Bioprinting Vascularized Cardiac Tissue: Overcoming Challenges in Regenerative Medicine

Abstract

cardiovascular disease remains the number one global cause of death, and therefore a top-priority target for emerging treatment paradigms. Cardiac tissue engineering is a very promising field for myocardial function regeneration, but the discipline is confronted with overwhelming challenges, namely, to replicate the complex vascular channels necessary for tissue survival and integration. Bioprinting technology delivers spatial resolution to precisely position cells and deposit biomaterials at well-defined locations within three-dimensional, vascularized cardiac tissue constructs. In this review, the state of the art of bioprinting technologies for cardiac applications is critically evaluated, highlighting strengths and limitations of different methods such as inkjet, extrusion-based, laser-guided, and stereolithography processes. The selection of biomaterial and biomaterial/bioink design for the viability, mechanics, and electrical conductivity of cardiac tissue is considered. Vascularization issue is informed by the review—case-making for techniques such as revascularization, endothelial cell co-printing, angiogenic factor addition, and sacrificial templating for hierarchical vascular network formation. Functionality of different cellular components and maturation under mechanical and electrical stimulation are also evaluated. The review concludes by mentioning technology, biology, and regulatory problems and views future trends in terms of the integration of artificial intelligence, 4D bioprinting, and tissue constructs tailored to individuals. From an integrative synthesis of recent progress and existing problems, this review attempts to map future research directions to clinically translational vessel-engineered cardiac tissue cultured via bioprinting.