Compositions for regenerating defective or absent myocardium
View Patent ↗Compositions of the invention for regenerating defective or absent myocardium comprise an emulsified or injectable extracellular matrix composition. The composition may also include an extracellular matrix scaffold component of any formulation, and further include added cells, proteins, or other components to optimize the regenerative process and restore cardiac function.
1. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising small intestine submucosa (SIS), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising a collagen Type IV protein, said supplemental collagen Type IV protein comprising at least 0.1% by weight of said composition, said supplemental collagen Type IV protein being linked to said ECM, wherein said supplemental collagen Type IV protein interacts with said MMPs to modulate activity thereof and said VEGF to control and enhance angiogenesis and, thereby, matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue.
2. The composition of claim 1 , wherein said ECM further comprises an exogenously added cytokine.
3. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement submucosa (LBS), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising a collagen Type IV protein, said supplemental collagen Type IV protein comprising at least 0.1% by weight of said composition, said supplemental collagen Type IV protein being linked to said ECM, wherein said supplemental collagen Type IV protein interacts with said MMPs to modulate activity thereof and said VEGF to control and enhance angiogenesis and, thereby, matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue.
4. The composition of claim 3 , wherein said ECM further comprises an exogenously added cytokine.
5. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement membrane (LBM), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising a collagen Type IV protein, said supplemental collagen Type IV protein comprising at least 0.1% by weight of said composition, said supplemental collagen Type IV protein being linked to said ECM, wherein said supplemental collagen Type IV protein interacts with said MMPs to modulate activity thereof and said VEGF to control and enhance angiogenesis and, thereby, matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue.
6. The composition of claim 5 , wherein said ECM further comprises an exogenously added cytokine.
7. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising urinary bladder submucosa (UBS), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising a collagen Type IV protein, said supplemental collagen Type IV protein comprising at least 0.1% by weight of said composition, said supplemental collagen Type IV protein being linked to said ECM, wherein said supplemental collagen Type IV protein interacts with said MMPs to modulate activity thereof and said VEGF to control and enhance angiogenesis and, thereby, matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue.
8. The composition of claim 7 , wherein said ECM further comprises an exogenously added cytokine.
9. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising stomach submucosa (SS), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising a collagen Type IV protein, said supplemental collagen Type IV protein comprising at least 0.1% by weight of said composition, said supplemental collagen Type IV protein being linked to said ECM, wherein said supplemental collagen Type IV protein interacts with said MMPs to modulate activity thereof and said VEGF to control and enhance angiogenesis and, thereby, matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue.
10. The composition of claim 9 , wherein said ECM further comprises an exogenously added cytokine.
11. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising placental extracellular matrix, said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising a collagen Type IV protein, said supplemental collagen Type IV protein comprising at least 0.1% by weight of said composition, said supplemental collagen Type IV protein being linked to said ECM, wherein said supplemental collagen Type IV protein interacts with said MMPs to modulate activity thereof and said VEGF to control and enhance angiogenesis and, thereby, matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue.
12. The composition of claim 11 , wherein said ECM further comprises an exogenously added cytokine.
13. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising heart extracellular matrix, said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising a collagen Type IV protein, said supplemental collagen Type IV protein comprising at least 0.1% by weight of said composition, said supplemental collagen Type IV protein being linked to said ECM, wherein said supplemental collagen Type IV protein interacts with said MMPs to modulate activity thereof and said VEGF to control and enhance angiogenesis and, thereby, matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue.
14. The composition of claim 13 , wherein said ECM further comprises an exogenously added cytokine.