Computational biomechanics, 3D printing and hiPSCs: towards the generation of a biological ventricular assist device

M M Mazo Vega(1, 13)   O Iglesias-García(13)   A Sánchez-Bueno(14)   M Pérez Araluce(14)   M E Fernández Santos(2)   P Legazpi(2)   A Sánchez de la Nava(2)   S Janssens(10)   F Fernández-Avilés(2)   N Montserrat(12)   M Serra(11)   N Laita(3)   M Rosales(3)   E Peña(3)   E Pueyo(3)   M Doblaré(3)   F Prosper(1)   J Malda(6)   J Gröll(9)

1: Clinica Universidad de Navarra    2: Fundación para la Investigación Biomédica del Hospital General Universitario Gregorio Marañón    3: Universidad de Zaragoza    4: Leartiker S. Coop    5: EBERS Medical Technology    6: Utrecht University    7: Boston Scientific    8: Technical University - TU Eindhoven    9: University Hospital Würzburg    10: Katholieke Universiteit Leuven    11: iBET    12: Institute for Bioengineering of Catalonia (IBEC)    13: CIMA    14: Universidad de Navarra

The explosive technological development in impacting areas such as human pluripotent stem cells (hiPSCs), biomaterials or additive manufacturing have put us closest to the aim of fabricating human tissues therapeutic tissues in the lab. However, there are crucial remaining factors, some technical, some economical, some regulatory, that hinder the final fulfilment of this ambitious aim. In the specific case of the myocardium, one such stepping stone is the relationship between cardiac muscle alignment and contractile output. In the project H2020 BRAV3, we are aiming at using computational modelling fed by cardiac-specific geometrical and mechanical data, to fabricate a biological ventricular assist device (BioVAD) to treat ischemic hearts. This BioVAD will supply new functional myocardium able to contract in the specific way a given myocardial ischemia requires (personalized). In order to do this, we are use a composite materials approach by which a melt electrospun scaffold in 3D printed in medical grade polycaprolactone, complying with the specific mechanical requirements of the heart. Human induced pluripotent stem cells are differentiated to the main cardiac phenotypes (cardiomyocyte, cardiac fibroblast, endothelium and smooth muscle), and employed to investigate the building of a functional BioVAD using either natural or synthetic biomaterials. At the same time, a large electromechanical bioreactor is designed and built, in order to promote the functional maturation of the fabricated BioVADs. All in all, the project results are advancing towards the aim of devising a new and potentially definitive therapeutic for myocardial infarction.