Cartilaginous and osteochondral substitute comprising multilayer structure and use thereof

• US 9,155,818 B2
• Filed: 03/02/2006
• Issued: 10/13/2015
• 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: Tampieri, Anna, Pressato, Daniele, Di Fede, Sergio, Landi, Elena, De Luca, Claudio
• Primary Examiner(s): GHALI, ISIS A D
• Application Number:
  US11/817,172
• Publication Number:
  US 20090232875A1
• Time in Patent Office: 3,512 Days
• US Class Current: 1/1
• 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. Cartilaginous or osteochondral substitute comprising a multilayer structure including:

an upper layer consisting of crosslinked collagen fibers; and

one or more lower layers consisting of crosslinked collagen fibers and crystals of Mg- and CO₃-substituted hydroxylapatite wherein said crystals are nucleated between and parallel to the crosslinked collagen fibers and have dimensions ranging from 10 to 20 nm;

wherein said upper layer and said one or more lower layers are in direct contact with each other, and wherein said multilayer structure comprises a collagen-hydroxyapatite gradient characterized by a quantity of crosslinked collagen fibers of 100% in the upper layer and ranging down to between 99% and 1% in at least one lower layer, and wherein the gradient further comprises said crosslinked collagen fibers oriented in a vertical direction.

2. The cartilaginous or osteochondral substitute according to claim 1, wherein the multilayer structure is a scaffold for in situ attachment and differentiation of mesenchymal cells.

3. The cartilaginous or osteochondral substitute according to claim 1, wherein the multilayer structure is loaded ex-vivo with a concentrate from medullary blood or with a platelet concentrate or with growth factors or factors capable of promoting trophism and cell differentiation.

4. The cartilaginous or osteochondral substitute according to claim 1, 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.

5. The cartilaginous or osteochondral substitute according to claim 1, wherein the multilayer structure is loaded with pharmacologically active substances selected from the group consisting of:

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

6. The cartilaginous or osteochondral substitute according to claim 1, wherein the crosslinked collagen fibres are crosslinked with hyaluronic acid or a salt thereof or a derivative thereof.

7. The cartilaginous or osteochondral substitute according to claim 1, wherein the crosslinked collagen fibres are crosslinked with BDDGE or a derivative thereof.

8. The cartilaginous or osteochondral substitute according to claim 1, wherein the crosslinked collagen fibres are crosslinked with at least one crosslinker selected from the group consisting of:

glutaraldehyde or a derivative thereof, and bis-epoxides.

9. The cartilaginous or osteochondral substitute according to claim 1, in a freeze-dried or dried form.

10. The cartilaginous or osteochondral substitute according to claim 1, in a sterilized form.

11. 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 1.

12. The cartilaginous or osteochondral substitute according to claim 1, wherein at least one lower layer consists of crosslinked collagen fibers in a weight quantity between 75 and 45% and hydroxylapatite in a weight quantity between 25 and 55%.

13. The cartilaginous or osteochondral substitute according to claim 1, wherein at least one lower layer consists of crosslinked collagen fibers in a weight quantity between 45 and 25% and hydroxylapatite in a weight quantity between 55 and 75%.

14. The cartilaginous or osteochondral substitute according to claim 1, wherein at least one lower layer consists of crosslinked collagen fibers in a weight quantity between 75 and 45% and hydroxylapatite in a weight quantity between 25 and 55% and another lower layer consists of crosslinked collagen fibers in a weight quantity between 45 and 25% and hydroxylapatite in a weight quantity between 55 and 75%.

15. The cartilaginous or osteochondral substitute according to claim 1, wherein the collagen of the crosslinked collagen fibers is selected from the group consisting of:

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

16. The cartilaginous or osteochondral substitute according to claim 1, wherein at least one lower layer consists of crosslinked collagen fibers in a weight quantity between 95 and 75% and hydroxylapatite in a weight quantity between 5 and 25%.

17. The cartilaginous or osteochondral substitute according to claim 1, wherein at least one lower layer consists of crosslinked collagen fibers in a weight quantity between 90 and 70% and hydroxylapatite in a weight quantity between 10 and 30%.

18. The cartilaginous or osteochondral substitute according to claim 1, wherein the quantity of crosslinked collagen fibers ranges down to less than 10% in the last lower layer.