Bone-like prosthetic implants

• US 9,987,394 B2
• Filed: 04/07/2009
• Issued: 06/05/2018
• Est. Priority Date: 04/10/2008
• Status: Active Grant

• Current Assignee: Shai Meretzki
• Original Assignee: Shai Meretzki
• Inventors: Meretzki, Shai
• Primary Examiner(s): Kim, Taeyoon
• Application Number:
  US12/937,273
• Publication Number:
  US 20120003185A1
• Time in Patent Office: 3,346 Days
• Field of Search: 424 937, 424422, 424549, 424 931, 435325, 435373
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3843 Connective tissue
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A prosthetic implant comprising a biocompatible three-dimensional scaffold and at least two cell types selected from the group consisting of osteoblasts, osteoclasts, and endothelial cells or progenitors thereof.

Claims

1. A mineral implant having a biocompatible, pre-shaped, three-dimensional mineral scaffold comprising ex vivo expanded mesenchymal cells and at least one cell type selected from the group consisting of:

osteoblasts, osteoclasts, chondrocytes, endothelial cells and progenitors thereof, wherein said mesenchymal cells and said at least one cell type are organized in more than one layer in a 3-D interaction, wherein said mesenchymal cells comprise a combination of osteoprogenitor cells and mesenchymal stem cells, wherein said mesenchymal cells and at least one cell type are at a density of at least 10⁶ cells/ml in said implant, wherein said pre-shaped is adapted for insertion into a bone lesion.

2. The implant claim 1, wherein said scaffold comprises a bone particle selected from the group consisting of:

a dry bone particle, a frozen bone particle and a dematerialized bone particle.

3. The implant claim 1, wherein said scaffold comprises a material selected from the group consisting of:

calcium phosphate derivatives, calcium sulfate derivatives, calcium hydroxyapatite, silicate matrices, hydroxyapatite, and beta-3 calcium phosphate.

4. The implant claim 1, wherein said scaffold comprises a pore size in the range of 50 microns to 2000 microns.

5. The implant claim 1, wherein said scaffold comprises a coating layer.

6. The implant claim 5, wherein said coating layer comprises a material selected from the group consisting of:

poly-D-lysine, collagen, fibronectin ECM and hydrogel, or a combination thereof.

7. The implant claim 1, wherein said scaffold is pre-shaped to be fitted into a bone lesion.

8. The implant claim 1, wherein said mesenchymal cells and at least one cell type selected from the group consisting of:

osteoblasts, osteoclasts, chondrocytes, endothelial cells and progenitors thereof were exposed to shear forces.

9. A method of producing a mineral implant in accordance with claim 1, comprising isolating, expanding and co-cultivating mesenchymal cells and at least one cell type selected from the group consisting of osteoblasts, osteoclasts, chondrocytes, endothelial cells and progenitors thereof on a biocompatible, pre-shaped, three-dimensional scaffold, wherein said mesenchymal cells and said at least one cell type are organized in more than one layer in a three-dimensional interaction, wherein said mesenchymal cells comprise a combination of osteoprogenitor cells and mesenchymal stem cells, wherein said mesenchymal cells and at least one cell type are at a density of at least 10⁶ cells/ml in said implant, wherein said pre-shaped is adapted for insertion into a bone lesion.

10. The method of claim 9, wherein said method is performed in a bioreactor.

11. The method of claim 9, wherein said at least one cell type is obtained from a source selected from the group consisting of an autologous source, a syngeneic source, and an allogeneic source, or a combination thereof.

12. The method of claim 11, wherein said source is selected from the group consisting of bone marrow, placenta, adipose tissue, cord blood, cord vein, peripheral blood, mobilized peripheral blood, and embryonic stem cells.

13. The method of claim 2, wherein said three-dimensional scaffold has a pore size in the range of about 50 microns to about 2000 microns.

14. The method of claim 9, wherein said three-dimensional scaffold comprises a coating layer.

15. The method of claim 14, wherein said coating layer comprises a material selected from the group consisting of poly-D-lysine, collagen, fibronectin, ECM and hydrogel, or a combination thereof.

16. The method of claim 9, wherein said mesenchymal cells and at least one cell type are isolated from bone marrow, fat tissue, placenta or cord vein.

17. The method of claim 9, wherein said co-cultivation comprises subjecting said cells to an osteogenic stimulus.

18. The method of claim 17, wherein said step of subjecting said cells to an osteogenic stimulus comprises contacting the cells with a molecule selected from the group consisting of dexamethasone, sodium B-glycerophosphate, 1,25 dihydroxycholecalciferol calcitriol and, L-ascorbic acid-2-phosphate.