Energetic three-dimensional artificial cardiac patch and uses thereof

Abstract

In some embodiments, the present disclosure provides a method for fabricating a three-dimensional artificial cardiac patch construct. In some embodiments, such method includes the steps of coating a substrate with an organic polymer; allowing the organic polymer coating to air dry; mounting anchors on the organic polymer coating; and sterilizing the organic polymer coating and the anchors. In further embodiments, the method includes the steps of forming a biodegradable gel-based support scaffold on top of the organic polymer coating and seeding the biodegradable gel-based support scaffold with neonatal cardiac cells. In yet further embodiments, the method comprises culturing the neonatal cardiac cells in vitro to form a real cardiac layer, under culture conditions that are suitable for the cells to self-organize into a monolayer and detach from the substrate to form the three-dimensional cardiac patch. In some embodiments, the present disclosure pertains to a method of treatment of cardiac tissue injury in a subject in need thereof. In some embodiments, the method includes implanting the three-dimensional artificial cardiac patch described above in the injured area of the subject. In another embodiment the present disclosure provides a composition comprising the three-dimensional artificial cardiac patch described above. Additional embodiments of the present disclosure pertain to a medicament including the three-dimensional artificial cardiac patch described above.

What is claimed is: 
     
         1 . A method for the treatment of cardiac tissue injury comprising:
 implanting a fabricated three-dimensional artificial cardiac patch in a subject in need thereof, wherein the fabrication of the three-dimensional artificial cardiac patch comprises:
 coating a substrate with an organic polymer; 
 allowing the organic polymer coating to air dry; 
 mounting anchors on the organic polymer coating; 
 sterilizing the organic polymer coating and the anchors; 
 forming a biodegradable gel-based support scaffold on top of the organic polymer coating; 
 seeding the biological support scaffold with neonatal cardiac cells; and 
 culturing the neonatal cardiac cells in vitro to form a real cardiac layer, 
   wherein the culture conditions are suitable for the cells to self-organize and detach from the substrate to form the three-dimensional cardiac patch.   
     
     
         2 . The method of  claim 1 , wherein the cardiac tissue injury is due to acute or chronic stress, atheromatous disorders of blood vessels, ischemia, myocardial infarction, inflammatory disease and cardiomyopathies or myocarditis. 
     
     
         3 . The method of  claim 2 , wherein the acute or chronic stress is due to systemic hypertension, pulmonary hypertension or valve dysfunction. 
     
     
         4 . The method of  claim 2 , wherein the atheromatous disorder of blood vessels is coronary artery disease. 
     
     
         5 . The method of  claim 1 , wherein the anchors are secured to the substrate, and
 wherein the anchors are utilized to define outer perimeters of the three-dimensional cardiac patch.   
     
     
         6 . The method of  claim 5  further comprising the step of trimming the real cardiac layer around the outer perimeters defined by the anchors, wherein the real cardiac layer detaches from the substrate to form the three-dimensional cardiac patch. 
     
     
         7 . A three-dimensional artificial cardiac patch comprising:
 an organic polymer coated on a substrate;   a biodegradable gel-based support scaffold formed on top of the organic polymer; and   cardiac cells, wherein the cardiac cells are seeded on the biodegradable gel-based scaffold.   
     
     
         8 . The three-dimensional artificial cardiac patch of  claim 7  further comprising at least one agent from the group consisting of survival factors, growth factors, pharmacological agents, angiogenic factors, beta-blockers or ACE inhibitors. 
     
     
         9 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the patch is implanted in a suitable recipient. 
     
     
         10 . The three-dimensional artificial cardiac patch of  claim 9 , wherein the recipient suffers from a cardiac tissue injury or a congenital heart disease. 
     
     
         11 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the organic polymer is a silicone elastomer. 
     
     
         12 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the silicone elastomer is polydimethylsiloxane elastomer (PDMS). 
     
     
         13 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the biodegradable gel-based support scaffold is biocompatible and non-immunogenic. 
     
     
         14 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the biodegradable gel-based support scaffold is fibrin. 
     
     
         15 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the seeding of the biodegradable gel-based support scaffold comprises layering the cardiac cells onto the scaffold. 
     
     
         16 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the seeding of the biodegradable gel-based support scaffold comprises embedding the cardiac cells into the biodegradable gel-based support scaffold. 
     
     
         17 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the cardiac cells comprise neonatal cardiac cells. 
     
     
         18 . The three-dimensional artificial cardiac patch of  claim 17 , wherein the neonatal cardiac cells comprise fibroblasts, cardiomyocytes, endothelial cells, smooth muscle cells and cardiac stem cells. 
     
     
         19 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the artificial three-dimensional patch is spontaneously contractile. 
     
     
         20 . The three-dimensional artificial cardiac patch of  claim 7 , wherein the fabricated artificial three-dimensional patch exhibits contractile twitch force.