Artificial silk based innervated cornea
In some embodiments, the present invention provides tissue compositions including a first silk scaffold comprising a plurality of epithelial cells, a second silk scaffold comprising a plurality of stromal cells, and a plurality of neurons. In some embodiments, provided compositions can function as physiologically relevant corneal model systems for, inter alia, testing of therapeutics for corneal disease and/or injury and production of functional corneal tissue (e.g., for transplant, etc). The present invention also provides methods for making and using provided compositions.
1. A tissue composition comprising
a first silk scaffold comprising a plurality of epithelial cells;
a second silk scaffold comprising a plurality of stromal cells;
and a plurality of neurons;
wherein one or more silk scaffold has a porosity of at least 10%.
2. The composition of claim 1 , wherein the plurality of neurons are present in a third silk scaffold.
3. The composition of claim 2 , wherein the third silk scaffold at least partially surrounds the first and second silk scaffolds.
4. The tissue compostion of claim 1 , further comprising a third silk scaffold.
5. The composition of claim 1 , wherein the neurons are human neurons.
6. The composition of claim 1 , wherein the stromal cells comprise keratocytes and/or corneal stromal fibroblast cells.
7. The composition of claim 1 , wherein at least one silk scaffold is selected from a silk film, a silk sponge, silk hydrogel and a silk-collagen mix hydrogel.
8. The tissue composition of claim 1 , wherein the first silk scaffold and/or the second silk scaffold is optically clear.
9. A method of making a tissue composition comprising
providing a first silk scaffold comprising a plurality of epithelial cells;
associating a second silk scaffold comprising a plurality of stromal cells with the first silk scaffold to form a silk scaffold stack; and
introducing a plurality of neurons to the silk scaffold stack to form a tissue composition,
wherein at least some of the plurality of neurons innervate at least one of: a portion of the epithelial cells, and a portion of the stromal cells;
wherein one or more silk scaffold has a porosity of at least 10%.
10. A tissue composition comprising
a first silk scaffold comprising a plurality of epithelial cells;
a second silk scaffold comprising a plurality of stromal cells;
a plurality of neurons; and
a tear-like fluid;
wherein the tear-like fluid is or comprises an aqueous solution including at least one lipid, at least one antibiotic, and at least one neurotrophic peptide.
11. The tissue composition of claim 1 , wherein the first silk scaffold and the second silk scaffold are associated to form a silk scaffold stack.
12. The tissue composition of claim 10 , wherein the plurality of neurons are present in a third silk scaffold.
13. The tissue composition of claim 12 , wherein the third silk scaffold at least partially surrounds the first and second silk scaffolds.
14. The tissue composition of claim 10 , wherein the neurons are human neurons.
15. The tissue composition of claim 10 , wherein the first silk scaffold and the second silk scaffold are associated to form a silk scaffold stack.
16. The tissue composition of claim 10 , wherein the first silk scaffold and/or the second silk scaffold is optically clear.