Process for producing a multi-layered scaffold suitable for osteochondral repair

• US 8,613,943 B2
• Filed: 01/25/2010
• Issued: 12/24/2013
• 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:
  US13/145,970
• Publication Number:
  US 20120015003A1
• Time in Patent Office: 1,429 Days
• Field of Search: None
• US Class Current: 424/425
• 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 multilayer collagen composite scaffold.

Claims

1. A process for producing a multi-layer scaffold in which each layer has a porous structure, the process comprising an iterative layering technique in which each layer is independently formed by freezing, or lyophilisation followed by rehydration with an acidic solvent, prior to addition of a following layer, wherein the final layer is formed by lyophilisation.

2. A method as claimed in claim 1 in which all layers in the scaffold are formed by lyophilisation.

3. A method according to claim 1 for producing a three layer collagen scaffold, the method comprising the steps of:

preparing a first homogenous suspension of collagen and lyophilising the suspension to provide a first layer;

rehydrating the formed first layer with an acidic solvent;

preparing a second homogenous suspension of collagen and pouring the second homogenous suspension onto the re-hydrated first layer to form a two-layered composite, and lyophilising the two-layer composite;

re-hydrating the two-layer composite; and

preparing a third homogenous suspension of collagen and pouring the third homogenous suspension onto the two-layer composite to form a three-layer composite, and lyophilising the three-layer composite to form the three-layer collagen scaffold.

4. A method according to claim 1 for preparing a three layer collagen scaffold suitable for use as an osteochondral repair scaffold, the method comprising the steps of:

preparing a first suspension of Type I collagen and HA in the form of a slurry and freezing or lyophilising the slurry to provide a first layer;

when the first layer is formed by freeze-drying, rehydrating the formed first layer with an acidic solvent;

preparing a second suspension of Type I collagen, Type II collagen, and HA in the form of a slurry and adding the slurry onto the first layer to form a two-layer composite, and freezing or lyophilising the two-layer composite;

when the second layer is formed by freeze-drying, rehydrating the second layer with an acidic solvent;

preparing a third suspension of Type I and Type II collagen and optionally a polymer and/or a biologic, and adding the third suspension onto the two-layer composite to form a three-layer composite, and lyophilising the three layer composite to form the three-layer collagen scaffold; and

optionally, crosslinking one or more of the layers of the scaffold.