Device for guiding cell migration and method of guiding cell migration implementing such a device

Patent metadata

Field	Value
Publication number	US-9469840-B2
Application number	US-201214345836-A
Country	US
Kind code	B2
Filing date	Sep 17, 2012
Priority date	Sep 19, 2011
Publication date	Oct 18, 2016
Grant date	Oct 18, 2016

Abstract

A guiding device in which cells are confined between a support surface and a textured surface of a substrate, said textured surface having an anisotropic three-dimensional structure having a repeating pattern that repeats according to a repeat axis, said repeating pattern having a succession of guide spaces adjacent to one another according to the repeat axis, each of said guide spaces being capable of receiving at least one portion of one of the cells and being oriented according to a direction of anisotropy to guide a movement of the cells in the direction of anisotropy.

First claim

The invention claimed is:

1. A device for guiding cell migration, comprising a support surface provided with cells, and a substrate, said substrate having a textured surface placed facing the support surface at a distance along a vertical direction, said textured surface being in contact with the cells placed on the support surface such that the cells are confined in the vertical direction between the support surface and the textured surface, said textured surface having a base surface and an anisotropic three-dimensional structure presenting a repeating pattern along a repeat axis perpendicular to the vertical direction, said repeating pattern having a succession of guide spaces adjacent to one another along the repeat axis, the anisotropic three-dimensional structure comprising a plurality of pairs of guide surfaces, said pairs of guide surfaces being adjacent to each other along the repeat axis and defining the repeating pattern, each pair comprising first and second guide surfaces which extend from the base surface facing one another and which define between them one of the guide spaces, each of said guide spaces being capable of receiving at least a portion of one of the cells and being oriented in a direction of anisotropy perpendicular to the vertical direction in order to guide movement of the cells in the direction of anisotropy.

2. The guiding device according to claim 1 , wherein the anisotropic three-dimensional structure comprises a plurality of guide elements projecting from the base surface, said guide elements being adjacent to each other along the repeat axis and each carrying one of the first guide surfaces and one of the second guide surfaces, the first guide surface of one of the guide elements facing the second guide surface of the adjacent guide element.

3. The guiding device according to claim 1 , wherein the first and second guide surfaces of each pair are adapted so that the direction of anisotropy extends along the repeat axis.

4. The guiding device according to claim 3 , wherein in each pair of guide surfaces, the first guide surface is adapted to block movement of the cells in a direction opposite to the second guide surface and the second guide surface is adapted to allow movement of the cells in a direction opposite to the first guide surface, such that the orientation of the direction of anisotropy is from the first guide surface towards the second guide surface.

5. The guiding device according to claim 4 , wherein the first guide surface is perpendicular to the repeat axis and the second guide surface extends away from the first guide surface along the repeat axis.

6. The guiding device according to claim 5 , wherein the second guide surface is perpendicular to the base surface and has a concavity directed towards the first guide surface.

7. The guiding device according to claim 6 , wherein the anisotropic three-dimensional structure comprises a plurality of rows of triangular projections adjacent along the repeat axis, each of said rows comprising at least two projections aligned along a transverse axis perpendicular to the repeat axis, each of the guide spaces comprising a substantially triangular cavity with a base formed on the first guide surface of one of the rows of triangular projections and a vertex formed on the second guide surface of the adjacent row of triangular projections.

8. The guiding device according to claim 5 , wherein the first guide surface is perpendicular to the repeat axis and the second guide surface is sloped relative to a plane perpendicular to the base surface.

9. The guiding device according to claim 1 , wherein the first and second guide surfaces of each pair are adapted so that the direction of anisotropy extends along a transverse axis perpendicular to the repeat axis.

10. The guiding device according to claim 9 , wherein, in each pair of guide surfaces, the first and second guide surfaces are adapted to block the movement of the cells in either direction of the repeat axis.

11. The guiding device according to claim 10 , wherein the anisotropic three-dimensional structure comprises a plurality of elongated projections adjacent along the repeat axis, each of said elongated projections extending along the transverse axis, each guide space comprising a groove between the first guide surface of one of the elongated projections and the second guide surface of the adjacent elongated projection.

12. The guiding device according to claim 1 , wherein the guide space has a maximum dimension, measured between the first and second guide surfaces, that is less than 200 μm.

13. The guiding device according to claim 1 , wherein the guide space has a depth measured along the vertical direction of less than 200 μm.

14. The guiding device according to claim 1 , wherein the substrate is non-adhesive to the cell.

15. The guiding device according to claim 14 , wherein the non-adhesive substrate consists of a non-adhesive material.

16. The guiding device according to claim 1 , wherein the substrate is adhesive to the cell.

17. The guiding device according to claim 1 , wherein the support surface on which the cells move is an artificial surface chosen among a cell culture surface, a glass slide, and the interior of a microfluidic channel.

18. The guiding device according to claim 1 , wherein the support surface and the textured surface are spaced apart by a distance of less than 10 μm.

19. The guiding device according to claim 18 , wherein at least one of the surfaces chosen from among the support surface and the textured surface comprises at least one additional projection for controlling the distance between the support surface and the textured surface.

20. The guiding device according to claim 19 , wherein the additional projection is in the form of a pillar with a diameter of between 100 μm and 500 μm and a height of less than 10 μm.

21. The guiding device according to claim 1 , provided in the form of a dressing, an implant, a prosthesis, a support for artificial tissue, a microfluidic channel, or a lab-on-a-chip with integrated channels.

22. A method of guiding cell migration using the guiding device according to claim 1 , said method comprising a step of bringing the cells placed on the support surface in contact with the textured surface of the substrate so that the cells are confined between the support surface and the textured surface, the cells moving in the direction of anisotropy.

23. The guiding device according to claim 12 , wherein the maximum dimension of the guide space is less than 100 μm.

24. The guiding device according to claim 12 , wherein the maximum dimension of the guide space is between 5 μm and 60 μm.

25. The guiding device according to claim 12 , wherein the maximum dimension of the guide space is between 15 μm and 30 μm.

26. The guiding device according to claim 13 , wherein the depth of the guide space is less than 100 μm.

27. The guiding device according to claim 13 , wherein the depth of the guide space is less than 6 μm.

28. The guiding device according to claim 15 , wherein the non-adhesive material is a fluoropolymer.

29. The guiding device according to claim 14 , wherein the non-adhesive substrate consists of a material rendered non-adhesive by chemical treatment.

30. The guiding device according to claim 29 , wherein the non-adhesive substrate consists of a

Assignees

• Inst Curie
• Centre Nat De La Rech Scientifique—Cnrs
• Soc De Dev Et De Rech Ind

Inventors

• Le Berre Maël
• Piel Matthieu
• Liu Yanjun

Classifications

• C12N5/0068 Primary

  General culture methods using substrates (for specific animal cell type C12N5/06) · CPC title

• C12N2533/52

  Fibronectin; Laminin · CPC title

• C12N2533/32

  Polylysine, polyornithine · CPC title

• C12N2533/30

  Synthetic polymers · CPC title

• C12N2539/00

  Supports and/or coatings for cell culture characterised by properties · CPC title