Production of tissue engineered heart valves

• US 9,248,015 B2
• Filed: 03/10/2006
• Issued: 02/02/2016
• Est. Priority Date: 03/11/2005
• Status: Active Grant

• Current Assignee: Wake Forest University Health Sciences
• Original Assignee: Wake Forest University Health Sciences
• Inventors: Atala, Anthony, Yoo, James
• Primary Examiner(s): Noble, Marcia S
• Application Number:
  US11/373,066
• Publication Number:
  US 20060253192A1
• Time in Patent Office: 3,616 Days
• US Class Current: 1/1
• CPC Class Codes: A61F 2/2415 Manufacturing methods
• CPC Class Codes: A61L 27/3604 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 Class Codes: A61L 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3808 Endothelial 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 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• 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: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12N 2533/90 Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/069 Vascular Endothelial cells

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.

Claims

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.