Element provided with a fibrin layer, preparation and use thereof

• US 7,226,657 B1
• Filed: 11/04/1999
• Issued: 06/05/2007
• Est. Priority Date: 11/04/1998
• Status: Expired due to Fees

• Current Assignee: Baxter International Inc.
• Original Assignee: Baxter International Inc.
• Inventors: Vermeulen, Pierre, Belot, Nathalie, Delmotte, Yves, Tasiaux, Nicole
• Primary Examiner(s): Vo; Hai
• Application Number:
  US09/831,121
• Time in Patent Office: 2,770 Days
• Field of Search: 428/316.6, 428/306.6, 428/308.4, 428/315.5, 428/315.7, 428/315.9
• US Class Current: 428/306.6
• CPC Class Codes: A61L 27/225 Fibrin; Fibrinogen
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin
• CPC Class Codes: B01D 69/10 Supported membranes; Membrane supports
• CPC Class Codes: B01D 71/74 Natural macromolecular material or derivatives thereof B01D71/08, B01D71/24 take precedence
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: Y10T 428/249955 Void-containing component partially impregnated with adjacent component
• CPC Class Codes: Y10T 428/249958 Void-containing component is synthetic resin or natural rubbers
• CPC Class Codes: Y10T 428/249978 Voids specified as micro
• CPC Class Codes: Y10T 428/249979 Specified thickness of void-containing component [absolute or relative] or numerical cell dimension
• CPC Class Codes: Y10T 428/24998 Composite has more than two layers
• CPC Class Codes: Y10T 428/249981 Plural void-containing components

Abstract

An element provided with a layer based on fibrin- or fibrinogen-containing material, said element comprising (a) a hydrophobic or substantially hydrophobic support, which has a porous part with a thickness of 0.1 to 5 mm, and whose pores, extending across its thickness have a node spacing of 5 to 100 μm, one face of said porous part being treated with a compound based on fibrin and/or a fibrinogen-containing material, and (b) a fibrin-based layer covering said treated surface of the support, characterized in that said fibrin-based layer is substantially uniform and homogeneous on said treated surface, and that the fibrin layer and at least the face of the support in contact with the fibrin layer are substantially free of fibrinogen.

Claims

1. An element comprising:

a support having a thickness and a face;

the face having at least two pores extending through the entire support thickness and spaced from one another to define a node spacing, one of the at least two pores having a diameter from about 10 μ

m to about 20 μ

m, the other pore having a diameter greater than about 20 μ

m; and

a substantially fibrinogen-free non-hydrolyzed fibrin network in direct contact with the face and extending into each pore a distance from about 2 μ

m to about 20 μ

m.

2. The element according to claim 1 wherein the support is substantially hydrophobic.

3. The element according to claim 1 wherein the support has a thickness from about 0.1 mm to about 5 mm.

4. The element according to claim 1 wherein the fibrin network extends over the pores.

5. The element according to claim 1 wherein the node spacing is from about 5 μ

m to about 100 μ

m.

6. The element of claim 1 wherein the fibrin network has a substantially uniform thickness across the entire face.

7. The element according to claim 1 wherein the fibrin network contains less than 1% by weight of unreacted fibrinogen.

8. The element according to claim 1 wherein the fibrin network contains from less than about 0.5% to less than about 0.1% by weight of unreacted fibrinogen.

9. The element according to claim 1 wherein the fibrin network contains no unreacted fibrinogen.

10. The element according to claim 1 wherein the node spacing is substantially homogeneous and uniform.

11. The element according to claim 1 wherein the fibrin network extends from about 10 μ

m to about 20 μ

m into the at least one pore.

12. The element according to claim 1 wherein the pores are free of fibrinogen.

13. The element according to claim 1 wherein the fibrin network further includes a first surface and a second surface.

14. The element according to claim 13 wherein first surface is in contact with the support.

15. The element according to claim 14 wherein second surface is stabilized by at least partial cross-linking to form a network of adjacent alveoli.

16. The element according to claim 15 wherein the at least partially cross-linked fibrin network is 0.5 to 100 μ

m thick when measured in the dry state.

17. The element according to claim 16 wherein the at least partially cross-linked fibrin network is 2.5 to 50 μ

m thick when measured in the dry state.

18. The element according to claim 15 wherein the alveoli are formed between the cross-linked fibrin.

19. The element according to claim 18 wherein the alveoli have a volume from about 5 μ

m³ to about 25 μ

m³.

20. The element according to claim 19 wherein the alveoli have an average thickness from about 1 μ

m to about 5 μ

m when measured in the dry state.

21. The element according to claim 13 wherein the fibrin network is provided with cells.

22. The element according to claim 21 wherein the cells mediate cell-fibrin bonds.

23. The element according to claim 13 wherein the fibrin network is provided with proteins.

24. The element according to claim 23 wherein the proteins mediate cell-fibrin bonds.

25. The element according to claim 1 wherein the pores further comprise inner pore faces, the inner pore faces at least partially covered by a component selected from the group consisting of water-soluble or substantially water-soluble protein, and an organic additive.

26. The element according to claim 1 wherein the fibrin network is at least partially covered by a water-soluble or substantially water-soluble protein.

27. The element according to claim 1 wherein the fibrin network further comprises a polar additive.

28. The element according to claim 1 wherein the polar additive is selected from the group consisting of glycerol, sugars, sucrose, glucose, mannitol and mixtures thereof.

29. The element according to claim 1 wherein the fibrin network has a moisture content of less than 0.5%.

30. The element according to claim 1 wherein the fibrin network contains fibronectin.

31. The element according to claim 30 wherein the fibronectin content is from about 0.5% to about 15%.

32. The element according to claim 1 wherein the fibrin network contains calcium.

33. The element according to claim 32 herein the calcium content is from about 1 μ

g to about 100 μ

g per cm³ of the fibrin network volume.

34. The element according to claim 32 wherein the calcium is calcium chloride.

35. The element according to claim 1 wherein the support further includes a second fibrin network superimposed on the fibrin network.

36. The element according to claim 35 wherein the fibrin network is in contact with the support.

37. The element according to claim 36 wherein the fibrin network contains alveoli.

38. The element according to claim 35 wherein the second fibrin network contains alveoli.

39. The element according to claim 35 wherein the alveoli of the fibrin network have larger volumes than the alveoli of the second fibrin network.

40. The element according to claim 1 wherein the support is biocompatible and/or biodegradable.

41. The element of claim 1 wherein the element is a membrane for a device selected from the group consisting of a bioreactor and a filter.

42. The element of claim 1 wherein the element is an implant for a component selected from the group consisting of an artificial internal organ, an artificial vein, an artificial artery, an antithrombotic material, and a cardiac valve.

43. The element of claim 1 wherein the element is an artificial skin.

44. A filter including a membrane element comprising:

a support having a thickness and a face;

the face having at least two pores extending through the entire support thickness and spaced from one another to define a node spacing, one of the at least two pores having a diameter from about 10 μ

m to about 20 μ

m, the other pore having a diameter greater than about 20 μ

m; and

a substantially fibrinogen-free non-hydrolyzed fibrin network in direct contact with the face and extending into each pore a distance from about 2 μ

m to about 20 μ

m.