Engineering of strong, pliable tissues

• US 5,855,610 A
• Filed: 05/19/1995
• Issued: 01/05/1999
• Est. Priority Date: 05/19/1995
• Status: Expired due to Term

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Shin'oka, Toshiraru, Vacanti, Joseph P., Breuer, Christopher K., Chaignaud, Beverly E.
• Primary Examiner(s): Isabella, David J.
• Application Number:
  US08/445,280
• Time in Patent Office: 1,327 Days
• Field of Search: 623/1, 623/2, 623/11, 623/12, 623/66, 424/425, 424/426
• US Class Current: 623/2.13
• CPC Class Codes: A61F 2/2415 Manufacturing methods
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3645 Connective tissue
• 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: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

It has been discovered that improved yields of engineered tissue following implantation, and engineered tissue having enhanced mechanical strength and flexibility or pliability, can be obtained by implantation, preferably subcutaneously, of a fibrous polymeric matrix for a period of time sufficient to obtain ingrowth of fibrous tissue and/or blood vessels, which is the removed for subsequent implantation at the site where the implant is desired. The matrix is optionally seeded prior to the first implantation, after ingrowth of the fibrous tissue, or at the time of reimplantation. The time required for fibrous ingrowth typically ranges from days to weeks. The method is particularly useful in making valves and tubular structures, especially heart valves and blood vessels.

Claims

1. A cell-matrix structure comprising

a fibrous matrix formed of a biocompatible, biodegradable synthetic polymer, and

seeded with dissociated human cells,

wherein the matrix is configured to form a tissue structure having mechanical strength and flexibility or pliability,

wherein the cell-matrix structure is formed by seeding the matrix, implanting the seeded matrix into a recipient human or animal for a period of time sufficient to form extracellular matrix;

and harvesting of the resulting cell-matrix structure.

2. The cell-matrix structure of claim 1 wherein the matrix is configured to form a tube.

3. The cell-matrix structure of claim 1 wherein the matrix is configured to form a valve in a blood vessel, intestine, or heart.

4. The cell-matrix structure of claim 3 wherein the matrix is configured to form a heart valve.

5. The cell-matrix structure of claim 1 wherein the cells are selected from the group of consisting of parenchymal and connective tissue cells.

6. A tissue-engineered heart valve formed of a porous polymeric matrix seeded with dissociated endothelial and fibroblast cells, wherein the cells form extracellular matrix following implantation into a human or animal recipient, and wherein the extracellular matrix is shaped to form a heart valve.

7. The heart valve of claim 6 wherein the matrix is formed of a polymer selected from the group consisting of poly(lactic acid), poly(glycolic acid), and combinations thereof.

8. The heart valve of claim 7 wherein the matrix is formed of polymer fibers having an interstitial spacing of between 100 and 300 microns and having pore sizes and structure to control the pattern and extent of fibroblastic tissue ingrowth following implantation.

9. The heart valve of claim 7 wherein the matrix was seeded with dissociated cells selected from the group consisting of fibroblasts, myofibroblasts, and endothelial cells and includes elastin fibers.