Production of tissue engineered heart valves

Patent metadata

Field	Value
Publication number	US-9248015-B2
Application number	US-37306606-A
Country	US
Kind code	B2
Filing date	Mar 10, 2006
Priority date	Mar 11, 2005
Publication date	Feb 2, 2016
Grant date	Feb 2, 2016

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

The invention claimed is:

1. A method for producing a preconditioned heart valve, comprising:
isolating progenitor cells comprising at least one of endothelial progenitor cells and smooth muscle progenitor cells;
differentiating, ex vivo, the progenitor cells into endothelial cells or smooth muscle cells;
seeding a matrix having a heart valve shape with the differentiated cells such that the cells attach to the matrix to form at least one cell layer;
attaching the seeded matrix to an attachment element in a preconditioning chamber, wherein the attachment element has a channel that is fluidly coupled to a fluid flow system;
preconditioning the seeded matrix prior to implantation with the flow system by moving a biological fluid through the seeded matrix, wherein a flow rate and a pulse rate of the biological fluid is controlled so that the seeded matrix is exposed to conditions that mimic flow of blood through a native heart valve, wherein the pulse rate induces a pressure in a range of about 60 mmHg to about 200 mmHg; and
continuing exposure of the cells on the surface of the matrix to the flow rate and the pulse rate to allow the seeded cells to develop under fluid flow conditions;
wherein the matrix is an electrospun matrix comprising at least one natural component, at least one synthetic polymer component, and a therapeutic agent;
wherein the therapeutic agent is coupled to a quantum dot encapsulated in a polymer and the quantum dot is configured to release the coupled therapeutic agent when heated by radiation at a wavelength in the range of about 700 nm to about 1000 nm is applied.

2. The method of claim 1 , wherein the quantum dot is configured to alter the ultrastructure of the at least one synthetic polymer component when heated by radiation at a wavelength in the range of about 700 nm to about 1000 nm.

Assignees

• Atala Anthony
• Yoo James
• Univ Wake Forest Health Sciences

Inventors

• Atala Anthony
• Yoo James

Classifications

• C12N2533/90

  Substrates of biological origin, e.g. extracellular matrix, decellularised tissue · CPC title

• C12N5/0068

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

• C12N5/069

  Vascular Endothelial cells · CPC title

• A61L27/3604

  characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel · CPC title

• A61L27/3826

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