Biomimetic vascular network and devices using the same

• US 8,591,597 B2
• Filed: 03/22/2010
• Issued: 11/26/2013
• Est. Priority Date: 04/12/2007
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Hoganson, David M., Vacanti, Joseph P., Pryor, Howard I.
• Primary Examiner(s): GHERBI, SUZETTE JAIME J
• Application Number:
  US12/728,557
• Publication Number:
  US 20100274353A1
• Time in Patent Office: 1,345 Days
• Field of Search: 623 2364- 2371, 623 142- 148, 424/422
• US Class Current: 623/23.64
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61F 2/04 Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts A61F2/18, A61F2/20 take precedence; devices, other than stent-grafts, providing patency to, or preventing collapsing of, tubular structures of the body other than stent-grafts, e.g. stents A61F2/82; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61F 2/062 Apparatus for the production of blood vessels made from natural tissue or with layers of living cells prostheses made from natural tissue or living cells A61L27/507
• CPC Class Codes: A61F 2002/068 Modifying the blood flow model, e.g. by diffuser or deflector
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics

Abstract

The invention provides method of fabricating a scaffold comprising a fluidic network, including the steps of: (a) generating an initial vascular layer for enclosing the chamber and providing fluid to the cells, the initial vascular layer having a network of channels for fluid; (b) translating the initial vascular layer into a model for fluid dynamics analysis; (c) analyzing the initial vascular layer based on desired parameters selected from the group consisting of a characteristic of a specific fluid, an input pressure, an output pressure, an overall flow rate and combinations thereof to determine sheer stress and velocity within the network of channels; (d) measuring the sheer stress and the velocity and comparing the obtained values to predetermined values; (e) determining if either of the shear stress or the velocity are greater than or less than the predetermined values, and (f) optionally modifying the initial vascular layer and repeating steps (b)-(e). The invention also provides compositions comprising a vascular layer for use in tissue lamina as well as a medical devices having a vascular layer and kits.

Claims

1. An artificial vascular layer comprising:

a substrate defining a network of channels arranged in a radial pattern having at least one central output channel, a plurality of radially outward input channels, and a plurality of intermediate channels connecting the input channels and the at least one output channel, each channel having a height, a length, a width, and a diameter, wherein the intermediate channels undergo multiple branching and rejoining to form hexagonal areas intermediate to the intermediate channels,

the intermediate channels being formed by varying said height and width with respect to adjacent portions of the channels and the length of a smallest of the intermediate channels is formed based on the respective diameter whereby said smallest intermediate channel has a biomimetic length.

2. An artificial vascular layer as recited in claim 1, wherein the channels are rectangular with an aspect ratio of 1:

1.

3. An artificial vascular layer as recited in claim 1, wherein the intermediate channels successively branch and rejoin, in a bifurcating manner, into successively smaller and larger portions, respectively, with bifurcation angles of 45 degrees.

4. An artificial vascular layer as recited in claim 1, wherein a smallest diameter intermediate channels is preferably 200 um in diameter while a largest initial intermediate channel from the input channels are 608 um in diameter.

5. An artificial vascular layer as recited in claim 1, wherein the biomimetic lengths of all of the channels are scaled in an equal fashion.

6. An artificial vascular layer as recited in claim 1, wherein the intermediate channels have radii of curvature to improve the flow characteristics.

7. An artificial vascular layer as recited in claim 1, wherein the substrate is collagen.

8. An artificial vascular layer as recited in claim 1, further comprising elastin in the collagen substrate.

9. An artificial vascular layer as recited in claim 1, further comprising fibronectin in the collagen substrate.

10. An artificial vascular layer as recited in claim 1, wherein the channels carry a fluid and the fluid is blood, plasma or media.

11. An artificial vascular layer as recited in claim 1, wherein the layer comprises a medical device for assisting or replacing an organ.

12. An artificial vascular layer as recited in claim 1, wherein the layer comprises a tool for drug discovery, development and/or evaluation.

13. An artificial vascular layer as recited in claim 1, wherein the layer comprises a platform for in vitro or ex vivo research and testing.

14. An artificial vascular layer as recited in claim 1, further comprising a second header layer having a nozzle in fluid communication with the at least one output channel to connect to a vein.

15. An artificial vascular layer as recited in claim 1, wherein the intermediate channels trifurcate at least once.

16. An artificial vascular layer comprising:

a substrate defining a network of channels arranged in a radial pattern having at least one central output channel, a plurality of radially outward input channels, and a plurality of intermediate channels connecting the input channels and the at least one output channel, each channel having a height, a length, a width, and a diameter, wherein the intermediate channels undergo multiple branching and rejoining to form hexagonal areas intermediate to the intermediate channels,

the intermediate channels being formed by varying said height and width with respect to adjacent portions of the channels and the length of a smallest diameter of the intermediate channels is formed based on the respective diameter whereby said smallest diameter channel has a biomimetic length.

17. An artificial vascular layer comprising:

a substrate defining a network of channels arranged in a radial pattern having at least one central output channel, a plurality of radially outward input channels, and a plurality of intermediate channels connecting the input channels and the at least one output channel, each channel having a height, a length, a width, and a diameter, wherein the intermediate channels undergo multiple branching and rejoining to form hexagonal areas intermediate to the intermediate channels,

the intermediate channels being formed by varying said height and width with respect to adjacent portions of the channels and the length of a smallest of the intermediate channels is formed based on the respective diameter whereby said smallest channel has a biomimetic length.