Hybrid tissues for tissue engineering

• US 20050002982A1
• Filed: 12/01/2003
• Published: 01/06/2005
• Est. Priority Date: 11/17/1997
• Status: Abandoned Application

• Current Assignee: Andrea N. Ferguson, Byung-Soo Kim, Charles A. Vacanti, Craig R. Halberstadt, David J. Mooney, Jennifer J. Marler
• Original Assignee: Andrea N. Ferguson, Byung-Soo Kim, Charles A. Vacanti, Craig R. Halberstadt, David J. Mooney, Jennifer J. Marler
• Inventors: Mooney, David J., Marler, Jennifer J., Ferguson, Andrea N., Halberstadt, Craig R., Kim, Byung-Soo, Vacanti, Charles A.
• Application Number:
  US10/726,072
• Publication Number:
  US 20050002982A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/3826 Muscle cells, e.g. smooth muscle cells
• CPC Class Codes: A61L 27/383 Nerve cells, e.g. dendritic cells, Schwann cells
• CPC Class Codes: A61L 27/3847 Bones
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: C12N 2502/1317 Chondrocytes
• CPC Class Codes: C12N 2502/28 Vascular endothelial cells
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 5/0697 Artificial constructs associating cells of different lineages, e.g. tissue equivalents blood vessels C12N5/0691

Abstract

The present invention comprises an implantable device that provides artificial tissues for repair, augmentation and reconstructive surgery which have mechanical properties comparable to the natural tissues that they supplement or replace. Such devices can be produced by a tissue engineering method comprising seeding a polymer matrix with a first cell type and a second cell type and culturing the seeded matrix under conditions suitable for cell growth or maintenance, whereby a tissue comprising a mixed cell population containing both the first and second cell types is produced. The tissue produced by this method contains a mixed population in which the two cell types are intimately associated without apparent stratification and has mechanical properties which are intermediate between similarly produced tissues containing either one of the two cell types. This invention is particularly useful in forming implantable structural members.

Claims

1. A cell-containing implant for implantation into a patient comprising:

a polymeric matrix shaped in the form of the desired implant; and

a mixture of dissociated cells comprising smooth muscle cells and cells of at least one other cell type deposited on and in the matrix.

2. The cell-containing implant of claim 1, wherein the cells of at least one other cell type are chondrocytes or osteoblasts, and further wherein the implant provides structural support with a structural strength that exceeds that of natural cartilage.

3. The cell-containing implant of claim 1, further comprising an angiogenic compound.

4. The cell-containing implant of claim 1, wherein the polymeric matrix comprises polymers coated with agar, agarose, gelatin, gum arabic, or a mixture of two or more of these substances.

5. An implantable structural member for use in treating a patient having an anatomical defect that requires structural support, the structural member comprising

(a) a polymeric matrix shaped in the form of the desired support member;

and

(b) a mixture of cells containing at least dissociated cartilage-forming cells and non-cartilage cells, wherein the non-cartilage cells comprise smooth muscle cells deposited on and in the matrix,

such that when the matrix is implanted, a structural support member is formed.

6. The implantable structural member of claim 5, wherein the matrix is in the form of a sheet, a column, a fluted column, a polygon, or a sphere.

7. The implantable structural member of claim 5, wherein the matrix comprises polyglycolide, polylactide, collagen, alginate, or a mixture thereof.

8. The implantable structural member of claim 5, further comprising an angiogenic compound.

9. The implantable structural member of claim 5, wherein the polymeric matrix comprises polymers coated with agar, agarose, gelatin, gum arabic, or a mixture of two or more of these substances.

10. A tissue engineering method comprising

seeding a polymer matrix with a mixture containing smooth muscle cells and cells of at least one other type;

and

culturing the mixture of cell types under conditions suitable for cell growth or maintenance,

whereby a hybrid tissue is formed comprising a mixed cell population containing at least the smooth muscle cells and the cells of at least one other type.

11. The tissue engineering method of claim 10, wherein expanded populations of the smooth muscle cells and the cells of at least one other type are produced by culturing after both types of cells are seeded onto the matrix.

12. The tissue engineering method of claim 10, wherein expanded populations of the smooth muscle cells and the cells of at least one other type are produced before seeding unto the matrix.

13. The tissue engineering method of claim 10, wherein the cells of the at least one different cell type are chondrocytes or osteoblasts, and further wherein the hybrid tissue provides structural support with a structural strength that exceeds that of natural cartilage.

14. The tissue engineering method of claim 10, wherein the matrix is in the form of a sheet, a column, a fluted column, a polygon, or a sphere.

15. The tissue engineering method of claim 10, wherein the matrix comprises polyglycolide, polylactide, collagen, alginate, or a mixture thereof.

16. A method for treating a patient having an anatomical defect of a type that can be treated, at least in part, by providing structural support to adjacent tissue, said method comprising the steps of:

providing a polymeric matrix shaped in the form of a desired support member, the polymer matrix having deposited thereon a mixture of dissociated cells comprising smooth muscle cells and cells of at least one other cell type to produce a matrix/cell construct; and

implanting the matrix/cell construct in the patient at a site that needs structural support so that the construct forms a structural member with controlled biomechanical properties to provide the required structural support in the defect area.

17. The method of claim 16, wherein the cells of the at least one other cell type include cartilage-forming cells and the construct forms a cartilaginous structure member.

18. The method of claim 16, wherein the shape of the polymer matrix is determined by CAT scan or MRI imaging of a patient before surgery.

19. The method of claim 16, wherein the polymer matrix is manufactured in a solid block and altered in shape before or after seeding with a mixture of cells.

20. The method of claim 19, wherein the shape of the polymer matrix is fabricated by hand or by computer aided design-computer aided manufacturing (CAD-CAM) systems.