Computational biomechanics and bioengineering 3D printing to develop a personalized regenerative biological ventricular assist device to provide lasting functional support to damaged hearts (BRAV3)

Ischemic heart disease is the main cause of death in the EU, straining patients and economies. Regenerative Medicine has failed at delivering a definitive solution, and even the breakthrough of cell reprogramming, biomaterials or 3D printing, have not been able to find a curative solution. Generating a muscle with efficient pumping requires a careful recapitulation of the myocardial architecture. BRAV∃ is born with the ambition of shaping this quantum leap in the field. The overall concept is to provide a lasting functional support to injured hearts through the fabrication of regenerative personalized advanced tissue engineering-based biological ventricular assist devices (BioVADs). To do so, we will apply multimodal deep cardiac phenotyping, coupled to advanced Computational Modelling and biomechanical analysis in a large animal model of disease, to create a personalised 3D printable design. We will for the first time create a fibre-reinforced human heart-sized cardiac tissue able to recapitulate the low Young´s Modulus of the myocardium while withstanding pressures generated during the cardiac circle. Using the latest human induced pluripotent stem cell (hiPSC) technology and industrial-scale growth and differentiation, we will cellularize this novel human heart-sized constructs, creating a highly efficiently aligned cardiac tissue (including vasculature). BioVADs will be matured in in-Consortium built electromechanical stimulation bioreactors before transplantation in a porcine model of disease. We anticipate our BioVADs will constitute a one-shot regenerative treatment of IHD, decreasing the burden on healthcare providers and improving the quality of life of patients. Crucially, we will for the first time generate a wealth of information on heart development at a human scale. Delivering this novel application whilst developing the technological environment (bioreactor, chamber, pacemaker) will boost the capacity of the EU to grow economically and lead the field.