Mesh enclosed tissue constructs

Patent metadata

Field	Value
Publication number	US-9925296-B2
Application number	US-201414162617-A
Country	US
Kind code	B2
Filing date	Jan 23, 2014
Priority date	Mar 23, 2011
Publication date	Mar 27, 2018
Grant date	Mar 27, 2018

Abstract

Described is a heart valve leaflet manufactured from a mesh material. The mesh material may have an ability to capture circulatory/stationary/migratory cells of the body to become biologically active. In some cases, the mesh material is coated with a bioactive material, such as a molecule that binds to a cell adhesion molecule (CAM), a growth factor, an extracellular matrix molecule, a subendothelial extracellular matrix molecule or a peptide. The mesh has a stiffness that is comparable to a native heart valve leaflet, such that it functionally mimics a native heart valve.

First claim

What is claimed is:

1. A heart valve comprising a heart valve leaflet comprising a metal mesh material, wherein the metal mesh material comprises openings having dimensions of 0.0005-0.0200 inches, wherein the metal mesh has a thickness of 0.0004-0.0100 inches, wherein the leaflet functionally mimics a heart valve leaflet, and wherein the heart valve is compliant enough to open and close in response to a flow rate as low as 3 L/min.

2. The heart valve of claim 1 , wherein the metal has shape memory or is superelastic.

3. The heart valve of claim 1 , wherein the leaflet is configured to capture circulatory/stationary/migratory cells, when implanted in a body of a subject, to become biologically active.

4. The heart valve of claim 1 , wherein the leaflet has a modified surface, which facilitates growth of a tissue layer on the leaflet, such that the mesh may become enclosed in the tissue layer.

5. The heart valve of claim 4 , wherein said modified surface comprises a bioactive material coating on the leaflet, wherein said bioactive material is configured to capture and/or actively recruit cells and/or provide cell differentiation guidance.

6. The heart valve of claim 5 , wherein the bioactive material is selected from the group consisting of a molecule that binds to a cell adhesion molecule (CAM), a growth factor, an extracellular matrix molecule, a subendothelial extracellular matrix molecule and a peptide.

7. The heart valve of claim 6 , wherein the molecule that binds to a CAM is a CD34 antibody.

8. The heart valve of claim 6 , wherein the growth factor is selected from the group consisting of epidermal growth factor (EGF), fibroblast growth factor 1 (FGF1), FGF2, FGF3, FGF4, vascular endothelial growth factor-A (VEGF-A), VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PGF).

9. The heart valve of claim 6 , wherein the subendothelial extracellular matrix molecule is selected from the group consisting of fibulin-5 and fibrillin-1.

10. The heart valve of claim 6 , wherein the peptide is an RGD-peptide.

11. The heart valve of claim 4 , wherein the surface of the leaflet is modified by plasma coating.

12. The heart valve of claim 4 , wherein the surface of the mesh is micropatterned to enhance cell binding.

13. The heart valve of claim 1 , wherein the mesh has opening dimensions of about 0.0088 inches.

14. The heart valve of claim 1 , wherein the mesh has a thickness of about 0.001 inches.

15. The heart valve of claim 1 , wherein the metal is nitinol or stainless steel.

16. The heart valve of claim 1 , further comprising at least one layer of cells at each side of the metal mesh material, wherein the at least one layer of cells encloses the metal mesh material, such that the at least one layer of cells on the first side interacts with the at least one layer of cells on the second side through the network of holes to provide structure integration.

17. The heart valve of claim 1 , further comprising at least two layers of cells at each side of the metal mesh material, wherein the at least two layers of cells enclose the metal mesh material, such that the at least two layers of cells on the first side interacts with the at least two layers of cells on the second side through the network of holes to provide structure integration.

18. The heart valve of claim 1 , further comprising at least three layers of cells at each side of the metal mesh material, wherein the at least three layers of cells enclose the metal mesh material, such that the at least three layers of cells on the first side interacts with the at least three layers of cells on the second side through the network of holes to provide structure integration.

Assignees

• Univ California

Inventors

• Alavi Seyedhamed
• Kheradvar Arash

Classifications

• A61L27/34

  Macromolecular materials · CPC title

• A61L27/3826

  Muscle cells, e.g. smooth muscle cells · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L2300/606

  Coatings · CPC title

• C12N5/0691

  Vascular smooth muscle cells; 3D culture thereof, e.g. models of blood vessels · CPC title