Technologies for engineered heart tissues

Abstract

Cardiovascular diseases are the most prevalent cause of death worldwide, especially in developed countries. The heart is the least regenerative organ because cardiac muscle consists mainly of cardiomyocytes that have limited capacity for regeneration. Heart transplantation is the most effective solution to restore the function of the heart but there are not enough donor hearts and there is always a risk of rejection. Engineered heart tissues (EHTs) offer a promising approach because they can be beneficial in the future both in promoting heart tissue regeneration and in drug screening and disease modelling.

This bachelor’s thesis investigates elaborately what kind of technologies there are for engineered heart tissues, what are their manufacturing methods, uses and differences. The thesis also discusses the development history of these technologies and their applicability to medical research and the treatment of heart diseases. EHTs are technologies that aim at modelling cardiac tissues. These cardiac tissues include 3D cell culture of cardiac cells and scaffolding polymers, and they are constructed with engineering techniques. Used cardiomyocytes are either derived from animals like rats or they can be differentiated from stem cells into cardiomyocytes. To generate engineered heart tissues cells and polymers are typically cast in a PDMS-mold. EHTs are capable of contracting like the heart, and this contraction force is often measured.

Several different technologies have been developed for modelling EHTs, like frame-based EHTs, ring-EHTs, pillar-based EHTs, wire-based EHTs and EHT-patches. Their size varies from a few millimeters to a couple of centimeters. Smaller EHTs are used in drug testing and disease modelling whereas the bigger ones are used for cardiac regeneration.

Frame-based EHTs are EHTs that have cells and scaffolding polymers inside the frame. Velcro-tubes or nylon frames can act as frames. The first generated EHTs have been frame-based EHTs. In ring-EHTs, the principle is otherwise the same as in frame-based EHTs, but in them the cells are cast in ring-shaped molds. There are various types of pillar-based EHTs in which pillars are located above or below the molds and cells. The purpose of the pillars is to attach the tissue, limit its contraction and measure the force. In wire-based EHTs the tissues with striations are growing between two parallel wires that allow the measurement of force. One of the newest technologies are different EHT patches that are mesh-structured tissue patches. Such EHT-patch can correlate to human heart size.

EHTs combine biology and engineering, and they can be used to model heart diseases and develop new treatments. In the future, they may reduce the need for animal testing and provide an alternative for demanding heart transplants.