Biomaterials for cardiac tissue engineering

Abstract

The heart is the first organ to start functioning in a human (at three weeks gestation), often before a mother knows she is expecting. It is also the last organ that remains functional, just before death. The first beats are relatively slow and irregular, peaking at 7 weeks gestation at around 3 Hz, more specifically 175 bpm, then decreasing gradually to 140–150 bpm before birth [1]. Subsequently, in the post-natal period, during childhood and into adulthood, the beating rate will further decrease gradually to reach the resting rate of 1 Hz, 60 bpm, on average, in an adult human. The heart will beat approximately 2.5–3.2 billion times and in a life-time [2] of an individual, pumping 175–224 millions of liters of blood throughout the body. This remarkable and truly unique function of the heart is afforded by a sub-set of unique cells in the heart muscle, termed cardiomyocytes, that have an ability to contract in response to electrical stimulation. Heart muscle, the myocardium, is a powerhouse that works to pump the blood throughout the body. The synchronous and integrated action of the myocardial cardiomyocytes is afforded by several structural characteristics: the cells are aligned in parallel with the orientation angle changing through the ventricular wall enabling the ventricle to twist as it contracts, in an attempt to push as much blood out as possible. Cardiomyocytes are intimately connected to one another, directly through gap junctions, enabling electrical impulses to travel around as well as through the cells contributing to the synchronous contractile response. Cardiomyocytes have limited ability to proliferate, as recent studies have conclusively shown that adult humans will replace at most of 50% of the cardiomyocytes they were born with during the average lifetime of 80 years, with an average proliferation rate less than 1% per year [3]. The vision of cardiac tissue engineering is to develop in the laboratory, high-fidelity mimics of native human tissue for modelling of physiology and disease, or ultimately to repair the damaged or impaired heart muscle. For this effort to be successful, one needs to carefully select the source of cardiomyocytes, develop biomaterials that will support the function and assembly of these cells, and often to cultivate these constructs in bioreactors that are focused on providing appropriate electromechanical stimulation. This special section is focused on biomaterials for cardiac tissue engineering. In general, the appropriate biomaterial for cardiac tissue engineering should be as unique as the heart itself: it should be highly flexible, elastic and capable of enduring millions of contraction cycles, while supporting the seeded cell viability and differentiated phenotype both in vitro and in vivo. The special section combines original research papers and review articles that present recent progress in development of cardiac tissue engineering biomaterials. It discusses potential cell sources in original papers [4, 5] and reviews [6]. The use of various hydrogels for cardiovascular tissue engineering is reviewed [7, 8] and original papers on development of brand new scaffold materials that incorporate architectural complexity of the native myocardium are presented [9, 10]. An approach to increase smooth muscle cell elastogenesis in vitro is presented, an important step towards increasing elasticity during matrix remodelling in engineered tissues [11]. The featured reviews present recent progress in assembling cells and matrix into functional tissues by 3D printing [12], and microfabrication for the purposes of personalization, disease modelling and drug discovery [6, 13]. Once the cells are injected or placed with a biomaterial matrix at the desired site in the heart, their fate needs to be tracked in vivo and this special section brings an original paper on in vivo tracking of angiogenic cells transplanted into rodent hearts [14]. Finally, the progress of in vivo pre-clinical studies with engineered cardiac tissues on biomaterial matrices are reviewed [15].