed cells develop into tissue (22, 24) by the printing and/or after the printing.

15. An organ tissue (22, 24 produced by the method according to claim 1.

16. The method according to claim 7, wherein the organ tissue is selected from the group consisting of liver tissue, kidney tissue, heart tissue, skin tissue, muscle tissue, and combinations thereof.

17. The method according to claim 7, wherein the partial or complete organ is for transplantation and is optionally selected from liver, kidney, heart and/or skin.

18. The method according to claim 9, wherein the tissue is selected from the group consisting of blood vessels, vessel walls, channels, structural frameworks, matrices, and/or scaffolds.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0068] It is shown schematically in each case:

[0069] FIG. 1 a support for cell tissue and a printing screen or printing stencil arranged above it in perspective view,

[0070] FIG. 2 two tissues produced by a process according to the invention on a support according to FIG. 1 in perspective view.

DETAILED DESCRIPTION

[0071] In FIG. 1, a support 10 for cell tissue, cell cultures and/or cell agglomerations is shown in perspective view. The support 10 can in particular be a machine-based support onto which a printing medium can be printed. Such a machine-based support 10 can be firmly connected to a printing system not shown here, in particular a 3D screen printing system. Likewise, the support 10 can be a carrier structure, a cell culture plate, an object carrier or a so-called array for cell tissue, cell cultures and/or cell agglomerations. Such a support can be positioned in a printing system for the respective printing operation or printing process and then removed from it again.

[0072] The support 10 may be suitable or configured for positioning, holding, and/or developing cell tissues, cell cultures, and/or cell agglomerations not shown in more detail herein. In particular, a printing medium containing living cells, not shown in greater detail herein, may be fed by printing onto a surface 12 of the support 10, as will be discussed in greater detail below. Once such printing medium is disposed on the surface 12, it may develop into cell tissue, cell cultures, and/or cell agglomerations. Similarly, a printing medium already consisting of cell cultures and/or cell agglomerations and/or containing cell cultures and/or cell agglomerations may be disposed on the surface 12 by printing and thereby develop into tissue. Accordingly, the printing medium may develop into cell tissue by printing and/or after printing.

[0073] FIG. 1 also shows a printing stencil 14 in schematic perspective view. The printing stencil 14 can be formed by a plate 16. Instead of the printing stencil 14, a printing screen not shown here can also be provided. The printing stencil 14 can have at least one cutout 18, 19 or also a plurality of cutouts 18, 19 for the passage of a printing medium. In the case of a plurality of cutouts 18, 19, these may in particular be formed separately from one another. The cutout 18 can, for example, have a diameter of from 1 mm to 100 mm, in particular from 2 mm to 50 mm, preferably from 2 mm to 40 mm, preferably from 2 mm to 30 mm, more preferably from 3 mm to 30 mm, more preferably from 3 mm to 25 mm, more preferably from 3 mm to 20 mm, even more preferably from 4 mm to 20 mm, more preferably from 4 mm to 15 mm, more preferably from 4 mm to 10 mm, even more preferably from 4 mm to 9 mm, more preferably from 4 mm to 8 mm, even more preferably from 5 mm to 10 mm, more preferably from 5 mm to 8 mm. The cutout 19 may have a size corresponding to the diameter-based size specifications mentioned above. The cutouts 18 and 19 may have different diameters and/or sizes or identical diameters and/or sizes.

[0074] In accordance with the present invention, a printing medium containing living cells is printed through a printing screen and/or through the printing stencil 14.

[0075] For printing the printing medium, a printing screen and/or the printing stencil 14 can be arranged above the support 10, as shown in FIG. 1. The printing blade 20 further shown schematically in FIG. 1 can be used for printing a printing medium through a printing screen and/or through the printing stencil 16. Thereby, the printing medium can be printed through a printing screen and/or the printing stencil 16 by at least one blading process and/or at least one printing blade movement, in particular by a plurality of blading operations of the printing blade 20 and/or a plurality of printing blade movements of the printing blade 20. In this way, the printing medium can be fed onto the support 10 in a particularly reliable manner.

[0076] Printing of the printing medium by means of a printing screen and/or by means of the printing stencil 14 and/or the printing blade 20 can be carried out in particular using a screen printing process. The screen printing process can in particular be a 2D screen printing process or 3D screen printing process.

[0077] It is also possible for the support 10, in particular when formed as a carrier structure, to be printed together and/or alternately with the printing medium containing living cells. In particular, the printing of the printing medium containing living cells can be carried out together and/or alternately with the printing of a support 10 formed as a carrier structure in a 3D screen printing process. Further, the support 10 may be printed prior to printing the printing medium containing living cells, in particular by 3D screen printing. Likewise, a support 10 formed as a carrier structure may be otherwise manufactured and provided prior to printing the printing medium containing living cells.

