METHOD AND DEVICE FOR FORMING A THREE-DIMENSIONAL ARRANGEMENT OF BIOLOGICAL CELLS

• US 20100190249A1
• Filed: 06/06/2008
• Published: 07/29/2010
• Est. Priority Date: 06/20/2007
• Status: Active Grant

• Current Assignee: Fraunhofer Gesellschaft Zur Foerderung Der Angewandten Forsching E.V.
• Original Assignee: Fraunhofer Gesellschaft Zur Foerderung Der Angewandten Forsching E.V.
• Inventors: Kruse, Charli, Ciba, Philipp, Fuhr, Guenter
• Granted Patent: US 8,546,117 B2
• Time in Patent Office: Days
• US Class Current: 435/366
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 5/0062 General methods for three-dimensional culture
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

A method for forming a three-dimensional cell arrangement (1) of biological cells is disclosed, including the steps of preparation of the cell arrangement (1) on a flexible substrate (10) and deformation of the substrate (10), wherein the deformation of the substrate (10) is brought about by an attractive force exerted by the cells (2) on the substrate (10). A substrate (10), is also disclosed, made from a flexible material and including a substrate surface (11) for adhesion of a cell arrangement (1) of biological cells, wherein the substrate surface (11) has a number of force attachment points arranged to exert an attraction force which may be transmitted from the cells to the substrate (10) and the substrate (10) has a flexibility such that the substrate (10) is deformable with the action of the attraction force.

Claims

1. A method for forming a three-dimensional cell arrangement of biological cells, comprising the steps of:

providing the cell arrangement on a flexible substrate;

exerting an attractive force by the cells on the substrate; and

deforming the substrate, wherein the deforming of the substrate is produced by the attractive force.

2. The method according to claim 1, wherein the deforming comprises a bending of the substrate such that the cell arrangement forms a spatially curved planar layer of cells.

3. The method according to claim 1, wherein the deforming comprises a folding of the substrate such that the cell arrangement forms a three-dimensional pile of cells.

4. The method according to claim 1, wherein the cells are adherently arranged on a substrate surface of the substrate and form a continuous layer of cells.

5. The method according to claim 1, wherein a directional deformation of the substrate is provided with at least one predetermined main deformation direction.

6. The method according to claim 5, wherein the at least one main deformation direction is determined by a predetermined geometric arrangement of at least one of deformation regions and force action points of the substrate.

7. The method according to claim 1, wherein the deformed substrate forms a cavity.

8. The method according to claim 7, wherein the deformed substrate forms a tubular shape or a spherical shape.

9. The method according to claim 1, wherein the deforming of the substrate comprises a shape change of at least one substrate part, wherein at least one of a position and an alignment of the at least one substrate part relative to a remainder of the substrate is varied by the deforming.

10. The method according to claim 1, wherein the deforming of the substrate comprises a shape change of at least one planar substrate layer, including at least one of changing a shape of the at least one substrate layer and separating the at least one substrate layer from a remainder of the substrate.

11. The method according to claim 1, further comprising at least one of the following steps:

culturing of the cells in the cell arrangement,

supplying further cells to the cell arrangement,

dissolution and/or removal of the substrate, and

joining of a plurality of deformed substrates.

12. The method according to claim 11, wherein deforming of the substrate and forming of the cell arrangement take place while or after the cells are cultured.

13. The method according to claim 1, wherein there acts upon the substrate at least one additional deformation force which comprises at least one of an external mechanical force and an internal reaction force in a material of the substrate.

14. The method according to claim 1, wherein the substrate:

is made from at least one of plastic, metal and a resorbable material,

has a continuous substrate surface,

has a substrate surface broken by holes or depressions,

has a lattice structure, or

has a modification layer.

15. A substrate, which is made from a flexible material and has a substrate surface for adhesion of a cell arrangement of biological cells, wherein:

the substrate surface has a plurality of force action points which are adapted for exerting an attractive force that is transmissible from the cells to the substrate, and

the substrate has a flexibility such that the substrate is deformable under the action of the attractive force.

16. The substrate according to claim 15, which substrate has at least one of:

at least in one section, a lattice structure with a plurality of lattice elements that form the force action points; and

at least in one section, a continuous substrate surface on which the force action points are formed.

17. The substrate according to claim 15, wherein the flexibility is at least one of anisotropic and locally variable.

18. The substrate according to claim 15, which substrate has at least one predetermined deformation region that comprises at least one of at least one bending region and at least one stiffening region.

19. The substrate according to claim 17, which substrate has at least one predetermined main deformation direction that is determined by a geometric arrangement of at least one of the at least one bending region, the at least one stiffening region and the force action points.

20. The substrate according to claim 15, which substrate has at least one deformable substrate part, wherein at least one of a position and an alignment of the at least one deformable substrate part relative to a remainder of the substrate is variable.

21. The substrate according to claim 20, wherein the at least one deformable substrate part comprises at least one planar substrate layer.

22. The substrate according to claim 15, which substrate:

is made from at least one of plastic, metal and a resorbable material, or

has a modification layer.

23. The substrate according to claim 15, which substrate is adapted for deformation by at least one additional deformation force which comprises at least one of an external mechanical force and an internal reaction force in the material of the substrate.

24. The substrate according to claim 15, wherein, the cell arrangement is arranged on the substrate surface and the substrate is deformed under the action of the attractive force of the cells.

25. A method for forming a of biological cells, said method comprising:

providing the biological cells and a substrate according to claim 15; and

forming the three-dimensional arrangement of biological cells.