Cardiovascular diseases are the main cause of death in the world and are often associated with the occurrence of arrhythmias due to disruption of myocardial electrical integrity. Pathologies involving dysfunction of the specialized cardiac excitatory/conductive tissue are also common and constitute an added source of morbidity and mortality since current standard therapies withstand a great number of limitations. As electrical integrity is essential for a well-functioning heart, innovative strategies have been bioengineered to improve heart conduction and/or promote myocardial repair, based on: (1) gene and/or cell delivery; or (2) conductive biomaterials as tools for cardiac tissue engineering. Herein we aim to review the state-of-art in the area, while briefly describing the biological principles underlying the heart electrical/conduction system and how this system can be disrupted in heart disease. Suggestions regarding targets for future studies are also presented.

The use of engineered cardiac tissue for high-throughput drug screening/toxicology assessment remains largely unexplored. Here we propose a scaffold that mimics aspects of cardiac extracellular matrix while preserving the contractility of cardiomyocytes. The scaffold is based on a poly(caprolactone) (PCL) nanofilm with magnetic properties (MNF, standing for magnetic nanofilm) coated with a layer of piezoelectric (PIEZO) microfibers of poly(vinylidene fluoride-trifluoroethylene) (MNF+PIEZO). The nanofilm creates a flexible support for cell contraction and the aligned PIEZO microfibers deposited on top of the nanofilm creates conditions for cell alignment and electrical stimulation of the seeded cells. Our results indicate that MNF+PIEZO scaffold promotes rat and human cardiac cell attachment and alignment, maintains the ratio of cell populations overtime, promotes cell-cell communication and metabolic maturation, and preserves cardiomyocyte (CM) contractility for at least 12 days. The engineered cardiac construct showed high toxicity against doxorubicin, a cardiotoxic molecule, and responded to compounds that modulate CM contraction such as epinephrine, propranolol and heptanol.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detach from the chip after a few days of culture; this process is mediated by the upregulation of metalloprotease 13 (MMP13). Importantly, double-mutant Lmna G609G/G609G Mmp13 −/− mice or Lmna G609G/G609G Mmp13 +/+ mice treated with a MMP inhibitor show lower SMC loss in the aortic arch than controls. MMP13 upregulation appears to be mediated, at least in part, by the upregulation of glycocalyx. Our HGPS-SMCs chip represents a platform for developing treatments for HGPS individuals that may complement previous pre-clinical and clinical treatments.