Recent advances on bioengineering approaches for fabrication of functional engineered cardiac pumps: A review.

The field of cardiac tissue engineering has advanced over the past decades; however, most research progress has been limited to engineered cardiac tissues (ECTs) at the microscale with minimal geometrical complexities such as 3D strips and patches. Although microscale ECTs are advantageous for drug screening applications because of their high-throughput and standardization characteristics, they have limited translational applications in heart repair and the in vitro modeling of cardiac function and diseases. Recently, researchers have made various attempts to construct engineered cardiac pumps (ECPs) such as chambered ventricles, recapitulating the geometrical complexity of the native heart. The transition from microscale ECTs to ECPs at a translatable scale would greatly accelerate their translational applications; however, researchers are confronted with several major hurdles, including geometrical reconstruction, vascularization, and functional maturation. Therefore, the objective of this paper is to review the recent advances on bioengineering approaches for fabrication of functional engineered cardiac pumps. We first review the bioengineering approaches to fabricate ECPs, and then emphasize the unmatched potential of 3D bioprinting techniques. We highlight key advances in bioprinting strategies with high cell density as researchers have begun to realize the critical role that the cell density of non-proliferative cardiomyocytes plays in the cell-cell interaction and functional contracting performance. We summarize the current approaches to engineering vasculatures both at micro- and meso-scales, crucial for the survival of thick cardiac tissues and ECPs. We showcase a variety of strategies developed to enable the functional maturation of cardiac tissues, mimicking the in vivo environment during cardiac development. By highlighting state-of-the-art research, this review offers personal perspectives on future opportunities and trends that may bring us closer to the promise of functional ECPs.