Production Of Tissue Engineered Heart Valves

Patent metadata

Field	Value
Publication number	US-2016199179-A1
Application number	US-201614987601-A
Country	US
Kind code	A1
Filing date	Jan 4, 2016
Priority date	Mar 11, 2005
Publication date	Jul 14, 2016
Grant date	—

Abstract

The invention is directed to methods for preparing artificial heart valves by preconditioning a matrix seeded with endothelial cells and smooth muscle cells differentiated from isolated progenitor cells. These cell seeded matrices are exposed to fluid conditions that mimic blood flow through the heart to produce tissue engineered heart valves that are analogous to native heart valves.

First claim

1 - 27 . (canceled)

28 . A preconditioned tissue engineered heart valve, comprising:
a biocompatible matrix seeded with at least one population of endothelial cells differentiated from progenitor cells ex vivo, wherein the seeded cells form at least one cell layer on the biocompatible matrix; wherein the biocompatible matrix is selected from the group consisting of a decellularized matrix, an electrospun matrix, and a synthetic polymer matrix.

29 . The heart valve of claim 28 , further comprising a population of smooth muscle cells differentiated from progenitor cells and seeded onto the endothelial cell layer.

30 . The heart valve of claim 29 , wherein at least one cell of the population of endothelial cells, the population of smooth muscle cells, or a combination thereof is a cell engineered to produce an anti-inflammatory factor.

31 . The heart valve of claim 30 , wherein the anti-inflammatory factor is selected from the group consisting of anti-GM-CSF, anti-TNF, anti-IL-1 and anti-IL2.

32 . The heart valve of claim 28 , wherein biocompatible matrix is a decellularized heart valve.

33 . The heart valve of claim 28 , wherein the electrospun matrix is a crosslinked matrix.

34 . The heart valve of claim 33 , wherein the electrospun matrix comprises poly(lactide-co-glycolides) (PLGA).

35 . The heart valve of claim 34 , wherein the PLGA is high molecular weight PLGA.

36 . The heart valve of claim 33 , wherein the electrospun matrix comprises nanofibers having a diameter of about 50 nanometers to about 1000 nanometers and wherein the distance between the fibers is about 50 nanometers to about 500 nanometers.

37 . The heart valve of claim 33 , wherein the electrospun matrix has a pore size of about 0.1 μm 2 to about 100 μm 2 .

38 . The heart valve of claim 28 , wherein the biocompatible matrix is coated with a basement membrane component.

39 . The heart valve of claim 43 , wherein the basement membrane component is selected from the group consisting agar, agarose, gelatin, gum arabic, collagens, fibronectin, laminin, glycoaminoglycans, and mixtures thereof.

Assignees

• Univ Wake Forest Health Sciences

Inventors

• Atala Anthony
• Yoo James

Classifications

• A61L27/3826

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

• C12N5/0068

  General culture methods using substrates (for specific animal cell type C12N5/06) · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61L27/3886

  comprising two or more cell types · CPC title

• A61L27/383

  Nerve cells, e.g. dendritic cells, Schwann cells · CPC title