Method and device for forming a three-dimensional arrangement of biological cells

• US 8,546,117 B2
• Filed: 06/06/2008
• Issued: 10/01/2013
• 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
• Primary Examiner(s): Weber, Jon P
• Assistant Examiner(s): UNDERDAHL, THANE E
• Application Number:
  US12/664,933
• Publication Number:
  US 20100190249A1
• Time in Patent Office: 1,943 Days
• Field of Search: 435/41, 435/174
• US Class Current: 435/174
• 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 cells which are cultured in an arrangement on a flexible substrate, which is capable of both cell adhesion and being deformed by the attractive force exerted by the cells;

allowing the cells to exert an attractive force on the substrate that deforms the substrate, wherein the substrate curves to provide a deformed substrate having a tubular shape or a spherical shape.

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 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.

8. The method according to claim 1, wherein the deforming of the substrate comprises:

(a) a shape change of at least one planar substrate layer, or (b) a shape change of the at least one planar substrate layer and a separation of the at least one planar substrate layer from a remainder of the substrate.

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

supplying further cells to the cell arrangement,

dissolution and/or removal of the substrate, and

joining of a plurality of deformed substrates.

10. The method according to claim 9, wherein deforming of the substrate and forming of the cell arrangement take place while or after the cells are cultured.

11. 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.

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

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

has a continuous substrate surface, or

has a substrate surface broken by holes or depressions, or

has a lattice structure, or

has a modification layer.

13. The method according to claim 1, wherein only a portion of the substrate curves.