[0078] In FIG. 2, several tissues 22 and 24 are shown on a support 10 in perspective view. The tissues 22 and 24 are, in particular, biological cell tissues and tissue structures, respectively. The tissues 22 and 24 may be parts or sections of an organ, in particular parts or sections of a human or animal organ. Likewise, a complete organ may also be printed. Single or multi-layered tissues 22 and 24 may be produced by printing the printing medium, which is not shown in detail herein. Similarly, printing of the printing medium can create single or multi-layered and/or single or multi-layered cell agglomerations 24, which then develop into the tissues 22 and or 24.

[0079] Further, by printing the printing medium on the carrier structure 10, a three-dimensional cell culture and/or cell agglomeration can be generated. After printing the printing medium onto the carrier structure 10, the respective cell culture and/or cell agglomeration can develop into a three-dimensional tissue 22, 24.

[0080] It is also possible that structural matrixes and/or scaffolds are provided in printing sections 26 and tissues 22, 24, respectively, which are also not shown in more detail here. Such structural matrixes and/or scaffolds can be printed together with the printing medium and/or be contained therein.

[0081] In a particularly preferred manner, several sections of the surface 12 of the support 10 can be printed and/or filled with the printing medium simultaneously and/or in one printing process and/or by one blading process. Likewise, different sections of the surface 12 of the support 10 can be printed and/or filled in chronological sequence according to their distance from each other and according to the respective printing blade speed.

[0082] By printing the printing medium onto the support 10, printing sections 26 that are independent of one another and/or fluid-technically separate can be generated. In particular, one printing section 26 can be generated per surface section. A printing section 26 may form or develop into a tissue 22, 24 and/or a cell culture and/or a cell agglomeration. Further, the cell cultures and/or the cell agglomerations may develop into tissue after printing.

[0083] In the arrangement according to FIG. 2, the individual tissues 22, 24 and/or cell cultures and/or cell agglomerations may be the same with respect to the metabolic state of the cells, the cell age and/or the number of cells and/or the dimension of the number of cells. Likewise, it is possible that in the arrangement 11 according to FIG. 2 deviations with respect to the metabolic state of the cells, the cell age and/or the number of cells are less than 20%, in particular less than 10%, less than 5%, less than 3%, less than 2% or less than 1%.

[0084] The printing medium or the tissues 22, 24 and/or cell cultures and/or cell agglomerations produced therewith may contain cells capable of division and/or cells that can be induced to divide. The living cells of the printing medium and/or the tissues 22, 24 and/or cell cultures and/or cell agglomerations may be human, animal and/or plant cells. In particular, the printing medium and/or the tissues 22, 24 and/or cell cultures and/or cell agglomerations may contain all types of human, animal and/or plant cells. Particularly preferably, the living cells of the printing medium and/or the tissues 22, 24, the cell cultures and/or cell agglomerations can be all cells of the human or animal body or of plants that are capable of division or can be induced to divide.

[0085] Furthermore, the printing medium or a tissue 22, 24 produced therefrom and/or a cell culture and/or cell agglomeration produced from the printing medium may comprise living cells from the group of primary cells, in particular all types of human, animal and/or plant primary cells. Similarly, the printing medium or a tissue 22, 24 generated therefrom or a cell culture and/or cell agglomeration generated therefrom may comprise living cells from the group of cell lines, in particular all types of human, animal and/or plant established cell lines. Finally, the printing medium or a tissue 22, 24 generated therefrom or a cell culture and/or cell agglomeration generated therefrom may contain different cells and/or cell types.

[0086] Furthermore, the printing medium or a tissue 22, 24 produced therefrom or a cell culture and/or cell agglomeration produced therefrom may contain at least one growth factor and/or at least one protein and/or extracellular matrix protein, in particular a growth factor and/or protein from the group of cytokines, in particular as growth regulators, interferons and/or interleukins, membrane components, laminins, collagens, in particular collagen type 4, proteoglycans, entactins, nidogens, cell adherence factors, in particular fibronectin and/or vitronectin, growth factors, in particular of the EGF family, the TGF family, PDGF, VEGF, somatomedins, in particular IGF, NGF, PTGF, and/or protective factors, in particular tissue-specific plasminogen activators, serum albumin and/or CMC. Likewise, the printing medium or a tissue 22, 24 produced therefrom or a cell culture and/or cell agglomeration produced therefrom may comprise at least one or more of these substances from the aforementioned groups.

[0087] The tissues 22, 24 or cell cultures and/or cell agglomerations produced according to the methods described above are particularly preferably suitable for carrying out medical treatments and/or pharmacological examinations.