The production of a functional cardiac tissue to be transplanted in the injured area of the infarcted myocardium represents a challenge for regenerative medicine. Most cell-based grafts are unviable because of inadequate perfusion; therefore, prevascularization might be a suitable approach for myocardial tissue engineering. To this aim, cells with a differentiation potential towards vascular and cardiac muscle phenotypes have been cocultured in 2D or 3D appropriate scaffolds. In addition to these basic approaches, more sophisticated strategies have been followed employing mixed-cell sheets, microvascular modules, and inosculation from vascular explants. Technologies exerting spatial control of vascular cells, such as topographical surface roughening and ordered patterning, represent other ways to drive scaffold vascularization. Finally, microfluidic devices and bioreactors exerting mechanical stress have also been employed for high-throughput scaling-up production in order to accelerate muscle differentiation and speeding the endothelialization process. Future research should address issues such as how to optimize cells, biomaterials, and biochemical components to improve the vascular integration of the construct within the cardiac wall, satisfying the metabolic and functional needs of the myocardial tissue. 1. Introduction One of the most ambitious objectives for cardiac tissue engineering aimed at repairing an infarcted cardiac region is the production of a stem cell-based functional tissue that can be fully integrated within native myocardium [1–3]. However, although basic researches and preclinical studies have paved the way for translational applications of cell therapy for cardiac repair, so far clinical trials have failed to reproduce relevant positive results [4]. Ongoing efforts are thus needed to optimize most steps involved with a therapeutic approach to myocardial infarction and failure using stem cells, including cell preparations, cell delivery techniques, and cell survival [5]. Up to now, stem cells transplanted alone or carried onboard of polymeric devices have shown a short survival in the heart because these grafts were not adequately perfused by coronary vessels [6, 7]; hence, most grafted cells rapidly die or migrate near the border zone of the infarcted area, close to the coronary vessels [8]. To provide sufficient oxygen and nutrients for survival, metabolically active grafts should be supplied by a vascular network reaching cardiomyocytes within a 150–200?μm distance [9]. Therefore, the laboratory realization of prevascularized
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