Electroprocessed fibrin-based matrices and tissues

• US 7,759,082 B2
• Filed: 01/26/2004
• Issued: 07/20/2010
• Est. Priority Date: 02/25/1999
• Status: Expired due to Fees

• Current Assignee: Virginia Commonwealth University
• Original Assignee: Virginia Commonwealth University
• Inventors: Carr, Marcus E. Jr., Simpson, David G., Bowlin, Gary L., Wnek, Gary E., Lam, Philippe
• Primary Examiner(s): Weber; Jon P
• Assistant Examiner(s): Singh; Satyendra K
• Application Number:
  US10/764,691
• Publication Number:
  US 20040229333A1
• Time in Patent Office: 2,367 Days
• Field of Search: None
• US Class Current: 435/13
• CPC Class Codes: A61K 2035/126 Immunoprotecting barriers, e.g. jackets, diffusion chambers
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61L 15/32 Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin A61L15/225 takes precedence
• CPC Class Codes: A61L 2400/04 Materials for stopping bleeding
• CPC Class Codes: A61L 27/225 Fibrin; Fibrinogen
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: B29C 41/006 using an electrostatic field for applying the material
• CPC Class Codes: C07K 14/75 Fibrinogen
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: C12N 2503/00 Use of cells in diagnostics
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 2533/56 : Fibrin; Thrombin
• CPC Class Codes: C12N 5/0012 : Cell encapsulation
• CPC Class Codes: C12N 5/0062 : General methods for three-dimensional culture
• CPC Class Codes: C12N 5/0068 : General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0622 : Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells

Abstract

The invention is directed to formation and use of electroprocessed fibrin as an extracellular matrix and, together with cells, its use in forming engineered tissue. The engineered tissue can include the synthetic manufacture of specific organs or tissues which may be implanted into a recipient. The electroprocessed fibrin may also be combined with other molecules in order to deliver the molecules to the site of application or implantation of the electroprocessed fibrin. The fibrin or fibrin/cell suspension is electrodeposited onto a substrate to form the tissues and organs.

Claims

1. Electrodeposited fibrin matrix with cells, wherein the cells are delivered to the matrix during fabrication of the electrodeposited fibrin matrix, wherein the cells are suspended in a solution comprising molecules capable of forming fibrin during delivery to the matrix, and wherein the cells are oriented through application of stretching mechanical force to the electrodeposited fibrin matrix.

2. The electrodeposited fibrin matrix with cells of claim 1, further comprising one or more substances.

3. The electrodeposited fibrin matrix with cells of claim 2, wherein the one or more substances is a growth factor, differentiation inducer, anti-oxidant, vitamin, hormone, nucleic acid, drug, peptide, emollient, humectant, conditioner or cosmetic.

4. A method of evaluating a biological response of a cell to a substance, comprising:

applying the substance to the electrodeposited fibrin matrix with cells of claim 1; and

,

evaluating the biological response of the cell.

5. The method of claim 4, wherein the cell is a cancer cell.

7. The electrodeposited fibrin matrix with cells of claim 1, wherein the cells are spread in parallel with the applied stretching mechanical force.

8. The electrodeposited fibrin matrix of any one of claims 1, 6 or 7, further comprising a cross-linking agent.

9. The electrodeposited fibrin matrix of any one of claims 1, 6, or 7, further comprising calcium.

6. An electrodeposited fibrin matrix with cells, wherein the cells are entrapped within the matrix during fabrication of the electrodeposited fibrin matrix, wherein the cells are suspended in a fibrinogen solution during delivery to the matrix, and wherein the cells are oriented through application of stretching mechanical force to the electrodeposited fibrin matrix.