CARTILAGINIFORM AND OSTEOCHONDRAL SUBSTITUTE COMPRISING A MULTILAYER STRUCTURE AND USE THEREOF

• US 20090232875A1
• Filed: 03/02/2006
• Published: 09/17/2009
• Est. Priority Date: 03/04/2005
• Status: Active Grant

• Current Assignee: Fin-Ceramica Faenza S.p.A.
• Original Assignee: Fin-Ceramica Faenza S.p.A.
• Inventors: Landi, Elena, De Luca, Claudio, Tampieri, Anna, Pressato, Daniele, Di Fede, Sergio
• Granted Patent: US 9,155,818 B2
• Time in Patent Office: Days
• US Class Current: 424/444
• CPC Class Codes: A61L 24/102 Collagen
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/32 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/425 of phosphorus containing material, e.g. apatite
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

The present invention relates to a multilayer structure (1) including a first upper layer (2) consisting of an organic matrix including collagen and at least a lower layer (3, 4, . . . 10) consisting of a composite matrix including hydroxylapatite and collagen. Furthermore, the present invention relates to a cartilaginous substitute including said multilayer structure (1) as well as an osteochondral substitute including said multilayer structure (1). Finally, the present invention relates to the use of said multilayer structure (1) for the preparation of said cartilaginous substitute and said osteochondral substitute for the treatment of cartilaginous defects and osteochondral defects or for the neo-formation of a cartilaginous tissue and/or a subchondral bone tissue.

Claims

1-22. -22. (canceled)

23. Multilayer structure including:

a first upper layer consisting of an organic matrix including collagen; and

one or more lower layers consisting of a composite matrix including hydroxylapatite and collagen.

24. Multilayer structure according to claim 23, wherein at least one lower layer consists of a composite matrix including collagen in a weight quantity between 85 and 75% and hydroxylapatite in a weight quantity between 5 and 25%.

25. Multilayer structure according to claim 24, wherein at least another lower layer consists of a composite matrix including collagen in a weight quantity between 75 and 45% and hydroxylapatite in a weight quantity between 25 and 55%.

26. Multilayer structure according to claim 25, wherein at least one further lower layer consists of a composite matrix including collagen in a weight quantity between 45 and 25% and hydroxylapatite in a quantity between 55 and 75%.

27. Multilayer structure according to claim 25, wherein at least one further lower layer consists of a composite matrix including collagen in a weight quantity lower than 5% and hydroxylapatite in a weight quantity to give 100%.

28. Multilayer structure according to claim 27, wherein the collagen has a concentration gradient starting from the upper layer, in which 100% of collagen is present, passing through at least one lower layer in which the collagen is present in a quantity from 95 to 75%, reaching at least one further lower layer, in which the collagen quantity is lower than 5%.

29. Multilayer structure according to claim 23, wherein said hydroxylapatite in said composite matrix is directly nucleated on the collagen fibres.

30. Multilayer structure according to claim 23, wherein the collagen is selected from;

collagen of type I, type II, type VI or mixtures thereof.

31. Cartilaginous or osteochondral substitute including a multilayer structure according to claim 23.

32. Substitute according to claim 31, wherein the multilayer structure is a scaffold for in situ attachment and differentiation of mesenchymal cells.

33. Substitute according to claim 31, wherein the multilayer structure is loaded ex-viva with a concentrate from medullary blood or with a platelet concentrate (PRP) or with growth factors or factors capable of promoting trophism and cell differentiation.

34. Substitute according to claim 31, wherein the multilayer structure is loaded ex-vivo with mesenchymal cells which are undifferentiated or maintained in a culture for a time period required for multiplication and/or differentiation in parent cells of osteoblasts and chondrocytes.

35. Substitute according to claim 31, wherein the multilayer structure is loaded with pharmacologically active substances selected from:

anti-inflammatory corticosteroids, FANS, immunosuppressors, antibiotics, antiblastics, antiproliferatives and anitvirals.

36. Substitute according to claim 31, wherein the multilayer structure is crosslinked with hyaluronic acid or a salt thereof or a derivative thereof;

preferably, with a molecular weight between 10,000 and 2,000,000 kd.

37. Substitute according to claim 31, wherein the multilayer structure is crosslinked with BDDGE or a derivative thereof.

38. Substitute according to claim 31, wherein the multilayer structure is crosslinked with at least one crosslinker selected from:

glutaraldehyde or a derivative thereof, and bis-epoxides (diglycidyl ether).

39. Substitute according to claim 31, in a freeze-dried or dried form.

40. Substitute according to claim 31, in a sterilized form.

41. Method for treating articular cartilaginous defects or osteochondral defects or for the neo-formation of a cartilaginous tissue and/or a subchondral bone tissue, which comprises implanting a cartilaginous or osteochondral substitute according to claim 31.