Method and structure for growing living organic tissue

• US 20040203147A1
• Filed: 06/14/2004
• Published: 10/14/2004
• Est. Priority Date: 09/11/2001
• Status: Abandoned Application

• Current Assignee: Isis Innovation Limited
• Original Assignee: Isis Innovation Limited
• Inventors: Ye, Hua, Cui, Zhangfeng, Triffitt, James Tomlinson, Xia, Zhidao
• Application Number:
  US10/489,248
• Publication Number:
  US 20040203147A1
• Time in Patent Office: Days
• US Class Current: 435/400
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: C12M 29/10 Perfusion
• CPC Class Codes: C12M 29/16 Hollow fibers hollow fiber modules in general B01D63/02

Abstract

A method and structure for growing living organic tissue in which a scaffold is provided on which cells of the tissue may be seeded and on which the tissue may be grown and a plurality of membrane capillaries are provided for conveying a nutrient fluid, the plurality of membrane capillaries being interspersed through the scaffold and having membranes which are permeable to nutrients and oxygen such that the tissue may be grown throughout the scaffold and whereby upon in vivo implantation a supporting nutrient tissue supply rapidly establishes.

Claims

1. A structure for growing living organic tissue including:

a scaffold on which cells of the tissue may be seeded and on which the tissue may be grown; and

a plurality of membrane capillaries, separate from the scaffold, each membrane capillary including a respective membrane wall defining an internal passageway for conveying a nutrient fluid, wherein the membrane walls are permeable to nutrients and oxygen and the plurality of membrane capillaries are interspersed through the scaffold along freely chosen paths such that the shape of the scaffold may be freely chosen with the plurality of membrane capillaries interspersed throughout the scaffold so as to enable the tissue to be grown throughout the scaffold.

2. A structure according to claim 1 wherein the scaffold comprises a plurality of fibres of relatively small diameter compared to the plurality of membrane capillaries.

3. A structure according to claim 1 wherein the membrane capillaries do not follow paths contained only within laminar sheet layers.

4. A structure according to claim 1 wherein at least one of the membrane capillaries follows a path which is neither in nor parallel with the laminar sheet layer in which the path of another of the membrane capillaries lies.

5. A structure according to claim 1 wherein at least one of the membrane capillaries follows a convoluted path not contained within a laminar sheet layer.

6. A structure according to claim 1 wherein the membrane capillaries are omni-directional.

7. A structure according to claim 1 wherein the scaffold has a relatively large extent in three mutually orthogonal directions.

8. A structure according to claim 1 wherein at least some of the membrane capillaries are open at opposite ends so as each to provide a passage for flow of nutrient fluid through the tissue such that nutrient fluid provides nutrients to the tissue.

9. A structure according to claim 1 wherein at least some of the membrane capillaries are blocked at one end such that nutrient fluid may be supplied to the open end so as to provide nutrients to the tissue.

10. A structure according to claim 1 wherein at least some of the membrane capillaries are blocked at both ends.

11. A structure according to claim 1 wherein at least some of the plurality of membrane capillaries have membranes walls permeable to metabolic waste and are suitable for conveying fluid containing metabolic waste away from the tissue.

12. A structure according to claim 1 further comprising an additional plurality of membrane capillaries separate from the scaffold and having membrane walls permeable to metabolic waste and which are interspersed through the scaffold along freely chosen paths so as to convey metabolic waste fluid away from the tissue.

13. A structure according to claim 12 wherein at least some of the additional plurality of membrane capillaries are blocked at one of opposite ends such that metabolic waste fluid may be drawn away from the tissue out of the open ends.

14. A structure according to claim 12 further including a waste extractor for drawing metabolic waste fluid from the additional plurality of membrane capillaries.

15. A structure according to claim 1 wherein the membrane capillaries are bio-degradable or bioresorbable.

16. A structure according to claim 15 wherein the membrane capillaries are constructed from one of poly-lactic acid, poly-glycolic acid, poly-lactic-co-glycolic acid and poly caprolactone.

17. A structure according to claim 15 wherein the membrane capillaries are constructed from a material having pores which, as the membrane capillaries degrade, increase in size so as to provide an increased supply of nutrient fluid to the tissue.

18. A structure according to claim 1 wherein the membrane capillaries are between substantially 10 μ

m and 2 mm diameter, preferably 0.1 mm and 1 mm.

19. A structure according to claim 1 wherein the membrane capillaries are spaced no closer than substantially 0.5 mm apart.

20. A structure according to claim 19 wherein the membrane capillaries are approximately 1 mm apart.

21. A structure according to claim 1 wherein at least some of the membrane capillaries extend through the scaffold parallel to one another.

22. A structure according to claim 1 wherein at least some of the membrane capillaries follow respective circuitous paths through the scaffold.

23. A structure according to claim 1 further including a nutrient fluid supply for providing nutrient fluid to the plurality of membrane capillaries.

24. A tissue structure including:

living organic tissue; and

a plurality of artificial membrane capillaries each membrane capillary including a respective membrane wall defining an internal passageway for conveying a nutrient fluid, wherein the membrane walls are permeable to nutrients and oxygen and the plurality of membrane capillaries are interspersed through the tissue along freely chosen paths such that the shape of the tissue may be freely chosen with the plurality of membrane capillaries interspersed throughout the tissue so as to support life of the tissue.

25. A method of growing living organic tissue including:

freely defining a volume of desired shape and size;

providing a plurality of membrane capillaries along freely chosable paths interspersed through the volume, each membrane capillary including a respective membrane wall which is permeable to nutrients and oxygen and which defines an internal passageway for conveying a nutrient fluid;

forming a scaffold in the volume around the plurality of membrane capillaries, the scaffold being suitable for seeding of tissue cells and tissue growth;

seeding cells of the tissue in the scaffold; and

providing a flow of nutrient fluid through the plurality of membrane capillaries.

26. A method according to claim 25 further including:

forming the scaffold with a plurality of fibres of relatively small diameter compared to the membrane capillaries.

27. A method according to claim 25 wherein the membrane capillaries are not constrained to follow paths within laminar sheet layers.

28. A method according to claim 25 further including:

providing at least one of the membrane capillaries along a path which is neither in nor parallel with the laminar sheet layer in which the path of another of the membrane capillaries lies.

29. A method according to claim 25 further including:

providing at least one of the membrane capillaries along a convoluted path not within a laminar sheet layer.

30. A method according to claim 25 including:

providing the plurality of membrane capillaries along omni-directional paths.

31. A method according to claim 25 wherein said volume is defined by choosing a desired shape and size for a mould.

32. A method according to claim 25 further including:

providing the plurality of membrane capillaries in said mould.

33. A method according to claim 25 further including:

introducing scaffold material into said mould around said plurality of membrane capillaries.

34. A method according to claim 33 further including mixing cells with the scaffold material before introducing the scaffold material into the mould.

35. A method according to claim 25 further including:

introducing endothelial cells into the membrane capillaries and stimulating growth of blood vessels in place of the membrane capillaries.