Decellularized biologically-engineered tubular grafts
This disclosure describes decellularized, biologically-engineered tubular grafts and methods of making and using such decellularized, biologically-engineered tubular grafts.
1. A decellularized, biologically-engineered graft, made by a method comprising:
combining matrix-producing cells, fibrinogen and thrombin to produce a cell-seeded fibrin gel,
shaping and conditioning the gel in the presence of culture medium to result in a cell-produced extracellular matrix comprising circumferentially aligned fibers, wherein the conditioning comprises stretching or distending the gel and/or the extracellular matrix, during which and axial length of the gel and/or the extracellular matrix shortens; and
decellularizing the extracellular matrix to produce the decellularized, biologically engineered graft.
2. The decellularized, biologically-engineered graft of claim 1 , wherein the number of matrix-producing cells is between about 10 2 matrix-producing cells and about 10 12 matrix-producing cells.
3. The decellularized, biologically-engineered graft of claim 1 , wherein the matrix-producing cells are fibroblasts.
4. The decellularized, biologically-engineered graft of claim 3 , wherein the fibroblasts are dermal fibroblasts.
5. The decellularized, biologically-engineered graft of claim 1 , wherein shaping comprises molding the cell-seeded fibrin gel into a tube.
6. The decellularized, biologically-engineered graft of claim 5 , wherein the tube is hollow.
7. The decellularized, biologically-engineered graft of claim 1 , wherein the decellularized graft is tubular.
8. The decellularized, biologically-engineered graft of claim 7 , wherein the tubular graft is hollow.
9. The decellularized, biologically-engineered graft of claim 1 , wherein the graft exhibits greater tensile stiffness in the circumferential direction than in the longitudinal direction.
10. The decellularized, biologically-engineered graft of claim 1 , wherein the graft exhibits a burst pressure of at least 2000 mm Hg.
11. The decellularized, biologically-engineered graft of claim 1 , wherein the decellularized graft is a vascular graft.
12. The decellularized, biologically-engineered graft of claim 11 , wherein the decellularized graft is an arterial graft.
13. The decellularized, biologically-engineered graft of claim 11 , wherein the decellularized graft is a venous graft.
14. The decellularized, biologically-engineered graft of claim 1 , wherein the decellularized graft is selected from the group consisting of a urethra graft, a fallopian tube graft, a Vas deferens graft, or a Eustachian tube graft.
15. The decellularized, biologically-engineered graft of claim 1 , wherein the decellularized graft has an average diameter of about 0.5 mm to about 6 mm.
16. The decellularized, biologically-engineered graft of claim 1 , wherein the decellularized graft has an average diameter of about 5 mm to about 12 mm.
17. The decellularized, biologically-engineered graft of claim 1 , wherein the decellularized graft has an average diameter of about 10 mm to about 20 mm.
18. The decellularized, biologically-engineered graft of claim 1 , the method further comprising anchoring one end of the decellularized graft at two or more positions to shape the decellularized graft into a leaflet valve.
19. The decellularized, biologically-engineered graft of claim 18 , wherein the anchoring is at two positions to shape the decellularized graft into a bi-leaflet valve.
20. The decellularized, biologically-engineered graft of claim 18 , wherein the anchoring is at three positions to shape the decellularized graft into a tri-leaflet valve.
21. The decellularized, biologically-engineered graft of claim 18 , wherein the anchoring is at four positions to shape the decellularized graft into a quad-leaflet valve.
22. The decellularized, biologically-engineered graft of claim 18 , wherein the one end of the decellularized graft is anchored at two or more positions to a stent.
23. A decellularized, biologically-engineered tissue, made by a method comprising:
combining fibrinogen or fibrinogen-like material, thrombin, and matrix-producing cells to produce a cell-seeded gel composition;
conditioning the gel composition in the presence of culture medium to remodel the composition into a cell-produced extracellular matrix comprising circumferentially aligned fibers, wherein the conditioning comprises stretching or distending the gel composition and/or the extracellular matrix, during which and axial length of the gel composition and/or the extracellular matrix shortens; and
decellularizing the extracellular matrix to produce a decellularized tissue.