Tissue engineered blood vessels and apparatus for their manufacture
The invention is a tissue engineered blood vessel (TEBV) made from a cultured fibroblast sheet rolled into a multilayer vessel which has sufficient burst strength to withstand physiological blood pressure without the inclusion of smooth muscle cells or synthetic scaffolding. The TEBV is made in a bioreactor having an enclosed chamber, a sheet growth module, a rollable mandrel, and a clamp for holding the sheet to the mandrel for rolling.
1. A TEBV consisting of:
a) an inner layer of endothelial cells;
b) a middle layer of denatured fibroblasts; and
c) an outer layer of living fibroblasts.
2. The TEBV of claim 1 which is prepared as follows:
a) providing a first fibroblast layer which is a cultured fibroblast sheet rolled into a multilayer vessel which has been matured and then denatured;
b) rolling a cultured fibroblast sheet around the first fibroblast layer to form a second fibroblast layer;
c) maturing the second fibroblast layer; and
d) forming a layer of endothelial cells on the inner surface of the first fibroblast layer.
3. The TEBV of claim 1 wherein the fibroblasts are stimulated to produce an extracellular matrix (ECM).
4. The TEBV of claim 1 wherein the fibroblasts are autologous.
5. The TEBV of claim 1 wherein the fibroblasts are allogenic.
6. The TEBV of claim 1 wherein the fibroblasts are genetically modified.
7. The TEBV of claim 1 wherein the endothelial cells are autologous.
8. The TEBV of claim 1 having two ends adapted to be attached to a human blood vessel.
9. The TEBV of claim 8 wherein staples are attached to one end.
10. The TEBV of claim 8 wherein sutures are attached to one end.
11. The TEBV of claim 8 wherein sutures are attached to both ends of the TEBV.
12. The TEBV of claim 8 wherein staples are attached to both ends of the TEBV.
13. The TEBV of claim 8 wherein the ends are tapered.
14. The TEBV of claim 4 , wherein the autologous fibroblasts are obtained from a subject having a vascular disease.
15. The TEBV of claim 11 wherein the two ends are flared.
16. The TEBV of claim 1 wherein the fibroblasts are obtained from skin or a blood vessel.
17. The TEBV of claim 1 wherein the endothelial cells are obtained from skin or a blood vessel.
18. The TEBV of claim 1 wherein at least one fibroblast layer is matured after rolling.
19. The TEBV of claim 1 which is prepared by rolling a cultured fibroblast sheet into a multilayer vessel, selectively denaturing at least one inner layer of the vessel and forming a layer of endothelial cells on the inner surface of the denatured fibroblast layer.
20. The TEBV of 19 wherein the rolled fibroblast sheet is matured prior to denaturation.