Layered collagen and HA scaffold suitable for osteochondral repair

• US 9,615,910 B2
• Filed: 05/29/2015
• Issued: 04/11/2017
• 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:
  US14/725,337
• Publication Number:
  US 20150257870A1
• Time in Patent Office: 683 Days
• 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 lyophilizing 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 lyophilizing the layers, wherein when the layer formed in the previous step is formed by lyophilization the lyophilized 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 method of repairing a bone or cartilage defect in a mammal, comprising the steps of providing a multi-layer collagen scaffold, shaping the scaffold to fit into the defect, and inserting the scaffold into the defect, wherein the multi-layer collagen scaffold comprises 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. The method of claim 1, further comprising incorporating a biologic into the scaffold, either before or after shaping.

3. The method of claim 2, wherein the biologic is selected from the group consisting of:

a nucleic acid;

a protein;

a peptide;

a cytokine;

a hormone;

a cell; and

a growth factor.

4. The method of claim 1, wherein the scaffold has a base layer comprising collagen and HA, and wherein the scaffold is inserted into the defect such that the base layer abuts the deepest part of the defect.

5. The method of claim 1, wherein the tissue defect is selected from the group consisting of:

osteochondral defects;

cardiovascular defects;

mandibular/maxillofacial defects;

tracheal reconstruction;

cartilage defect repair within an articulating joint within the skeletal system;

soft tissue defect within the body;

cartilage damage due to an arthritis;

collateral damage at articulating joints due to trauma;

ankle joint defects; and

soft tissue reconstruction.

6. The method of claim 5, wherein the articulating joint within the skeletal system is hip, knee, shoulder, ankle, hand, foot, neck, or spine.

7. The method of claim 5, wherein the collateral damage at articulating joints due to trauma is anterior cruciate Ligament, torn rotator cuff, dislocated/broken ankle, or meniscal repair.

8. The method of claim 5, wherein the soft tissue reconstruction is maxillofacial or tissue augmentation.

9. A method of claim 1, wherein:

(i) the multi-layer collagen 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;

or

(ii) The multi-layer collagen scaffold wherein the interface between each layer is seamless, and in which the pore architecture of at least two of the layers is typically different;

or

(iii) the multilayer collagen scaffold comprises continuous physical integration at the interface of each adjacent layer and wherein each layer comprises a pore architecture characteristic that is different to the other layers.

10. The method of claim 1, wherein a ratio of HA in the first layer to HA in the second layer is at least 1:

1 (w/w).