Current Challenges and Solutions to Tissue Engineering of Large-scale Cardiac Constructs.

purpose of reviewLarge-scale tissue engineering of cardiac constructs is a rapidly advancing field; however, there are several barriers still associated with the creation and clinical application of large-scale engineered cardiac tissues. We provide an overview of the current challenges and recently (within the last 5 years) described promising solutions to overcoming said challenges. RECENT

findingsThe five major criteria yet to be met for clinical application of engineered cardiac tissues are successful electrochemical/mechanical cell coupling, efficient maturation of cardiomyocytes, functional vascularization of large tissues, balancing appropriate immune response, and large-scale generation of constructs. Promising solutions include the use of carbon/graphene in conjunction with existing scaffold designs, utilization of biological hormones, 3D bioprinting, and gene editing. While some of the described barriers to generation of large-scale cardiac tissue have seen encouraging advancements, there is no solution that yet achieves all 5 described criteria. It is vital then to consider a combination of techniques to achieve the optimal construct. Critically, following the demonstration of a viable construct, there remain important considerations to address associated with good manufacturing practices and establishing a standard for clinical trials.