Prosthetic Tissue Valves

Abstract

A prosthetic valve comprising a conical shaped sheet member comprising an extracellular matrix (ECM) composition, the sheet member having a plurality of open slit regions that are disposed uniformly on linear planes that are parallel to the sheet member longitudinal axis, a proximal annulus engagement end diameter and length ratio in the range of 5:1 to 2:1 and at least one valve leaflet.

What is claimed is: 
     
         1 . A prosthetic valve, comprising:
 a conical shaped sheet member comprising a first extracellular matrix (ECM) composition, said first ECM composition comprising first acellular ECM from a first mammalian tissue source,   said sheet member further comprising a longitudinal axis, inner and outer surfaces, a proximal annulus engagement end,   said sheet member further comprising a plurality of open slit regions that are disposed uniformly on linear planes that are parallel to said sheet member longitudinal axis,   said sheet member further comprising a proximal annulus engagement end diameter and length ratio in the range of 5:1 to 2:1,   said sheet member further comprising at least one internal valve leaflet,   said sheet member being configured to induce host cell and tissue proliferation, remodeling of damaged cardiovascular tissue and regeneration of new cardiovascular tissue and tissue structures with site-specific structural and functional properties, when said sheet member is disposed proximate a valve annulus.   
     
     
         2 . The prosthetic valve of  claim 1  wherein said sheet member has a length from said proximal annulus engagement end to said distal end in the range of 5 mm to 150 mm. 
     
     
         3 . The prosthetic valve of  claim 2 , wherein said slit regions comprise in the range of 10% to 98% of said sheet member length. 
     
     
         4 . The prosthetic valve of  claim 1 , wherein said first mammalian tissue source is selected from the group consisting of small intestine submucosa (SIS), urinary bladder submucosa (UBS), urinary basement membrane (UBM), liver basement membrane (LBM), stomach submucosa (SS), mesothelial tissue, subcutaneous extracellular matrix, large intestine extracellular matrix, placental extracellular matrix, omentum extracellular matrix, heart extracellular matrix and lung extracellular matrix. 
     
     
         5 . The prosthetic valve of  claim 1 , wherein said first ECM composition further comprises at least one exogenously added first biologically active agent. 
     
     
         6 . The prosthetic valve of  claim 5 , wherein said first biologically active agent comprises a cell selected from the group consisting of a human embryonic stem cell, fetal cardiomyocyte, myofibroblast, and mesenchymal stem cell. 
     
     
         7 . The prosthetic valve of  claim 5 , wherein said first biologically active agent comprises a first growth factor selected from the group consisting of a transforming growth factor-alpha (TGF-α), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2), and vascular epithelial growth factor (VEGF). 
     
     
         8 . The prosthetic valve of  claim 1 , wherein said first ECM composition further comprises at least a first pharmacological agent. 
     
     
         9 . The prosthetic valve of  claim 8 , wherein said first pharmacological agent comprises a first agent selected from the group consisting of an antibiotic, anti-viral agent, analgesic, anti-inflammatory, anti-neoplastic, anti-spasmodic, and anticoagulant and antithrombic agent. 
     
     
         10 . The prosthetic valve of  claim 8 , wherein said first pharmacological agent comprises a first statin selected from the group consisting of atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. 
     
     
         11 . The prosthetic valve of  claim 1 , wherein said sheet member further comprises an annulus ring, said annulus ring being disposed on said proximal annulus engagement end of said sheet member. 
     
     
         12 . The prosthetic valve of  claim 11 , wherein said annulus ring comprises a second ECM composition, said second ECM composition comprising second acellular ECM from a second mammalian tissue source selected from the group consisting of small intestine submucosa (SIS), urinary bladder submucosa (UBS), urinary basement membrane (UBM), liver basement membrane (LBM), stomach submucosa (SS), mesothelial tissue, subcutaneous extracellular matrix, large intestine extracellular matrix, placental extracellular matrix, ornomentum extracellular matrix, heart extracellular matrix and lung extracellular matrix. 
     
     
         13 . The prosthetic valve of  claim 12 , wherein said second ECM composition further comprises at least one exogenously added second biologically active agent. 
     
     
         14 . The prosthetic valve of  claim 13 , wherein said second biologically active agent comprises a growth factor selected from the group consisting of TGF-α, TGF-β, FGF-2, and VEGF. 
     
     
         15 . The prosthetic valve of  claim 11 , wherein said annulus ring comprises poly(urethane urea). 
     
     
         16 . The prosthetic valve of  claim 11 , wherein said annulus ring comprises poly(glycerol sebacate). 
     
     
         17 . The prosthetic valve of  claim 1 , wherein said sheet member further comprises a structural ring that is disposed on said distal end of said sheet member, said structural ring being configured to receive said distal end of said sheet member therein. 
     
     
         18 . The prosthetic valve of  claim 17 , wherein said structural ring comprises a shape memory alloy. 
     
     
         19 . The prosthetic valve of  claim 17 , wherein said structural ring comprises poly(urethane urea). 
     
     
         20 . The prosthetic valve of  claim 17 , wherein said structural ring comprises poly(glycerol sebacate). 
     
     
         21 . The prosthetic valve of  claim 1 , wherein said sheet member further comprises an outer coating comprising a pharmacological composition.