Why are Tissue Engineered Cardiac Muscle Replacements Needed?

Tissue engineering aims to develop, restore, repair, maintain or replace tissues and organs using various combinations of cells, biomaterials, and biologically active molecules. Cardiac muscle tissue engineering focuses on creating a functional cardiac muscle constructs. The potential applications for these constructs are to repair diseased hearts, to investigate drug interactions in cardiac tissue, and to model cardiac development, functions, physiology, and diseases. Since the human heart cannot regenerate (adult cardiac myocytes are terminally differentiated and cannot replicate after injury), a major breakthrough would be the ability to use these tissue engineered cardiac muscle constructs for replacement therapy for individuals with congestive heart failure and myocardial infarction. Heart failure and myocardial infarction represent the main causes of death in the United States . Further, there are an alarming number of individuals who are diagnosed with heart failure or who have suffered a myocardial infarction. In addition, the incidence of heart failure and myocardial infarction is still increasing each year.

Congestive heart failure (CHF) , or heart failure, results from an underlying cardiac condition that impairs the ability of heart pump a sufficient amount of blood throughout the body to satisfy the needs of the cells of the body. A myocardial infarction, or a heart attack, occurs when an area of the cardiac muscle dies or is permanently damaged due to an inadequate supply of oxygenated blood to that area from a sudden blockage of a coronary artery. The damaged or dead cardiac muscle will be replaced by scar tissue, which will not function as muscle and thus, how impaired the heart becomes dependent on the amount of damage. The best solution to individuals who survive an extensive myocardial infarction and those who develop heart failure is heart transplantation but there is a lack of donors. Mechanical devices provide a temporary alternative but they serve as a conduit to transplantation. Thus, there is great necessity to develop alternative therapeutic strategies to reverse these common and deadly diseases.

Current treatment options for CHF and myocardial infarctions are limited by the inability of myocardial tissue to regenerate after injury, by the limited potential of medications, by the limited functions and complications of the mechanical devices that assist the heart and by the lack of organs for transplantation and the complications with transplantation. The main treatments for CHF and myocardial infarctions (medications, devices, and transplantation) are all temporary measures to improve the weaken heart. Thus, developing a functional tissue engineered cardiac muscle construct as an alternative treatment to replace dead or severely damaged cardiac tissue will allow for regeneration of the injured heart to restore or enhance the contractile function of the failing myocardium.

Why use Tissue Engineering over Cell Transplantation?

Several research groups have shown that injecting directly cell suspensions of various cell types, such as embryonic or adult stem cell derived cardiomyocytes, into the ventricular walls or in the coronary vessels of myocardial infarcts improved the remodeling and function of the heart. However, the concept of tissue engineering has advantages over cell transplantation. (1) With tissue engineering, the size, shape, strength and composition of the graft in vitro can be controlled. (2) The efficacy of cell engraftment is very low since more than 90% of the cell suspension injected is lost. (3) Tissue engineering provides a solution to replacing failing heart tissue.