Multilayer tissue regeneration system
A system for growing tissue based upon layers of an inorganic matrix, wherein each layer of the inorganic matrix is designed to dissolve at a separate rate and result in sequential growth factor delivery upon its dissolution.
1. A tissue regeneration system comprising:
a template having thereupon at least one synthetic, degradable extracellular matrix layer; and
at least one biomolecule releasably associated with the layer, the biomolecule comprising a cell-affecting portion and a matrix-binding portion, wherein the cell-affecting portion is selected from the group consisting of fibroblast growth factor 2, bone morphogenetic protein-2, bone morphogenetic protein-7 and vascular endothelial growth factor.
2. A tissue regeneration system as recited in claim 1 , wherein the template comprises polar oxygen groups.
3. A tissue regeneration system as recited in claim 2 , wherein the polar oxygen groups are selected from the group consisting of carboxylic acids, phosphates, aldehydes, ketones, alcohols, carbonyls, hydroxyls and metal oxides.
4. A tissue regeneration system as recited in claim 1 , wherein the template is selected from the group consisting of polycarboxylates, polyanhydrides, poly(α-hydroxy esters), poly(ethylene terephthalate), poly(carbonates), poly(amides), poly(lactones), poly(saccharides) and poly(acrylates).
5. A tissue regeneration system as recited in claim 1 , wherein the extracellular matrix layer comprises ions of a mineral.
6. A tissue regeneration system as recited in claim 5 , wherein the mineral is selected from the group consisting of hydroxyapatite, α-tricalcium phosphate, β-tricalcium phosphate, amorphous calcium phosphate, dicalcium phosphate, octacalcium phosphate and calcium carbonate.
7. A tissue regeneration system as recited in claim 1 , wherein the at least one biomolecule does not natively interact with the matrix.
8. A tissue regeneration system as recited in claim 1 , wherein the matrix-binding portion is a calcium-binding protein or a calcium-binding portion of a calcium-binding protein.
9. A tissue regeneration system as recited in claim 1 , wherein the matrix-binding portion is selected from the group consisting of SEQ ID NOs: 1-3.
10. A tissue regeneration system as recited in claim 1 , further comprising cells associated with an outer surface of the template.
11. A tissue regeneration system as recited in claim 10 , wherein the template defines pores therein and wherein the cells are associated with the pores.
12. A method for making a tissue regeneration system as recited in claim 1 , comprising the step of:
exposing ions of an inorganic mineral in a solution at a physiological temperature and pH to a template until an inorganic mineral matrix layer is deposited on the surface of the template; and
exposing at least one biomolecule having a cell-affecting portion and a matrix-binding portion to the matrix layer until the matrix layer has associated therewith the at least one biomolecule, wherein the cell-affecting portion is selected from the group consisting of fibroblast growth factor 2, bone morphogenetic protein-2, bone morphogenetic protein-7 and vascular endothelial growth factor.
13. A method as recited in claim 12 , wherein the template has polar oxygen groups on a surface thereof, and wherein the polar oxygen groups are selected from the group consisting of carboxylic acids, phosphates, aldehydes, ketones, alcohols, carbonyls, hydroxyls or metal oxides.
14. A method as recited in claim 12 , wherein the template is selected from the group consisting of polycarboxylates, polyanhydrides, poly(α-hydroxy esters), poly(ethylene terephthalate), poly(carbonates), poly(amides), poly(lactones), poly(saccharides) and poly(acrylates).
15. A method as recited in claim 12 , wherein the mineral is selected from the group consisting of hydroxyapatite, α-tricalcium phosphate, β-tricalcium phosphate, amorphous calcium phosphate, dicalcium phosphate, octacalcium phosphate and calcium carbonate.
16. A method as recited in claim 12 , wherein the cell-affecting portion comprises SEQ ID NO: 4.
17. A method as recited in claim 12 , wherein the cell-affecting portion comprises SEQ ID NO: 5.
18. A method as recited in claim 12 , wherein the cell-affecting portion comprises SEQ ID NO: 6.
19. A method as recited in claim 12 , wherein the cell-affecting portion comprises SEQ ID NO: 7.
20. A method as recited in claim 12 , wherein the matrix-binding portion is selected from the group consisting of SEQ ID NOs: 1-3.
21. A method as recited in claim 12 , wherein the exposing step is repeated at least twice to deposit on the template a plurality of layered mineral matrices having at least one biomolecule associated therewith.
22. A method as recited in claim 12 , wherein the at least one biomolecule is provided on the surface of a first layer, and a second layer is provided on the surface of the first layer.