FABRICATION OF INTERCONNECTED MODEL VASCULATURE

• US 20120058174A1
• Filed: 08/17/2011
• Published: 03/08/2012
• Est. Priority Date: 02/17/2009
• Status: Active Grant

• Current Assignee: Rice University, University of Pennsylvania
• Original Assignee: Rice University
• Inventors: West, Jennifer L., Chen, Christopher S., Miller, Jordan S., Yang, Michael T.
• Granted Patent: US 9,452,239 B2
• Time in Patent Office: Days
• US Class Current: 424/443
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges

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

1. A method comprising:

forming a non-woven fiber network comprising a plurality of fibers and a void space;

backfilling the void space of the non-woven fiber network; and

removing the plurality of fibers to form a substantially interconnected vascular network comprising fluidic channels.

2. The method of claim 1 wherein forming a non-woven fiber network comprises using electrospinning with an unstable Taylor cone.

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

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

5. The method of claim 1 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, methylcelluose, poly(lactic acid), poly(ethylene glycol), and chitosan.

6. The method of claim 1 wherein the step of backfilling the void space of the non-woven fiber network comprises backfilling the void space with at least one material selected from the group consisting of a biomaterial, a plurality of cells, and a biomaterial comprising a suspension of living cells.

7. The method of claim 6 wherein the biomaterial comprises at least one biomaterial selected from the group consisting of:

polydimethylsiloxane, a polyamide, poly(siloxane), a poly(silicone), poly(ethylene), poly(vinyl pyrrolidone), poly(-hydroxy ethyl methacrylate), poly(N-vinyl pyrrolidone), poly(methyl methacrylate), poly(vinyl alcohol), poly(acrylic acid), poly(vinyl acetate), polyacrylamide, poly(ethylene-co-vinyl acetate), poly(ethylene glycol), poly(methacrylic acid), poly(lactic acid), poly(glycolic acid), poly(lactide-co-glycolides), a polyanhydride, a polyorthoester, poly(carbonate), poly(acrylo nitrile), poly(ethylene oxide), polyaniline, polyvinyl carbazole, polystyrene, poly(vinyl phenol), a polyhydroxyacid, poly(caprolactone), a polyhydroxyalkanoate, 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.

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

9. The method of claim 1 wherein the step of backfilling the void space of the non-woven fiber network comprises backfilling the void space with a biomaterial comprising a suspension of living cells;

and

wherein the step of removing the fibers does not damage the living cells.

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

11. The method of claim 1 further comprising surface coating the fiber network with 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.

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

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

14. The method of claim 1 wherein the distance between the fibers is no more than about 100 μ

m.

15. The method of claim 1 wherein the distance between the fibers is no more than about 200 μ

m.

16. The method of claim 1 wherein the distance between the fibers is no more than about 500 μ

m.

17. The method of claim 1 wherein the distance between the fibers is no more than about 1 millimeter.

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

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

forming a fiber network comprising a plurality of fibers and a void space;

surface coating the fiber network with a surface coating material;

backfilling the void space of the fiber network with a biomaterial; and

removing the fibers to form a substantially interconnected vascular network comprising fluidic channels.

20. The method of claim 19 wherein forming a fiber network comprises using electrospinning with an unstable Taylor cone, a plurality of melt extrusion dies or melt extrusion speeds, a three-dimensional printer, or a combination thereof.

21. The method of claim 19 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, methylcelluose, poly(lactic acid), poly(ethylene glycol), and chitosan.

22. The method of claim 19 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.

23. The method of claim 19 wherein the biomaterial comprises at least one biomaterial selected from the group consisting of:

polydimethylsiloxane, a polyamide, poly(siloxane), a poly(silicone), poly(ethylene), poly(vinyl pyrrolidone), poly(-hydroxy ethyl methacrylate), poly(N-vinyl pyrrolidone), poly(methyl methacrylate), poly(vinyl alcohol), poly(acrylic acid), poly(vinyl acetate), polyacrylamide, poly(ethylene-co-vinyl acetate), poly(ethylene glycol), poly(methacrylic acid), poly(lactic acid), poly(glycolic acid), poly(lactide-co-glycolides), a polyanhydride, a polyorthoester, poly(carbonate), poly(acrylo nitrile), poly(ethylene oxide), polyaniline, polyvinyl carbazole, polystyrene, poly(vinyl phenol), a polyhydroxyacid, poly(caprolactone), a polyhydroxyalkanoate, 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.

24. The method of claim 19 wherein the biomaterial 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.

25. The method of claim 19 wherein the biomaterial further comprises a human bone morphogenic protein or a DNA plasmid that encodes for a protein that stimulates mineralization and bone formation.

26. The method of claim 19 wherein the step of removing the fibers is performed by wet etching or dissolution.

27. The method of claim 19 wherein the step of removing the fibers is performed by degradation.

28. A method comprising:

providing a fiber network, the fiber network comprising a plurality of fibers; and

coating at least a portion of the surface of the fibers with a surface coating material so as to at least partially inhibit wet etching or dissolution of the fiber network.

29. The method of claim 28 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.

30. The method of claim 28 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, methylcelluose, poly(lactic acid), poly(ethylene glycol), and chitosan.

31. A composition comprising:

a biomaterial; and

a plurality of substantially interconnected fluidic channels disposed within the biomaterial wherein the fluidic channels have a total volumetric density of between about 5% and 95% of the biomaterial and wherein the distance between the fluidic channels is no more than about 1 mm.

32. The composition of claim 31 wherein the distance between the fibers is no more than about 100 μ

m.

33. The composition of claim 31 wherein the distance between the fibers is no more than about 200 μ

m.

34. The composition of claim 31 wherein the distance between the fibers is no more than about 500 μ

m.

35. The composition of claim 31 wherein the biomaterial comprises at least one biomaterial selected from the group consisting of:

polydimethylsiloxane, a polyamide, poly(siloxane), a poly(silicone), poly(ethylene), poly(vinyl pyrrolidone), poly(-hydroxy ethyl methacrylate), poly(N-vinyl pyrrolidone), poly(methyl methacrylate), poly(vinyl alcohol), poly(acrylic acid), poly(vinyl acetate), polyacrylamide, poly(ethylene-co-vinyl acetate), poly(ethylene glycol), poly(methacrylic acid), poly(lactic acid), poly(glycolic acid), poly(lactide-co-glycolides), a polyanhydride, a polyorthoester, poly(carbonate), poly(acrylo nitrile), poly(ethylene oxide), polyaniline, polyvinyl carbazole, polystyrene, poly(vinyl phenol), a polyhydroxyacid, poly(caprolactone), a polyhydroxyalkanoate, 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.

36. The composition of claim 31 wherein the biomaterial 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.

37. The composition of claim 31 wherein a portion or all of the fluidic channels are coated with living endothelial cells.

38. The composition of claim 31 wherein the biomaterial further comprises living mammalian cells.

39. A composition comprising:

a plurality of fibers arranged in a substantially interconnected network in which the distance between the fibers is no more than about 1 mm.

40. The composition of claim 39 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, methylcelluose, poly(lactic acid), poly(ethylene glycol), and chitosan.

41. The composition of claim 39 wherein the distance between the fibers is no more than about 100 μ

m.

42. The composition of claim 39 wherein the distance between the fibers is no more than about 200 μ

m.

43. The composition of claim 39 wherein the distance between the fibers is no more than about 500 μ

m.

44. The composition of claim 39 wherein the fibers are at least partially coated with a surface coating material.

45. The composition of claim 39 wherein the fibers are at least partially coated with a surface coating material comprising 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.