Layered collagen and HA scaffold suitable for osteochondral repair

• US 9,072,815 B2
• Filed: 11/19/2013
• Issued: 07/07/2015
• Est. Priority Date: 01/23/2009
• Status: Active Grant

• Current Assignee: Royal College of Surgeons in Ireland
• Original Assignee: Royal College of Surgeons in Ireland
• Inventors: Gleeson, John P., Levingstone, Tanya J., O'Brien, Fergal J.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US14/084,164
• Publication Number:
  US 20140105954A1
• Time in Patent Office: 595 Days
• US Class Current: 1/1
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2002/30762 Means for culturing cartilage
• CPC Class Codes: A61F 2002/30766 Scaffolds for cartilage ingrowth and regeneration
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61L 15/28 Polysaccharides or their derivatives A61L15/225 takes precedence
• CPC Class Codes: A61L 15/325 Collagen
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/3612 Cartilage, synovial fluid
• CPC Class Codes: A61L 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: A61L 27/3691 characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• 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 27/54 : 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: A61P 19/00 : Drugs for skeletal disorders
• CPC Class Codes: C12N 2533/54 : Collagen; Gelatin
• CPC Class Codes: C12N 2535/00 : Supports or coatings for cell culture characterised by topography
• CPC Class Codes: C12N 5/0654 : Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth

Abstract

The invention relates to a method for producing a multi-layer collagen scaffold. The method generally comprises the steps of: preparing a first suspension of collagen and freezing or lyophilising the suspension to provide a first layer; optionally preparing a further suspension of collagen and adding the further suspension onto the layer formed in the previous step to form a further layer, and freezing or lyophilising the layers, wherein when the layer formed in the previous step is formed by lyophilisation the lyophilised layer is re-hydrated prior to addition of the next layer; optionally, repeating the aforementioned step to form one or more further layers; and preparing a final suspension of collagen and pouring the final suspension onto the uppermost layer to form a final layer, and freeze-drying the layers to form the multi-layer collagen composite scaffold.

Claims

1. A multilayer collagen scaffold comprising a three freeze-dried layers in which a first layer comprises Type I collagen and HA, a second layer comprises Type I collagen and a Type II collagen and HA, and a third layer comprises Type I and Type II collagen and a polymer and/or biologic.

2. A three-layer collagen scaffold as claimed in claim 1 in which the polymer in the third layer comprises a GAG.

12. A multilayer collagen scaffold of claim 1 that is capable of inducing the differentiation of mesenchymal stem cells (MSCs) into chondrocytes in the cartilage region of the scaffold and into osteoblasts in the bone region of the scaffold.

13. A multilayer collagen scaffold of claim 1 in which the scaffold has a porosity of at least 95%.

14. A multilayer collagen scaffold of claim 13 in which the scaffold has a porosity of at least 98%.

15. A multilayer collagen scaffold of claim 1 in which the scaffold has an average pore diameter of at least 90 microns.

3. A multi-layer collagen scaffold comprising a plurality of freeze-dried layers in which a first layer consists essentially of collagen and HA, a second layer consists essentially of a collagen and HA, and a third layer consisting essentially of collagen, wherein a ratio of HA in the first layer to HA in the second layer is at least 1:

1 (w/w), wherein the collagen component in the first layer comprises Type I collagen, and the collagen component of the second and third layers comprises Type I and II collagen.

4. A multi-layer collagen scaffold as claimed in claim 3 in which the ratio of HA in the first layer to HA in the second layer is at least 3:

1 (w/w).

5. The multi-layer collagen scaffold of claim 3, wherein the scaffold has a continuous pore architecture extending across the layers.

6. A multi-layer collagen scaffold as claimed in claim 5 in which the porous scaffold layers are seamlessly integrated.

8. A multi-layer collagen scaffold as claimed in claim 5 in which the scaffold comprises a pore architecture gradient extending across the layers.

7. A multi-layer collagen scaffold comprising a plurality of porous freeze-dried layers in which the scaffold has a continuous pore architecture extending across the layers, and in which the pore architecture of at least two of the layers is typically different.

9. A multi-layer collagen scaffold comprising a plurality of porous freeze-dried layers in which the interface between each layer is seamless, and in which the pore architecture of at least two of the layers is typically different.

10. A multilayer collagen scaffold with continuous physical integration at the interface of each adjacent layer, wherein each layer comprises a pore architecture characteristic that is different to the other layers.

11. A multilayer collagen scaffold as claimed in claim 10 in which the pore architecture characteristic is selected from pore size, pore size homogeneity and pore size distribution.