Cardiac Tissue Engineering

The cardiac myocyte is the most physically energetic cell in the body, contracting more than 3 billion times in an average human lifespan, and pumping over 7,000 liters of blood per day along 100,000 miles of blood vessels. In native heart, oxygen is supplied by diffusion from capillaries that are spaced ~20 µm apart, by blood containing hemoglobin. We are trying to pursue a “biomimetic” approach to cardiac tissue engineering driven by the conditions derived from developmental biology.

To engineer a thick and compact cardiac muscle consisting of viable cells, we culture the cells on porous and elastic scaffolds containing an array of channels perfused with culture medium (to mimic blood flow through the capillary network) which in turn can be supplemented by an oxygen carrier (to mimic the role of hemoglobin). The relationships between oxygen supply and consumption were studied with the aid of mathematical modeling that enabled us to derive quantitative criteria for the design of cardiac tissue engineering systems.

Another factor crucial for the development and function of native myocardium is the orderly coupling between electrical pacing signals and the macroscopic contractions. The application of electrical signals designed to mimic those in the heart and applied to induce synchronous contractions of cultured tissue constructs markedly enhanced functional assembly of the engineered tissue via physiologically relevant mechanisms. We are now extending these studies to the use of human stem cells, with the goal to engineer thick, compact, electro-mechanically functional, and vascularized cardiac tissue. For these experiments, we are developing customized scaffolds and bioreactors with electrical stimulation, medium perfusion and real-time imaging.