Modelling, design, fabrication and characterization of engineered human myocardium made with melt electrowriting and cardiac cells derived from hiPSCs

The adult human heart has evolved to become a highly specialized organ, whose continuous pumping of blood is critical for survival. However, its ability to regenerate or self-repair following injury is very limited, so consequently any event or disease resulting in damage to the heart poses a serious threat to the patient. Moreover, cardiovascular diseases represent one of the most pressing healthcare concerns nowadays, as they are the leading cause of death worldwide, and the number of cases is only expected to increase in the following years. Despite great progress made over the years to treat cardiovascular diseases, to date there is no therapy able to fully cure a heart that has been damaged. In consequence, there is a dire need to generate new strategies to repair the heart damage and restore the lost cardiac function, as well as to develop accurate modelling platforms to advance in the understanding of disease progression and assess the effectiveness of new drugs. Since its advent, cardiac tissue engineering and regenerative medicine has been regarded as a promising candidate to realise this enormous challenge. Given its interdisciplinary nature, scientific breakthroughs in different areas such as cellular reprogramming, polymer chemistry, and additive manufacturing technologies have resulted in the advancement of cardiac tissue engineering and regenerative medicine over the years. One of such cornerstone discoveries was the generation of induced pluripotent stem cells and subsequent differentiation to different cardiac phenotypes, and the present Thesis revolves around their application to generate patient-specific cardiac disease models and humanised engineered functional cardiac minitissues. Firstly, we reprogrammed peripheral blood mononuclear cells from a transthyretin amyloid cardiomyopathy patient, resulting in the generation of a new cell line carrying a c.128G>A (p.Ser43Asn) mutation in the transthyretin gene. Experiments demonstrated the efficacy and safety of the approach, confirming the ...