Fibrous scaffold for use in soft tissue engineering
The present invention relates to a fibrous scaffold for use as a substrate in soft tissue applications, in particular for preparing annulus fibrosus (AF) tissue. In aspects, the present invention also relates to an engineered biological material comprising AF tissue; constructs comprising one or more engineered biological materials; methods for producing the biological materials and constructs; and methods of using the biological materials and constructs.
1. A fibrous scaffold for culturing soft tissues on its surface, said scaffold comprising fibres comprising a blend of biodegradable polyurethane polymers and anionic dihydroxyl oligomers, wherein the concentration of the oligomers in the blend is less than about 5 wt % and the anionic dihydroxyl oligomers are characterized by one or both of the following properties:
a) absorption bands in the about 600 cm −1 to about 4000 cm −1 region by Fourier transform infrared spectroscopy (FTIR); or
b) a peak corresponding to a urethane group at about 1680 to about 1750 cm −1 , by FTIR.
2. A fibrous scaffold according to claim 1 , wherein the fibres are random.
3. A fibrous scaffold according to claim 1 , wherein the fibres are aligned.
4. A fibrous scaffold according to claim 1 , which is a nanofiber porous scaffold.
5. A fibrous scaffold according to claim 1 , wherein the biodegradable polyurethane polymers comprise hydrolysable polyurethane chains.
6. A fibrous scaffold according to claim 1 , wherein the biodegradable polyurethane polymers are polycarbonate urethane polymers.
7. A fibrous scaffold according to claim 1 having a fibre thickness of between about 130 to about 1500 nm.
8. A process for preparing a fibrous scaffold as claimed in claim 1 , comprising
blending the biodegradable polyurethane polymers and anionic dihydroxyl oligomers to form a biodegradable polyurethane formulation, wherein the concentration of the oligomers in the formulation is less than about 5 wt %; and
electrospinning the formulation to form the fibrous scaffold.
9. An engineered biological material characterized by a continuous layer of annulus fibrosus tissue on a fibrous scaffold according to claim 1 .
10. A process for producing an engineered biological material of claim 9 comprising:
(a) forming a layer of isolated annulus fibrosus cells on a fibrous scaffold for culturing soft tissues on its surface, said scaffold comprising fibres comprising a blend of biodegradable polyurethane polymers and anionic dihydroxyl oligomers; and
(b) culturing the annulus fibrosus cells in culture media so that the annulus fibrosus cells accumulate extracellular matrix and form a continuous layer of annulus fibrosus tissue.
11. A method of replacing or repairing damaged, degenerated or deficient intervertebral discs or portions thereof of a patient, said method comprising implanting an engineered biological material according to claim 9 or annulus fibrosus tissue therefrom into the site of the damaged, degenerated or deficient intervertebral disc or portions thereof, of the patient.
12. A fibrous scaffold according to claim 1 , wherein said biodegradable polyurethane polymers comprise lysine diisocyanate groups.
13. A fibrous scaffold according to claim 1 , wherein said biodegradable polyurethane polymers are polyester urethane polymers.
14. A fibrous scaffold according to claim 1 , wherein the concentration of the oligomers in the blend is less than about 0.5 wt %.
15. A fibrous scaffold according to claim 1 , wherein said soft tissues are grown on the surface of said fibrous scaffold.
16. A fibrous scaffold for culturing soft tissues on its surface, said scaffold comprising fibres comprising a blend of biodegradable polyurethane polymers and anionic dihydroxyl oligomers, wherein the concentration of the oligomers in the blend is less than about 5 wt % and about 50% to about 70% of the anionic groups of said anionic dihydroxyl oligomers comprise carboxylic acid groups.
17. A fibrous scaffold according to claim 16 , wherein the fibres are random.
18. A fibrous scaffold according to claim 16 , wherein the fibres are aligned.
19. A fibrous scaffold according to claim 16 , which is a nanofiber porous scaffold.
20. A fibrous scaffold according to claim 16 , wherein the biodegradable polyurethane polymers comprise hydrolysable polyurethane chains.
21. A fibrous scaffold according to claim 16 , wherein the biodegradable polyurethane polymers are polycarbonate urethane polymers.
22. A fibrous scaffold according to claim 16 having a fibre thickness of between about 130 to about 1500 nm.
23. A process for preparing a fibrous scaffold as claimed in claim 16 , comprising
blending the biodegradable polyurethane polymers and anionic dihydroxyl oligomers to form a biodegradable polyurethane formulation, wherein the concentration of the oligomers in the formulation is less than about 5 wt %; and
electrospinning the formulation to form the fibrous scaffold.
24. An engineered biological material characterized by a continuous layer of annulus fibrosus tissue on a fibrous scaffold according to claim 16 .
25. A process for producing an engineered biological material of claim 24 comprising:
(a) forming a layer of isolated annulus fibrosus cells on a fibrous scaffold for culturing soft tissues on its surface, said scaffold comprising fibres comprising a blend of biodegradable polyurethane polymers and anionic dihydroxyl oligomers; and
(b) culturing the annulus fibrosus cells in culture media so that the annulus fibrosus cells accumulate extracellular matrix and form a continuous layer of annulus fibrosus tissue.
26. A method of replacing or repairing damaged, degenerated or deficient intervertebral discs or portions thereof of a patient, said method comprising implanting an engineered biological material according to claim 24 or annulus fibrosus tissue therefrom into the site of the damaged, degenerated or deficient intervertebral disc or portions thereof, of the patient.
27. A fibrous scaffold according to claim 16 , wherein said biodegradable polyurethane polymers comprise lysine diisocyanate groups.
28. A fibrous scaffold according to claim 16 , wherein said biodegradable polyurethane polymers are polyester urethane polymers.
29. A fibrous scaffold according to claim 16 , wherein the concentration of the oligomers in the blend is less than about 0.5 wt %.
30. A fibrous scaffold according to claim 16 , wherein said soft tissues are grown on the surface of said fibrous scaffold.