IP Library Granted Patent US 9,452,239
Granted Patent B2
US 9,452,239 · App. 13/211,478 · Granted Sep 27, 2016

Fabrication of interconnected model vasculature

Inventors: Jennifer L. West (Houston, TX); Christopher S. Chen (Princeton, NJ); Jordan S. Miller (Philadelphia, PA); Michael T. Yang (Philadelphia, PA)
Assignees: William Marsh Rice University; University of Pennsylvania
A61L27/56A61L27/38A61L2400/18
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Quick Facts
Patent No.
US 9,452,239
App. No.
13/211,478
Granted
Sep 27, 2016
Kind
B2
Abstract

Methods of fabricating a substantially interconnected model vasculature, as well as compositions formed from such methods are provided. In some embodiments, the methods may comprise forming a non-woven fiber network comprising a plurality of fibers and a void space; backfilling the void space of the fiber network; and removing the fibers to form a substantially interconnected vascular network.

Claims (21)

1. A method of forming a substantially interconnected vascular network, comprising:

forming a fiber network comprising a plurality of fibers and a void space, wherein the plurality of fibers is capable of dissolving or degrading in water;

surface coating the plurality of fibers with a surface coating material, wherein the surface coating material does not backfill the void space;

backfilling the void space of the fiber network with an aqueous solution comprising a biomaterial, wherein the biomaterial and the surface coating material are different materials;

cross-linking the biomaterial to form a hydrogel in the void space; and

removing the fibers to form a substantially interconnected vascular network comprising fluidic channels wherein the fibers comprise at least one material selected from the group consisting of: photoresist, agarose, gelatin, carbohydrates, sucrose, glucose, fructose, lactose, isomalt, dextran, cellulose, methylcellulose, poly(lactic acid), poly(ethylene glycol), and chitosan, and

wherein the surface coating material comprises at least one material selected from the group consisting of: polylactic acid, a solution of polylactic acid in dichloromethane, poly(lactic co-glycolic acid), a solution of poly(lactic co-glycolic acid) in chloroform, collagen, gelatin, zein, shellac, a starch, and petroleum jelly.

2. The method of claim 1 wherein forming a fiber network comprises using electrospinning with a Taylor cone that produces fiber diameters with a standard deviation greater than about plus or minus 10%, a plurality of melt extrusion dies or melt extrusion speeds, a three-dimensional printer, or a combination thereof.

3. The method of claim 1 wherein the biomaterial comprises at least one biomaterial selected from the group consisting of: a polyamide, poly(2-hydroxy ethyl methacrylate), poly(vinyl alcohol), polyacrylamide, poly(ethylene glycol), a polyurethane, collagen, agarose, albumin, alginate, chitosan, starch, hyaluronic acid, gelatin, fibrin, matrigel, glycerol, glycol, mannitol, inositol, xylitol, adonitol, glycine, arginine, biological polymeric molecules, albumin, peptide amphiphiles, and monomers, dimers, and oligomers thereof.

4. The method of claim 1 wherein the aqueous solution further comprises at least one component selected from the group consisting of: a suspension of living cells, a protein, DNA, a nanoparticles, and a moiety used for drug delivery.

5. The method of claim 1 wherein the aqueous solution further comprises a human bone morphogenic protein or a DNA plasmid that encodes for a protein that stimulates mineralization and bone formation.

6. The method of claim 1 wherein the step of removing the fibers is performed by wet etching or dissolution.

7. The method of claim 1 wherein the step of removing the fibers is performed by degradation.

8. The method of claim 1 wherein forming a fiber network comprises using electrospinning with a Taylor cone that produces fiber diameters with a standard deviation greater than about plus or minus 10%.

9. The method of claim 1 wherein forming a fiber network comprises using a plurality of melt extrusion dies or varying melt extrusion speeds.

10. The method of claim 1 wherein forming a fiber network comprises using a three-dimensional printer.

11. The method of claim 1 wherein the fiber network is a non-woven fiber network.

12. The method of claim 1 wherein the aqueous solution further comprises a suspension of living cells; and wherein the step of removing the fibers does not damage the living cells.

13. The method of claim 1 wherein the plurality of fibers are hollow.

14. The method of claim 1 wherein the plurality of fibers are solid.

15. The method of claim 1 further comprising applying heat to at least a portion of the fiber network prior to backfilling the void space of the fiber network.

Assignments (4)
CONFIRMATORY LICENSE Recorded Sep 17, 2013
From: RICE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 031288/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 16, 2011
From: WEST, JENNIFER L.
To: WILLIAM RICE MARSH UNIVERSITY
Reel/Frame 027238/0988 →
CORRECTIVE ASSIGNMENT TO CORRECT THE NAME OF THE ASSIGNEE PREVIOUSLY RECORDED ON REEL 027238 FRAME 0988. ASSIGNOR(S) HEREBY CONFIRMS THE THE ASSIGNEE NAME SHOULD BE CHANGED FROM WILLIAM RICE MARSH UNIVERSITY TO WILLIAM MARSH RICE UNIVERSITY. Recorded Nov 16, 2011
From: WEST, JENNIFER L.
To: WILLIAM MARSH RICE UNIVERSITY
Reel/Frame 027242/0085 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 13, 2011
From: CHEN, CHRISTOPHER S.; MILLER, JORDAN S.; YANG, MICHAEL T.
To: UNIVERSITY OF PENNSYLVANIA
Reel/Frame 027058/0769 →
Continuity (3)
Continuation In Part PCTUS2010024457 · Feb 17, 2010
Provisional Application 61153096 · Feb 17, 2009
Related Publication 20120058174A1 · Mar 8, 2012