Micro blood vessels and tissue ducts

Patent metadata

Field	Value
Publication number	US-10208289-B2
Application number	US-201514789269-A
Country	US
Kind code	B2
Filing date	Jul 1, 2015
Priority date	Jun 9, 2005
Publication date	Feb 19, 2019
Grant date	Feb 19, 2019

Abstract

A fiber includes one or more layers of polymer surrounding a central lumen, and living animal cells disposed within the lumen and/or within at least one of the one or more layers, wherein the fiber has an outer diameter of between 5 and 8000 microns and wherein each individual layer of polymer has a thickness of between 0.1 and 250 microns. Also disclosed are model tissues including such fibers, and method of making such fibers. The fibers can serve as synthetic blood vessels, ducts, or nerves.

First claim

What is claimed is:

1. A model tissue comprising:
a fiber comprising one or more layers of polymer surrounding a hollow central lumen with an inner polymer surface nearest the lumen;
a hydrogel matrix serving as three-dimensional scaffold and at least partially surrounding the fiber;
an inlet port and an outlet port at opposing ends of the fiber and operable to direct fluid through the lumen; and
living animal cells disposed in the model tissue and comprising at least endothelial cells adhered to the inner polymer surface and in intimate contact with the lumen, and optionally a second cell type within the one or more layers of polymer and/or the three-dimensional scaffold,
wherein the fiber remains intact during a condition of fluid flow through the lumen sufficient for the fiber to serve as physiological model of a blood vessel, and the fiber has an outer diameter of between 5 and 8000 microns and wherein each individual layer of polymer has a thickness of between 0.1 and 250 microns.

2. The model tissue of claim 1 , wherein said fiber is configured as a blood vessel, tissue duct, or nerve.

3. The model tissue of claim 1 , comprising a plurality of said fibers, wherein a single inlet port and a single outlet port are operably connected to the plurality of fibers.

4. The model tissue of claim 1 , further comprising cells adhered to an exterior surface of said fiber.

5. The model tissue of claim 1 , wherein the fiber is free of cell attachment along a surface.

6. The model tissue of claim 1 , wherein the polymer in at least one of said one or more layers is biodegradable.

7. The model tissue of claim 1 , wherein the polymer in at least one of said one or more layers comprises a material is selected from the group consisting of collagen, agarose, polyelectrolytes, chitosan, gelatin, polyethylene glycol, peptides, and combinations thereof.

8. The model tissue of claim 1 , wherein at least one of said one or more layers further comprises a nucleic acid and/or a factor to modify cell growth, adhesion, and/or differentiation.

9. A model tissue comprising:
a fiber comprising: at least two concentric layers of polymer surrounding a central lumen, and
living animal cells disposed within at least one of the at least two concentric layers of polymer and comprising at least endothelial cells adhered to the inner polymer surface and in intimate contact with the lumen, and optionally within the lumen,
wherein at least two different animal cells are disposed in different layers of polymer and/or lumen, and an inlet port and an outlet port at opposing ends of the fiber and operable to direct fluid through the lumen;
wherein the fiber remains intact during a condition of fluid flow through the lumen sufficient for the fiber to serve as physiological model of a blood vessel, and the fiber has an outer diameter of between 5 and 8000 microns and wherein each individual layer of polymer has a thickness of between 0.1 and 250 microns, and
wherein the fiber is at least partially surrounded by a hydrogel matrix serving as a three-dimensional scaffold for cells, the hydrogel matrix being distinct from that of an outer-most of the at least two concentric layers of polymer.

10. The model tissue of claim 9 , wherein said fiber is configured as a blood vessel, tissue duct, or nerve.

11. The model tissue of claim 9 , comprising a plurality of said fibers, wherein a single inlet port and a single outlet port are operably connected to the plurality of fibers.

12. The model tissue of claim 9 , further comprising cells adhered to an exterior surface of said fiber.

13. The model tissue of claim 9 , wherein the polymer in at least one of said one or more layers is biodegradable.

14. The model tissue of claim 9 , wherein the polymer in at least one of said one or more layers comprises a material is selected from the group consisting of collagen, agarose, polyelectrolytes, chitosan, gelatin, polyethylene glycol, peptides, and combinations thereof.

15. The model tissue of claim 9 , wherein at least one of said one or more layers further comprises a nucleic acid and/or a factor to modify cell growth, adhesion, and/or differentiation.

16. The model tissue of claim 1 , wherein the living animal cells include human umbilical vein endothelial cells surrounding the central lumen, primary coronary artery smooth muscle cells in one of the layers, and human dermal fibroblasts in another one of the layers, exterior to the layer including the primary coronary artery smooth muscle cells.

17. The model tissue of claim 9 , where said at least two different animal cells include human umbilical vein endothelial cells surrounding the central lumen, primary coronary artery smooth muscle cells in one of the layers, and human dermal fibroblasts in another one of the layers, exterior to the layer including the primary coronary artery smooth muscle cells.

18. The model tissue of claim 1 ,
further comprising a microfluidic chip having a chamber space defined by chamber walls housing the hydrogel matrix,
wherein the fiber passes through the chamber space and through the chamber walls with the lumen open at each end outside the chamber space.

19. The model tissue of claim 9 ,
further comprising a microfluidic chip having a chamber space defined by chamber walls housing the hydrogel matrix,
wherein the fiber passes through the chamber space and through the chamber walls with the lumen open at each end outside the chamber space.

Assignees

• Adams Andre A
• Daniele Michael
• Ligler Frances S
• Us Navy

Inventors

• Adams André A
• Daniele Michael
• Ligler Frances S

Classifications

• B29D99/0078

  Producing filamentary materials · CPC title

• G02B2006/0325

  Fluid core or cladding · CPC title

• G02B6/032

  with non solid core or cladding {(G02B6/02295 takes precedence)} · CPC title

• B01J2219/00831

  Glass · CPC title

• B01L2300/0838

  Capillaries · CPC title